- NUF Congress 2015

Transcription

- NUF Congress 2015

NUF Congress
3 - 5 June 2015
30 th
Congress
Anniversary
Abstract Book
Malmö Arena
NUF Congress, 3-5 June 2015
WIFI. Net: MalmöArenaGuest
Poster Area
Exhibition
Plan A
Arenarummet
Registration
Entrance
A1
A20
Wardrobe
Stairs to NP
NP
(Nedre Plan)
Palissad Väst
Speakers service
center
Palissad Öst
Palissad Syd
Stairs from Plan A
2015.04.26
©Destination Öresund
Content
Oral presentation #1
Urolithiasis and Urological Infection
Wednesday 3rd June, 16.30 - 17.30
Palissad VÄST
5
Localized Prostate Cancer,
Early Detection, Epidemiology and Imaging
Wednesday 3rd June, 16.30 - 17.30
Arenarummet
10
Localized Prostate Cancer Treatment
Thursday 4th June, 14.00 - 15.00
Palissad VÄST
16
Renal/Penile Cancer & Reconstructive Surgery
Palissad VÄST
25
BPH, LUTD & Andrology
Palissad ÖST
32
Urothelial Cancer
Friday 5th June, 08.00 - 09.30
Palissad VÄST
37
Prostate Cancer (various)
Palissad VÄST
44
Prostate Cancer (various)
Arenarummet
52
Oral presentation #A
Nurses Programme
Palissad ÖST
61
Authors index
64
ORAL PRESENTATION #1
Wednesday 3rd June
16.30 - 17.30
Palissad VÄST
#01 DOES THE INTERNAL STRUCTURE OF RENAL CALCULI ON
NCCT PREDICT ESWL OUTCOME?
Frederikke Eichner Christiansen, Kim H.
Andreassen, Susanne S. Osther and Palle J.S.
Osther.
Urological Research Center, Dept. of Urology,
Lillebaelt Hospital, University of Southern Denmark, Fredericia, Denmark.
INTRODUCTION AND OBJECTIVES:
The internal structure of renal calculi can
be determined on CT- imaging using bone
window, and can be classified as homogeneous
(solid) or inhomogeneous (rough). In vitro
studies have shown that homogeneous stones
are less responsive to shock wave lithotripsy
(SWL). Thus the internal structure might be a
predictor for a successful outcome of extracorporeal shock wave lithotripsy (ESWL). The
objective was to evaluate outcome of in vivo
ESWL in patients with inhomogeneous versus
homogeneous kidney stones.
MATERIALS AND METHODS: 111
patients with solitary renal calculi treated with
ESWL (Storz Medical Modulith® SLX F2)
were included. Treatment data were registered
prospectively and follow-up data were collected retrospectively. All patients had NCCT
performed prior to ESWL and at follow-up
after three months. The stones were categorized
as homogeneous or inhomogeneous on bone
window of the CT-scan using magnification.
Stone size (the largest diameter) was mean 10
mm [95% CI: 9-11 mm]. Male/female ratio
was 55/45%. At follow-up the patient’s stone
status was registered. Stone free was defined as
no residuals or clinically insignificant residual
fragments ≤ 3 mm on NCCT. Retreatment and
auxiliary procedures were registered.
STATISTICS: logistic regression and chisquared test (Stata 13)
RESULTS: Overall stone free rate (SFR) was
50,5% and the efficacy quotient (EQ) was
39,5 %. Odds for being stone free were lower
in patients with inhomogeneous stones, but
compared to patients with homogeneous stones
the difference was not significant (OR= 0.48,
p= 0.90). There was a significant difference
in stone size between the two groups 12 mm
[95% CI: 10-13 mm] vs 8 mm [95% CI: 8-9
mm], OR= 1.2, p=0.001. When we adjusted
for stone size, there was no difference in odds
for being stone free in the two groups. There
was no difference in retreatment rates in the
two groups (p=0.87).
CONCLUSION: Internal structure of renal
calculi is no predictor for ESWL success in
vivo.
#02 RIGID PATIENT SELECTION
FOR TUBELESS PCNL MAY NOT
BE WARRANTED - THE AARHUS
EXPERIENCE
S. Fuglsig, A. M. Ryhammer and F. Schmidt.
Dept. of Urology, Aarhus University Hospital
Skejby, Aarhus, Denmark
INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is considered standard of care
for large, multiple or complex kidneystones and
even some ureteric stones. Recent years have
seen an increasing interest in simplifying PCNL
by using the supine position and/or a tubeless
procedure without postoperative nephrostomy.
We present our results for a combined supine
tubeless procedure with an indwelling JJ-stent
placed peroperatively.
Material and methods: During an 11 month
period the 2 involved surgeons performed 45
PCNLs . All patients were independently of
pre-operative characteristics considered eligible
for a supine tubeless procedure and would only
be excluded in case of bleeding, perforation of
the collecting system, occluding ureteric stones
or if a tubeless procedure was deemed substandard by the surgeon. Apart from being tubeless
the procedure was done according to depart5
ment standards. Five patients had an indwelling
nephrostomy pre-operatively. Two patients had
2 procedures due to bilateral stones. Patient
data were recorded pre-operatively along with
OR-time and complications.
RESULTS: Of 45 eligible patients 31(23
males) had a tubeless procedure. Median age
was 54 (range 26-76years), ASA was 1 or 2
apart from 2 being ASA 3. Median BMI was
26.5 (range 16.7 - 41.6). Four patients were
seriously physically handicapped.
Twentyone patients had multiple stones,
5 patients had staghorn calculi. Largest stone
size ranged from 7 to 60 mm (median 15.5
mm). Four staghorn stones were only described
as ””large””. Mean OR-time was 110 (range
27 - 199) minutes and all but 4 patients were
stonefree - largest residual stone was 9mm in
one of the patients with staghorn. Only minor
complications were observed. Two patients
developed postoperative fever, easily treated
with antibiotics. Three patients had nausea
and dizziness after being anaesthetized, 1 had
bother from the JJ-stent needing early removal,
1 patient presented with bleeding 7 days after
discharge and 1 patient with hypercalcaemia
developed a large encrustation on the JJ-stent.
CONCLUSION: Most published series of
tubeless PCNL have been quite rigid in preoperative selection of the included patients
excluding patients of high age, high BMI,
significant comorbidity or large stone burden.
Our approach of deeming all patients eligible for a tubeless procedure regardless of preoperative status seems feasible and a very strict
selection of patients does not seem justified.
remains unknown. Foreign bodies lodged in a
penile urethra diverticulum are very uncommon clinical entities.
CASE PRESENTATION: A 59-year-old healthy male was referred to our practice because
of a penile ventral bulging and displacement of
the penile shaft. He reported local discomfort
and recurrent urinary tract infections for a few
months as well as an occasional painful and
difficulty voiding. He described the need to
pull the mass down in order to properly void.
His background was unremarkable for any
kind of medical problems, and he was on no
medication whatsoever. He described a urethral
procedure as a child; some form of grafting was
made, but he could not supply us with further
information.
Physical examination revealed a ventral
mid-shaft large non-tender mass displacing the
penile urethra. Penile urethrosonography and
urethral MRI revealed a solid homogeneous
and calcified mass, measuring 4x3cm. Endoscopically we found the mass was in fact to be
long-standing lithiasis associated with a scrotal
graft, with the scrotal hair serving has a nidus
for lithiasis formation. We had to convert to an
open procedure. An open urethral diverticulectomy followed by primary urethral reconstruction was then performed, over a Foley catheter.
Post-operative period was uneventful. He is
asymptomatic after 3 months of follow-up.
CONCLUSION: Male urethra diverticulum is
an uncommon entity. Careful anamnesis may
reveal clues to disease’s etiology. Diverticulum
excision and primary urethral reconstruction
may be the only solution in complicated cases.
#03 ACQUIRED MALE URETHRA
DIVERTICULUM WITH LITHIASIS
PRESENTING AS A PENILE MASS
#04 SPECTRUM AND INCIDENCE
OF DEFINITIVE SURGERY FOR
NEPHROLITHIASIS IN ANKYLOSING SPONDYLITIS AND GENERAL POPULATION: A PROSPECTIVE POPULATION-BASED SWEDISH
NATIONAL COHORT STUDY WITH
MATCHED GENERAL POPULATION COMPARATOR SUBJECTS
Sandro Gaspar, João P. Marcelino, Francisco
Martins, José Dias and Tomé M. Lopes
Department of Urology, University of Lisbon
School of Medicine, Hospital Santa Maria,
Lisbon, Portugal
INTRODUCTION: Urethra diverticulum in
a male is a very rare condition; its incidence
6
AK Jakobsen1, LTH Jacobsson2, 4, O Patschan1,
Hopfgarten T1, J Askling3 and LE Kristensen4, 5
Dept of Urology, Skåne University Hospital,
Malmö, Sweden; 2Dept of Rheumatology and
Inflammation Research, Sahlgrenska Academy at
University of Gothenburg, Gothenburg, Sweden;
3
Clinical Epidemiology Unit and Rheumatology
Unit, Dept of Medicine (Solna), Karolinska
Institutet; Stockholm, Sweden; 4Dept of Clinical Sciences, Section of Rheumatology, Malmö,
Lund University, Malmö, Sweden; 5The Parker
Institute, Dept of Rheumatology; Copenhagen
University Hospital, Frederiksberg, Denmark.
1
BACKGROUND: Nephrolithiasis (NL) poses
a substantial and growing healthcare burden worldwide. Ankylosing spondylitis (AS)
patients have been demonstrated to have a
two-fold risk of NL.
OBJECTIVE: To estimate rates and type
of definitive intervention for NL in Swedish
patients with AS compared to the general
population.
METHODS: A prospective national cohort
study based on linkage of data from several
Swedish population-based registries, January
2001 through December 2009, was performed.
Incidence rates and the spectrum of interventions for NL during follow-up in patients
with AS was compared to general population
comparator (GPC) subjects matched on age,
sex and area of residence.
RESULTS: 8,572 AS patients were followed
for 49,959 person-years (py) and 39,639
matched general population comparators were
followed for 225,221 py. Mean age at study
entry was 46 years (inter quartile range 36 - 56
years), 65% were males. A diagnosis of NL
was recorded in 466 of GPC compared to 250
of the AS patients during the study period.
Twenty-nine % of AS patients with a diagnosis
of NL during the study period underwent an
intervention for NL, compared to 24% of GPC
(p=0.21). As illustrated in figure 1, Shock Wave
Lithotripsy (ESWL) was the dominating type
of intervention in AS (63%) and in comparators (64%), followed by ureteroscopic procedures (URS) (26% and 25%, respectively) and
percutaneous nephrolithotomy (PCNL) (9%
and 6%, respectively). Open surgery constituted 1% in AS patients and 2 % in comparators.
Based on 72 vs. 114 first interventions during
the study period, the Rate Ratio in overall AS
patients was 2.9 (95% CI 2.1 to 3.8). In subjects with a diagnosis of NL prior to the study
period, the rate ratio for AS patients compared
to GPC increased to 3.7 (95% CI 1.8 to 7.7),
but for subjects without prior NL was 2.1
(95% CI 1.5 to 3.0).
CONCLUSIONS: Patients with AS are at a
nearly three-fold increased risk of definitive surgical interventions for kidney stones compared
to the general population and the subgroup of
AS patients with recurrent NL are at a 3.7-fold
increased risk of a definitive intervention. The
fraction and choice of surgical management is
similar in AS and general population.
#05 TOPIRAMATE-INDUCED
NEPHROLITHIASIS
Ida Erika Wieborg von Rosen and Kim Hovgaard Andreassen.
Department of Urology, Hospital Lillebaelt,
Denmark. Urological Research Center, Institute of
Regional Health Research, University of Southern
Denmark.
Drug induced nephrolithiasis is rare. The
antiepileptic drug topiramate was introduced
in 1996, initially for prevention of epileptic
seizures. Indications and off-label use has since
been expanded to migraine prophylaxis, neuropathic pain, alcohol- and cocaine addiction,
obsessive-compulsive disorder, for weight
loss, bipolar disorders, bulimia nervosa, post
traumatic stress disorder, idiopathic intracranial
hypertension, infantile spasm, smoking cessation, cluster headache, trigeminal neuralgia
and type 2 diabetes. Topiramate is a carbonic
anhydrase inhibitor and can cause mixed renal
tubularacidosis (RTA) resulting in an increased
risk of stone formation. The first 2 cases of
topiramate-induced nephrolithiasis (TIN) were
published in 2002. The risk of developing RTA
from topiramate is 26-32%. The number of
patients treated with topiramate in Denmark
7
is approximately 5500, why the number of
persons at risk of developing RTA is estimated
to be approximately 1650. The objective is
to draw attention to this cause of urolithiasis,
which is presumed to be under-diagnosed.
Material and methods: Five cases of nephrolithiasis in patients receiving topiramate have
been identified in our department within a
1-year period. The clinical and biochemical
findings are presented, and selective preventive
measures are proposed.
RESULTS: All 5 patients were males, with a
median age of 40 years (range 27-48 years).
Patients had a history of urolithiasis for 1 - 15
years (median 10 years), and had underwent
0 - 11 stone treatments before the underlying
cause of stone formation was recognized. They
all received topiramate for epilepsy. The precise
duration of treatment with topiramate was
unknown in most of the patients. As a result
of alkaline urine, patients formed phosphate
stones. Stone analysis was available in three patients: 100 % carbonate apatite, 50% carbonate
apatite + 50% brushite and 40% carbonate
apatite + 60% calcium oxalate monohydrate.
24-hour urine samples revealed marked hypocitraturia in all patients, and hypercalciuria in
one. Blood samples revealed hyperchloraemic
metabolic acidosis with low bicarbonate. Two
patients have ceased topiramate. Three patients
were treated with potassium citrate, and one
with potassium citrate and thiazide. Recurrence
rate after intervention is not available due to a
short follow-up period.
CONCLUSIONS: RTA in stone formers receiving topiramate should be recognized without
delay, and the responsible neurologist should be
consulted about the possibility to discontinue
topiramate. If this is not feasible, the metabolic
acidosis should be corrected by potassium-citrate to decrease the risk of stone recurrence.
#06 ANTIBIOTIC PROPHYLAXIS
FOR PROSTATE BIOPSIES – A PROSPECTIVE, RANDOMIZED STUDY
OF TRIMETHOPRIM SULFAMETHOXAZOLE VS. CIPROFLOXACIN
8
Mygland V, Tjessem L, Nilsen FS, Grønning
LE and Müller S
Department of Urology, Akershus University
Hospital, Denmark
Infection after ultrasound-guided transrectal
prostate biopsies (TRUS-B) is a serious complication that often leads to hospitalisation. E.coli
is the most frequent pathogenic agent in postTRUS-B infection. EAU guidelines recommend profylactic for prostate biopsies. Over the
past years, an increasing resistence to quinolones which has led to a rise in severe infections
after biopsies has been reported. Moreover,
increasing use of quinolones leads to increasing
resistence. In our department, we have traditionally used trimethoprim sulfamethoxazole (TS)
as prophylaxis for TRUS-B. Data from the
Norwegian surveillance system for antibiotic
resistence of microbes (NORM) indicates that
20 % and 24 % of E.coli isolates in urine and
blood cultures, respectively, are resistent to TS
compared to only 5 % and 8,9% resistency
to ciprofloxacin. We set out to register our
baseline infection rate requiring hospitalization
after TRUS-B with TS prophylaxis and subsequently compare the infection rate of TS versus
ciprofloxacin in a randomized fashion.
MATERIALS AND METHODS: During a 6
month period (march – october 2011), seven
out of 193 (3,6%) patients were admitted with
severe infection after TRUS-B with TS prophylaxis. From november 2011 until september
2013, patients referred for TRUS-B were consecutively randomized to receive either 2 tablets
of Trimethoprim Sulfamethoxazole 80/400 mg
at biopsy followed by 2 tablets 6 hours postTRUS-B or 1 tablet of 750 mg ciprofloxacin at
biopsy. Patients with a history of UTI within
the past year, indwelling catheter or intermittent self-catheterization were excluded from the
study. Infections requiring hospitalization were
recorded prospectively.
RESULTS: During the randomization period,
1068 TRUS-B procedures were recorded. Forty
patients were excluded from the study and
received other prophylaxis or antibiotic treat-
ment. The infection rate was 2,6% (13/512)
for trimethoprim sulfamethoxazole and 2,9%
(15/516) for ciprofloxacin. There was no statistically significant difference between groups.
All patients with infection met SIRS criteria
at hospital admission. E.coli was detectable in
urine and/or blood culture in 75% of the admitted patients. Length of stay was 5 (median,
range 1-8) days.
CONCLUSION: There was no statistical
difference in the rate of severe infections after
TRUS-B with TS or ciproxin prophylaxis in
our patient population. Given the resistencydriving properties of quinolones, we will
continue to use TS as antibiotic prophylaxis for
TRUS-B and monitor our infection rate.
#07 A CASE OF FULMINANT EMPHYSEMATOUS PYELONEPHRITIS
Stefan Nilsson, Johan Brändstedt, Helgi Engilbertsson and Bengt Uvelius
Department of Surgery and Urology, Skåne University Hospital, Malmö, Sweden
INTRODUCTION: Emphysematous pyelonephritis is an acute necrotizing renal infection
caused by gas-forming bacteria, usually E. coli.
It affects both renal parenchyma and perirenal
tissue. The patients are usually middle-aged and
95 % are diabetic. UT obstruction is common.
Almost all patients present with the triad of
fever, vomiting and flank pain. CT scan reveals
the presence of gas in the renal parenchyma.
Absence of fluid in CT images is associated
with rapid destruction of renal parenchyma and
a more than 50 % mortality rate. Other factors
indicating poor prognosis are: 1. Systolic
blood pressure less than 90, 2. increased serum
creatinine level, 3. thrombocytopenia. Treatment includes percutaneous drainage if fluid
is present, or, in fulminant cases, emergency
nephrectomy.
CASE REPORT: Female 63 years, diabetes
type 1. BMI 31. Retinopathy, peripheral
neuropathy. Hypertension. Medication: Adalat,
ramipril, insulin. Creatinine around 120.
Day 1: Right abdominal pain, vomiting. No
UT symptoms. Fever. Stayed home.
Day 3: 1300: Admitted at the Lund emergency
Dept, and transferred to the Intensive Care
Unit. CRP 498. Creatinine 289. B-glucose 20.
BP 140/70. CT-scan did not show the expected
cholecystitis, right kidney slightly swollen,
suspicion of pyelonephritis. Tazosin i.v. Blood
culture.
Day 4: Deteriorating. Diuresis 0-20 ml/h. CRP
485. Creatinine 376, K 4.6. Result from blood
culture: E. coli (ESBL). New CT-scan showed
fully developed emphysematous pyelonephritis,
gas also in right renal vein and ureter.
1500: Transferred to Malmö Intensive Care
Unit. Pre-shock. Thrombocytes 58. Change to
Meronem-Nebcina. Now needing inotropic
support to keep systolic BP 130. Citrate dialysis. Emergency nephrectomy decided.
1830- 2030: Extraperitoneal right subcapsular
nephrectomy performed. Bleeding 400 ml. Despite inotropic support: Systolic BP below 100.
After surgery: Out of respirator and extubated
next day. Blind. Toxic or hypotensive damage
to optic nerves suspected. Postoperative dialysis
for 3 days.
Lab results after 2 weeks: Creatinine 180,
Thrombocytes 419, CRP 37.
CONCLUSION: In an emergency case, like
ours, decision making has to be rapid. Repeated
CT scans for diagnosis. Our patient deteriorated rapidly, fulfilling the ”worst case” criteria
in Introduction (no fluid to drain, low systolic
pressure necessitating inotropic support,
increased serum creatinine, thrombocytopenia).
We chose emergency nephrectomy.
9
Wednesday 3rd June
16.30 - 17.30
Arenarummet
#08 ERG PROTEIN EXPRESSION
OVER TIME - FROM DIAGNOSTIC
BIOPSIES TO RADICAL PROSTATECTOMY SPECIMENS IN CLINICALLY LOCALIZED PROSTATE
CANCER
Berg K.D.1, Brasso K.1, Thomsen F.B.1, Røder
M.A.1, Rossing H.H.2, Toft B.G.2, Vainer B.2,
Iversen P.1
Copenhagen Prostate Cancer Center, Department
of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 2Department of
Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
1
INTRODUCTION: It has been shown that
ERG protein expression harbours prognostic
value in prostate cancer (PCa). However, the
impact of sampling error and the extent of
reclassification in ERG-status over time due to
tumour heterogeneity is unknown. Consistency
in ERG protein expression from diagnostic
specimens through re-biopsies to radical prostatectomies (RPs) was evaluated in patients with
clinically localised PCa initially managed on
active surveillance to investigate the validity of
ERG-status in biopsies. Moreover, the concordance between fluorescence in situ hybridization (FISH) assessment of TMPRSS2-ERG
rearrangement and immunohistochemistry
(IHC) analyses for ERG protein expression was
analysed.
Material & Methods: From the institutional
active surveillance program, 265 patients followed with PSA measurements, digital rectal
examinations, and 10-12-core re-biopsies were
included. Based on protocolled progression
criteria, 86 patients underwent RP. Included
tissue samples consisted of 625 biopsy-sets and
86 RP specimens. Five tissue micro array blocks
10
were constructed from malignant foci in the
RP specimens. ERG protein expression was
assessed by IHC in new sections from tumourcontaining biopsies and RP samples (anti-ERG,
clone: EPR3864; Roche/Ventana). Patients
were labelled ‘ERG-positive’ if minimum one
tumour focus demonstrated ERG expression
and ‘ERG-negative’ if all foci were negative.
A triple-colour TMPRSS2-ERG FISH assay
(FISH ZytoLight® TriCheck™ Probe, SPEC
ERG/TMPRSS2; Zytovision) was applied to 74
biopsies according to manufactures instructions. FISH results were dichotomised into
presence or absence of ERG rearrangement and
were correlated with the IHC findings.
RESULTS: The concordance between FISH
(+/- ERG rearrangement) and IHC (+/- ERG
protein expression) was 97.3%. IHC demonstrated a sensitivity and specificity for ERG
rearrangement of 100% and 95.5%, respectively. Applying IHC in diagnostic specimens
showed that 46.4% of patients were ERGpositive and 53.6% were ERG-negative. The
majority of patients (88.2%) did not experience
ERG reclassification during up to four rounds
of re-biopsies. The concordance in ERG-status
between biopsies and RP specimens was 89.594.2% depending on the number of re-biopsies
included. Sampling bias was assumed to explain
most (81.3%) of the mismatches in ERGstatus, as ERG reclassification was caused by
the finding of an ERG positive tumour focus in
a novel sextant of an otherwise ERG negative
gland, or vice versa.
CONCLUSIONS: Consistency in ERG-status
ranged from 90-95% for patients undergoing
serial biopsies and RP. This indicates that biopsies can be used reliably to investigate ERG’s
prognostic and predictive value.
#09 RISK OF MALIGNANT MELANOMA IN MEN WITH PROSTATE
CANCER, NATIONWIDE POPULATION-BASED STUDY
Frederik B. Thomsen1, Yasin Folkvaljon2, David
Robinson3,4, Christian Ingvar5, Stacy Loeb6,
Mats Lambe2,7, Pär Stattin3
Dept. of Urology, Frederiksberg Hospital, Frederiksberg, Denmark; 2Regional Cancer Centre,
Uppsala/Örebro, Uppsala University Hospital,
Uppsala Sweden; 3Dept. of Surgical and Perioperative Sciences, Urology and Andrology, Umeå
University, Umeå, Sweden; 4Dept. of Urology,
Ryhov Hospital, Jönköping, Sweden; 5Dept. of
Surgery, Clinical Sciences, Lund University,
Skåne University Hospital, Lund, Sweden; 6Dept.
of Urology, New York University and Manhattan Veterans Affairs Medical Center, NY, USA;
7
Dept. of Medical Epidemiology and Biostatistics,
Karolinska Institutet, Stokholm, Sweden
1
INTRODUCTION: Previous studies have reported an increased risk of malignant melanoma (MM) in men with prostate cancer (PCa).
The aim of this study was to investigate this
association including data on risk category for
MM and PCa as well as socioeconomic factors.
MATERIAL AND METHODS: From
1998‐2012, we identified men diagnosed with
PCa in the Prostate Cancer Database Sweden
3.0. For each case, 5 PCa-free men matched
on birth year and county of residency were
identified. Men diagnosed with MM prior to
PCa diagnosis or 2005 were excluded. The final
cohort included 115,160 men with PCa and
598,438 PCa-free men. Multivariable models
were used to assess the relationship between
PCa and MM including PCa risk-categories,
marital status, education level and income.
Using a case-control approach, the converse
relationship was analyzed, using different stages
of MM as the exposure. Results: On multivariable analysis, PCa was associated with an
increased risk of stage 0 MM, HR 1.22 (95%
CI 1.06-‐1.40) and stage I MM, HR 1.17
(1.04-1.31) but not stage II-IV MM, HR 1.10
(0.95-1.27). Low-risk PCa, HR 1.19 (1.04-
‐1.36) and intermediate‐risk PCa, HR 1.35
(1.18-1.54) were associated with MM, whereas
high‐risk PCa was not, HR 1.05 (0.93-1.19).
Married men, HR 1.29 (1.21-1.38), men
with the highest educational level, HR 1.53
(1.42-1.66) and men in the highest quartile of
income, HR 1.58 (1.43-1.75) had an increased
risk of MM. In a reversed analysis of risk of
PCa in the cohort of men who were free of PCa
at recruitment, we found increased odds of PCa
in men with low stage MM (stage 0 MM: OR
1.27 [95% CI 1.02‐1.58], stage I MM: OR
1.21 [95% CI 1.00-1.46], stage II-IV MM:
OR 1.08 [95% CI 0.80‐1.45]).
CONCLUSION: We found a significant association between low‐stage MM and low‐ and
intermediate‐risk PCa, whereas there was no association between advanced MM and high‐risk
PCa. Since the diagnosis of early MM and PCa
are both associated with high socioeconomic
status our results indicate that the association
between MM and PCa is mainly driven by
shared risk factors related to lifestyle.
#10 A RANDOMIZED CONTROLLED TRIAL TO ASSESS AND COMPARE THE OUTCOMES OF 2-CORE
MRI/TRUS-IMAGE-FUSION GUIDED PROSTATE BIOPSY AND TRADITIONAL 12-CORE SYSTEMATIC
BIOPSY
Eduard Baco1,4, Erik Rud2,4, Lars Magne Eri1,4,
Gunnar Moen1, Ljiljana Vlatkovic3, Aud Svindland3,4, Heidi B. Eggesbø2,4, Osamu Ukimura5
Department of Urology, 2Radiology and 3Pathology Oslo University Hospital, Oslo, Norway,
4
University of Oslo, Norway, 5USC Institute of
Urology, Keck School of Medicine, University of
Southern California, Los Angeles, USA
1
BACKGROUND: The prostate biopsy with
computer-assisted image-fusion of magnetic
resonance imaging (MRI) and transrectal ultrasound (TRUS) [MRI-group] has not yet been
compared with 12-core random biopsy (RB)
[control-group] in a randomized controlled
trial (RCT). The aim of this study was to compare cancer detection rate (CDR) of clinically
significant prostate cancer (CsPca) between the
two groups. Material and method: One hundred and seventy five biopsy-naïve patients with
suspicion for prostate cancer, randomized to
MRI-group (n=86) and control-group (n=89)
during 09/2011-06/2013. In the MRI-group
using computer-assisted image-fusion system
11
(Koelis), 2-core MRI/TRUS image-fusion
targeted-biopsy (TB) of MRI-suspicious lesion
was followed by 12-core-RB. In the controlgroup, 2-core-TB towards abnormal digital
rectal examination (DRE) and/or TRUS-suspicious lesion and 12-core-RB were performed.
In patients with normal MRI or DRE/TRUS
only 12-core-RB was performed. CDRs for any
cancer, and CsPca were compared between the
two groups as well as between TB and RB.
RESULTS: Comparing MRI-group vs controlgroup, CDRs of any cancer (51/86, 59% vs.
48/89, 54%; p=0.4) as well as CsPca (38/86,
44% vs. 44/89, 49%; p=0.5) showed no significant difference. CDR of CsPca by 2-core-MRI/
TRUS-TB (33/86, 38%) was comparable to
that by 12-core-RB in control group (44/89,
49%) [p=0.2]. In subset analysis of patient with
normal DRE, CDR of CsPca by 2-core-MRI/
TRUS-TB (14/66, 21%) was approximately
equal to that by 12-core-RB in control group
(15/60, 25%) [p=0.7]. Among the biopsyproven CsPca in MRI-group, 87% (33/38) was
detected by MRI/TRUS-TB.
CONCLUSION: Overall CDR for CsPca was
similar between MRI-group and control-group.
A 2-core-MRI/TRUS-TB was comparable to
12-core-RB to detect CsPca.
#11 DIAGNOSTIC POTENTIAL OF
18F-FACBC PET/MRI IN HIGH RISK
PROSTATE CANCER
Bertilsson H1,5, Kruger-Stokke B2, Selnæs K3,
Elschot M3, Kjøbli E5, Halvorsen D5, Tessem
MB3, Størkersen Ø6, Axcrona K1,5, Moestue S3,
Willoch F4, Angelsen A3 and Bathen TF3
Dept of cancer research and molecular medicine,
NTNU, 2Dept of Radiology, Trondheim, 3Dept
of circulation and medical Imaging, NTNU,
4
Institute of basic medical sciences, Oslo, 5Dept
of Urology, Trondheim, 6Dept of Pathology,
Trondheim
1
INTRODUCTION: Detection of lymphnode metastases in high risk prostate cancer
using MRI has limitations due to low accuracy
and the probability of lymph node invasion
is mainly based on nomograms. Imaging
12
techniques giving information about the exact
metastatic site could be a step towards an individualized risk-adapted extended pelvic lymph
node dissection (ePLND) template. The aim of
this prospective study is to evaluate the benefit
of 18F-FACBC PET/MRI in preoperatively
detection of lymph node metastasis in 32 high
risk prostate cancer patients.
MATERIAL AND METHOD: High risk
prostate cancer patients (Gleason score ≥8 and/
or PSA>20 and/or ≥cT3a cancer) scheduled
for prostatectomy with ePLND were recruited
for the study and underwent a fully integrated
PET/MRI examination (3T Biograph mMR,
Siemens) prior to surgery. Two radiologists
evaluated the MR examination according to the
PIRADS criteria while the PET-data is currently being evaluated by a nuclear radiologist. The
lymph gland packages were removed separately
from four localizations from each side (right/
left), using a standardized template corresponding to predefined anatomic boarders. After
surgery a pathologist examined HES stained
slides of the prostate gland and resected lymph
nodes and outlined cancer foci and described
cancer stage (TNM) and grade (Gleason score).
Preliminary results: Twenty-four patients have
so far been included in the study (median
age 66,2, mean PSA 17,2, cTNM T2-T3b,
Gleason score from diagnostic biopsies 3+4 to
5+4. A total of 46 histopatologically confirmed
lymph node metastases were found in 8 out of
21 patients. FACBC PET uptake has been observed in several histopathologically confirmed
lymph node metastases (Figure 1), and final results will include comparisons of the diagnostic
accuracy on a per-region basis comparing MR
with PET/MR using histopathology as the gold
standard.
Hospital, Skejby, Denmark, 3Dept of Pathology,
Aarhus University Hospital, NBG, Denmark.
Figure Ca ppatient, atient, 66 Figure 1: 1P: PCa 66 years o
ld, c
linical s
tage T
years old, clinical stage 3b, T3b, and Gleason score from and Gleason score from diagnostic biopsies 4+4. Low diagnostic iopsies PSA (PSA 3b.7 ng/ml), 4b+4. ut Low heterogeneous tracer ubptake PSA (PSA 3.7 ng/ml), ut throughout t
he p
rostate nd heterogeneous tracer uaptake one positive LN clearly visible throughout the prostate and one positive LN clearly visible CONCLUSION: This is the first study
presenting preliminary results on the diagnostic accuracy with PET/MR for preoperative
lymphnode staging in high risk PCa patients.
Intitial observations indicate that investigation of patients with FACBC-PET does not
add significant value to MR for detection of
small LN metastases (< 6 mm). However, in
larger lymphnodes traditionally characterized as
metastatic on MR or CT, PET could possibly
aid in differentiating between metastatic disease
and benign hypertrophy.
#12 PROSTATE CANCER: MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING OF THE PROSTATE RECLASSIFIES PATIENTS
ELIGIBLE FOR ACTIVE SURVEILLANCE
Maria Carlsen Elkjær1, Bodil Ginnerup Pedersen2, Søren Høyer3, Michael Borre1
Dept of Urology, Aarhus University Hospital, Skejby, Denmark, 2Dept of Radiology, Aarhus University
1
Pathological examination of the extracted
prostate after radical prostatectomy often
reveals that trans-rectal ultrasound (TRUS) and
TRUS-guided biopsy (TRUS-bx) underestimated the tumor’s true size and aggressiveness.
This clinical problem seems to defy a satisfactory solution to the dilemma of whether to
enroll patients in active surveillance (AS) or to
offer the patient active treatment. We present
the preliminary results of an on-going trial
in which we investigate if multi-parametric
magnetic resonance imaging (mpMRI) of the
prostate detects significant prostate cancer (PC)
better than TRUS and TRUS-bx, and if we
may in this way make selection of patients for
active surveillance safer.
MATERIALS AND METHODS: From
November 2014 patients enrolled in an AS program at Aarhus University Hospital, Denmark,
were offered an mpMRI 8 weeks after TRUSbx. All patients were AS candidates according
to national guidelines. The mpMRI consisted
of one anatomic sequence (T2-weigthed, high
resolution) and two functional sequences (a diffusion-weighted sequences with high b-values
and a dynamic contrast enhanced sequence).
All lesions detected on the mpMRI were scored
according to the Prostate Imaging Reporting
and Data System (PI-RADS) classification.
MRI-guided in-bore biopsies (MRGB) were
performed on lesions with a score of 4 or 5.
RESULTS: Up until now, 12 patients have
been scanned. One patient was excluded due
to severe claustrophobia. Of the 11 patients
with sufficient quality scans, five PI-RADS 4
or 5 lesions were detected in 4 patients (two
transition-zone lesions and three peripheralzone lesions). MRGB pathology revealed that
all 4 patients (36%, (95%CI: 8%; 64%)) had
significant cancer according to University
College London definition 2. Two patients
had a Gleason score up-grade (Gleason score 7
(3+4) and 7 (4+3), respectively). In the other
two cases, MRGB pathology revealed foci of
13
Gleason score 6 (3+3) with 13.7 mm and 7.6
mm cancer core length, respectively.
CONCLUSION: Additional mpMRI in AS
patients seems to re-classify a substantial number of patients eligible for active surveillance,
where significant PC have escaped the initial
TRUS and TRUS-bx diagnostic strategy.
#13 PERFORMANCE CHARACTERISTICS OF MULTIPARAMETRIC
MAGNETIC RESONANCE IMAGING
(MPMRI) PRIOR TO RADICAL PROSTATECTOMY – WHICH PROSTATE
CANCERS ARE MISSED?
Kimia Kohestani1, Ole Martin Sponga2,
Andreas Josefsson1, Mikael Hellström3, Jonas
Hugosson1, Sigrid Carlsson1,4
Department of Urology, Institute of clinical
sciences, Sahlgrenska Academy at University of
Gothenburg, 2Department of Radiology, Carlanderska Hospital, 3Department of Radiology,
Institute of clinical sciences, Sahlgrenska Academy
at University of Gothenburg, 4Urology Service at
the Department of Surgery, Memorial SloanKettering, New York, USA
1
INTRODUCTION AND OBJECTIVE:
This single surgeon series sought to assess the
accuracy of preoperative mpMRI in detecting
significant prostate cancer (PC) in patients
subjected to radical prostatectomy (RP) with
pathoanatomical analysis of specimens. Characteristics of men whose PCs were missed at
mpMRI were examined.
MATERIALS AND METHODS: We identified 85 men (median age 62 years at surgery)
with clinically localized PC (clinical stage T2 or
less, biopsy Gleason Score (GS) 6-9, PSA <30
ng/mL) who underwent RP performed by one
surgeon (JH) at one hospital in Gothenburg,
Sweden between Jan 1st 2012 and June 30th
2014 and who had a preoperative mpMRI
of the prostate (median 4 weeks prior to RP,
IQR 2-9 weeks). The majority of the mpMRIs
(71%) were performed at the same hospital
using a body-array coil at a field strength of
1.5 Tesla with 3-phase imaging; T2-weighted,
14
contrast enhanced and diffusion weighted
images. In total, 20 radiologists reported the
mpMRIs in the clinical routine, of which 3
readers reported two thirds of the images. We
then categorized the mpMRI reports into high,
moderate, low, and no suspicion of cancer. The
reported mpMRI findings were subsequently
correlated to RP pathology reports. Two different pathoanatomical definitions of significant
PC were chosen upfront: 1) ≥ 10 mm in diameter in any one sector and 2) pathologic GS
≥ 7 in any one sector. Tumor characteristics for
patients with negative mpMRI were examined.
RESULTS: 68 of the 85 patients (80%) had
strong or equivocal suspicion for cancer on
preoperative mpMRI. Sensitivity, specificity,
positive predictive value and AUC of mpMRI
for detecting significant PC were 85%, 40%,
95%, 0.551 for tumors ≥ 10 mm and 88%,
41%, 80%, 0.646 for GS ≥ 7. Five men had
GS ≥ 8, all of which were detected on mpMRI.
17 patients (20%) were reported having no or
low suspicion of cancer on mpMRI. Data was
available for review for 16 of these; one patient
had pT0, 8 patients had GS 6 of which 4 were
≥ 10 mm in size, 7 patients had GS 7, 6 of
which were ≥ 10 mm. 13% of GS 7 tumors
were missed and 15% of tumors ≥ 10 mm.
Only 2 of these 16 patients had extracapsular
extension and none had seminal vesicle invasion. A majority of the negative mpMRIs were
performed during the early study period. The
rate of negative mpMRIs declined over time;
33% in 2012, 17% in 2013 and 11% in 2014.
CONCLUSION: With increasing reader
experience most PCs were detected by mpMRI.
Negative mpMRI mainly missed tumors of low
malignant potential; none of the tumors with
GS ≥ 8 were missed.
#14 DAPCAR – THE DANISH PROSTATE CANCER REGISTRY. A NEW
COMPREHENSIVE DATABASE OF
MEN EVALUATED FOR PROSTATE
CANCER IN 1995-2011
Helgstrand J.T.1, Klemann N.1, Røder M.A.1,
Vainer B.2, Brasso K.1, Iversen P.1
Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of
Copenhagen, Copenhagen, Denmark, 2Department of Pathology, Rigshospitalet, University of
Copenhagen, Copenhagen, Denmark
1
BACKGROUND: The national pathology
registry (Patobank) was initiated in 1995 and
is a nationwide database of histopathological
data on Danish residents who have had tissue
evaluated by a pathologist in Denmark. Based
on Patobank, we intended to create a nationwide database of all Danish men evaluated for
prostate cancer (PCa) in the period 1995-2011
allowing future combinations of histopathological data with various epidemiological parameters and clinical outcome of the disease.
MATERIALS AND METHODS: In April
2012, a dataset consisting of all Danish men
who underwent histopathological assessment of
prostatic tissue in 1995-2011 was provided by
Patobank. Raw- data included social security
number (i.e. central persons registry number,
CPR), diagnosis, type of specimen and the
pathology department involved for each of the
167,338 specimens in the dataset. Histological
data were registered in the format of complex
Systematized Nomenclature of Medicine
(SNOMED)-codes. First step in creating
DaPCaR was to translate and prioritize 26,295
unique combinations of SNOMED-codes into
conclusions including tissue type and diagnosis
using the official SNOMED-classification. Approx. 45,000 specimens had imprecise coding
and in all these patients an individual review of
the patient files was performed before reaching
a final classification.
RESULTS: A total of 167,338 specimens from
113,804 men were included. Of the 167,338
specimens, 88,662 were transrectal ultrasound (TRUS) guided biopsies of the prostate
and 55,442 were transurethral/transvesical
resections. The remaining 23,234 specimens
included radical prostatectomies, cystoprostatectomies, seminal vesicle biopsies, gastro-intestinal surgery, bladder biopsies and autopsies.
A total of 64,778 men had, on average, 1,37
sets of TRUS guided biopsies taken. A total
of 38,282 men had PCa confirmed by TRUS
guided biopsies. An additional 9,439 men had
PCa confirmed by transurethral/transvesical
resection and thus 47,721 men in DaPCaR
have histopathologically proven PCa based on
TRUS guided biopsy or transurethral/transvesical resection. Some patients in DaPCaR were
diagnosed before 1995, but the vast majority of
the 47,721 men with PCa-positive specimens
were diagnosed during the investigated period.
CONCLUSION: DaPCaR is based on
data from Patobank and represents the first
comprehensive Danish database of histopathological data from the 113,804 Danish men
who had prostatic tissue histologically assessed
from 1995 to 2011. Data from DaPCaR are
currently combined with data from other
national registries, including measurement of
prostate-specific antigen (PSA), post- interventional complications, clinical stage and causes
of death. DaPCaR is now operational and we
anticipate that the database serves as a platform
of histopathological parameters in future epidemiological studies.
#15 LOCAL INSIGHTS INTO THE
NATIONAL DETECTION OF PROSTATE CANCER
A Dyal, S Ubee, S Rai, PH Rajjayabun
Alexandra Hospital, Redditch (Worcestershire
Acute NHS Trust, UK)
INTRODUCTION: Worcestershire has an
above average incidence of prostate cancer.
The county town of Kidderminster has independently offered a biannual voluntary PSA
testing service for almost a decade. We aimed
to analyse the impact of this on local rates of
prostate cancer diagnosis, management and
service delivery.
METHODS: All men who volunteered to
have their PSA tested between July 2011 and
October 2013 were included in the study. Age,
postcode, PSA and previous service use were
recorded. All men who had a raised age-related
PSA were identified and their management
plans captured as per their natural history up to
the time of data collection.
15
RESULTS: 1251 men underwent PSA testing.
Sixty six (5%) men had raised age-related PSA.
Complete data for 52 men were available.
31 declined biopsy and 27 continue with
monitoring. Overall 12 men (1%, age 58-79
years) were found to have prostate cancer and 9
underwent active treatment.
DISCUSSION: Community based PSA testing may be contributing to increased prostate
cancer detection rates in Worcestershire and additional service and financial pressure. A wider
population and demographics based study is
needed to fully interrogate this phenomenon.
Currently no NHS backed UK PSA screening
programme is in place. Our findings suggest
that there is an appetite for PSA testing.
#16 THE EFFECT OF SOCIOECONOMIC STATUS IN THE FINNISH
PROSTATE CANCER SCREENING
TRIAL
Kilpeläinen Tuomas P1, Tammela Teuvo LJ2,
Raitanen Jani3, Määttänen Liisa4, Talala Kirsi4,
Kujala Paula5,Taari Kimmo1, Auvinen Anssi3
Dept. of Urology, University of Helsinki and
Helsinki University Hospital, FI-00029 Helsinki,
Finland, 2Dept. of Urology, University of Tampere
and Tampere University Hospital, FI-33521
Tampere, Finland, 3School of Health Sciences,
University of Tampere, FI-33014 Tampere,
Finland, 4Finnish Cancer Registry, FI-00130
Helsinki, Finland, 5Fimlab Laboratories, Dept.
of Pathology, Tampere University Hospital, FI33521 Tampere, Finland
1
INTRODUCTION: Prostate cancer (PC)
screening with PSA (prostate-specific antigen) remains controversial. We investigated
whether screening is especially beneficial in any
socioeconomic status (SES) stratum. Income,
education and housing tenure status were used
as surrogate for SES.
MATERIALS AND METHODS: A total
of 72,139 men from the population-based
randomized Finnish Prostate Cancer Screening
Trial were analyzed in this study, of which 40%
were in the screening arm (SA) and 60% in the
control arm (CA). The men in the SA were in16
vited to PSA test at a four-year interval and the
men in the CA were not contacted. Individual
SES data were obtained from official registries
(Statistics Finland). Mean follow-up was 12.7
years in both arms.
RESULTS: In the CA, higher SES was associated with increased incidence of low-to-moderate risk PC (risk ratio (RR) varying by SES from
1.17 to 1.44) but conversely a decreased risk
for advanced PC (RR 0.45 - 0.73, p < 0.02).
The men with higher SES were more likely to
participate in screening by all SES strata (OR
1.89-2.75, p < 0.0001) compared to men with
the lowest SES. Higher income and education
were associated with significantly lower PC
mortality both in the CA and SA (RR 0.480.69, p < 0.05). Organized screening had only
limited effect in diluting SES gradients in PC
incidence or mortality.
CONCLUSIONS: Substantial gradients by
SES were observed in the CA in PC incidence
and PC mortality. Higher SES was associated
with overdiagnosis of low risk PC and conversely lower risk of incurable PC and thus lower
PC mortality. The effect of organized screening
to dilute this gradient was not substantial. The
men with higher SES were more likely to participate in screening programme. Special attention should be directed in recruiting men with
low SES to population-based cancer screening.
Thursday 4th June
14.00 - 15.00
Palissad VÄST
#17 PROGNOSTIC VALUE OF PSA
KINETICS IN PATIENTS WITH
LOCALISED PROSTATE CANCER
MANAGED OBSERVATIONALLY:
A SUB-GROUP ANALYSIS OF THE
SPCG-6 STUDY
Frederik B. Thomsen1, Klaus Brasso1,
Kasper D. Berg1, Thomas A. Gerds2, Jan-Erik
Johansson3, Anders Angelsen4, Teuvo L. J.
Tammela5 and Peter Iversen1 on behalf of the
Scandinavian Prostate Cancer Group
Copenhagen Prostate Cancer Center, Dept. of
Urology, Rigshospitalet, University of Copenhagen, 2Dept. of Biostatistics, University of Copenhagen, Copenhagen, Denmark, 3Dept. of Urology,
Örebro University Hospital, Örebro, Sweden,
4
Faculty of Medicine, Norwegian University of
Technology and Science, Trondheim, Norway,
5
Dept. of Surgery, Tampere University Hospital
and School of Medicine, University of Tampere,
Tampere, Finland
1
INTRODUCTION & OBJECTIVES: We
investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAv), and
PSA velocity risk count (PSAvRC) and causespecific mortality in patients with localised
prostate cancer (PCa) managed observationally.
MATERIAL & METHODS: The SPCG‐6
study was a randomized trial comparing bicalutamide 150 mg/daily with placebo in patients
with hormone-naïve, non‐metastatic PCa.
This sub-group analysis included patients with
clinically localized PCa (cT1‐2, N0/Nx), who
were randomized to, and remained on, placebo
for minimum of 18 months. All patients
survived at least two years and had minimum
three PSA values available. The prognostic
value of PSA kinetics was analyzed according to
baseline PSA: ≤10 ng/mL, 10.1-25 ng/mL, and
>25 ng/mL. 15‐years cumulative incidence of
PCa-specific mortality and non-PCa mortality
were estimated with competing risk analysis
(Aalen-Johansen method). Associations were assessed with multiple cause-specific proportional
hazard models for PCa-specific mortality.
RESULTS: 263 patients were included of
which n=116, n=76 and n=71 had a baseline
PSA ≤10, 10.1-24.9, and ≥25, respectively. The
median follow-up was 15.8 years. In patients
with PSA between 10.1-25 ng/mL, the hazard
rate of PCa mortality was reduced with 28%
for each 1 year increase in PSAdt (HR 0.72
[95% CI:0.56-0.92], p=0.009), and increased
with 4% for every 1 ng/mL/year increase
in PSAvel (HR 1.04 (95% CI:1.01‐1.06),
p=0.001). Likewise, in the same patients, a
PSAvRC of 2 compared to a PSAvRC of 0-
was associated with a 14-fold increase in PCa
mortality (HR 14.64 (95% CI:1.94-110.60),
p=0.001). In patients with baseline PSA ≤10
ng/mL or >25 ng/mL none of the PSA kinetics
was significantly associated with PCa mortality.
CONCLUSION: PSA kinetics following two
years of observation is only associated with
PCa- specific mortality in patients with a baseline PSA between 10.1-24.9 ng/ml. In contrast,
there is no prognostic value of PSA kinetics
for patients with lower or higher baseline PSA.
Trial registration number: NCT00672282.
#18 SYSTEMATIC REVIEW AND
META-ANALYSIS OF DECISION
AIDS FOR LOCALISED PROSTATE
CANCER TREATMENT CHOICE
Kari A.O. Tikkinen1, Thomas Agoritsas2, Paul
Alexander3, Jarno Riikonen4, Henrikki Santti5,
Arnav Agarwal6, Neera Bhatnagar7, Philipp
Dahm8, Victor Montori9, Gordon H. Guyatt10,
and Philippe D. Violette11
Depts, of Urology and Public Health, University
of Helsinki and Helsinki University Hospital,
Helsinki, Finland, 2Dept. of Clinical Epidemiology and Biostatistics, McMaster University,
Hamilton, ON, Canada; and Divisions of
General Internal Medicine and Clinical Epidemiology, University Hospitals of Geneva, Geneva,
Switzerland, 3Dept. of Clinical Epidemiology
and Biostatistics, McMaster University, Hamilton, ON, Canada, 4Dept. of Urology, Tampere
University Hospital, Tampere, Finland, 5Dept.
of Urology, University of Helsinki and Helsinki
University Hospital, Helsinki, Finland, 6Faculty
of Medicine, University of Toronto, Toronto, ON,
Canada; and Dept. of Clinical Epidemiology
and Biostatistics, McMaster University, Hamilton, ON, Canada, 7Health Sciences Library,
McMaster University, Hamilton, ON, Canada,
8
Dept. of Urology, University of Minnesota and
Minneapolis Veterans Affairs Health Care System,
Minneapolis, MN, USA, 9Knowledge and Evaluation Research Unit, Division of Endocrinology
and Diabetes, Depts. of Medicine and Health
Sciences Research, Mayo Clinic, Rochester, MN,
1
17
USA, 10Depts. of Clinical Epidemiology and
Biostatistics and Medicine, McMaster University,
Hamilton, ON, Canada, 11Division of Urology,
Dept. of Surgery, Western University, London,
ON, Canada; Dept. of Clinical Epidemiology
and Biostatistics, McMaster University, Hamilton, ON, Canada; Woodstock General Hospital
Woodstock, ON, Canada
INTRODUCTION: Patients diagnosed with
localized prostate cancer need to make critical
treatment decisions that are sensitive to their
values and preferences. The role of decision‐aids
in facilitating these decisions is unknown. We
conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) of
decision aids for localized prostate cancer.
MATERIAL AND METHODS: We searched
MEDLINE, EMBASE, PsycINFO, CINAHL,
Cochrane databases, without language limits
up to August 2014. We performed screening, data extraction, risk of bias and quality
assessments in duplicate, independently. We
sent our data extraction to the original authors
for verification. We analyzed treatment effects
between decision aids and usual care using the
DerSimonian-Laird random-effects inverse
variance method for continuous outcomes
and Cochran-Mantel-Haenszel method for
18
treatment choice.
RESULTS: Of 2,737 reports, 14 RCTs proved
eligible (n=3,377 men). Of these, 11 RCTs
compared decision aids to usual care and 3 to
other decision aids. Overall, 13 RCTs were
at high risk of bias; only 1 was at low risk of
bias. We evaluated 9 decision aids provided by
authors. Decision aids reported positive and
negative consequences of alternative management strategies well (9 of 9, 100%) but
presented event rates less frequently (56%),
and did not typically make direct comparison
of probabilities possible (44%). Two trials suggested a modest positive reduction in decisional
regret (Figure 1a). Results varied widely for
decisional conflict (4 trials), satisfaction with
decision (2 trials) and knowledge (2 trials).
We found no impact on treatment choices (6
trials) (Figure 1b). A values clarification exercise
was associated with a reduction in regret and
improved preparation for decision making. The
decision aids tested in these trials were designed
to provide patients with information to prepare
for the clinical encounter. No decision aid
was primarily designed for use in the clinical
encounter and no trial directly assessed the
impact of the decision aid on collaborative
deliberation and shared decision making.
CONCLUSION: Limited evidence suggests
variable impact of existing decision aids on a limited set of decisional processes and outcomes.
Work in this area would benefit from usercentered design of decision aids that promote
shared decision making.
#19 PATIENT SATISFACTION AFTER
RADICAL PROSTATECTOMY: THE
INFLUENCE OF ONCOLOGICAL
AND FUNCTIONAL OUTCOMES
Mikkel Fode, Anders Frey, Henrik Jakobsen,
Jens Sønksen
Department of Urology, Herlev Hospital, Herlev,
Denmark
INTRODUCTION: Oncological control,
the absence of urinary incontinence and a
satisfactory sexual function are the generally
accepted goals of radical prostatectomies in
the treatment of prostate cancer. The purpose
of this study is to assess how the three factors
influence patient satisfaction with surgery.
MATERIAL & METHODS: The data used
in this study was collected as part of a cross
sectional, questionnaire based study in radical
prostatectomy patients conducted between
December 2012 and February 2013. Patients
who had undergone radical prostatectomy at
Herlev University Hospital 3 months to 3 years
prior to the study and who had a good preoperative erectile function were included. Disease
characteristics and information regarding the
surgeries were retrieved from hospital records.
A good oncological outcome was defined as
negative surgical margins. Incontinence was
defined as loss of more than “a small amount”
of urine once per week on the ”International
Consultation on Incontinence Questionnaire”
(ICIQ) and a satisfactory erectile function was
defined as an “International Index of Erectile
Function” questionnaire (IIEF-5) score ≥17
with or without erectogenic aids. Patients were
also asked about their general satisfaction with
the treatment (divided into “satisfied” or “not
satisfied” for this analysis).
RESULTS: A total of 242 patients were
available for this analysis. The median age was
64 (range 45-77) and the median time since
surgery was 17 (range 3 to 36) months. According to the D’Amico risk classification 26%
were high risk, 64% were intermediate risk and
10% were low risk. 33% had undergone bilateral nerve-sparing. In 77% the surgical margins
were negative. At follow-up 62% patients were
considered continent and 29% were sexually
19
active with satisfactory erectile function. Overall 91% were satisfied with their treatment.
Neither surgical margins, nor continence status
or satisfactory erectile function predicted satisfaction on univariate analyses. Likewise, none
of the factors were independent predictors on
a multivariate logistic regression analysis. Even,
when grouped together, patients who achieved
the trifecta outcome of oncological control,
continence, and satisfactory erections were not
significantly more likely to be satisfied than
those who did not (p= 0.57).
CONCLUSION: Patient satisfaction after
radical prostatectomy cannot be easily explained
by the trifecta outcome. Psychological factors
and additional functional outcomes may be of
importance. More research is needed in the area.
#20 THE SINGLE QUESTION APPROACH IS A ROBUST ALTERNATIVE TO THE INTERNATIONAL
INDEX OF ERECTILE FUNCTION
ERECTILE FUNCTION DOMAIN
WHEN EVALUATING POST RADICAL PROSTATECTOMY ERECTILE
DYSFUNCTION
Anders Frey, Henrik Jakobsen, Mikkel Fode,
Jens Sønksen
Department of Urology, Herlev Hospital, Herlev,
Denmark
INTRODUCTION: Evaluation of post
radical prostatectomy (RP) erectile dysfunction
(PRPED) is controversial. The erectile function
domain from “The international index of erectile dysfunction” (IIEF6) has been one of the
most frequently used questionnaires for evaluating PRPED. Recently, we validated a Danish
version of the “Erection Hardness Scale” (EHS)
for face validity and reproducibility in a group
of RP. The aim of this study is to investigate
whether there is correlation between the IIEF6
and the EHS. As a secondary outcome, we
want to establish if there is a reasonable coherence between IIEF6 ED severity categories and
EHS scores.
MATERIALS AND METHODS: The data
20
used in this study was collected as part of a
cross sectional, questionnaire based study in
RP patients. Patients who had undergone RP
at Herlev University Hospital 3 months to 3
years prior to the study and were sexually active
at the time of the study were included in the
analysis. Information regarding the surgeries
was retrieved from hospital records. The IIEF6
is consists of six questions providing a detailed
picture of erectile capabilities while, the EHS
is a single question designed to evaluate the
hardness of erections. The IIEF6 is providing
scores from 0 to 30 and the EHS is providing
scores from 0 to 4. The IIEF6 categories are as
follows: Severe erectile dysfunction(ED) (0 to
6), moderate ED (7 to 12), mild to moderate
ED (13 to 18), mild ED (19 to 24), and no
ED (25 to 30).
RESULTS: A total of 196 patients were included in the analysis. The median age at the time
of the surgery was 63 (range 43 to 76) years
and the median time since the surgery was 17
(range 3 to 36) months. The median IIEF6
score was 15 (range 1 to 30) and the median
EHS score was 2.5 (range 0 to 4). A linear
regression showed a strong correlation between
the IIEF6 and the EHS with a Correlation
coefficient of 0.11 (r=0.82; 95% CI 0.10 to
0.12; p<0.00001). When applying the linear
regression model we found that EHS scores
corresponded well with their intuitive IIEF6
category counterparts (table 1).
CONCLUSION: These results show that the
single question approach to evaluating PRPED
could be a robust alternative to more cumbersome questionnaires. Further studies are needed
in order to establish if the IIEF6 and the EHS
correctly reflects the patients self-perceived
erectile capabilities.
#21 ANASTOMOTIC COMPLICATIONS AFTER RADICAL PROSTATECTOMY – A COMPARISON OF
OPEN AND ROBOT ASSISTED
PROCEDURES
Jacobsen A1, Berg K.D., Røder M.A., Brasso
K, Iversen P
of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
INTRODUCTION: Radical prostatectomy
was introduced in Denmark in August 1995
as open retropubic procedure (RRP). In the
mid-2000s, robot assisted radical prostatectomy
(RARP) was introduced at several academic
institutions and has been available at our
department since 2009. Today, RARP comprises of 70% of all procedures. Anastomotic
complications are well-known after RP. The
vesico-urethral anastomosis is handled differently in the two surgical approaches with a
6-single suture anastomosis during RRP and an
over-and-over running suture during RARP.
Whether this results in a different risk of anastomotic complication is unknown. The aim of
this study was to investigate if the frequency
of anastomotic leakages and -strictures differed
between patients undergoing RRP or RARP.
Moreover, we aimed at identifying risk factors
associated with anastomotic complications.
MATERIAL & METHODS: 735 patients
who underwent either RRP (n=499) or RARP
(236) at the Department of Urology, Rigshospitalet, Denmark, from 1st January 2010 to
31th December 2012 were included. Data on
anastomotic complications, defined as urinary
leakage and/or urethral strictures located at
the anastomosis were collected through chart
review. Uni- and multivariate logistic regression
analysis was used to analyse for associations
between surgical procedure (RRP vs. RARP)
and anastomotic complications. Univariate
analyses included age, smoking status, diabetes,
hypertension, surgeon, prostate volume, and
urinary leakage as variables. Due to a low
number of event, multivariable analyses only
included smoking status, diabetes, and prostate
volume for urinary leakages and age, smoking
status, prostate volume, and urinary leakage for
anastomotic strictures.
Results: The overall frequency of anastomotic
leakages was 21 (2.9%), and 36 (4.9%) patients
experienced anastomotic strictures during
follow-up. No differences were found in the
frequency of anastomotic leakages (3.2% vs.
2.1%; p=0.35) or -strictures (5.4% vs. 3.8%;
p=0.35) between RRP and RARP procedures.
None of the included variables was demonstrated as risk factors for anastomotic leakages.
Univariate analysis demonstrated an association between surgeon and risk of anastomotic
strictures in RRP patients (p=0.02). No other
risk factors for anastomotic strictures were
identified.
CONCLUSION: Overall, our anastomotic
complication rates are similar to international
results. We could not identify a difference in
the risk of anastomotic complications between
RRP and RARP. Univariate analysis suggested
a surgeon dependent association to the risk of
anastomotic strictures, which needs further
evaluation. No other independent risk factors
for anastomotic complications were identified,
likely related to the lack of statistical power.
#22 BRACHY THERAPY FOR PROSTATE CANCER IN ICELAND, PRIMARY RESULTS
Oddason ,Karl E.1, Myrdal, Gardar2, Henrysdottir, Hanna B.2, Kristjansson, Baldvin3
Helsingborg Lasarett, Urology department,
University Hospital of Iceland, Radiotherapy
department, 3University Hospital of Iceland,
Urology department
1
2
INTRODUCTION: Brachy therapy (BT) is
one treatment possibility for localized prostate
21
cancer (PC). Before brachy therapy began in
Iceland in 2012, patients underwent this type
of treatment in Sweden. The aim of this study
was to evaluate the primary results of brachytherapy in Iceland.
MATERIAL AND METHODS: Prospective
study including all patients that underwent
brachy therapy in 2012 and 2013 in Iceland
with one year follow up. Patients were evaluated preoperatively with urological evaluation,
including transrectal ultrasound, international
prostate symptom score (IPSS), international
index of erectile dysfunction (IIEF-5), serum
prostate-specific antigen (PSA), uroflowmetry
and residual volume. Postoperative evaluation
after 1, 3, 6, 9 and 12 months was performed
with PSA, IPSS, IIEF-5, uroflowmetry, residual
volume and an interview with an urologist. Self
reported rectal symptoms were noted and signs
of urinary infection were evaluated with urine
culture. Dosimetric parameters V100 and D90
were also analyzed.
RESULTS: 27 men with localized prostate cancer were treated with BT in Iceland. Average
preoperative PSA was 9,4 ng/ml (range 1,2
– 12,2 ng/ml). Dosimetric parameters were all
within planned range (V100 > 98% and D90
160 – 200 Gy). Three patients (11 %) had an
urine infection in the first month postoperatively and two (7.5%) reported rectal symptoms.
Four patients (15%) had a PSA bounce (PSA
rise ≥ 0.2 ng/ml) one year after treatment, thereof one (3.5%) with biochemical failure (nadir
PSA + 2 ng/ml). Average IPSS scores were
calculated, no significant difference in IPSS
score before and one year after treatment was
found (IPSS score 7.5/1.0 vs. 7.7/0.8, p=0.93).
IIEF-5 score continues to decline one year after
treatment (IIEF-5 score 19.5 vs. 16.4, p=0.16).
CONCLUSION: Results of the first two years
for Brachytherapy in Iceland are promising
and are in line with other international studies.
Prostate symptoms have mostly disappeared
one year after the treatment, while erectile
dysfunction prevails.
#23 RISK OF BIOCHEMICAL
RECURRENCE AFTER RADICAL
22
PROSTATECTOMY FOR PROSTATE
CANCER - UPDATED ANALYSIS OF
THE RIGSHOSPITALET COHORT
Røder M.A., Berg K.D., Kurbegovic S., Thomsen F.B., Gruschy L., Helgstrand J.T., Brasso
K., Iversen P.
of Urology, Rigshospitalet. University of Copenhagen, Denmark.
INTRODUCTION: Radical prostatectomy
(RP) for localised prostate cancer was introduced in Denmark at Rigshospitalet in 1995.
Since, patients at Rigshospitalet have been
followed prospectively according to our institutional protocol. We have previously described
morbidity, functional and oncological outcome
in the first 1200 operated patients. Here we
present an updated analysis of biochemical
outcome in the consecutive cohort of patients
who underwent RP from 1995-2013.
1995-2013, 2168 patients underwent RP at
our department. A total of 120 patients were
excluded from analysis because of missing
information regarding Gleason scores (GS),
leaving 2048 patients for analysis. Patients have
been followed with quarterly PSA measurements for the first year after surgery, biannual
PSA measurements during the second, and
annual measurements thereafter. Biochemical
recurrence was defined as the first PSA ≥0.2
ng/ml. Competing-risk analysis was used to
assess the risk of BR using death before BR as
a competing event. Multiple cause-specific Cox
regression model was used to weigh the impact
of covariates on the risk of BR.
RESULTS: Median follow-up was 5.4 years
(95%CI: 4.9-5.2). Median age at surgery was
63.8 years (IQR: 59.7-67.4). Median PSA was
8.3 ng/ml (IQR: 5.8-12.0). According to the
D’Amico classification, 402 (19.6%), 1157
(56.6%), and 487 (23.8%) were classified
as having low-, intermediate-, and high-risk
disease, respectively. A total of 514 (25%)
patients had pathologically extraprostatic
extension after RP. The overall margin positive
rate was 33.8%. The cumulative incidence of
BR was 15.3%, 31.3% and 46.5% after 10
years for low-, intermediate-, and high-risk
patients, respectively. The incidence of BR
was statistically significant different between
the three D’Amico groups. In multivariable
analysis, PSA (hazard ratio (HR) = 1.2 (95%
CI:1.1-1.4), pT3a (HR=2.3, 95%CI: 1.43.6), pT3b (HR=3.9, 95%CI: 2.5- 6.3), pT4
(HR=9.0, 95%CI: 2.6-31), margin positivity
(1.8, 95%CI: 1.5-2.2), specimen Gleason score
(sGS) 7 (4+3) (HR=2.1, 95%CI. 1.5-2.9), sGS
8 (HR=2.9, 95%CI: 1.9-4.4), and sGS 9-10
(HR=4.2, 95%CI2.8-6.5) were all statistically
significant predictors of BR.
CONCLUSION: In our updated analysis with
additional 1000 patients and approximately 2
additional years of follow-up we consolidate
previously reported results from our institution. The preoperative D’Amico classification
remains an important predictor of biochemical
outcome after RP. Moreover, adverse specimen
pathological features after RP are independent
predictors of BR after RP. Our results concur
with international findings.
#24 THE IMPACT OF THE MOVEMBER CAMPAIGN ON REFERRAL
PATTERNS, DIAGNOSIS AND TREATMENT OF PROSTATE CANCER
Frederik B. Thomsen1, Marta K. Mikkelsen1,
Rikke B. Hansen1, Klaus Brasso2
Department of Urology, Frederiksberg Hospital,
Denmark, 2Copenhagen Prostate Cancer Center,
Department of Urology, Rigshospitalet, University
of Copenhagen, Denmark
1
INTRODUCTION: We investigated the
effect of the Movember campaign, launched in
Denmark November 2011, on referral patterns,
diagnosis and treatment of prostate cancer
(PCa).
MATERIAL AND METHODS: All men
referred to Frederiksberg Hospital ‐ a primary
referral centre - in the period January 1, 2007
until January 31, 2014 were identified. Based
on referral date patients were categorized as
pre‐Movember (January 1, 2007‐January 31,
2011) and Movember (February 1, 2011-Janu-
ary 31, 2014), respectively. We reviewed charts
on all men (n=2,818) referred with suspicion of
PCa. Prostate‐specific antigen (PSA), findings
on digital rectal examination and prostate
biopsies were recorded. Low-risk PCa was
defined as: PSA <10 ng/ml, Gleason score ≤6
and clinical tumour category ≤2a. The effect
of the Movember campaign was assumed to be
present in the months November, December
and January (Nov‐Jan). Mann- Whitney‐U
tests were used to compare continuous data and
incidence rates were compared using rate‐ratio
(RR) test.
RESULTS: The median age was 68 years
(p=0.92) in both periods. The median PSA
at referral dropped significantly from 9.8 ng/
ml in 2007‐2011 to 7.9 ng/ml in 2011‐2014,
p<0.001. The incidence of men referred with
suspicion of PCa in the Movember period
was 168/100.000 person years, while the
incidence rate was 134/100.000 person years
in the pre‐Movember period (RR 1.25 (95%
CI:1.16‐1.35, p<0.001). The RR for men
referred with suspicion of PCa during Nov‐Jan
in the Movember period compared to Nov‐Jan
in the pre‐Movember period was 1.03 (95%
CI:0.89‐1.19, p=0.71). There was no difference
between the incidences of men referred with
suspicion of PCa in Nov-Jan compared to the
rest of the months during 2011-2014, RR 0.95
(95% CI:0.84-1.07, p=0.39). The RR of men
diagnosed with PCa in Nov-Jan in the preMovember period compared to the Movember
period was 1.02 (95% CI 0.81-1.28, p=0.90)
and 1.43 (95% CI:0.82-2.52, p=0.22) for men
diagnosed with low-risk PCa. Finally, there
were no differences in the percentage of men
diagnosed with PCa (RR 1.02 [95% CI:0.841.23, p=0.88]) or low-risk PCa (RR 1.24 [95%
CI:0.80-1.91, p=0.35]) in Nov-Jan 2011‐2014
compared to the other months.
CONCLUSION: A significant decline in PSA
level and increase in number of patients referred under suspicion of PCa was observed in
2011-2014 compared to 2007‐2011; however
we detected only minor differences in referral
patterns and PCa diagnosis. The results indicate
that the Movember campaign had limited im23
mediate effect on referral, however it may have
increased the general awareness of PCa.
#25 FOCAL ONE® – MORE THAN
SIMPLE HIFU
Daniel Koch1, Andreas Blana1, Daniel Eberli2,
Daniel Baumunk3, Roman Ganzer4, Nina
Harke5, Timur Kuru6, Jost von Hardenberg7,
Johann Wendler3, Tullio Sulser2, Jörn Witt5,
Maurice-Stephan Michel7, Jens-Uwe Stolzenburg4, Axel Heidenreich6, Martin Schostak3
Dept. of Urology, Hospital of Fürth, Germany,
Dept. of Urology, University of Zurich, Switzerland, 3Dept. of Urology, University of Magdeburg,
Germany, 4Dept. of Urology, University of Leipzig, Germany, 5Dept. of Urology, St.-Antonius
Hospital of Gronau, Germany, 6Dept. of Urology,
University of Aachen, Germany, 7Dept. of Urology, University of Mannheim, Germany
1
2
INTRODUCTION: High-intensity focused
ultrasound (HIFU) is a technology to ablate
prostate cancer.
MATERIAL AND METHODS: The next
generation Focal One® device has been used at
various prostate cancer centers in Europe since
2014. It displays substantial improvements:
fusion of multiparametric MRI (mpMRI) and
transrectal ultrasound (TRUS) images, doubled
lesion height enabling treatment of larger
glands, dynamic focusing and intraoperative
effectiveness monitoring by contrast-enhanced
ultrasound. Precise treatment area contouring
within the gland for focal therapy has now
become easier. This study describes results
obtained in patients treated with Focal One® at
6 German centers and Zürich.
RESULTS: A total of 126 HIFU treatments
were performed: 72 as focal/partial therapy (22
x Hemiabladation), 38 as whole-gland therapy
and 16 as salvage therapy (8 after percutaneous
radiotherapy, 6 after LDR brachytherapy
and two after primary HIFU). Transurethral
resection of the prostate was performed in 42
patients before and one patient after HIFU
(21%). 75 (60%) patients received pretreatment mpMRI and 41 MRI of the pelvis.
The average length of hospital stay was 3 days
24
(average and median; 2-13). The indwelling
catheter use was 2,2 days in the average.There
were no complications of the rectum but two
cases of incontinence grade I. Other complications occurred in 12 cases (2 x Clavien grade
I, 9 x Clavien grade 2, 1 x Clavien grade 3
(TUR-P 2 weeks after HIFU)). On the other
hand, 65 % of the patients were completely
free of subjective complaints after treatment. In
the group of focal treated patients the Gleason
Score was 6 (Median; 42 x 6, 20 x 7a, 8 x 7b,1
x 8, 1 x 9), psa was 6.4ng/ml in the average.
The clinical stage was cT2a in 16 of the focally
treated patients and cT1c in the others.
CONCLUSION: Through markedly improved
technology, the next generation Focal One®
device goes beyond the scope of hitherto standard HIFU treatments (primary whole-gland
treatment and salvage after radiotherapy) to
enable much more precise, less traumatic and
now also focal treatment. The new procedure
has a remarkably low morbidity compared to
previous generations of devices. For an assessment of oncological outcome and possible late
complications the Follow-up is still too short.
Pretreatment transurethral resection was rarely
required. #26 HETEROGENEITY OF
D’AMICO INTERMEDIATE-RISK
PROSTATE CANCER – AN ANALYSIS
OF BIOCHEMICAL RECURRENCE
AFTER RADICAL PROSTATECTOMY AT RIGSHOSPITALET.
Røder M.A., Berg K.D., Kurbegovic S., Thomsen F.B., Gruschy L., Klemann N., Brasso K.,
Iversen P.
of Urology, Rigshospitalet. University of Copenhagen, Denmark.
INTRODUCTION: The D’Amico classification was originally derived from analysis of risk
of biochemical recurrence (BR) following surgery or radiation therapy for localised prostate
cancer. Today, the model is widely accepted
as a pre-treatment risk stratification model.
Intermediate-risk patients are defined as having
PSA 10-20 ng/ml, Gleason score 7 or clinical
T-category T2b. This allows for heterogeneity
as intermediate-risk patients can harbour
between one and three risk factors at diagnosis.
Herein, we examine biochemical outcome in
the consecutive cohort of intermediate-risk
patients who underwent radical prostatectomy
(RP) at our department from 1995-2013, and
investigate the impact of the number of risk
factors.
MATERIAL AND METHODS: From 19952013, 2168 patients underwent RP at Dept. of
Urology, Rigshospitalet, Denmark. A total of
1122 patients were classified as intermediaterisk prior to RP. Patients have been followed
with quarterly PSA measurements for the first
year after surgery, biannual PSA measurements
during the second year, and annually measurements thereafter. Biochemical recurrence was
defined as the first PSA ≥0.2 ng/ml. Competing-risk analysis was used to assess risk of BR
using death before BR as a competing event,
and multiple cause-specific Cox regression
model was applied.
RESULTS: Median follow-up was 4.9 years
(95% CI: 4.6-5.1). Median PSA was 8.7 ng/
ml (IQR: 6.1-12.0). A total of 431 (38.4%)
patients had biopsy Gleason score (bGS)≤ 6,
while 570 (50.8%) had bGS=3+4, and 121
(10.8%) had bGS=4+3. A total of 523 (46.6%)
patients had cT1 disease. The proportion
of patients with one risk factor was 56.4%,
whereas 33.9% and 9.7% had two and three
risk factors, respectively. The cumulative
incidence of BR after 10 years was 23.3%
(95CI:18.1-28.6), 38.6% (95%CI:30.2-46.9),
and 42.3% (95%CI:30.5-54.0) in patients with
one, two or three risk factors, respectively. After
multivariable adjustment, PSA (10-20 vs. < 10;
HR=1.71, 95%CI: 1.31-2.23) and cT category
(cT2b vs. cT1; HR=1.68, 95%CI: 1.26-2.22)
were significant predictors of BR. In contrast,
intermediate-risk bGS was not significantly
associated with risk of BR (bGS 7 vs. bGS 6;
HR=1.29, 95%CI: 0.97-1.70).
CONCLUSION: There is a clinical important
degree of heterogeneity in the risk of BR after
RP among patients with intermediate-risk
prostate cancer. Patients harbouring more risk
factors are at an increased risk of BR after RP
compared to patients with one risk factor. PSA
and cT category are the most important risk
factors for BR in the intermediate-risk group.
Thursday 4th June
15.30 - 16.45
Palissad VÄST
#27 SURGICAL TREATMENT OF
LOCALIZED RENAL CELL CARCINOMA (RCC) IN NORWAY 2008 -2012.
KM Hjelle2,3, T B Johannesen1, C Beisland2,3
Norwegian Cancer Registry, Oslo, Norway,
Haukeland University Hospital, Department of
Urology, Bergen, Norway, 3University of Bergen,
Department of Clinical Medicine, Norway
1
2
OBJECTIVE: The aim of this study was to
investigate patterns and possible changes in
kidney cancer surgery in Norway between 2008
and 2012.
MATERIAL & METHODS: Data were
extracted from the Norwegian Cancer Registry
(NCR). Patients who were diagnosed with
kidney cancer in the period from 01.01.2008
till 31.12.2012 were included. From NCR,
information is collected from histopathology
reports and clinical report. After manual control of all report forms by one person (KMH),
all data regarding Fuhrman grade, size, stadium
and type of surgical treatment were transferred
to an SPSS data file for further analysis. Type
of surgical treatment was further compared to
the data in the national patient administrative
data system.
RESULTS: Data from the Norwegian Cancer
Registry revealed that 2589 patients underwent
curative intended surgical treatment for kidney
tumours. An increase of 25.7% is observed
during these years in radically treated patients
from 462 in 2008 till 581 in 2012. The use of
partial nephrectomy increased from 22.5% in
25
2008 till 37.7 % in 2012 irrespectively of size.
Of tumours up to 4 cm, a total of 54.1 % were
treated with partial nephrectomy during the
five year period. The percentage for each year
demonstrated clearly an increase during the
period. The figures were for 2008: 39.9%, for
2009: 43.3 %, for 2010: 49.8 %, for 2011:
66.0% and for 2012: 64.7%. The use of partial
nephrectomy for tumours between 4 and 7
cm was only 12.4% during the whole period.
However, a slight increase from 9 % in 2008 to
16.1% in 2012 was observed.
The number of patients that each year
underwent nephrectomy was relatively stable
over the 5-year period (358, 377, 338, 357
and 365). During the study period only three
patients got minimally ablative treatment.
CONCLUSION: Data from the Norwegian
Cancer Registry shows that the number of
localized and radically treatable RCC increases
in Norway. An increasing frequency in the use
of partial nephrectomy is seen especially in tumours up to 4cm use of partial nephrectomies.
These changes are in line with internationally
reported trends.
#28 RISK FACTORS FOR RENAL
CELL CANCER IN ICELAND– A
NATION-WIDE, PROSPECTIVE
EPIDEMIOLOGICAL STUDY
Mariusdottir E1,3, Ingimarsson JP1, Jonsson E1,
Einarsson GV1, Aspelund T2,3, Guðnason V2,3
and Gudbjartsson T3
Dept. of Urology and Surgery, Landspitali
University Hospital, 2Icelandic Heart Association, 3Faculty of Medicine, University of Iceland,
Reykjavik, Iceland
1
OBJECTIVES: There is less information on
risk factors for renal cell carcinoma (RCC)
than for most other cancers. Furthermore, the
risk factors already identified (i.e. smoking,
hypertension, and obesity) only have a weak
association. By using centralised registries in
Iceland, our aim was to prospectively investigate multiple risk factors for RCC, with focus on
certain occupations that are possibly associated
with increased risk.
26
MATERIALS AND METHODS: From
the Reykjavik study database, 18,840 men
and women born in the period 1907‒1935
were linked with a population-based registry
containing all RCCs diagnosed in Iceland from
1971 to 2005 (n=910). A prospective analysis
of the risk factors for RCC was performed
using Cox regression analysis, from the time of
entry into the Reykjavik study to the diagnosis of RCC, death, or end of follow-up. The
hazard ratio was then calculated for age, gender,
BMI, smoking, hypertension, diabetes, kidney
disease, and occupational history.
RESULTS: Male gender (HR 1.65,
CI=1.14‒2.38, p≤0.001), BMI over 25 kg/m2
(HR 1.41, CI=1.06‒1.88, p=0.02), and age
(HR 1.04, CI=1.03‒1.07, p≤0.001) increased
the risk of RCC, as did severe hypertension
(>160/100 mmHg) (HR 1.46, CI=1.05‒2.03,
p=0.02) and history of kidney disease (HR
1.55, CI=1.11‒2.16, p=0.009), however
smoking and diabetes were not significantly associated with the disease. The risk of RCC was
significantly increased in painters (HR 2.97,
CI=1.31‒6.74, p=0.02), aircraft mechanics
(4.51, CI=1.11‒18.28 p=0.03), and shipbuilders (HR 2.03, CI=1.06‒3.84, p=0.04).
CONCLUSIONS: Together with male gender,
advanced age, hypertension, BMI over 25 kg/
m2, and history of kidney disease, the risk of
RCC was significantly increased in painters,
aircraft mechanics, and ship builders, suggesting a link to occupational exposure.
#29 PROPHYLACTIC MESH PLACEMENT FOR PREVENTING PARASTOMAL HERNIAS IN PATIENTS
RECEIVING A BRICKER ILEAL
CONDUIT
Oskar Fagerström and Tomas Jerlström
School of Health and Medical Sciences, Department of Urology, University of Örebro, Örebro,
Sweden
BACKGROUND: Parastomal herniation is
a common complication occurring after construction of stomas and may require additional
medical resources and affects the patient’s
quality of life. Surgical techniques for repairing
parastomal hernias show less than ideal results
with high recurrence rates and morbidity.
Studies regarding stomas in colorectal surgery
have shown a decreased incidence of parastomal hernia using a prophylactic mesh net
reinforcement of the abdominal wall at the
primary stoma operation. The pathophysiological mechanisms for occurrence of parastomal
hernia in urinary diversions such as the Bricker
ileal conduit are likely similar and therefore allow for similar prophylactic measures, the first
study on the subject was recently published.
Aims: The primary aim of this project was to
compare the frequency of parastomal hernia
in patients receiving a Bricker ileal conduit at
the urology department of Örebro University
Hospital with or without the placement of a
prophylactic mesh.
METHOD: A retrospective review of urological, surgical and emergency medical records
for 40 consecutive patients who did not receive
prophylactic mesh reinforcement and 42 consecutive patients who did receive mesh reinforcement of the abdominal wall during primary
Bricker conduit construction was conducted.
Appurtenant radiological records were also
reviewed. Statistical comparative and descriptive analyses were performed on collected data
using IBM SPSS.
RESULTS: A total of 82 patients’ medical
records were reviewed. 40 patients did not
receive prophylactic mesh implantation and 42
had the implantation, retaining two homogenous groups with no significant demographic
differences. 19 (23%) patients, 10 in the group
without mesh and nine in the group with
mesh, developed parastomal hernias in a mean
time of 16 months. Five of the patients without
mesh and one with mesh required surgery
due to their parastomal hernias. There was no
significant difference between the mesh and nomesh group regarding frequency of parastomal
hernia or need of treatment due to parastomal
hernia.
CONCLUSION: This project failed to identify
prophylactic mesh placement as a method of
reducing the frequency of parastomal hernias in
patients with Bricker ileal conduits. High BMI
was identified as a significant risk factor for
hernia development.
Due to the low power of this study no applicable conclusions can be made. Nevertheless
it highlights the need for further, larger and
prospective randomized studies of the subject.
#30 LONG-TERM OUTCOME
AFTER CONTINENT CUTANEOUS
DIVERSION A.M. LUNDIANA IN
198 PATIENTS
Liedberg F1, Abai X1, Bendahl P-O2, Davidsson
T4, Gudjonsson S1 and Månsson W3
Section of Urology, Skåne University Hospital,
Lund University, Malmö, Sweden, 2Dept Clinical
Sciences, Lund University, Lund, Sweden, 3Dept
Surgery, Kristianstad County Hospital, Lund
University, Sweden, 4Dep Urology, Haukeland
University Hospital, Bergen, Norway
1
The Lundiana Pouch for continent cutaneous
diversion is a modification of the Indiana
Pouch. In the former the ileocecal valve is
diminished in diameter and fixed against
the cecal wall as a flap valve using stapling
instruments. Complications and functional
outcomes at long-term follow-up have to be
balanced against other types of reconstruction
and patients’ preferences.
MATERIALS & METHODS: During 19922007 diversion a.m. Lundiana was performed
in 198 patients. In a retrospective survey
information on complications and functional
outcome (renal function and continence)
was ascertained from the patient charts. 159
patients had a pelvic malignancy and 39
patients were operated for benign disease. Five
patients died within 90 days of surgery and
were excluded from the functional outcome
analysis. Median follow-up was 8 years (IQR
3-13 years). Complications were registered according the Clavien-classification (3 or higher)
at 90 days.
RESULTS: Complications Clavien grade 3 or
more occured in 39/198 patients (20 %) within
90 days of surgery, of whom 21 were reopera27
ted (11 %). During follow-up 101/193 (52 %)
patients were reoperated at least once including
reoperations during the first three months.
Reasons for reoperation were; pouch stone (24
(13 %)), ureterointestinal stricture (22 (12
%)), revision of the outlet (15 (8 %)), stomal
stenosis (14 (7 %)), hernia (10 (6 %)), pouch
perforation (9 (5 %), nephrectomy (7 (4 %))
and miscellanous reasons (16 (8 %)). Reoperation was more common in patients operated
for benign disease (26/39 (67 %) compared to
diversion after tumour surgery (75/154 (49 %))
(p=0.045). Febrile UTI requiring hospitalisation occurred in 25/193 patients. Continence
was achieved in 174/188 (93 %) patients starting CIC. Median increase in S-creatinine was
7 micromol/L, and 16 patients had more than
50 % decrease in eGFR at end of follow-up.
CONCLUSION: Continent cutaneous diversion a.m. Lundiana achieves high continence
rates, however complications from upper urinary tracts, pouch and outlet are common, and
every second patient suffered from a reoperation. Patients with urinary diversion have to be
under life-long surveillance.
#31 URETHRAL RECONSTRUCTION FOLLOWING ARTIFICAL
URINARY SPHINCTER CUFF
INFECTION-EROSION
Francisco E. Martins, João P. Marcelino, Anatoliy Sandul, Sandro Gaspar, Pedro Oliveira and
Tomé M. Lopes
Department of Urology, University of Lisbon
School of Medicine, Hospital Santa Maria,
Lisbon, Portugal
Artificial urinary sphincter (AUS) cuff
infection-erosion is a distressing complication
and a surgical challenge traditionally managed
with device removal, antibiotic coverage and
urethral catheter placement. Urethral stricture
can develop as a result of the healing process,
often delaying AUS re-implantation or making
it more difficult. We carried out a retrospective
review of 19 patients who experienced infection
and/or erosion of AUS cuff and the manage28
ment options used to resolve this challenging
complication, and compared the urethral stricture rates with patients who were treated with
simultaneous urethral reconstruction.
MATERIALS AND METHODS: We identified 19 patients who had removal of AUS
for cuff infection-erosion between 2008 and
2015. We grouped the patients in 2 cohorts:
A) 10 patients treated with urinary diversion
only (Foley urethral catheter placement or
suprapubic cystostomy), and B) 9 underwent
simultaneous urethral reconstruction (1-stage
or 2-stages). Records of patients were analyzed for demographic, clinical data (including
etiology of urinary incontinence, risk factors
for infection-erosion, medical co-morbidities),
retrograde urethrogram, flexible urethrocystoscopy and reconstructive options used in the
simultaneous urethral reconstruction patient
cohort.
RESULTS: Of the total 19 patients identified, 10 underwent AUS removal and catheter
urinary diversion (urethral Foley catheter
placement in 7 and suprapubic catheter in 3)
and 9 were treated with simultaneous urethral
reconstruction, 3 of whom received a temporary 1st-stage perineal urethrostomy due
to associated purulent discharge and abscess
formation in 2, and due to development of
partial bulbar urethral and perineal necrosis in
1. The surgical procedures used were the following: dorsal urethrorraphy in 1, dorsal onlay
MB graft in 1, and bulbar urethral segment
excision and primary anastomosis (EPA) in 4.
Patient age ranged from 58 to 81 years (mean
75). Follow-up ranged from 4 to 81 months
(mean 48). Cohort A patients had a higher rate
of urethral stricture formation (7/10, 70%)
compared to patients who underwent urethral
reconstruction (3/9, 33%; p = 0.049). Patients
treated with AUS removal and simultaneous
urethral reconstruction experienced less surgical
complications, they underwent fewer surgical
procedures before AUS replacement, and were
more likely to undergo successful secondary
AUS implantation (6/9, % vs 4/10, %, p = )
compared to those who were treated with urinary diversion only at the time of AUS removal
for cuff infection-erosion.
CONCLUSION: Simultaneous urethral
reconstruction at the time of AUS removal for
cuff infection-erosion apparently is associated
with a lower rate of urethral stricture formation
and, consequently, leading to more successful
AUS replacement later.
#32 MANAGEMENT OF IATROGENIC URORECTAL FISTULAE IN
PELVIC CANCER
Francisco E. Martins¹, Sandro Gaspar¹, Pedro
Oliveira¹, Natália M. Martins² and Luís C.
Pinheiro²
¹Department of Urology, Hospital Santa Maria,
Lisbon, Portugal. ²Department of Urology, Hospital S. José, Lisbon, Portugal
Urorectal fistulae (URF) is a devastating complication following pelvic cancer treatment and
a surgical challenge for the reconstructive surgeon. Despite it’s increasing incidence associated
with the expanding use of different radiation
therapeutic modalities, with or without surgery,
it still remains a relatively uncommon entity.
Spontaneous closure of URF is very unlikely
and surgical repair is deemed necessary in the
majority of cases. Various surgical options have
been utilized with high failure/recurrence rates,
particularly in irradiated URF. We report our
limited experience in the management of URF
associated with pelvic cancer treatments.
MATERIALS AND METHODS: Between
October 2008 and February 2015, 10 patients
with URF were referred to our institutions. We
analyzed the patients’ charts for age, symptoms,
presence of co-morbidities, diagnostic workup,
fistula type and etiology, type of surgical
repair, follow-up (FU) and outcomes. Patients
with non-neoplastic/inflammatory URF were
excluded.
RESULTS: Mean age from the ten patients was
68 years. Seven patients developed a URF following treatment of prostate cancer (PCa): 2 after
low-dose brachytherapy (LDB) combined with
external beam radiotherapy (ERBT); 3 after
radical retropubic prostatectomy (RRP), with
adjuvant ERBT in 1; 1 after LDB followed by
transurethral resection of prostate (TURP) for
prostatic obstruction; and 1 after HIFU and
ERBT. Two patients developed a URF following treatment of rectal cancer, with ERBT in
1. One patient with a rectal cancer developed
lymph node and liver metastases 4 months after
diagnosis of the URF while on treatment for a
post-operative pelvic abcess and, therefore, was
excluded from surgery. No patient experienced
spontaneous fistula closure. Nine patients
underwent surgical with a temporary diverting
colostomy and urethral or suprapubic catheter,
while waiting for surgical repair. An exclusive
perineal approach was used in 5 patients, and
a combined abdominoperineal approach in 4.
Successful closure was achieved in 4 patients
after 1 surgical attempt, 2 patients required
a 2nd operation, whereas 1 patient needed a
three-staged surgical procedure to achieve a
successful resolution. Surgical repair failed in 2
patients. These 2 patients and 1 who had a successful repair still have a colostomy. Mean time
of FU was 25.5 months (range 3 – 75).
CONCLUSIONS: URF is an infrequent
but devastating complication of pelvic cancer
treatment, usually associated with debilitating
morbidity and poor quality of life. Although
successful surgical repair of iatrogenic URF
may be extremely difficult, success can be
achieved in most cases through an aggressive
perineal or abdominoperineal approach with
healthy tissue interposition, when needed.
#33 A MULTI-INSTITUTIONAL EVALUATION OF THE MANAGEMENT
AND OUTCOMES OF LONG-SEGMENT URETHRAL STRICTURES
Jonathan Warner, Ibraheem Malkawi, Mohammad Dhradkeh, Pankaj M. Joshi, Sanjay B.
Kalkarny, Massimo Lazzeri, Guido Barbagli,
Ryan Mori, Kenneth W. Angermeier, Oscar
Storme, Rodrigo Campos, Laura Velarde,
Reynaldo G. Gomez, Justin S. Han, Christopher M. Gonzalez, David Martinho, Anatoliy
Sandul, Francisco E. Martins, and Richard
Santucci
29
University of Lisbon, School of Medicine, Hospital
Santa Maria, Lisbon, Portugal
Ellertsson-Csillag, S., Hilmarsson, R. and
Geirsson, G.
OBJECTIVE: To evaluate the treatment
options and surgical outcomes of long-segment
urethral strictures - a revies of the largest, international, multi-institutional series.
METHODS: A retrospective review was
performed of patients treated with strictures
≥ 8 cm at 8 international centers. Endpoint
analyzed included surgical complications and
recurrence.
RESULTS: Four hundred sixty-six patients
were identified. Treatment intervals ranged
from December 27, 1984 to November 9,
2013. Dorsal onlay buccal mucosa graft
(BMG) was the most common procedure (223,
47.9%); others included first- and second-stage
Johanson urethroplasty (162, 34.8% and 56,
12%, respectively), fasciocutaneous (FC) flaps
(8, 1.7%), and a combination of flap and graft
(17, 3.6%). Overall success was achieved in
361 patients (77.5%) with a mean follow-up of
20 months. Second-stage Johanson urethroplasty was found to have a higher recurrence
rate compared with that of 1-stage BMG
urethroplasty (35.7% vs 17.5%, respectively:
P< 0.01). This was also true in cases of lichen
sclerosus (14.0% vs 47.8%, respectively; P <
0,01). Otherwise, success rates were similar.
Urethroplasties performed with FC flaps had a
higher complication rate compared with those
without (32% vs 14%, respectively; P = 0,02).
Prior dilation or urethrotomy, higher number
of prior dilations or urethrotomies, abnormal
VCUG, and skin grafts all portend a higher
recurrence rate. On logistic regression analysis,
only secons-stage Johanson had an increased
odds ration of recurrence compared with that
of BMG (2.82 [1.41 – 5.86]9.
CONCLUSION: Long-segment strictures can
be treated with high success rates in experienced hands. BMG was more successful than
second-stage Johanson. FC flaps, although
successful, had high complications rates.
University of Iceland
#34 PENIS CANCER IN ICELAND
1989-2014. INCIDENCE AND SURVIVAL
30
INTRODUCTION/OBJECTIVES: The aims
of the study was to explore the incidence and
survival of all consecutive men diagnosed with
invasive penile cancer in Iceland between 1 Jan
1989 and Dec 31 2014, to assess whether these
parameters have changed significantly over the
period, and to compare our results to what has
been observed in the other Nordic countries.
METHODS: A total of 61 men were diagnosed with invasive penile cancer in Iceland in the
study period. All patients were followed from
diagnosis until death or Dec 31 2014. The
mean and median follow-up period was 56 and
29 months respectively. Age-adjusted incidence
rate was calculated using world standardization.
Survival analysis was performed using KaplanMeier estimation and Cox regression analysis.
RESULTS: The mean age adjusted incidence
rate for the time period is 1.07 / 100.000 men.
No significant change was observed between the
periods 1989-2001 and 2002-2014 (p =0.374).
The mean age at diagnosis was 67.9 years.
Fifty-eight out of 61 (98%) had squamous cell
carcinoma. Pathological staging of primary
tumors was as follows: T1 40 (69%), T2
14(24%), T3 3(5%), and TX 1(2%). Nodal
involvement at diagnosis was found in 6 (10%)
cases and 1 case (2%) had distant metastasis at
diagnosis. A total number of 13 (22%) cases
had a recurrence of the disease, 4 penile, 6
nodal, and 3 extra nodal. Fifty-six (97%) of the
primary tumors, 5 (83%) with positive nodes
at diagnosis, and 2 (33%) with nodal recurrences received curative care.
The 5-year overall survival was 55% and the
disease specific survival was 76%. Furthermore,
when the disease specific survival was stratified
into T1, T2-T3 and T1-3 & N1+ categories
the predicted 5-year survival rates were 94%,
70%, and 17% respectively (p<0.05). However,
there was no significant difference in the
survival rate between the periods 1989-2001
and 2002-2014 (p= 0.42). The only statistically
significant factor concerning disease specific
survival was nodal involvement (p< 0.05).
CONCLUSION: The results of this whole
population study shows that both the incidence
and survival of penis cancer has remained fairly
stable for the last 25 years with no significant
change observed between the earlier and later
halves. The incidence and survival of penis cancer in Iceland largely correlates with what has
been observed in the other Nordic countries
with nodal involvement being the most important factor concerning long-term survival.
#35 UNINTENTIONAL WEIGHT
LOSS BUT NOT OBESITY PREDICTS CANCER-SPECIFIC SURVIVAL IN PATIENTS WITH INVASIVE
PENILE CANCER
Jakob Kristian Jakobsen1, Kim Predbjørn
Krarup2, Peter Sommer2, Henrik Nerstrøm2,
Bjarne Kromann-Andersen4, Vivi Bakholdt3,
Jens Ahm Sørensen3, Kasper Ørding Olsen1
and Jørgen Bjerggaard Jensen1
Aarhus University Hospital, Dept of Urology,
Rigshospitalet, Copenhagen University Hospital,
Dept of Urology, 3Odense University Hospital,
Dept of Plastic Surgery, 4Herlev University Hospital, Dept of Urology
1
2
INTRODUCTION: In breast cancer, colorectal cancer and prostate cancer, elevated
body mass index (BMI) has been established as
an independent prognostic factor for cancerspecific mortality. A recent American study
was the first to introduce elevated body mass
index (BMI) as an ominous predictor in penile
cancer. This finding could not be verified in a
large European database.
OBJECTIVE: To investigate the prognostic
importance of BMI and patient reported
unintentional weight loss at diagnosis in a large
retrospective Danish cohort of 429 men with
invasive penile cancer. Furthermore, to compare BMI for 325 penile cancer patients with
11,238 age-matched healthy Danish men in a
case-control design.
PATIENTS AND METHODS: A retrospective penile cancer cohort from the period
2000 - 2010 was established by chart review
at five Danish university hospitals. Data for
the healthy control group was derived from
the national health and morbidity studies by
Department of Public Health, University of
Southern Denmark 2000-2010. We assessed the role of BMI as a prognostic factor by
splitting the retrospective cohort in two at BMI
below and above 30 kg / m2 in. Cox regression
with 95% confidence intervals was used for
penile cancer-specific survival analysis.
RESULTS: 325 penile cancer cases (60.9 ±
9.2 years) were compared with 11,238 healthy
controls (60.4 ± 10.7 years) and had significantly higher BMI 28.4 ± 5.5 kg/m2 vs. 26.2 ±
3.6 kg/m2, p <0.0001. In contrast, Cox hazard
ratio when comparing penile cancer patients
with a BMI below and above 30 kg/m2 was
0.74 (0.47 to 1.18), p = 0.20, corresponding
to the survival curves for the two BMI-groups
overlying each other. When comparing patients
with reported unintended weight loss at diagnosis (n = 29) and patients without mention
of weight loss in the medical history (n = 400),
the hazard ratio was 6.0 (3.5 to 10.1) p <0.001.
CONCLUSION: Danish penile cancer
patients have significantly higher BMI than
healthy controls of the same age. BMI at
diagnosis has no significance as a prognostic
marker for Danish penile cancer patients, while
unintentional weight loss, not unexpectedly,
is a marker of poor prognosis. These data
confirmed the Dutch findings on a comparable
cohort, whereas US data from a cohort with
higher BMI, highlights high BMI as a poor
prognostic marker. There is a need for further
studies to analyse the importance of obesity in
the pathogenesis of penile cancer.
#36 LAPAROSCOPIC CRYOABLATION
OF ANGIOMYOLIPOMAS IN ADOLESCENTS AND YOUNG ADULTS: A
REPORT OF 4 CASES ASSOCIATED
WITH TUBEROUS SCLEROSIS AND 1
CASE OF SPORADIC ORIGIN
Karina Trelborg
Aarhus University, Dept of Clinical Medicine
Palle Juel-Jensens Blvd. 99 Aarhus, Denmark
31
PURPOSE: The present study reports the
first series of laparoscopic cryoablation of renal
angiomyolipomas (AML) in adolescents and
young adults.
October 2009 to September 2013 five patients
at our institution were diagnosed with AML
requiring treatment. Four patients had tuberous
sclerosis (TS) and one had AML of sporadic
origin, all five patients underwent laparoscopic
cryoablation. Perioperative data was prospectively registered in a nation-wide laparoscopy
database with follow-up data collected from the
patients’ chart. Independent radiologists reassessed all imaging.
RESULTS: Median age was 16 (13–27) years.
Eight AMLs in five patients, with a median size
of 3.9 (2.1-7.7) cm were treated. Indication for
intervention within the TS group was prophylactic due to tumor size and rapid growth. The
patient with sporadic AML was treated due
to tumor size and a former bleeding episode.
From time of diagnosis until intervention the
patients with TS were followed with renal imaging for a median time of 117 (1–140) months.
After cryoablation AML-status was followed by
CT and MRI for a median follow up time of
37 (6–59) months. On follow-up imaging, all
lesions showed a reduction in tumor size, and
no regrowth was recognized.
The procedure was well tolerated, with
few minor intraoperative complications and
all patients scored zero in the Clavien-Dindo
classification as no postoperative complications
occurred.
CONCLUSIONS: Treating AMLs with
laparoscopic cryoablation appears to be a safe
and feasible nephron-sparing approach in
adolescents and young adults, thus supporting
the future use of cryoablation in this patient
group. For inferior, lateral and peripherally
located lesions, percutaneous cryoablation is a
less invasive option, but none of our patients
had lesions appropriate for this approach. Treatment with mTOR inhibitors is an alternative
and promising non-invasive treatment for TSpatients with AMLs not requiring immediate
surgery.
32
Thursday 4th June
15.30 - 16.45
Palissad ÖST
#37 HOLEP DURING THE LEARNING CURVE VERSUS OPEN PROSTATECTOMY
Oliver Patschan
Department of Urology, Skåne University Hospital,
Malmö, Sweden
BACKGROUND: Transurethral enucleation
of the prostate with Holmiumlaser (HOLEP)
has been shown to have better short-‐term
results than open prostatectomy (OP) in the
treatment of obstructive benign prostatic enlargement (BPE) in large prostates. In Malmö,
HOLEP was started as a new treatment option
for BPE in October 2013.
OBJECTIVE: Aim of the study was to compare relevant pre-, peri- and postoperative clinical measures of the first cases of HOLEP with
OP in the same time period. Primary endpoint
was need for blood transfusions. Secondary
endpoints were catheterisation time, hospital
stay and use of postoperative analgetics.
MATERIALS AND METHODS: All patients
operated with OP or HOLEP for obstructive
bladder outlet obstruction during 1st October
2013 and 25th March 2015 in Malmö were
included in the study. Patient charts from all 27
patients were reviewed retrospectively. Perioperative parameters like age, BMI, micturition,
catheter use, S-Hb before and after surgery,
TRUL prostate volume, resection weight,
bleeding, blood transfusion rate, catheter time,
length of hospital stay, and use of Oxycodone
and Paracetamolpostoperatively. The study was
approved by the local ethicscommittee.
RESULTS: 12 patients were operated with
HOLEP, and 15 with OP. Mean age at operation was 72.2 yrs. vs. 70.3 yrs., BMI 27.2 vs.
27.1, Median TRUL prostate volume was
108ml (IQR 72 - 138) vs. 130ml (IQR 115 180), and resection weight 76g (IQR 36 - 90)
vs. 114g (IQR 100 - 170) in patients operated
with HOLEP and OP, respectively. S-Hb
decreased from 138g/l preoperatively to 123g/l
one day postoperatively in HOLEP, and from
147g/l to 112g/l in OP, respectively. Patients
operated with OP did at mean get 1 blood
transfusion per operation, whereas patients
operated with HOLEP did at mean get 0.4
blood-‐transfusion per operation. However,
the odds for getting a blood transfusion was
not statistical significant higher for OP than
for HOLEP patients (HR 2,4; CI95% 0.59
- 9.82; p=0.223). Catheterisation time was
shorter (Median 3d, IQR 2 - 7 vs. 10d, IQR
6 - 14; p=0.002), hospital stay was shorter
(Median 3.5d, IQR3 - 4.75 vs. 7d, IQR 6
- 9; p=0.0002), and use of both Oxycodone
and Paracetamol postoperatively was less for
patients operated with HOLEP than with OP
(Median 10mg Oxycodone/patient, IQR 10
17.5 vs. 65mg Oxycodone/patient, IQR 30
90; p=0.003. Median 9g Paracetamol/patient,
IQR 4.25 10 vs. 25g Paracetamol/patient,
IQR 16 32; p=0.002).
CONCLUSION: Even during the learning
curve, patients operated with HOLEP had less
bleeding, needed less blood transfusions, had
shorter catheterisation and hospitalisation time,
and needed less analgetics compared to patients
operated with OP. However, patients operated
with HOLEP had smaller prostates, which is a
selection bias.
#38 THE IMPACT OF NOCTURIA
ON MORTALITY: A SYSTEMATIC
REVIEW AND META-ANALYSIS
Pesonen JS1,2, Cartwright R3, Santti H4,
Mangera A5, Tähtinen RM6, Griebling TL7,
Riikonen J2, Pryalukhin AY8, Tsui JF9, Aoki Y10,
Guyatt GH11, Tikkinen KAO4
1
Dept. of Urology, Päijät-Häme Central Hospital,
Lahti, Finland, 2Dept. of Urology, Tampere University Hospital, Finland, 3Dept. of Epidemiology
& Biostatistics, Imperial College London, UK,
4
Dept. of Urology, Helsinki University Hospital,
Finland, 5Dept. of Urology, Sheffield Teaching
Hospitals, UK, 6Dept. of Obstetrics and Gyneco-
logy, Kuopio University Hospital, Finland, 7Dept.
of Urology, University of Kansas, Kansas City,
USA, 8Dept. of Urology, North-Western State
Medical University Named After I.I. Mechnikov,
Saint Petersburg, Russia, 9Dept. of Urology, Lenox
Hill Hospital, New York City, USA, 10Dept. of
Urology, University of Fukui, Japan, 11Dept. of
Clinical Epidemiology & Biostatistics, McMaster
University, Hamilton, Canada
Several studies have shown that nocturia
increases risk of fractures and falls, but it may
also be associated with increased mortality.
Individuals with nocturia tend to be older and
are more likely to suffer comorbidities that may
increase risk of death, including obesity, hypertension and coronary heart disease. Possible bidirectional causality between nocturia and such
comorbidities necessitates careful adjustment of
confounders for reliable estimates of the independent association of nocturia and death.
MATERIALS AND METHODS: We
searched PubMed, Scopus, and CINAHL
through to October 2014, as well as AUA,
EAU, ICS and IUGA annual meeting abstracts
2005-2014. We included longitudinal studies
assessing nocturia at baseline with death as an
endpoint. We considered studies that did not
provide estimates adjusted at least for age, as
under-adjusted. We considered studies that
provided estimates adjusted for falls and/or
fractures, as potentially over-adjusted. We conducted random-effects meta-analyses and used
meta-regression to explore the effects of age,
gender, risk of bias and length of follow up as
potential determinants of heterogeneity, using
the Metan and Metareg packages (Stata 12.1).
RESULTS: We screened 3,861 abstracts
and retrieved 24 full texts. 10 trials enrolling 29,667 participants with more than 240
thousand person years of follow-up, provided
data. Of these 10 trials, seven, reporting hazard
ratios (HR) and five, reporting odds ratios
(OR) could be included in meta-analyses. The
pooled HR for participants of either gender
was 1.28 (96%CI 1.11- 1.47, I2 =60.8%). The
pooled OR was 1.50 (1.27-1.77, I2 =1.2%).
33
Estimates did not vary substantially when
excluding the single under-adjusted study
(pooled HR=1.23) or the single over-adjusted
study (pooled HR=1.34). In multivariate metaregression we found a negative association with
length of follow up (p=0.01), and suggestive
evidence of a smaller association among women
(p=0.077), but no difference by mean sample
age (p=0.206), or study risk of bias (p=0.221).
CONCLUSION: We found consistent evidence of increased mortality risk with nocturia,
equivalent to 28% excess risk per year. This
pooled estimate did not vary substantially
when accounting either for the age of included
samples or for the degree of adjustment possible in the primary studies. Nonetheless these
estimates may still be subject to confounding
or unmeasured bias. Clinicians should be aware
that nocturia may be an important marker
of ill health. The mediators of the association
between nocturia and death should be carefully
explored, and the impact of treatment for nocturia on healthy ageing should be tested.
#39 PREPARING FOR BLOOD
TRANSFUSION WITH BAS-TEST
PRIOR TO TUR-P SURGERY
Carin Sjöström, Helena Thulin, Ursula Pröckl,
Sirpa Nuorala, Mats Bergkvist & Anders
Kjellman
Karolinska Universitetssjukhuset Huddinge,
Department of Urology
BACKGROUND: Since 2009 the Department of Urology at Karolinska University
Hospital in Huddinge is using modern resection equipment when performing transurethral
resections of the prostate, TUR-P, the DRY
CUT technique (ERBE VIO system). Patients
undergoing TUR-P with monopolar technique
where risking heavy bleeding from the resection
area. From that previous experience all patients
have been prepared in advance for prompt
blood transfusion. Preparations for TUR-P
have been the same since the technique was
introduced in Sweden which includes blood
group control and anti body screening (BAS).
Post TUR-P patients are treated with irrigation
34
and the clinical observation is that the degree
of haematuria has decreased severely since the
introduction of DRY CUT technique. Studies
show equivocal results concerning risk of bleeding using bipolar technique.
MATERIAL: We reviewed the medical charts
of 807 patients undergoing TUR-P at our department from January 1st 2010 to December
31st 2014. We registered if the patients had received blood transfusion and if this was before
or after surgery.
RESULTS: We found 17 (2.1%) patients that
received a blood transfusion while admitted for their TUR-P. All 17 patients had co
morbidity (median 4,2 diagnoses; range 1-11).
Eight of the 17 patients had blood transfusion
prior to surgery. Nine patients (1.1%) received
transfusion post surgery. In the last year of the
study (2014), none of the 142 TUR-P patients
received blood transfusion while admitted.
CONCLUSION: The risk of blood transfusion
after TUR-P is very low. Our proposal is to
stop preparing all TUR-P patients with BAStest prior to surgery. We gather BAS-test only
from patients who during surgery show clear
risk for blood transfusion. An acute BAS-test
can be analyzed in 30 minutes and in a life
threatening situation erythrocyte concentration
can be given to a patient without a BAS-test.
#41 UTILITY AND RELIABILITY OF
TEST VIALS IN CRYOPRESERVATION OF HUMAN SEMEN
Christian F. S. Jensen1,4, Dana A. Ohl1, Jens
Sønksen4, Andre M. Da Rocha2, Laura M. Keller2, and Gary D. Smith1,2,3
Depts of Urology, 2Obstetrics and Gynecology,
Molecular and Integrative Physiology, University
of Michigan, Ann Arbor, USA and Department
of Urology, Herlev University Hospital, Herlev,
Denmark
1
3
INTRODUCTION AND OBJECTIVE:
Sperm cryopreservation is an essential tool
in preservation of fertility in oncology and
vasectomy patients, and when male partners are
unavailable during assisted reproductive technologies (ART). Test vials (TVs) are used to
determine cryosurvival (CS) and are important
for cryopreservation decision making and ART
counseling; yet no agreement exist on optimal
TV protocols. This study investigated the efficacy of pre-freeze semen parameters and TVs
in predicting CS of future ART procedure vials
(ARTVs) and the necessity of obtaining a TV
for every ejaculate a patient supplies.
METHODS: Patients having semen cryopreservation between 2004-11 had one TV and
ARTVs frozen per ejaculate. Test vials were
thawed within 24h of freezing to calculate
CS (post-thaw motility/pre-freeze motility).
The predictive ability of pre-freeze semen
parameters to CS of TVs was calculated using
general linear regression. Mann-Whitney U test
(MWU) and Spearman’s correlation coefficient
(r2) were calculated to determine the efficacy
of TVs in predicting CS of ARTVs within the
same ejaculate and CS of TVs and ARTVs in
different ejaculates within the same patient.
RESULTS: Progressive motility was the best
indicator of TV CS amongst initial semen
parameters (p=0.02; n=516). However, progressive motility was not an indicator of ARTV CS
(r2=0.1, p>0.5; n=30). Cryosurvival of TVs
(81%±3%; mean±SE) and ARTVs (83%±3%)
from the same ejaculate were similar and
correlated (p>0.5, MWU; r2=0.8, p<0.01).
Cryosurvival of the first TV (73%±14%,
n=166) obtained in a series of cryopreserved
ejaculates was comparable and correlated to
subsequent TVs (72%±12%, n=253) from
different ejaculates within the same patient
(p>0.7, MWU; r2=0.6, p<0.01). Similarly CS
of the first TV (81%±5%, n=9) to subsequent
ARTVs (88%±3%, n=22) was comparable and
correlated (p>0.1, MWU; r2=0.6, p<0.01).
CONCLUSIONS: Cryosurvival calculation is
essential for efficient and individualized fertility
preservation and ART treatments. Test vial CS
is an excellent predictor of ARTV CS and no
pre-freeze semen parameters are better. Freezing
a TV for each ejaculate a patient cryopreserves,
in a short period of time, is likely not needed;
as the first TV shows no significant difference in CS compared to subsequent TVs and
ARTVs. Removing the need for multiple TVs
per patient will make use of semen samples in
ART and fertility preservation more efficient.
#42 MULTIPLE NEEDLE-PASS PERCUTANEOUS TESTICULAR SPERM
ASPIRATION AS FIRST-LINE TREATMENT IN AZOOSPERMIC MEN
Christian F. S. Jensen1,2,4, Dana A. Ohl1,
Melissa R. Hiner2, Mikkel Fode3, Tariq Shah2,
Gary D. Smith1,2, and Jens Sønksen3,4
Depts of 1Urology and 2Obstetrics and Gynecology,
University of Michigan, 1500 E Medical Center
Dr, Ann Arbor, MI, United States, 48109,
3
Dept of Urology, Herlev University Hospital,
Herlev Ringvej 75, 2730 Herlev, Denmark; and
4
University of Copenhagen, Faculty of Health and
Medical Sciences, Blegdamsvej 3, 2200 Copenhagen, Denmark.
INTRODUCTION AND OBJECTIVE: Percutaneous testicular sperm aspiration (TESA)
has been known for decades as a simple,
minimally invasive approach to sperm retrieval
in azoospermic men. Due to lower reported
sperm retrieval rates (SRR) when compared
to microdissection testicular sperm extraction
(mTESE), many centers now use mTESE as
the first choice for retrieving sperm in nonobstructive azoospermia (NOA). Objectives of
this study were to evaluate the outcome and
safety of TESA and mTESE in the treatment of
azoospermia and to investigate the usefulness
of a prognostic TESA in order to individualize
protocols for couples and limit the use of invasive testicular procedures.
METHODS: IRB approval was obtained to
retrospectively evaluate 207 patients undergoing multiple needle-pass TESA between 19992014. Prognostic TESA was performed on
125 men with NOA and 82 with obstructive
azoospermia (OA). Nine NOA men and 31 OA
men with previously demonstrated sperm had a
subsequent therapeutic TESA while nine NOA
men with a failed TESA proceeded to mTESE.
Main outcome measures were complication
rates and SRR.
RESULTS: SRR of prognostic TESA was 30%
(38/125) for NOA men and 100% (82/82)
35
for OA men. Eight/nine NOA men and 31/31
OA men had spermatozoa found for intracytoplasmic sperm injection (ICSI) in a subsequent
therapeutic TESA. In nine NOA men in whom
a TESA produced no spermatozoa, only one
had sufficient spermatozoa found with mTESE.
Overall complication rates of TESA and
mTESE were 3% and 21% respectively.
CONCLUSIONS: TESA provides reasonable SRR and is a safe procedure. Successful
prognostic TESA indicates future success with
therapeutic. Men with a failed TESA have a limited chance of sperm retrieval using mTESE.
Approaching azoospermic men with an initial
prognostic TESA followed by either therapeutic
TESA and/or mTESE is an efficient algorithm
in the management of azoospermia and limits
the use of more invasive procedures.
#43 POLUORCHIDISM – A CASE
PRESENTATION AND A REVIEW
Grete Padkær1, Bassam Hamid Mahdi2 and
Lars Lund1,3
Dept of 1Urology and 2Radiology, Odense
University Hospital and University of Southern
Denmark3, Odense, Denmark
OBJECTIVE: Polyorchidism is a rare condition defined by the presence of more than two
testicles. Less than 200 cases are described in
the literature. Triorchidism is the most common type and the condition is often discovered
by incident but is also associated to abnormalities such as cryptorchidism (40 %), inguinal
hernia (30 %), testicular torsion (13%) hydrocele (9%) and hypospadias (1 %)
CASE: A 14-year old boy was seen in the
out-patient because of a palpatoric finding of
a third testicle in the scrotum. When he was
three-years old he had a hernia repair. The
patient had never had pain or any other symptoms from he’s extra testicle not even when he
was doing exercises or sports. At present examination his penis was normal and with a normal
testicle on the left side. On the right hemiscrotum two distinct masses above each other was
palpated, smooth and with same consistency
as normal testicles. By ultrasonography the
36
supernumerary right testicle was found with
normal structure and a common epididymis.
The kidneys were normal.
DISCUSSION: Polyorchidism can be classified into four types: Type A: The extra testicle
has no epididymis or vas deferens and no
connections to the normal ipsilateral testicle,
Type B: The supernumerary testicle has its own
epididymis but no vas deferens, Type C: The
supernumerary testicle has its own epididymis
and shares the vas deferens with the regular
testicle, and Type D: The supernumerary
testicle is a duplication of the regular testicle
with its own epididymis and vas deferens. Type
B is the most common type and together with
Type C they form 90 % of the cases and the
median age of the patients for diagnosis is 17
years. The patients can have reduced spermatogenesis (11%) or no spermatogenesis (26 %)
at all. Six % of the patients have a neoplasma
(embryonal carcinomas, germ cell tumours and
seminomas). The case we describe has is a right
sided triorchidism of type C
CONCLUSION: In young patients and if
the supernumerary testicle is not a part of the
spermatogenesis, it is recommended to remove
the testicle by inguinal access. Otherwise the
patients should be offered a lifelong yearly
control including a physical examination and
ultrasonography. In addition the patient, and
if necessary the family, should be informed of
the increased risks of cancer and be trained in
self-examination.
#44 SEXUALITY IN WOMEN UNDERGOING CYSTECTOMY: IS
THERE NEED FOR IMPROVEMENT
IN THE INFORMATION GIVEN TO
PATIENTS PRE- AND POSTOPERATIVELY?
Sjöfn Þórisdóttir1, Theodóra Th. Þórarinsdóttir1, Josephine Rathenborg1, Martha Haarh1,2
and Lars Lund1,2
Dept of Urology, Odense University Hospital,
Denmark, 2Clinical Institute of Southern University of Denmark
1
OBJECTIVE: The level of information on
sex-life and change in sexuality of women
who undergo urological pelvic surgery due to
cancer is minimal. The aim of this study was
to investigate what kind of information was
given to the women pre- and postoperatively,
as well as to examine the degree of information
these women would have liked to receive on
the changes they could expect, both anatomical
and emotional, due to the operation.
MATERIAL AND METHODS: A retrospective study of all women who had undergone
cystectomy due to cancer in the Department
of Urology, Odense University Hospital, in the
period 1997-2014. All surviving women were
mailed a validated questionaire “The Sexual
function – Vaginal changes Questionnaire
(SVQ)” . Interviews were offered to further
investigate the consequences of the operation
on their self-esteem, relationship, and sexuality and how they have coped with it. The
interviews focused on the degree of information given prior to, and after the operation
and investigate the degree of information these
women would have liked to have had on possible changes, anatomical and emotional, due
to the operation.
RESULTS: Ninety-one women, mean age 65
years old (range 35-83 years), underwent radical cystectomi in that period. Fifty-five women
(60%) were still alive at the date of the study.
Only three women (3,2%) were given information on some of the effects that the operation
could have on their sexual life. One woman
(1%) was referred to the Clinic of Sexology in
order to undergo vaginal dilatation. Total 47
women (86%) replied and 22 questionaires
(40%) have been returned. Five women (9%)
participated in the interviews.
CONCLUSION: This retrospective study
shows that only 3,2 % of women are informed
prior to operation. There is a need for increasing the level of information about sexuality
given to women before cystectomy.
Friday 5th June
08.00 - 09.30
Palissad VÄST
#45 RADICAL CYSTECTOMY IN
THE TREATMENT OF BLADDER
CANCER IN ICELAND: A POPULATION BASED STUDY
Oddur Björnsson1, Eiríkur Orri Guðmundsson1, Valur Þór Marteinsson2, Eiríkur Jónsson1
Dept of Urology, Landspitali University Hospital,
Dept of Surgery, Akureyri Hospital
1
2
OBJECTIVE: Radical cystectomy with pelvic
lymph node dissection and urinary diversion
is the standard treatment for muscle-invasive
bladder cancer. Post-operative complications
are frequent and are reported as high as 65%.
The objective of this study was to investigate
complications and survival in Icelandic patients
with bladder cancer who underwent radical
cystectomy.
MATERIAL AND METHODS: All patients
who had bladder cancer and underwent radical
cystectomy in Iceland between 2003 and 2013
were included. Information on patients was
obtained retrospectively from patients’ medical
records and from the Icelandic Cause of Death
Registry. Both early and late complications
were recorded and classified according to the
Clavien-Dindo classification system. KaplanMeier method was used in the survival analysis.
Only patients with transitional cell carcinoma
(TCC) were included in the survival analysis.
RESULTS: Overall, 108 patients underwent
the procedure during the study period and 99
of them had TCC. The majority were male
(81%) and the median age was 68 years. Ileal
conduit was performed in 86% of procedures
and orthotopic neobladder in 14%. The median operation time was 266 minutes and the
median blood loss during procedure was 1000
ml. No patient died within 30 days of surgery
but one patient (0,9%) died within 90 days
37
of surgery from complications of the surgery.
Fifty patients (46%) had pathological stage T3a
or higher. Complications were reported for 62
patients (57%) overall. Major complications
(Clavien: 3-5) were reported in 32 patients
(29%) and 30 patients (28%) had only minor
complications (Clavien: 1-2). The most common types of complications were infectious
(34%), gastrointestinal (25%) and genitourinary (19%). Twenty-six patients (24%)
underwent reoperation during the follow up
time. The median follow up for patients with
TCC was 41,4 months. Overall 5-year survival
was 54%. Higher pathological TNM-stage
was associated with significantly worse 5-year
survival (p < 0,001).
CONCLUSION: Morbidity after radical
cystectomy is high but similar to what is seen
in other studies. Long term survival of icelandic patients is comparable to neighbouring
countries.
#46 THE PCNA TARGETING PEPTIDE DRUG ATX-101 ENHANCES
THE EFFICACY OF INTRAVENOUS
CHEMOTHERAPY FOR MUSCLEINVASIVE BLADDER CANCER
Blindheim AJ1, Søgaard CD2,Gederaas OA2,
Viset T3, Arum CJ1 and Otterlei M2
Dept of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Dept of Urology and
Surgery, St Olavs Hospital, Trondheim University
Hospital, Trondheim, Norway, 2Dept of Cancer
Research and Molecular Medicine, Norwegian
University of Science and Technology, Trondheim,
Norway, 3Dept of Pathology and Medical Genetics, St Olavs Hospital, Trondheim University
Hospital, Trondheim, Norway.
1
BACKGROUND: For muscle-invasive bladder cancer (MIBC) five year survival-rate is
only 50%. Metastatic bladder cancer is almost
universally fatal. There have been few major
advances since the advent of DNA crosslinking
agent cisplatin in the late 1980s. Inhibition of cancer cells DNA repair systems is a
new strategy to augment cancer therapy, and
38
proliferating cell nuclear antigen (PCNA) is a
promising target. PCNA is an essential scaffold
protein in cellular processes including DNA
replication and repair. Many proteins involved
in stress responses, including proteins involved
in repair of DNA intra/interstrand-crosslinks
(ICLs) interact with PCNA through the AlkB
homologue 2 PCNA-interacting motif (APIM).
Objective: To target PCNA with the novel
APIM-containing peptide drug, ATX-101, to
inhibit repair of DNA damage introduced by
cisplatin, and thereby increase the efficacy of
cisplatin-containing treatment.
METHOD: The viability of a panel of seven
human and one rat urothelial cancer cell lines
treated with cisplatin-containing combinations
of chemotherapeutic drugs and ATX-101 was
measured using MTT assay.(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide).
Rats (n=57) were inoculated orthotopically
with AY-27 rat urothelial carcinoma cells
and left for three weeks to allow progression
into muscle-invasive cancers. Rats were then
treated with cisplatin ± ATX-101. Bladders
were harvested eight days after treatment and
tumor load evaluated by weight, macroscopic
and histopathological examination. Treatment
response in a rat orthotopic muscle-invasive
bladder cancer model with AY-27 transitional
cell carcinoma inoculation to intravenous
treatment with NaCl, cisplatin, ATX-101 or
ATX-101 and cisplatin was determined.
RESULTS: ATX-101 in combination with
cisplatin or cisplatin-containing combinations
inhibits cell growth of rat and human bladder
cancer cell-lines (fig.1). A significant (p=0.03)
decrease in tumor weight was found using the
unpaired student-t test in combination group
of cisplatin and ATX-101 compared to the
cisplatin group alone (Figure 2). No side effects
was observed in animals treated with cisplatin
and ATX-101 in combination compared to
those treated with ATX-101, cisplatin or NaCl
alone.
CONCLUSION: Our results show that
targeting PCNA with ATX-101 potentiates
the cytostatic effect of MVAC, and cisplatin in
several human bladder cancer cell-lines as well
as an animal model for MIBC. These results
suggest that ATX-101 has the potential to
improve the efficacy of current treatment for
advanced bladder cancer patients.
#47 ACCURACY ON VISUAL STAGING
OF BLADDER CANCER DURING
ENDOSCOPIC PROCEDURES
Sandro Gaspar, Tiago Oliveira, Pedro Oliveira,
José Dias, Francisco E. Martins and Tomé M.
Lopes
Department of Urology, Hospital Santa Maria,
Lisbon, Portugal
OBJECTIVE: To assess the accuracy of visual
staging of bladder cancer during cystoscopy
and TURB.
INTRODUCTION: Bladder cancer is the
ninth most commonly diagnosed cancer worldwide with over more than 380,000 new cases
each year (with a mortality of 150,000 deaths
per year). About 70% of patients with bladder
cancer are diagnosed as non-muscle-invasive
disease, confined to the mucosa (Ta-Cis) or
submucosa (T1) and about 30% have muscle
invasive cancer (>T2). The tumor, node,
metastasis (TNM) classification of malignant
tumours is the method most widely used to
stage the extent of cancer spread, and treatment
decisions depend on this distinction. Diagnosis
of bladder cancer is made by cystoscopy and
histological evaluation of resected tissue. It’s the
pathological examination of post-TURB (transuretral resection of the bladder) specimens that
plays the key role in this context, orienting
management of bladder tumours.
MATERIAL AND METHODS: We prospectively documented the data concerning 302
patients submitted to Cystoscopy either by a rigid or flexible instrument followed by a TURB
procedure in year of 2014. In all cases: gender,
estimated tumor size, appearance, number and
stage (T) were assessed by the treating urologist/surgeon and documented in an operation
protocol. Clinical results were then compared
with final pathological examination.
RESULTS: Of the 302 patients aged 37-92
(averaging 73,15) identified, 229 (76%) were
men and 24% were women. Findings were
the following: tumors <1cm: 121 (40%),
tumors 1-2cm: 86 (28,5%), tumors 2-3cm: 59
(19,5%), tumors >3cm: 36 (11,9%), papillary:
143 (47,3%), pediculated: 159 (52,6%), single:
110 (36,4%), and multiple: 192 (63,6%).
For a total of 147 (48,6%) patients with pTa,
accuracy was 63% in in Cystoscopy and (71%)
in TURB with a correct match in 63% of
cases. For a total of 60 (19.9%) patients with
pT1, accuracy in Cystoscopy was 35%, 75% in
TURB with a correct match in 35%. For a total of 36 patients with pT2, accuracy was 33%
during cystoscopy and 33% during TURB with
a correct match in 33%. For a total of 3 CIS
patients, accuracy in Cystoscopy and during
TURB was similar: 100%. A perfect match
was made in all patients (100%). Remaining
patients (n=56) had either no neoplastic tissue,
or only inflammatory tissue was found; 6 cases
were of follicular cystitis and 3 of endometriosis.
CONCLUSION: There is still a lack of accuracy on visually evaluating/staging a bladder
tumor. Reliability of cystoscopy alone to identify tumor stage is still debatable and histologic
stating must be the rule.
#48 ROBOT ASSISTED RADICAL
CYSTECTOMY (RARCX) AND INTRACORPORAL URINARY DIVERSION AS STANDARD CYSTECTOMY
PROCEDURE – 5 YEAR FOLLOW UP
ON ONCOLOGICAL RESULTS IN
225 CONSECUTIVE PATIENTS
Gitte W Lam, Magnus Annerstedt and
Kenneth Steven
Herlev Hospital, Denmark
Beginning March 2009 RARCx was introduced
as our standard cystectomy procedure. Extended PLND to the aortic bifurcation was done
unless in salvage procedures after radiation.
METHODS: We report perioperative prospective oncological results and 5 year follow up
concerning recidivant bladdercancer and dead
from bladdercancer in our initial patients.
39
RESULTS: Between March 2009 and juli
2014 a total of 225 consecutive patients,
median age 67 (34-82), 177 males and 49
females with invasive bladdercancer underwent
surgery with the intend to perform RARCx and
intracorporal urinary diversion. 21 were salvage
procedures after radiation and/or chemotherapy and 12 had neoadjuvent chemotherapy.
137 patients (61%) underwent ileal conduit
and 86 (38%) orthotopic neobladder reconstruction, 2 patients (1%) had no diversion
due to high resection of ureter or removal of
last kidney. 201 (89%) of the cases were done
intracorporal. Extended lympnode dissection
were done in 206 (92%) cases , though we did
not do this after pelvic radiation. The median
number of retrieved lymphnodes was 22 (range
8-58), 18,4% had lymphnode metastasis and
19,5% concomitant prostatecancer. Pathological classification is showed below. Total 6
(2,7%) patients had positive margins, 1 pt with
pT4b, 1 with pT2 in ureter and 4 female pt
(2 pT3b, 2 pT4a). Median follow up were 22
month (1-67) . Recurrencefree survival were
80 % as 47 (20%) pt had recurrence, 15 local,
12 Lymphnodes and 20 distant metastasis. 27
(12%) patients died from bladdercancer .
CONCLUSIONS: Our data from a large
consecutive serie support the contention that
RARCx including intracorporal urinary diversion can serve as a standard surgical procedure
for managing patient with invasive bladder
cancer with similar results on long term oncological follow up as in open series. Nevertheless
extended follow-up is needed to asces long term
results in bigger series of patients.
#49 COMPARISON OF THE PROGNOSTIC AND PREDICTIVE VALUE
OF THE BIOMARKERS EMMPRIN,
SURVIVIN AND KI67 IN PATIENTS
ENROLLED IN TWO RANDOMIZED STUDIES OF CYSTECTOMY
WITH OR WITHOUT NEOADJUVANT CHEMOTHERAPY
Tammer Hemdan1*, Per-Uno Malmström1*, ǂ,
Staffan Jahnson2, Ulrika Segersten1
40
Dept of Surgical Sciences, Uppsala University,
Uppsala, Sweden, 2Dept of Urology, IKE, Linköping University, Linköping, Sweden. * These
authors contributed equally to this work.
1
BACKGROUND: Neoadjuvant chemotherapy before cystectomy is recommended. The
subset of patients likely to benefit has not been
identified.
OBJECTIVE: Our aim was to validate emmprin, survivin and ki67 as markers of chemotherapy response, and as prognostic indicators for
surgery only.
Design, setting and participants: Tumor specimens were obtained before therapy from 250
patients with T1-T4 bladder cancer enrolled in
two randomized trials comparing neoadjuvant
chemotherapy before cystectomy with a surgery
only arm. Protein expression was determined
with immunohistochemistry.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Expression was categorized according to predefined cutoffs reported
in the literature. The data were analyzed with the
Kaplan-Meier method and Cox models.
RESULTS AND LIMITATIONS: Patients
in the chemotherapy cohort with negative
emmprin expression had a significantly higher
overall survival (OS) compared to those
with positive expression, 71 % versus 38 %,
p<0.001. The corresponding figures for cancerspecific survival (CSS) were 76 % and 56
%, p< 0.027. In the cystectomy only cohort,
emmprin expression was not associated with
either OS (46 % and 35 %, p=0.23) or CSS
(55 % and 51 %, p=0.64). The emmprin negative patients had an absolute risk reduction of
25% (CI 11-40) and a number needed to treat
(NNT) of 4 (CI 2.5-9.3). Survivin and ki67
expression were not useful as biomarkers in
this study. The limitations are the retrospective
design and heterogeneity coupled with the time
difference between the trials.
CONCLUSION: Patients with emmprin
negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than
those with positive expression.
PATIENT SUMMARY: In this report we
examined the possibilities for predicting
outcomes for invasive bladder cancer treated
with chemotherapy and removal of the bladder.
We found that the prediction of survival might
be improved by using one of the three tested
biomarkers.
#50 INVASIVE BLADDER CANCER
IN ELDERLY IN DENMARK, 20082012
Thor Knak Jensen1, Niels Viggo Jensen2, Simon
Møller Jørgensen , Peter Clark3,4 and Lars
Lund1,3. On behalf of the Age-care group
Denmark, 2Dept of Oncology, Odense University
Hospital, Denmark, 3Clinical Institute, University of Southern Denmark, Denmark, 4Dept of
Urology, Vanderbilt University Hospital, TN, USA
1
BACKGROUND: To report the incidence and
prevalence for muscle invasive bladder cancer
(MIBC) patients in Denmark in the years
1980-2012 in order to identify whether there
is a difference between younger and elderly
patients (those over age 70 or higher).
DESIGN: Data were derived from the
NORDCAN database with comparable data
on cancer incidence, mortality, prevalence and
relative survival in the Nordic countries, where
the Danish data are delivered from the Danish
Cancer Registry and the Danish Cause of
Death Registry
RESULTS: The prevalence of MIBC increased
twofold for both men and women in the period
1980 to 2012, (N=6 014 to 12 359, men),( N=
1 974 to 4 454, women). There was a relatively
higher proportional increase in prevalence
among elderly men compared to younger
patients. The incidence of MIBC has increased
from 1478 to 1810 (22%) in the period 1980
to 2012, primarily in the elderly population.
The annual number showed a downward trend
from 1980 to 2012 in men < 70 years of age
(581 to 570) compared to an increase in those
> 70 years (514 to 758). For women, on the
other hand, Tthere was an increase from 19802012 both for those < 70 years of age (177 to
198) and > 70 years of age (206 to 284). The
annual age adjusted mortality decreased both
in men and women < 70 year of age (men: 159
to 102, women: 54 to 42) but an increase in
patients > 70 years of age (men: 260 to 289,
women: 114 to 158). The 1- and 5-year relative
survival (RS) for MIBC improved significantly
for all age groups in men and women.
CONCLUSION: The incidence of MIBC
has increased with 22% in the period 1980
to 2012, primarily in the elderly population.
The 1- and 5-year relative survival for MIBC
improved significantly for all age groups in men
and women.
#51 MAINTENANCE BCG OVER 30
MONTHS IN NMIBC PATIENTS
Nilsen F1, Rooth I1, Rawal R1, Beisland C1.2,
Davidsson T1,2
Dept of Urology, Haukeland University Hospital,
Bergen, Norway, 2Dept of Surgical Sciences,
University of Bergen, Bergen, Norway
1
BACKGROUND: Instillation therapy with
BCG for non-muscle invasive bladder cancer
(NMIBC) has been used in our clinic since
1998. (BCG MEDAC since 2002). The intention of the maintenance BCG therapy was
to give 27 instillations in 30 months. The
effect of the treatment has been assessed with
cystoscopy, and when indicated, biopsy. If
tumour recurrence during BCG treatment or
unfavourable histology, more radical treatments
has been considered.
MATERIALS: During 2006 and 2007 a total
of 29 patients were included in our register for
treatment with BCG in a urological outpatient
setting. The indication for BCG therapy in the
29 patients was histology finding of pT1G2G3, CIS and anamnesis of frequent recurrence
of pTaG1-G2. The patients were 46 to 87 years
of age. A total revenue of 555 installations of
BCG, averaging 17.5 installations per patient
with a range of 6 to 27 installations.
RESULTS: 13 patients died during the
observation period. 8 of these due to unrelated
medical conditions, but all were TCC free at
their last control. The other 5 died due to progression in their bladder disease, but high age
41
and comorbidity, made them inoperable and
not candidates for other adjuvant treatment.
16 of the patients are still alive and are
currently being monitored at our outpatient
clinic. Only 6 patients have completed all
27 instillations. 5 patients discontinued the
treatment without any recorded reason (18-24
instillations) and 3 patients due to irritative
side effects. 2 patients progressed and underwent adjuvant treatment with good results.
One of these patients got full BCG treatment
(27 instillations), but 6 years later an unfavourable histology showed MIBC. The patient was
then given full dose radiotherapy, with good
outcome.
CONCLUSION: Instillation BCG immunotherapy has been used widely in the treatment
of NMIBC. The use of BCG is probably
underutilized, but the instillation therapy
seems to reduce the risk progression, showed in
our small study. The initial proposed treatment
with maintenance therapy, over 30 months
is probably more beneficial comparing with
treatment over 12 months, only. Signs of progress of the disease during treatment is a clear
indication to adjuvant treatment with cystectomy or radiotherapy. Interestingly, at control
cystoscopy up to 6 years after treatment, 21
patients showed no signs of macroscopic tumor
recurrence.
#52 LARGE REGIONAL DIFFERENCES IN THE APPLICATION OF
SECOND‐LOOK RESECTION IN
STAGE T1 BLADDER CANCER IN
SWEDEN
Oliver Patschan1, Sten Holmäng2, Oskar
Hagberg3, Abolfazl Hosseini4, Georg Jancke5,
Fredrik Liedberg1, Börje Ljungberg6, Per-Uno
Malmström7 and Staffan Jahnson8
Malmö, 2Dept of Urology, Sahlgrenska University
Hospital, Göteborg, 3Regional Cancer Center
South, Lund University, Lund, 4Dept of Urology,
Karolinska University Hospital, Stockholm, 5Dept
of Urology, University Hospital Linköping, 6Dept
of Urology, Northern University Hospital, Umeå,
1
42
Dept of Urology, Akademiska University Hospital, Uppsala, 8Regional Cancer Center Southeast,
Linköping University, Linköping; all Sweden
7
INTRODUCTION & OBJECTIVES: Stage
T1 urothelial bladder cancer has a heterogeneous outcome with a high risk of progression
to muscle invasive disease. Second look resection has been shown to increase the accuracy
of staging and to decrease the risk for recurrence. Furthermore, remaining tumour tissue
at second look resection has been suggested to
have a negative prognostic impact. The aim
of this study was to evaluate the use of second
look resection and to study the differences in
relative survival in a population based cohort
from Sweden.
MATERIAL & METHODS: All patients
diagnosed with stage T1 bladder cancer in
2008 - 2009 were identified in the National
Swedish Register for Urinary Bladder Cancer
(NSRUBC). Patient charts were re-evaluated
according TNM stage and grade, primary treatment and pathological reports from the second
look resection performed within 8 weeks of the
primary transurethral resection. Survival was
extracted from the National register of Death.
Relative survival was survival in the studied
group compared to survival from another
group of Swedish individuals comparable with
respect to age and gender. Differences between
groups were studied with the chi-squared test
and the Log-Rank test.
RESULTS: 1005 patients with the mean age
73 (range 28 - 99) years were included, of
whom 771 were men. Treatment was discussed
at a multidisciplinary tumour (MDT)-conference in 323 patients, and 431 patients received
multiple adjuvant intravesical instillations with
BCG or chemotherapy. A second look resection
was performed in 517 cases, and 171 (33%)
of these patients were tumour free, 89 (17%)
had Ta/Tis, 225 (44%) had T1, and 32 (6%)
had T2‐4 tumour at second look resection. The
use of second look resection varied between
health care regions: In the Stockholm/Gotland
Region 56% did get a second look resection, in
Uppsala/Örebro 46%, in South-eastern 80%,
in Southern 57%, in Western 17%, and in
Northern 62%. In a logistic regression model
re-resection was associated with intravesical
instillations, age below 70 years, discussion
at MDT-conference and treatment in the
Northern or South-eastern health care regions.
The 5-years relative survival for patients operated with second look resection was 91% when
no residual tumour was found, and 77%
when residual T1 tumour was found (Log‐
Rank chi2 10.6, p=0.001). Selection bias may
have influenced the results.
CONCLUSIONS: Significant geographic
differences in the use of re‐resection in bladder
cancer stage T1 exist in Sweden. The relative
survival for patients without residual tumour at
re‐resection was significantly better compared with patients with residual T1 tumour at
second look.
#53 EARLY AND LATE COMPLICATIONS AFTER CYSTECTOMY,
TRENDS OVER TIME
Alicia M Poulsen, Marie Salling, Lisbeth N
Sallling, Peter Thind
Dept of urology, Rigshospitalet, Copenhagen
INTRODUCTION: Cystectomy is one of
the major urological procedures, and as known
related to some mortality, but quite high
morbidity rates. In Denmark 300 cystectomies
are performed every year, and the number has
increased since 2000. In literature there is a
tendency towards a reduction in both mortality
and morbidity, though few studies report complications later than 90 days postoperatively.
Most complications affect the length of hospital
stay and later possibly also the quality of life.
AIM: This study documents complications
measured as reoperations, (early and late) and
survival after cystectomy.
METHODS: Retrospective single centre study.
All patients who underwent cystectomy from
2000-09 at Dept. Of Urology, Rigshospitalet,
Copenhagen, were included.
STATISTICS: Median, min. and max. Kaplan-Meier survival statistics to describe time to
reoperation and death. Level of sign. P < 0,05.
MATERIALS: 528 pts. had a cystectomy, 13
were lost to follow-up. 159 women, 356 men.
Age 63 years (23-79), BMI 25,3 (15,9-60,2).
Indications for cystectomy: Bladder cancer
(BC): 479 pts., other cancer 26 pts., benign:
10 pts. Overall observation time 94 months
(58- 172).
RESULTS: Operating time 185 min (601060), blood loss 1500 ml (200-10800). Urinary diversion: 37% had a continent diversion,
(Neobladder or Indiana Pouch), 57 % had
an ileal conduit. 6% had ureterocutaneostoma; nephrostomy or already had a urinary
diversion. Length of stay (LOS) 10 days (2-94).
From 2000-09 we observed a significant reduction in operating time, blood loss, in LOS and
in mortality, (p<0,05).
196 pts. (38%) had a complication that
required reoperation. 63 pts. were reoperated
more than once. 124 pts. were reoperated
within 90 days post-op. Early complications
(<90 days): Wound rupture 45 pts., ileus 19
pts., hydronephrosis 16 pts. and bleeding 12.
Late complications (>90 days): Incisional hernia
37 pts., hydronephrosis 11 pts., ileus 11 pts.
And fistula 10. 287 pts. died in the observation
period. Overall survival 73 months (58-88).
CONCLUSION: In the observed timespan we
found a significant reduction in operating time,
blood loss, LOS and mortality. Complication
rates (reoperation rates) are comparable with
current literature, but many studies do not report complications later than 90 days post-op.
This study contributes to a more realistic understanding of the morbidity that these patients
have to accept from the time of cystectomy and
the rest of their lifes.
#54 HIGH GRADE T1 BLADDER
UROTHELIAL CARCINOMA: OPTIMAL MANAGEMENT
Anmar Nassir and Hesham Saada
King Abdullah Medical City ,Makkah – Saudi
Arabia
BACKGROUND: High grade T1 bladder
urothelial carcinoma (HGT1)has a high risk
of recurrence and progression. Optimum
43
management is debatable. We aim to study its
progression and management.
METHOD: Five years retrospective review for
all HGT1diagnosedby transurethral resection
of bladder tumor (TURBT). Patient and tumor
characters were studied. Follow-up intervals
and time to recurrence were calculated. Cystectomies wither early or late were analyzed.
Routine Statistical was used.
RESULT: Thirty nine patients were diagnosed.
Average age was 65.6 years. Male to female
ratio, 12:1. Group 1 (Gr1) with multi-focal
or large tumors were found in 92%while 8%
had single smaller tumors in group 2 (Gr2).
CIS was found in 10%. A second look revealed
residual disease in 38%. Early radical cystectomy was done in 18%. All in Gr1. The rest
were treated with intra-vesical therapy.Average
follow-up was 60 months (36-84).Among
them:22% continued on maintenance BCG
without recurrence. The rest 78%developed
recurrence in time ranged of 3-29 months.
Deferred radical cystectomy with orthotopic
neobladderwas done in 22% for progression.
No progression was seen in56% and underwent
a second maintenance BCG.Failure was seen
in38%with further recurrence or progression.
All underwent defer radical cystectomy. The
remaining 19% continued on maintenance
BCG without any recurrence. Overall 5 year
survival was 86% and 63%,forearly and deferred cystectomy respectively.
CONCLUSION: Most patients has significant
risk of progression. Radical Cystectomy is a
strong option at the earliest opportunity.
Presenter: Hesham Saada
44
Friday 5th June
10.15 - 11.20
Palissad VÄST
#55 PREDICTING PROSTATE
BIOPSY RESULTS USING A PANEL
OF PLASMA AND URINE BIOMARKERS COMBINED IN A SCORING
SYSTEM
Mads Hvid Poulsen2, Maher Albitar1, Wanlong
Ma1 Ferras Albitar1, Kevin Diep1, Herbert A.
Fritsche3, Neal Shore4 and Lars Lund2
1
NeoGenomics Laboratories, Irvine, CA, 2Depts
of Urology, Odense University Hospital, Odense,
Denmark, 3Health Discovery Corporation, Savanah, Georgia; and 4Carolina Urologic Research
Center, Myrtle Beach, SC
BACKGROUND: Determining the need for
prostate biopsy is frequently difficult and more
objective criteria are needed to predict the
presence of high grade prostate cancer (PCa).
To reduce the rate of unnecessary biopsies, we
explored the potential of using biomarkers in
urine and plasma to develop scoring system to
predict prostate biopsy results and the presence
of high grade PCa.
METHODS: Urine and plasma specimens
were collected from 319 patients recommended
for prostate biopsies. We measured the gene expression levels of UAP1, PDLIM5, IMPDH2,
HSPD1, PCA3, PSA, TMPRSS2, ERG,
GAPDH, B2M, AR, and PTEN in plasma
and urine. Patient age, serum prostate-specific
antigen (sPSA) level, and biomarkers data were
used to develop two independent algorithms,
one for predicting the presence of PCa and the
other for predicating high-grade PCa (Gleason
score [GS] ≥7).
RESULTS: Using training and validation data
sets, a model for predicting the outcome of
PCa biopsy was developed with an area under
receiver operating characteristic curve (AUROC) of 0.87. The positive and negative pre-
dictive values (PPV and NPV) were 87% and
63%, respectively. We then developed a second
algorithm for identifying patients with highgrade PCa (GS ≥7). This algorithm’s AUROC
was 0.80, and had a PPV and NPV of 56% and
77%, respectively. Patients who demonstrated concordant results using both algorithms
showed a sensitivity of 84% and specificity of
93% for predicting high-grade aggressive PCa.
Thus, the use of both algorithms resulted in a
PPV of 90% and NPV of 89% for predicting
high-grade PCa with toleration of some lowgrade PCa (GS <7) being detected.
CONCLUSIONS: This model of biomarker
panel with algorithmic interpretation can be
used as a “liquid biopsy” to reduce the need for
unnecessary tissue biopsies, and help to guide
appropriate treatment decisions.
#56 TARGETING WNT5A AND
STAT3 PATHWAYS FOR THE TREATMENT OF PROSTATE CANCER
Giacomo Canesin1,2, Susan Evans-Axelsson2,
Rebecka Hellsten2, Anders Bjartell2 and
Tommy Andersson1
Cell and Experimental Pathology, Dept of
Laboratory Medicine Malmö, and 2Division of
Urological Cancers, Dept of Clinical Sciences
Malmö, Lund University, Sweden.
1
BACKGROUND AND AIMS: Wnt5a
protein levels are upregulated in prostate cancer
(PCa) compared to benign tissue and patients
with high Wnt5a protein levels have a better
outcome after radical prostatectomy compared
to patients with low Wnt5a levels (Syed Khaja
AS, 2011; 2012). Thus, the reconstitution of
the Wnt5a signaling pathway could be a promising therapeutic approach in PCa, as already
shown in breast cancer (Säfholm A, 2008).
Constitutively active STAT3 (pSTAT3) has
been correlated to PCa progression and disruption of its signaling pathway could represent a
promising strategy for the treatment of patients
with advanced PCa (Hellsten R, 2008). Using
in vitro and in vivo techniques we have explored the effect of the Wnt5a-mimicking peptide
Foxy5 for the reconstitution of the Wnt5a
pathway in PCa, and we have studied the effect
of the STAT3 inhibitor Galiellalactone (GL) on
PCa cell viability, apoptosis, invasion, tumor
growth and metastases.
METHODS: Cell viability was determined by
MTT assay; apoptotic cells were visualized with
M30 CytoDeath antibody 24h after treatment
with Foxy5 or GL. Cell invasion was analyzed
using matrigel pre-coated cell culture inserts in
the presence or absence of Foxy5 or GL. For
the animal study, NMRI nude mice were injected orthotopically with 1x106 DU145-Luc
cells, and treated IP with GL every day or with
Foxy5 every second day. Primary tumor growth
and metastatic spread were evaluated weekly by
in vivo luminescence using the IVIS Lumina
II system. 9 weeks after injection animals were
sacrificed and organs were analyzed for the presence of metastases. Primary tumors, regional
(RLN) and distal lymph nodes (DLN) were
also analyzed by immunohistochemistry for the
presence of tumor-derived cells, apoptotic cells
and actively proliferating cells.
RESULTS: Our results show that GL inhibits
viability and induces apoptosis of DU145-Luc
cells in vitro, and that it reduces tumor growth
and metastatic spread to lymph nodes in vivo.
Foxy5 treatment has no effects on cell viability
or on primary tumor growth, but it significantly reduces cell invasion in vitro and metastatic
spread to lymph nodes in vivo.
CONCLUSIONS: Our results confirm that
the activation of the Wnt5a pathway and the
inhibition of the STAT3 pathway are promising therapeutic approaches for the treatment
of PCa. We found that GL and Foxy5 are good
candidates for the treatment of PCa, as they
inhibit tumor growth and metastatic spread to
lymph nodes. Since these two compounds act
through different mechanisms, our future studies will explore the possibility of a combination of GL and Foxy5 for the treatment of PCa.
#57 EXPRESSION OF PSTAT3 IN
HORMONE-NAÏVE AND CASTRATE-RESISTANT PROSTATE CANCER
Don-doncow N1, Undvall-Anand A1,
45
Krzyzanowska A1, Gaber A1, Helczynski L2,
Klocker H3, Hellsten R1, Bjartell A1
Dept of Translational Medicine, Lund University, Malmö, Sweden, 2Dept of Medical Services,
SUS, Malmö, Sweden, 3Dept of Urology, Medical
University, Innsbruck, Austria
1
BACKGROUND: The Signal Transducer and
Activator of Transcription 3 (STAT3) pathway
is thought to be phosphorylated (pSTAT3) and
constitutively activated in prostate cancer. The
expression levels of pSTAT3 have not been fully
explored in different stages of prostate cancer.
METHODS: We studied two cohorts of prostate cancer patients, one with primary tumor
samples from patients undergoing radical
prostatectomy for localized disease (n=240) and
the other with tissue specimens from transurethral resection of the prostate from patients
with castrate resistant disease (CRPC) (n=21).
Sections from tissue microarrays were subjected
to immunohistochemical evaluation for expression of pSTAT3 and androgen receptor (AR).
RESULTS: The expression level of pSTAT3
in localized prostate cancer was commonly
low in contrast to CRPC where all tissue
specimens showed a strong immunoreaction.
A majority of the tumor samples from radical
prostatectomy showed high expression level of
AR whereas a variation was found in CRPC
samples. Evaluation of pSTAT3 as a possible
predictor of outcome in relation to biochemical
recurrence after radical prostatectomy showed
a weak but statistically significant association
between low pSTAT3 expression and shorter
time to biochemical relapse. We found an association between AR and pSTAT3 in CRPC
patients and a weaker correlation in localized
disease. The expression levels of pSTAT3 were
not related to Gleason score.
CONCLUSIONS: A strong expression of
pSTAT3 and a clear correlation with AR were
found in CPRC in contrast to hormonenaïve localized disease. Our data indicate that
pSTAT3 is involved in an escape mechanism
in CRPC and it supports the view of pSTAT3
inhibition as a new therapeutical option in
CRPC patients.
46
#58 CIRCULATING TUMOUR
CELLS AS TREATMENT PREDICTIVE BIOMARKER FOR ANDROGEN
DEPRIVATION THERAPY IN HORMONE NAÏVE PROSTATE CANCER
Andreas Josefsson1, Anna Linder1, Despina
Flondell-Sité2, Giacomo Canesin2, Anna
Stiehm2, Aseem Anand2, Anders Bjartell2, JanErik Damber1, Karin Welén1
Sahlgrenska Cancer Center, Dept of Urology,
Institute of Clinical Sciences at Sahlgrenska
Academy, University of Gothenburg, Gothenburg,
Sweden, 2Dept of Urology and Department of
Clinical Sciences, Division of Urological Cancers
Skåne University Hospital, Lund University,
Malmö, Sweden
1
BACKGROUND: Prostate cancer is still the
leading cause of cancer deaths in the male
population in Nordic countries. Circulating tumor cells (CTC) is a promising prognostic marker for metastatic castration-resistant prostate
cancer (mCRPC) while its use in earlier stages
is more questionable. The aim of this project
is to verify the effect of androgen deprivation
therapy (ADT) on CTC signals, and to investigate the potential of specific CTC expression
of PSA, PSMA and EGFR as biomarkers for
disease progression.
METHODS: Patients with PSA > 80 with
either locally advanced prostate cancer (median
Gleason Score = 9, range 7-10, ) and/or verified
metastases were included. CTC were sampled
before start of ADT, after three months, at
disease progression and/or at verified CRPC.
CTC were isolated and detected with AdnaGen
Select/Detect®. The prognostic potential of
pre-treatment variables, were evaluated for progression free survival for men with M1-disease,
with Kaplan-Meir analysis, uni- and multivariate Cox regression analysis, with progression (PSA doubling time < 6 months, skeletal
related event or PC-specific death) as event and
death from other causes or alive at follow up as
censored cases (only men with at least one year
follow up were included).
RESULTS: 53 patients were included before
January 2015. Median age was 75 years old
and 83%, 68% and 50% had M1 (Bone scan),
cT3-cT4 and Gleason score>7 respectively.
At inclusion 45/53 (85%) were CTC-positive
(based on detection of PSA (45/53), PSMA
(8/45) or EGFR (11/45) signals). Mean
PSA-value and ALP-value were 983 and 6,5
respectively. After three months of ADT,
19% of the patients were CTC-positiv. At
development of CRPC, 12/13 (92%) patients
were CTC-positive. In men with M1-disease
(n=27) neither PSA value, nor Gleason score,
nor T-stage, could prognosticate progression
free survival. Men with EGFR-positive CTC
before treatment (n=8) had significantly shorter
time to progression (6,5 months) compared to
CTC-positive men without EGFR-positivity
(Log rank chi square 6,26, p-value <0.05). In a
multivariate cox analysis EGFR-positive CTCs
was an independent prognostic marker for
progression free survival.
CONCLUSIONS: CTCs expressing EGFR
are associated with worse prognosis, illustrating
that CTC phenotype reflects disease progression. CTC detected and characterized with
AdnaTest is a promising prognostic marker of
ADT-response, and if verified in larger cohorts,
this could be of clinical value in selecting patients that would benefit from more aggressive
treatment in addition to ADT.
#59 UROKINASE PLASMINOGEN
ACTIVATOR RECEPTOR (UPAR) ASSESSMENT IN LOCALIZED-, HORMONE NAÏVE-, AND CASTRATION
RESISTANT PROSTATE CANCER
Solvej Lippert1, Kasper D Berg1, Gunilla
Høyer-Hansen2, Peter Iversen1, Ib J Christensen2,
Klaus Brasso1, and M. Andreas Røder1
Copenhagen Prostate Cancer Center and the
Department of Urology, Rigshospitalet, University
of Copenhagen, 2200 Copenhagen, Denmark,
2
Finsen Laboratory, Rigshospitalet, Copenhagen
Biocenter, 2200 Copenhagen, Denmark
1
World and as a consequence facilitated over
diagnosis and overtreatment of indolent PCa.
New biological markers in blood, urine and
tissue are warranted to distinguish between
indolent and aggressive PCa and individualize
treatment for patients. The urokinase plasminogen activator receptor (uPAR) plays
an important role in pericellular proteolysis
by binding urokinase plasminogen activator
(uPA). This is required for degradation of the
extracellular matrix and for cancer invasion. In
addition to binding uPAR, uPA cleaves uPAR
on the cell surface liberating domain I uPAR(I)
and leaving the cleaved uPAR(II-III) on the cell
surface. Intact, uPAR(I-III), and uPAR(II-III)
can be liberated from the cell surface resulting
in three different uPAR forms in circulation.
The different uPAR forms are strong prognostic
markers in several cancers. We measured the
uPAR forms in plasma from patients with
castration resistant PCa (CRPC), advanced
hormone naïve PCa and localized PCa.
METHODS: Between February 1, 2012 and
October 1, 2014 400 patients with PCa (clinically localized 318, advanced hormone naïve
49, and CRPC 30) had baseline plasma samples obtained and stored at -80ºC until analyses.
The levels of intact uPAR [uPAR(I-III)], intact
uPAR + cleaved uPAR domains II+III [uPAR(IIII) + uPAR(II-III)], and cleaved uPAR domain
I [uPAR(I)] were determined in citrated plasma
samples with two-site sandwich time-resolved
fluorescence immunoassays (TR-FIAs).
RESULTS: Plasma uPAR(I-III) + uPAR(IIIII) and uPAR(I) were significantly higher in
hormone naïve patients and CRPC patients
compared to patients with localized disease
(P < 0.0001 and P < 0.0001, respectively).
Quantification of intact uPAR(I-III) revealed
no significant differences between the three
groups (P = 0.54).
BACKGROUND: Prostate specific antigen
(PSA) testing has led to a dramatic increment
in the incidence of prostate cancer (PCa) in the
47
Table #59
CONCLUSION: Our findings suggest that
uPAR(I-III) + uPAR(II-III) and uPAR(I) are
associated with higher stage PCa disease. These
associations suggest that uPAR domains in plasma harbour prognostic value for PCa patients.
Further studies are warranted to validate the
use of uPAR forms as biomarkers for PCa.
#60 THE PREDICTIVE VALUE OF
ERG PROTEIN EXPRESSION FOR
DEVELOPMENT OF CASTRATIONRESISTANT PROSTATE CANCER –
ASSESSMENT OF HORMONE-NAÏVE ADVANCED PROSTATE CANCER
PATIENTS TREATED WITH PRIMARY ANDROGEN DEPRIVATION
THERAPY
Berg K.D.1, Røder M.A.1, Thomsen F.B.1, Vainer B.2, Gerds T.A.3, Brasso K.1 and Iversen P.1
Copenhagen Prostate Cancer Center, Dept of
Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 2Dept of Pathology,
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 3Dept of Biostatistics, University of Copenhagen, Copenhagen, Denmark
1
INTRODUCTION: Androgen deprivation
therapy (ADT) is the standard treatment for
patients with metastatic prostate cancer (PCa).
However, biomarkers predicting response to
ADT and time to castration-resistant prostate
cancer (CRPC) are lacking. We analysed the
predictive value of the androgen regulated ERG
oncoprotein in PCa patients diagnosed with
48
advanced and/or metastatic disease treated with
first-line castration-based ADT.
MATERIAL & METHODS: In total, 194
PCa patients managed with first-line castrationbased ADT were included whereof 41 (21%)
had no sign of dissemination at treatment
start, 38 (20%) had dissemination to lymph
nodes only and 115 (59%) had bone metastasis. Median follow-up was 6.8 years. Immunohistochemical staining (anti-ERG, clone:
EPR3864; Roche/Ventana) was performed on
formalin-fixed paraffin-embedded diagnostic
biopsies collected prior to ADT. Patients were
labelled ‘ERG-positive’ if minimum one focus
demonstrated ERG expression and ‘ERGnegative’ if all foci were negative. The primary
endpoint was CRPC defined according to
EAU guidelines. Multiple cause-specific Cox
regression analyses were applied with CRPC
as the endpoint and age, PSA, Gleason score,
clinical tumour stage and dissemination stage
as explanatory variables. Predictions for CRPC
obtained with a model stratified on ERG-status
were compared to those obtained with a second
model omitted ERG. Time-dependent area
under the ROC curves were used to assess the
effect of ERG on the discriminative ability.
RESULTS: In total, 105 patients (54%) were
ERG-positive and 89 (46%) were ERG-negative. The groups did not differ in age, alkaline
phosphatase, cT category, or tumour-stage, but
ERG-positive patients had lower PSA-values
(p=0.009) and Gleason scores (p=0.012). The
proportional hazard assumption was rejected
for ERG-status, thus an ERG stratified multiple
Cox regression model was applied. Only PSA
(HR: 1.33 for 2-fold differences [95%CI: 1.181.49], p<0.0001) was significantly associated
with increased hazard of CRPC. Compared
to a model omitting ERG-status, the multiple
cause-specific Cox regression model stratified
for ERG showed comparable AUC values
1 year (77.6% vs. 78.0%, p=0.82), 2 years
(71.7% vs. 71.8%, p=0.85), 5 years (68.5%
vs. 69.9%, p=0.32), and 8 years (67.9% vs.
71.4%, p=0.21) after ADT start.
CONCLUSIONS: Within the limitations of
our study, ERG-status was not identified as a risk
factor for CRPC development in advanced and/
or metastatic PCa patients treated with first-line
castration-based ADT. This implies that ERG is
not a predictive biomarker for ADT response.
#61 QUANTITATIVE TIME RESOLVED FLUORESCENCE IMAGING
OF ANDROGEN RECEPTOR AND
PROSTATE SPECIFIC ANTIGEN IN
PROSTATE TISSUE SECTIONS
Agnieszka Krzyzanowska1, Giuseppe Lippolis1,
Mari Peltola2, Kim Pettersson2, Leszek Helczynski3, Aseem Anand1, Hans Lilja4,5,6, Anders
Bjartell1
Lund University, Faculty of Medicine, Division
of Urological Cancers, Malmö Sweden, 2Dept
of Biotechnology, University of Turku, Turku,
Finland, 3University and Regional Laboratories
Region Skåne, Clinical Pathology, Malmö, Sweden, 4Depts of Laboratory Medicine, Surgery, and
Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, USA, 5Nuffield
Dept of Surgical Sciences, University of Oxford,
Oxford, UK, 6Dept of Translational Medicine,
Lund University, SE-205 02 Malmö, Sweden
1
INTRODUCTION: The androgen receptor
(AR) is involved in the normal maintenance
of the prostate. However, it also plays roles in
prostate cancer development and progression
and it is strongly overexpressed in castrationresistant prostate cancer. Currently available
techniques to evaluate AR expression patterns
do not allow for precise and reliable quantification of AR. Additionally, the activity of AR,
as an indicator of disease severity, could be
assessed by measuring the tissue expression of
prostate-specific antigen (PSA). The quantitative expression levels of both PSA and AR in
prostate tissues may provide valuable prognostic biomarkers.
MATERIAL AND METHODS: We present
here the quantification of AR and PSA staining
intensities in tissue microarray (TMA) samples
from prostate cancer patients, obtained with
the aid of a special immunofluorescence technique of Time Resolved Fluorescence (TRF)
imaging. The TRF method provides highly
specific immunostaining, with low background
which permits precise quantification of the
antigen content. We analysed the immunostained images with an algorithm allowing for an
unbiased quantification of protein levels based
on pixel intensities. Finally, with the aid of a
consecutive section immunostained for p63/
AMACR we were able to delineate benign and
AMACR positive (AMARC+) and AMACR
negative (AMACR-) cancer epithelium.
RESULTS: We found a significant increase in
AR intensity in the AMACR+ cancer areas and
a decrease in the AMACR- epithelium. PSA
significantly decreased in cancer areas overall,
and especially in the AMACR- glands. The AR/
PSA ratio varied significantly in the AMACR+
tumour cells, compared to benign glands, but
overall we found a poor correlation between the
expression of PSA and AR in the benign and
malignant epithelium. Univariate Cox regression analysis was performed to check if AR or
PSA protein expression, or their ratio could be
a predictor of BCR. No statistically significant
correlation was found, although there was a
tendency for decreased time to BCR in patients
with higher AR/PSA ratio in the AMACRareas.
CONCLUSION: Our study is limited by the
low number of samples examined (n=91). This
proof-of-principle study showed that the TRF
quantification method is robust and applicable
for the analysis of protein expression in prostate
TMAs and has unveiled some interesting trends
in the expression of AR in PSA. Future studies
involving expanding the cohort size are planned.
49
#62 TESTICULAR METASTASIS
FROM PROSTATE CANCER. A REVIEW OF THE LITERATURE
Louise Geertsen1, Mike Mortensen1,3, Birte
Engvad2, Niels Marcussen2,3, Lars Lund1,3
Dept of Pathology, Odense University Hospital,
3
Clinical Institute, University of Southern Denmark
1
2
Prostate cancer (PC) is the most common
cancer among men in the western world
and within Denmark the incidence is nearly
4300 new cases a year. PC metastasizes most
frequently to the regional lymph nodes and
bones. More rarely metastases from PC occur
in the testis. We decided to perform a literature
search to find out how many cases with testicular metastasis from PC have been reported
and how many cases we have diagnosed in the
Department of Urology, Odense University
Hospital (OUH).
MATERIAL AND METHODS: Publications
were identified through a literature search on
EMBASE, Cochrane and Pub Med. using
the search terms “prostatic neoplasm” AND
“testicular neoplasm/secondary”. This resulted
in 90 articles and case reports. Only articles in
English were included. Studies dealing with
metastasis to the epididymis or where the
primary tumour was not located in the prostate
were excluded. We have included 32 articles of
which 3 were found in a literature search in the
references. A review of the pathological database, Odense University Hospital (OUH), was
performed in order to find patients diagnosed
with testicular metastasis in the period 2002 to
2013. We included the patients with metastatic
spread from the prostate adenocarcinomae to
the testis.
RESULTS: Ten patients were diagnosed with
adenocarcinom metastases in the testes at
OUH in the period 2002 to 2013. Seven of
these patients had proliferation of a prostate
cancer. One patient had metastasis from a lung
cancer and two patients had metastasis from
a cancer in the GI tract. In the literature we
50
found a total number of 105 cases with metastases to the testis from PC in the period from
1938-2012. That gives a total number of 112
cases including the 7 cases we have diagnosed
at OUH.
CONCLUSIONS: Metastases to the testis
from PC occur relatively rare now shown by a
search of the literature. The condition could be
underreported and we recommend that tissue
of the testis that is removed should be sent for
a histological examination and thereby proper
staging of the patients disease.
#63 QUANTITATIVE IMAGING BY
AUTOMATED BONE SCAN INDEX
(BSI) AS A RESPONSE BIOMARKER
IN STANDARD CLINICAL CARE
OF PATIENTS WITH METASTATIC
CASTRATION RESISTANT PROSTATE CANCER (MCRPC) TREATED
WITH ENZALUTAMIDE
Anand A1, Lindgren-Belal S1, Reza M2, Edenbrandt L2, Bjartell A1
Malmö Sweden, 2Dept of Clinical Physiology and
Nuclear Medicine, Skåne University Hospital,
Malmö, Sweden
1
BACKGROUND: Enzalutamide, an androgen receptor antagonist therapy, was approved
for patients (pts) with mCRPC. However, in
standard of care for mCRPC pts, change in
prostate specific antigen (PSA) is not accepted
as an efficacy response measurement and radiological change during treatment is inadequately measured in an interpreter-dependent
subjective analysis of bone scan. Therefore, an
objective efficacy response biomarker is warranted. In this registry study, we evaluated BSI,
a quantitative analysis of bone scintigraphy, to
access response in CRPC pts being treated with
enzalutamide.
METHOD: Pts with mCRPC, at Skåne University Hospital (SUH), Sweden, who initiated
treatment with enzalutamide after failing chemotherapy were eligible for the study. Primary
objective was to associate the change in BSI and
PSA, after 12 weeks (wks) of treatment with
enzalutamide, with overall survival. Automated
BSI generated by EXINI boneBSI platform is
representation of tumor burden as a percent
of total skeletal mass. Bivariate cox regression
analysis was used to evaluate the association of
BSI and PSA with overall survival.
RESULT: Thirty-five pts, who initiated
enzalutamide treatment at SUH, were eligible
for the BSI analysis. Follow-up scans for the
BSI analysis were available from 24 pts. Median
baseline BSI value was 2.92 (range=0.0 to
11.72) and at follow-up median value was
2.83 (range=0.0 to 12.65). Overall survival
was associated with BSI at both baseline and
at follow-up as opposed to that of PSA (table
1). The change in BSI between baseline and
follow-up was also significantly associated with
overall survival.
CONCLUSION: Automated BSI and its
relative change were observed to be associated
with overall survival in mCRPC pts receiving
enzalutamide as standard of care treatment. The
result deserves further validation, in controlled
investigational studies, of BSI as a quantitative
imaging biomarker indicative of efficacy response to second-line treatment in CRPC pts.
#64 PSA NADIR AND TIME TO PSA
NADIR AS PROGNOSTIC MARKERS
FOR DEVELOPMENT OF CASTRATION-RESISTANT PROSTATE CANCER UPON TREATMENT WITH 1ST
LINE ANDROGEN DEPRIVATION
THERAPY
Helgstrand J.T.1, Berg K.D.1, Røder M.A.1,
Klemann N., Vainer B.2, Brasso K.1, Iversen P.1
Urology, Rigshospitalet, University of Copenha-
1
gen, Copenhagen, Denmark, 2Dept of Pathology,
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
BACKGROUND: Androgen deprivation
therapy (ADT) remains standard treatment
for advanced prostate cancer (PCa). Although
most cases of advanced PCa initially respond
to ADT, the vast majority develops castration‐
resistant PCa (CRPC). PSA nadir and time to
PSA nadir (TTN) have been suggested as possible prognostic markers for risk of CRPC. We
aimed to analyze the prognostic value of PSA
nadir and TTN for development of CRPC.
MATERIAL AND METHODS: In the period
2000-2012, a total of 223 patients with histologically verified advanced PCa were treated
with first-line castration-based ADT at our
institution. After assessment of extracted data
from patient charts, 35 patients were excluded
due to incomplete information or unreached
PSA nadir and thus 188 patients were eligible
for analysis. Patients were stratified according
to PSA nadir (≤0.2 ng/mL, 0.3‐4.0 ng/mL
or >4.0 ng/mL) and TTN (<6.0 months, 6.0
‐ <12.0 months or ≥12.0 months). With the
primary endpoint being CRPC defined according to EAU guidelines, time to CRPC was
calculated from date of PSA nadir. Competing‐risk analysis was used to assess the risk of
CRPC, where death prior to CRPC was treated
as a competing event. Univariate‐ and multiple
cause-specific Cox regression models were
applied to weigh the impact of covariates on
the risk of CRPC.
RESULTS: Median follow-up (from start of
ADT) was 6.8 years (95%CI: 6.2‐7.5). PSA
nadir was ≤0.2 ng/mL in 34.6%, 0.3‐4.0 ng/
mL in 47.3% and 18.1% had PSA nadir >4.0
ng/mL. TTN was <6.0 months in 42.6%, 6.0 ‐
<12.0 months in 28.2% and 29.3% had TTN
≥12.0 months. In univariate analyses, the risk
of CRPC increased significantly with higher
PSA nadir values (Gray’s test: p<0.0001) and
shorter TTN (Gray’s test: p=0.002). After adjusting for age, percentage of positive biopsies,
PSA at diagnosis, Gleason score, clinical tumor‐
stage, and metastatic stage, PSA nadir 0.3‐4.0
51
ng/mL (hazard ratio (HR): 6.48, 95%CI: 3.6511.53) and PSA nadir >4.0 ng/mL (HR: 10.86,
95%CI: 5.48-21.52) were found independently
associated with increased risk of CRPC as compared to PSA nadir ≤0.2 ng/mL. In the same
multivariate analysis, TTN ≥12.0 months (HR:
0.51, 95%CI: 0.30-0.85) was significantly
associated with a decreased risk of CRPC as
compared to TTN <6.0 months.
CONCLUSION: Within the limitations of the
present study, we found that higher PSA nadir
values and a shorter TTN are independently
associated with an increased risk of CRPC
development in advanced PCa.
Friday 5th June
10.15 - 11.20
Arenarummet
#65 FACTORS PREDICTING THE
OFF-TREATMENT DURATION
DURING INTERMITTENT ANDROGEN DEPRIVATION (IAD)
THERAPY WITH DEGARELIX IN
PROSTATE CANCER
Per-Anders Abrahamsson1, Laurent Boccon-Gibod2, Igle Jan de Jong3, Juan Morote4, Anders
Malmberg5, Anders Neijber5, Peter Albers6
Skåne University Hospital, Lund University,
Malmö, Sweden, 2Membre de l’Académie de Chirurgie, Expert près les Tribunaux, Paris, France,
3
University Medical Center Groningen, University of Groningen, the Netherlands, 4Vall d´Hebron
Hospital, Universitat Autónoma de Barcelona,
Barcelona, Spain, 5Ferring Pharmaceuticals A/S,
Copenhagen S, Denmark, 6Düsseldorf University
Hospital, Heinrich-Heine-University Düsseldorf,
Düsseldorf, Germany
1
Intermittent androgen deprivation (IAD) therapy is commonly used in prostate cancer due
to fewer side‑effects, and importantly provision
52
of an off-treatment period. The objective of
this multivariable analysis of trial data of IAD
therapy with degarelix in prostate cancer was
to establish how disease and other patient
characteristics were predictive for the median
duration of the first cycle off-treatment period.
MATERIALS & METHODS: This analysis
included 191 men with prostate cancer (all
stages, 48% previously received treatment with
curative intent) with a baseline prostate specific
antigen (PSA) >4 ng/mL or a PSA doubling
time <24 months and a maximum PSA of 50
ng/mL, and completed a 7-month induction
treatment period with monthly degarelix. A
PSA level <4 ng/mL was reached in all these
patients who then started an off-treatment
period. They remained off treatment as long as
PSA <4 ng/mL (biochemical failure) or for a
maximum of 24 months study duration. The
median times to PSA >4 ng/mL were estimated
using the Weibull model with 5 classifiers: PSA
at end of induction (eoiPSA), prostate cancer
stage/previous therapy, Gleason score, age and
baseline testosterone.
RESULTS: The model with all 5 factors could
not demonstrate that Gleason score (<8 versus
≥8) (p=0.29) and prostate cancer stage/previous
therapy (p=0.39) had any influence on the
time to PSA >4 ng/mL. A reduced model with
eoiPSA and age showed that eoiPSA was highly
predictive (p<0.0001) of the time to PSA >4
ng/mL with the lowest eoiPSA group (<0.1 ng/
ml - undetectable) having the longest OTP.
There was also an influence of age (p=0.05)
with older patients having longer times to
PSA >4 ng/mL. The median times to PSA >4
ng/mL according to eoiPSA are shown in the
figure. The relative delay in failure time (time
to PSA >4 ng/mL) for the eoiPSA <0.1 ng/mL
versus PSA ≥2.0 ng/mL subgroups was 6.33
(95% confidence interval [CI]: 4.50; 8.90), p
<0.0001. For example, the group of patients
with an eoiPSA <0.1 ng/mL had an estimated
median time to PSA >4 ng/mL (95% CI) of
745 (612; 907) days compared to 118 (90;
155) days for the group of patients with an
eoiPSA ≥2.0 ng/mL.
Table #65
CONCLUSIONS: Patients especially with
lower eoiPSA (<0.1 ng/mL - undetectable) and
older age have longer median off-treatment
periods after receiving IAD therapy with
degarelix.
#66 PROSPECTIVE OBSERVATIONAL ASSESSMENT OF THE EFFECTIVENESS OF ENZALUTAMIDE
TREATMENT IN PATIENTS WITH
METASTATIC CASTRATION-RESISTANT PROSTATE CANCER IN A
REAL-WORLD CLINICAL PRACTICE SETTING: PROTOCOL OF THE
ONGOING PREMISE STUDY
Borre, Michael1, De Santis, Maria2, Davidson,
Richard3, Snijder, Robert4, Payne, Heather5
Dept of Urology, Aarhus University Hospital,
Denmark, 2Ludwig Boltzmann Institute for
Applied Cancer Research, Kaiser Franz JosefSpital, Vienna, Austria, 3Astellas Pharma EMEA,
Chertsey, UK, 4Astellas Pharma Global Development, Leiden, the Netherlands, 5University
College London Hospitals, London, UK
1
INTRODUCTION: Enzalutamide is an
androgen receptor signalling inhibitor approved
in the EU for the treatment of asymptomatic/mildly symptomatic men with mCRPC
after failure of androgen deprivation therapy
in whom chemotherapy is not yet clinically
indicated, or those whose disease has progressed
on or after docetaxel therapy. While phase 3
enzalutamide studies provide efficacy and safety
data obtained under controlled conditions,
limited data are available on clinically relevant
endpoints in a real-world clinical setting. The
PREMISE study is designed to capture data
on effectiveness, health-related quality of life
(HRQoL), safety and characteristics of patients
with mCRPC who have been prescribed
enzalutamide in a clinical setting. Here, we describe the protocol for the ongoing multicentre
PREMISE study.
METHODS: PREMISE is a long-term
observational study in men with mCRPC who
have been prescribed enzalutamide as part of
standard clinical practice and who provided
informed consent to participate. As of February
2015, 1930 patients with mCRPC are planned
to be enrolled from 200 sites across Europe
and South Africa. Data collection is expected
to continue until the end of 2017. At time of
53
writing, three sites in Denmark are confirmed as suitable for study inclusion (following
completion of site selection visits); identification of other sites is ongoing. The final number
of study sites will be reported in the poster.
Ethics approval will be obtained from relevant
committees and the study will be conducted in
accordance with the Declaration of Helsinki.
Data will be collected at baseline, all routine
clinical visits (approximately every 3 months)
and at study completion or disease progression for the duration of patients’ treatment,
and then for a minimum 7-month follow-up
after discontinuation. The primary outcome of
interest is time to treatment failure, defined as
the time from baseline (treatment initiation)
to treatment discontinuation for any reason.
Secondary outcomes include effectiveness (time
to prostate-specific antigen [PSA] progression,
PSA response and time to disease progression
[radiographic, PSA or clinical]); reasons for
use and duration of treatment; pain and use
of analgesics (time to average pain progression
and time to opiate use); HRQoL (EuroQol
5-dimension, 5-level health state utility index
and Functional Assessment of Cancer Therapy–
Prostate); health resource use (hospitalisations
and visits to healthcare professionals) and safety
(adverse events, modification of treatment and
deaths). Data will be sourced from Serious
Adverse Event/Adverse Drug Reaction Worksheets, hospital medical records and patientcompleted questionnaires. Data will only be
reported descriptively.
#67 HIGH-DOSE ASCORBIC ACID
IN METASTATIC CASTRATIONRESISTANT PROSTATE CANCER:
EVALUATION OF EFFICACY AND
SAFETY IN A PHASE II TRIAL
Torben K. Nielsen1,2, Martin Højgaard1, Henrik E. Poulsen2,3, Jens Lykkesfeldt2, Niklas R.
Jørgensen4 and Kári J. Mikines1,2
Dept of Urology, Copenhagen University
Hospital Herlev, Denmark, 2Faculty of Health
and Medical Sciences, University of Copenhagen,
Denmark, 3Department of Clinical Pharmaco-
1
54
logy, Copenhagen University Hospital BispebjergFrederiksberg, Denmark, 4Department of Clinical
Biochemistry, Copenhagen University Hospital
Rigshospitalet - Glostrup, Denmark
BACKGROUND: Intravenous high dose ascorbic acid (AA) is provided to cancer patients
by physicians in the complementary/alternative
sector of medicine. Efficacy of the AA treatment has not been established. Until recently
only Docetaxel was proven to extend overall
survival in patients with metastatic castration
resistant prostate cancer (mCRPC). Here, we
evaluated AA efficacy and toxicity in a single
centre, single-arm phase-II study.
METHODS: Patients (≥18 yrs) with mCRPC
as defined by the PCWG-II guideline, no prior
chemotherapy, no prior treatment with curative
intent, good performance (ECOG≤2), good
heart and renal function were eligible. AA was
given as one weekly IV infusion (week 1 = 5g,
week 2 = 30g and week 3-12 = 60g) together
with 500mg AA oral daily. The primary efficacy endpoint was PSA response. A 50% PSA
reduction from baseline at week 12 opted for
an 8 week extension-arm. Secondary endpoints
included changes in bone metabolic markers (uNTx, PINP, bone-ALP), performance
status (ECOG) and quality of life (EORTC
C30+P25) Adverse events (AE) was registered
until 14 weeks post trial and classified according to CTCAE v. 4.03.
RESULTS: Twenty-three patients were enrolled and 20 completed efficacy evaluation at 12
weeks. Median age was 73.8yrs (IQR 69.2–
79.6). Median PSA at baseline was 43ng/ml
(IQR 20.5-71.5). After 12 weeks of treatment
with high dose AA the median increase in PSA
was 16.5ng/ml. No patients achieved 50% PSA
reduction. Five patients had lower PSA after
12 weeks but only one showed an absolute
PSA decrease >2.0ng/ml. All bone markers increased from baseline with about 10%. ECOG
performance score at 12 weeks was unchanged
in 17 pts (85%), two had worsened ECOG,
and one had better ECOG score. Overall
quality of life (QL2) remained unchanged, but
physical functioning (PF2) dropped by median
6.7 (transformed scale). In total, 53 AEs were
recorded. 24 ‘grade 1’, 15 ‘grade 2’, 12 ‘grade
4’ and 2 died in the post-trial period giving two
‘grade 5’ AEs. Eleven AEs were categorized as
serious. Three AEs were directly related to AA,
none were serious and all related events were
due to the fluid load (vehicle) given with the
60g AA.
CONCLUSIONS: Weekly infusions with high
dose AA does not appear to have impact on
cancer progression in patients with mCRPC.
Safety profile seems good with nearly all AEs
related to cancer progression. The study has
limitations due to sample size for secondary
outcomes. Clinicaltrials.gov: NCT01080352
#68 ANDROGEN DEPRIVATION
THERAPY: IS ORCHIECTOMY THE
PATIENT’S CHOICE?
Peter Østergren1, Mikkel Fode1, Caroline
Kistorp2, Finn Noe Bennedbæk2, Jens Faber2,
Jens Sønksen1
Denmark, 2Department of Endocrinology, Herlev
University Hospital, Denmark
1
BACKGROUND: Androgen deprivation
therapy (ADT) is a corner stone in the treatment of advanced prostate cancer. Orchiectomy remains the gold standard but has been
replaced, mainly by Gonadotropin Releasing
Figure #68
55
Hormone (GnRH) agonists, due to patient
and physician preference. Previous studies have
shown orchiectomy to be a well-tolerated form
of ADT and recent population based cohort
studies have suggested a preferable cardiovascular profile following orchiectomy compared
with GnRH agonists. We are currently comparing effects of medical and surgical ADT in a
randomized clinical trial. We here present data
on enrollment feasibility and choice of ADT.
DESIGN AND METHODS: Hormone naïve
prostate cancer patients commencing ADT
were eligible for inclusion (EudraCT 2013002553-29). Exclusion criteria were an ECOG
performance status >2, diabetes, coagulopathy,
treatment for osteoporosis or need for acute
androgen suppression. Endpoints are changes in body composition, glucose- and lipid
metabolism and bone density. Recruitment
period was September 2013 until March 2015.
Patients were screened by the treating physician
who referred eligible subjects to the investigator
for further oral and written information.
RESULTS: 180 hormone naïve patients were
assessed for inclusion with a mean age of
75.1 [95% CI 73.8– 76.3]. The enrollment
flowchart is seen in figure 1. Out of 91 eligible
patients only 33 (17 + 16) declined to participate whereas 58 accepted randomization. 102
patients were not referred to the investigator.
Of these patients 55 (54%) started a GnRH
agonist and as many as 38 (37%) underwent
subcapsular orchiectomy partly due to 21 needing acute androgen suppression. 16 patients
declined to participate in randomization after
information by the investigator: Only 6 chose
a GnRH agonist and 9 chose subcapsular
orchiectomy.
CONCLUSIONS: The concept of randomizing between a medical and surgical intervention proved feasible with the majority of
patients accepting the premises. Orchiectomy
is primarily used for acute androgen suppression. However, patients given thorough oral
and written information in a trial setup tended
towards choosing surgery.
56
#69 BICALUTAMIDE 150 MG DAILY
VS. PLACEBO IN HORMONE-NAÏVE, NON-METASTATIC PROSTATE
CANCER PATIENTS: LONG-TERM
SURVIVAL UPDATE OF THE SCANDINAVIAN PROSTATE CANCER
GROUP 6 STUDY
Frederik B. Thomsen1, Klaus Brasso1, Ib J.
Christensen2, Jan-‐Erik Johansson3, Anders
Angelsen4, Teuvo L. J. Tammela5 and Peter
Iversen1 on behalf of the Scandinavian Prostate
Cancer Group
Urology, Rigshospitalet, University of Copenhagen, 2The Finsen Laboratory, Copenhagen Biocenter and Biotech Research and Innovation Centre,
Denmark, 3Dept of Urology, School of Health
and Medical Sciences, Örebro University, Örebro,
Sweden, 4Faculty of Medicine, Norwegian
University of Technology and Science, Trondheim,
Norway, 5Dept of Surgery, Tampere University
Hospital and School of Medicine, University of
Tampere, Tampere, Finland
1
BACKGROUND: The optimal timing of
endocrine therapy in non-‐metastatic prostate
cancer (PCa) is not clear. There is a need for
more data from randomized trials.
METHODS: A randomized, double-‐blind,
parallel-‐group trial comparing bicalutamide
150 mg once daily with placebo in addition
to standard of care in patients with hormone‐naïve, non-‐ metastatic PCa. Kaplain-‐Meier
analysis was used to estimate overall survival
(OS) and multivariate Cox proportional hazard
model was performed to analyse time-‐to-‐
event (death).
RESULTS: A total of 1,218 patients were
included into the SPCG-‐6 study of which
607 were randomized to receive bicalutamide
in addition to their standard care and 611 to
receive placebo. Median follow-‐up was 14.6
years. Overall, 866 (71.1%) patients died,
428 (70.5%) in the bicalutamide arm and
438 (71.7%) in the placebo arm, p=0.87.
Bicalutamide significantly improved OS in
patient with locally advanced disease (HR=0.77
(95% CI:0.63-‐0.94, p=0.01), regardless of
baseline PSA, with a survival benefit which
was apparent throughout the study period. In
contrast, survival favored randomization to the
placebo arm in patients with localized disease
(HR=1.19 (95% CI:1.00-‐1.43), p=0.056).
However, a survival gain from bicalutamide
therapy was present in patients with localized
disease and a baseline PSA greater than 28 ng/
mL at randomization. In multivariate Cox
proportional hazard model, only including
patients managed on watchful waiting as their
standard of care (n=991) OS depended on age,
WHO grade, baseline PSA, clinical stage, and
randomized treatment.
CONCLUSIONS: Throughout the 14.6
years follow-‐up period the addition of early
bicalutamide to standard of care resulted in a
significant OS benefit in patients with locally
advanced PCa. In contrast, patients with
localized PCa and low PSA derived no survival
benefit from early bicalutamide. The optimal timing for initiating bicalutamide in non-‐metastatic PCa patients is dependent of disease stage
and baseline PSA. Trial registration number:
NCT00672282.
#70 SURVEILLANCE OF ADVERSE
EVENTS OF ABIRATERONE USING
SKYPE REMOTE CONSULTATIONS
Wolf PM, Kristensen VM, Hermann GG
Dept of Urology, BBH/Frederiksberg Hospital,
Copenhagen, Denmark
INTRODUCTION: Abiraterone (ABI) is an
androgen biosynthesis inhibitor used to treat
metastatic castration-resistant prostate cancer.
Most adverse events of ABI appear in the
first 3 months of the treatment and extensive
surveillance with clinical assessment and blood
samples are required. Adverse events are seen
primarily due to the increased secretion of aldosterone. In this study the initial 3 months of
treatment was monitored using Skype, which is
a free web-based software for visual communication, to perform remote consultations.
OBJECTIVE: The objective of the study was
to evaluate the safety using Skype to monitor
adverse events of ABI and to assess to what
degree adverse events could be managed using
Skype.
METHODS: The patients received 6 video
consultations during a period of 3 months. At
each consultation, the physician completed a
questionnaire in collaboration with the patient.
The questionnaire was designed to register ABI
induced adverse events, evaluate patient and
physician satisfaction with Skype, and record
Skype stability. Patients measured their blood
pressure and weight daily and had blood samples taken every 2 weeks. Adverse events were
graded according to CTCAE v. 4.03 where
applicable.
RESULTS: During 18 months, 39 patients
fulfilled the indications for ABI treatment. ABI
candidates fell into 2 categories: A. 23 patients
enrolled in the Skype program, 19 of which
completed it and 4 dropped out due to terminal illness related to prostatic cancer or lack of
response to ABI. B. 16 patients not qualifying
for Skype consultations due to language barrier or no computer access. From this group 9
completed the 3 months control program, 3
patients are currently being monitored and 4
patients did not complete the initial 3 months
of treatment. For the 19 patients completing
the Skype program 46 adverse events (grade
1-3) and 5 instances of minor edema of the
limbs were registered. In 30 instances, no
action was needed. 11 adverse events (grade
1-3) were treated using Skype only. 5 times
(grade1-2) a visit to an outpatient clinic was indicated and in 5 instances (grade 3) admission
to the hospital was required.
CONCLUSION: Based on the data, Skype
consultations appear to be a safe method of
monitoring patients starting treatment with
ABI and adverse events of less severity can be
managed via Skype.
#71 DIFFERENTIAL EFFECTS OF
MEDICAL ANDROGEN DEPRIVATION THERAPIES ON SERUM ALKALINE PHOSPHATASE LEVELS IN
MEN WITH PROSTATE CANCER
Zsolt Bosnyak1, E. David Crawford2, Bo-Eric
57
Persson3, Anders Malmberg1, Anders Neijber1
Global Clinical Research and Development, Ferring Pharmaceuticals A/S, Copenhagen, Denmark,
2
University of Colorado, Aurora, CO, USA, 3Läkarhuset and Uppsala University, Uppsala, Sweden
1
INTRODUCTION: Androgen‑deprivation
therapy (ADT) decreases bone mineral density
and may increase skeletal complications in
metastatic prostate cancer. However, luteinising hormone-releasing hormone (LHRH)
agonists and gonadotropin-releasing hormone
(GnRH) antagonists have differential effects
on follicle-stimulating hormone (FSH), which
regulates bone resorption. The current analysis
compared the effect of LHRH agonists and
the GnRH antagonist, degarelix, on serum
alkaline phosphatase (S‑ALP), a marker of bone
turnover, and the incidence of skeletal adverse
events (AEs).
METHODS: S-ALP was prospectively measured in men with metastatic prostate cancer
treated with leuprolide (7.5 mg; n=153) or
degarelix (240/80 mg or 240/480 mg; n=282)
in the CS21 and CS35 phase III randomised
trials. Skeletal AE data were derived from pooled analysis of five phase III/IIIb randomised
trials comparing GnRH agonists and degarelix.
RESULTS: After initial increases, S-ALP was
reduced below baseline by Day 56 with degarelix, compared with Day 84 for LHRH agonists.
Over one year, S-ALP was significantly lower
with degarelix (p=0.037; figure). In CS21/21A,
S‑ALP levels at Day 364 in men with metastatic disease were 96 IU/L with degarelix (n=37)
vs 179 IU/L with leuprolide (n=47) (p=0.013).
S-ALP returned to baseline levels in both
groups, but remained below baseline for 177
days longer with degarelix. In CS35, bone pain
was reduced with degarelix (p=0.001). In the
pooled analysis, fracture risk was lower with
degarelix vs. LHRH agonists (HR=0.42, 95%
CI 0.16–1.05); this was significant in men with
baseline testosterone >2 ng/mL (HR=0.32,
95% CI 0.12–0.89; p=0.028).
CONCLUSIONS: Degarelix suppressed SALP more quickly and for longer than LHRH
agonists. It also reduced bone pain and was
associated with a lower incidence of fractures.
Collectively, these data indicate that degarelix
provides better control of skeletal disease in
men with metastatic prostate cancer, an effect
that may be mediated by its differential effect
on FSH.
Figure #71
58
#72 HOSPITAL DISTRICT BUDGET
IMPACT ANALYSIS OF DEGARELIX IN THE TREATMENT OF MEN
WITH PROSTATE CANCER AND
HISTORY OF CARDIOVASCULAR
EVENT IN FINLAND
Nolvi K1, Toimela J1, Kautiainen K2, Kosunen
M2, Suomela M1
1
Ferring Lääkkeet Oy, Finland, 2AT Medical
Affairs Consulting (Medaffcon) Oy, Finland
therapy (ADT) is associated with increased risk
of cardiovascular morbidity. Approximately
4600 new prostate cancer cases are diagnosed
each year in Finland. This analysis modelled the
number of incidents and costs of avoided cardiovascular events (heart attack or stroke) and
morbidity following treatment with gonadotropin-releasing hormone (GnRH) antagonist
(degarelix) compared to treatment with agonist
(leuprolide) plus bicalutamide in men with a
history of a cardiovascular event. The analysis
was conducted from a Finnish hospital district
perspective.
METHODS: An Excel®-based budget impact
model was constructed to evaluate the consequences of treatment with degarelix versus
leuprolide when initiating ADT treatment to a
patient with a prior cardiovascular event. The
time horizon was 1 or 3 years. Basic assumptions of the model were based on the published
literature, Finnish Cancer Registry, Finnish
drug acquisition costs, Finnish drug administration costs, and the results of a PERFECT
(PERFormance, Effectiveness and Cost of
Treatment episodes), project which studied
hospital in-patient costs of treating heart attack and stroke. The model accounted for the
proportion of patients (%) initially treated with
degarelix versus leuprolide as well as the proportion (%) of heart attack versus stroke occurring among the patient population. Percentages
are changeable and can be adjusted according
to a prevailing situation. The model took into
account patients either using degarelix or leuprolide or switching current leuprolide medication to degarelix. No new patients entered the
model within the observation period.
RESULTS: According to the Finnish Cancer
Registry, 4601 new prostate cancer patients
were diagnosed in 2012 of which 22% (1012
patients) were eligible for ADT treatment. Of
these, 308 would have a prior cardiovascular
event if the incidence of cardiovascular events
at baseline is 30.4%. On a national level, if
patients were treated in the proportion of 50%
degarelix and 50% leuprolide, continuous
treatment with degarelix was expected to result
in 13.2 cardiovascular events and 7.2 deaths
whereas treatment with leuprolide was expected
to result in 27.4 cardiovascular events and 19.6
deaths over 3 years. Switching patients from
leuprolide to degarelix was expected to prevent
14.2 cardiovascular events and 12.4 deaths yielding total cost savings of 99424 € over 3 years.
CONCLUSION: Compared to treatment
with GnRH agonist, degarelix is a cost saving
alternative in the treatment of prostate cancer
for patients with a cardiovascular event history.
#73 ANDROGEN DEPRIVATION
THERAPY (ADT) AND CARDIOVASCULAR (CV) RISK – ANALYSIS
OF GERMAN STATUTORY HEALTH
INSURANCE (SHI) DATA
Christoph Rüssel1, Susanne Guthoff-Hagen2,
Verena Donatz3
1
Center for Urology, Borken, Germany, 2SGH
consulting, Hamburg, Germany; 3Ferring Arzneimittel GmbH, Kiel, Germany
INTRODUCTION: ADT is an established
part of the guideline-oriented therapy of
prostate cancer (PCa). Concerns regarding
increased CV risks associated with ADT were
raised by the FDA in 2010. Results from a pooled data-analysis of six prospective randomised
trials suggest a lower number of CV events in
patients treated with the GnRH antagonist
degarelix compared with GnRH agonist treated
patients with pre-existing CV disease. The
objective of this study was to investigate if SHI
data can be used to confirm the observation
that the risk for CV events varies depending on
the method used for ADT.
59
METHODS: Retrospective data sets of 4 million insured people from SHI funds between
2009–2012 were analysed to identify PCa
patients treated with either GnRH agonists or
GnRH antagonists. An age-adjusted reference
group with 1.1 million non-PCa persons was
identified in the data sets.
RESULTS: Overall 44,166 patients with PCa
were identified. Of those, 10,611 patients were
treated with ADT; 10,554 with GnRH agonists
and 132 with GnRH antagonists. An increased
prevalence for relevant baseline CV diseases was
observed in ADT treated patients compared
to the non-PCa reference group (diabetes mellitus: 28.66% vs 17.43%.; CAD: 35.77% vs
15.70%; heart failure: 27.54 % vs 9.64%). The
rate of heart attack and stroke (CV events) after
treatment with ADT began was determined.
The overall rate was 2.37% in the reference group and 5.9% in the PCa group. For
those receiving ADT, the rate was 7.8% in the
GnRH agonist group and 2.3% in the GnRH
antagonist group. All CV events in GnRH
antagonist group occurred in high risk patients.
The treating urologist examined and reported
the state of CV risk for 25% of the PCa patients. Urologists examine and treat statistically
significantly more patients with a combination
of PCa and CV events than general practitioners (30 vs. 5 per year/per physician).
CONCLUSIONS: This retrospective analysis
supports the hypothesis that the risk of CV
events varies depending on ADT treatment.
The risk might be lower with GnRH antagonists. Close collaboration of urologists, general
practitioners and cardiologists is therefore recommended in thse management of PCa patients.
#74 FUSION-GUIDED PROSTATE
BIOPSY WITH MULTIPARAMETRIC
MRI AND TRUS, EARLY EXPERIENCE
Sam Ladjevardi, Pär Dahlman, Per Liss, Anna
Tolf, Jan Weis, Håkan Jorulf and Michael
Häggman
Depts of Urology, Pathology and Radiology, Uppsala University Hospital, Sweden
60
INTRODUCTION: Great strides have been
made in the application of multiparametric
MRI for diagnosis of prostate cancer. Fusionguided biopsies of the prostate after MRI have
been introduced in recent years. A new fusion
guided ultrasound system with a robotic arm
stabilizing the probe has been utilized at our
institution, to increase the diagnostic accuracy
and we present preliminary results.
MATERIAL AND METHODS: Nineteen
patients, mean age 66 years (range 50-78), with
high suspicion of prostate cancer or minimal
positive findings on previous biopsies were
included. Seventeen patients had undergone
one or more previous 10-12 core biopsy sets.
The patients underwent multiparametric MRI
and all examinations were reviewed by an
experienced radiologist who identified regions
of interest (ROI). The patients were biopsied
utilizing the Eigen system (Eigen, 13366 Grass
Valley Ave., CA 95945, USA) which consists
of a computer with fusioning software and a
robotic arm with free hand motion fixating the
ultrasound probe and guiding it. An average of
5,7 cores (3-14) were taken. An average positive
biopsy length of 17 mm (1-62) was measured.
RESULTS: No immediate complications were
experienced. Histopathology from the ROI
showed positive biopsy in 13/19 cases. Four
of the 6 negative cases had no significant MRI
findings suggesting malignancy, the other two
had low ADC values. The 13 positive cases,
on the other hand, all had significant MRI
findings and low ADC values. Gleason scores
in the biopsies were 5 Gleason 6, 5 Gleason 7
and 3 Gleason 8 or above.
CONCLUSIONS: The application of the
novel Eigen fusion guided robotic system
increases the diagnostic accuracy of multiparametric MRI guided prostate biopsies. It appears
superior to other systems in the aspect of a
stabilized probe positioning, which probably
improves the hit rate. An adequately performed
and evaluated MRI of the prostate with conformal assessment is crucial for the success rate.
This will contribute to adequate decision making in localized prostate cancer. In the future
it may be utilized to guide focal therapies.
ORAL PRESENTATION #A
Friday 5th June
08.00 - 09.30
Palissad ÖST
#A1 GROUP BASED EXERCISE
WITH TRANSITION TO OUT OF
HOSPITAL TRAINING
Anne-Mette Ragle1, Solveig Øst2, Anders
Vinthera, Henrik Jakobsen2 and Peter Busch1
Østergren2
The Dept of Internal Medicine, Section of Physiotherapy, Herlev University Hospital, Denmark,
2
Denmark.
1
therapy (ADT) remains a cornerstone in the
management of patients with advanced prostate
cancer. However, the ADT induced suppression of testosterone has adverse effects on body
composition, cardiovascular risk factors, bone
health and functional capacity. We present
preliminary data from our interdisciplinary
patient course for men with prostate cancer
on ADT. The course includes a patient school
and a 12-weeks supervised group based exercise
program. The patient school focuses on ADT,
side effects and information about nutrition
and physical activity.
AIM: To investigate if a 12-week supervised
exercise program as part of an interdisciplinary
patient education could 1) mitigate the adverse
effects of ADT on functional capacity and 2)
prepare the patients for continued structured
exercise after the intervention.
METHODS: The group based exercise
intervention with the primary focus on progressive resistance training was performed
at our hospital twice weekly supervised by a
physiotherapist. After 12 weeks the patients
were introduced to a local fitness center by the
physiotherapist to ensure, that the patients felt
confident training on their own. Functional
capacity was assessed by the 30second Chair
stand test (30s-CST) and the Graded Cycling
Test combined with the Talk Test (GCT-TT) to
investigate lower extremity strength as well as
aerobic capacity. The patients were tested prior
to and after the supervised training and at 6
months follow up.
RESULTS: The study is ongoing and the
results are preliminary. Since August 2014,
61 patients have been included and so far 33
patients have completed the course. 33 and
31 patients had complete pre and post test
results for 30s-CST and GCT-TT, respectively.
Statistical significant increases in functional
capacity were observed with a mean increase
of 4 [95% CI 2-5] repetitions (p<0.001) in
30s-CST (pretest: 15 repetitions) and 15 [95%
CI 7-23] Watts (p=0.001) in GCT-TT (pretest
106 watts). By now 17 patients have completed
6 months follow-up. 88 % have maintained or
improved their 30s-CST performance and 71
% have maintained or improved their GCT-TT
performance.
CONCLUSION: To date all patients were able
to complete the exercise program and statistically significant improvements in functional
capacity were achieved. Promising 6 months
follow-up test results indicated that maintenance of functional capacity was highly feasible
using the present group based exercise intervention including a structured transition to out of
hospital training. Apparently, maintenance of
lower extremity strength is easier compared to
cardiovascular fitness.
#A2 STUDENT EXPERIENCE OF
SCHOOL TOILETS
Maja Norling1,2, Karin Stenzelius1,3, Nina
Ekman1,2 and Anne Wennick1
Malmö University, Faculty of Health and Society,
Dept of Care Science, Malmö, Sweden, 2Skåne
University Hospital, Dept of Pediatrics, Malmö,
Sweden, 3Skåne University Hospital, Dept of
Urology, Malmö, Sweden
1
BACKGROUND: Although it is well known
that irregular toilet habits contributes to urinary and bowel problems, studies performed on
children in elementary school demonstrate that
61
students avoid using school toilets. However, few
studies have been performed in high school.
AIM: The aim of this study was therefore to
elucidate the experiences of school toilets by
students aged 16-18 years.
METHODS: A qualitative interview study
was conducted in which data from 21 students
were analyzed according to the content analysis method. Students at four different high
schools were asked if they would be willing to
participate in the study by their school nurse.
Inclusion criteria were Swedish-speaking students in four selected high schools. Twenty-one
agreed to participate (15 girls and 6 boys). The
students were interviewed individually at a
location and time chosen by the participants.
RESULTS: The analysis of the interviews
yielded of three themes of the first was; Assessing the toilet environment. A major reason for
students withholding urine and stool at school
was inadequate locks. However, persistent elimination needs forced them to use the school
toilet. Before doing so they inspected the toilet
all over to make sure that it was secure as well
as clean enough to use. A second theme was;
Coping with the situation. For instance they
waited until class as they considered class was
preferable to recess. Another stressor, was the
sound of voiding or defecating, which often led
to difficulties voiding. Hence, the girls camouflaged possible sounds by turning on the water
tap. Some students found it impossible to use
the school toilets. Thus, during school hours
they avoided drinking to reduce the risk of
having to void. The third theme was Feeling exposed. Such feelings arouse when going to the
toilet did not offer the possibility of seclusion,
for instance, toilet cubicle that allowed others
a clear impression of, or to hear and even film,
the students. Thus, compared to toilet cubicles,
toilets in a secluded location with solid walls
and lockable, thick, full-sized doors created the
felt less exposed to use, and were thereby preferable. Overall the school toilets were generally
considered insecure, dirty and unpleasant.
CONCLUSIONS: There is an urgent need to
improve the school toilet environment in order
to respect the rights of all students’ to void or
62
defecate when necessary. This will require the
involvement of students, teachers, and other
school staff as well as the School Health Service.
#A3 URINARY SYMPTOMS AND
TOILETING BEHAVIOUR AMONG
YOUNGER WOMEN
Johanna Sjögren1 and Karin Stenzelius1, 2
Dept of Urology, Skåne university hospital,
Malmö University
1
2
BACKGROUND: Previous studies have demonstrated that even younger women do have
urinary tracts symptoms but the reason are unclear. However young women’s toilet habits and
bladder emptying behavior can affect bladder
function. A pilot survey of 100 students above
18 years showed that 65% always or often
worried about the cleanliness of public toilets
and 42% emptied the bladder as a measure of
precaution. Totally 33 % neglected the need to
go to the toilet to avoid using public toilet and
13% contrived often or always. The pilot study
showed that a dysfunctional way, neglecting the
need to go to the toilet or that psychological
factors affect emptying pattern.
AIM: The aim of this study was to investigate
urinary symptoms and toileting behavior among
younger women in the age of18-25 years.
METHOD: A postal questionnaire consisting
of three forms was distributed to 550 women
in the ages of 18-25 years randomly selected
from the population register in Skåne with
one reminder. However 519 persons were
reached due to addresses unknown. The first
section contained background questions and
the second part was about lower urinary tract
symptoms (BFLUTS) and the third about toilet
habits. The study was approved by local ethical
committee of southern Sweden.
RESULTS: Totally 168(32,3%) women responded to the questionnaire with a mean age
of 21.5 years. BMI were in mean 22.9 and 26
(15,6%) women were smokers and 20 (11,9%)
had given birth. Questionnaire on lower
urinary tract symptoms (BFLUTS) showed
that 37-40 women (21.6 -24%) in varying
degrees reported irritating bladder symptoms,
38 women (22.8%) reported difficulties in initiating emptying the bladder, 37 (21.6%) had
to strain to empty the bladder and 22 women
(13.8%) had varying problems with interruption in the urinary stream. Stress incontinence
occurred sometimes, often or always in 88
women (47.3%) while urge incontinence was
reported among 20 (12%). Leakage without
obvious reason was reported by 4 women
(5.4%). Most of the women (87%) were
worried about the cleanliness of public toilets
and 17% avoided to use them. Other women
used to empty the bladder just in case without
feeling a need to void.
CONCLUSION: There seems to be various
urinary symptoms even among younger women
even though the sample is not representative for the
whole population. Furthermore there are toileting
habits that may contribute to these symptoms.
#A4 QUALITY OF CARE AFTER
TUR-P IN SOUTHERN SWEDEN
Alicia Saavedra1, Oliver Patschan2 and Karin
Stenzelius2,3
Dept of Intensive- Perioperative care, Skåne
University Hospital, 2Dept of Urology, Skåne
University Hospital, 3Malmö University; all
Malmö, Sweden
1
OBJECTIVE: The aim of the study was to
retrospectively evaluate the time from hospitalisation until 6 months follow-up of patients
undergoing surgery with transurethral resection
of the prostate (TURP) with focus on pain,
sleep and micturition.
MATERIALS AND METHODS: Patients
at three hospitals operated for bladder outlet
obstruction with TURP in 2012 were included
in the study. Patient-charts from 177 patients
were reviewed retrospectively after obtaining
patients consent. Preoperative parameters like
micturition, international prostate symptom
score (IPSS), age, BMI, PSA, ASA-score, chronic catheter-use were recorded. Postoperative
complications (Clavien-Dindo classification),
weight of resected specimen, pain treatment,
VAS (visual analogue scale), sleeping problems,
catheterisation and hospitalisation time were
registered. At 3-6 months postoperatively,
incontinence, urethral stricture, bladder neck
obstruction, IPSS were registered. The study
was approved by the local ethics-committee.
RESULTS: Mean age of the patients was 69
years, BMI 26.1, prostate-volume was 53 ml.
Preoperatively, 31/177 patients (17.5%) used
an indwelling urinary catheter, and 43/177
(24.3%) used clean-intermittent-catheterisation
for bladder-emptying.
Mean operation-time was 75 minutes (SD
33), mean prostate resection-weight 23 gr
(SD 15), median bleeding 107 ml (IQR 245).
The majority (144/177; 82%) had grade I,
but 29/177 (16%) had grade II, and 2/177
(1%) had grade III complications according to
Clavien-Dindo. Median hospitalisation-time
and catheterisation-time were 3 days. Totally
158/177 (89%) were treated for pain, but only
in 90/177 (51%) cases the nurses had used
VAS. When pain was estimated, a score between 0 and 3 postoperatively was reported.
A majority of patients (147/177; 83%) had no
sleeping problems, but 35/177 patients (20%)
used sleeping pills during hospitalisation.
23/177 patients suffered from hematuria or urinary retention during the first 30 postoperative
days. During the first 6 months, 5/177 patients
(3%) were re-hospitalised because of hematuria, urinary retention or urgency. IPSS was 24.8
(SD 8.3) prior and 10.9 (SD 7.7) 3 months
after surgery (P< 0.001). Three months postoperatively, incontinence was reported in 10
(5.6%) patients, urinary stricture in 6 (3.4%),
and urinary tract infection in 10 (5.6%) patients. No case of bladder-neck obstruction was
observed. However, follow-up information was
not available in almost 50% of cases.
CONCLUSIONS: Although there was
limited documentation available about the care
during hospitalisation, TURP was generally
well tolerated and not associated with severe
postoperative pain- or sleeping-disorders. Mild
complications, like hematuria, are frequently
observed. Resection-weight in relation to
operation-time was low. However, short-term
results on bladder-emptying are good. Postoperative follow-up was unsatisfactorily.
63
AUTHOR INDEX
PRESENTING
AUTHOR
Abrahamsson
Anand
Baco
Bertilsson
Björnsson
Blindheim
Borisdottir
Borre
Bosnyak
Canesin
Christiansen
Don-Doncow
Dyal
Elkjaer
Ellertsson-Csillag
Fagerström
Fode
Frey
Fuglsig
Gaspar
Geertsen
Helgstrand JT
Hemdan
Hjelle
Jacobsen A
Jakobsen AK
Jakobsen JK
Jensen C
Jensen TK
64
ABSTRACT NO
PRESENTING
AUTHOR
ABSTRACT NO
#65
#63
#10
#11
#45
#46
#44
#66
#71
#56
#01
#57
#15
#12
#34
#29
#19
#20
#02
#03, #47
#62
#14, #64
#49
#27
#21
#04
#35
#41, #42
#50
Josefsson
Koch
Kohestani
Krzyzanowska
Ladjevardi
Lam
Liedberg
Mariusdottir
Martins FE
Mygland
Nassir
Nielsen TK
Nilsen F
Nilsson S
Nolvi
Norling
Oddason
Padkaer
Patschan O
Pesonen
Poulsen A
Poulsen MH
Ragle
Rüssel
Røder MA
#58
#25
#13
#61
#74
#48
#30
#28
#31, #32
#06
#54
#67
#51
#07
#72
#A2
#22
#43
#37, #52
#38
#53
#55
#A1
#73
#08, #23,
#26, #59, #60
#A4
#A3
#39
Saavedra
Sjögren
Sjöström
AUTHOR INDEX
PRESENTING
AUTHOR
ABSTRACT NO
Taari
Thomsen FB
#16
#09, #17,
#24, #69
#18
#36
#33
#05
Tikkinen
Trelborg
Warner
Wieborg von
Rosen
Wolf
Østergren
#70
#68
65
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- NUF Congress 2015

Transcription

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