The 4Kscore® blood test for risk of aggressive prostate

The 4Kscore® blood test for
risk of aggressive prostate cancer
Early detection of aggressive prostate cancer
Challenges
•  Serum PSA has a high false positive rate
•  Over 1 million prostate biopsies performed annually in US
•  75% biopsies will have low-grade, indolent (Gleason 6) or no prostate cancer
•  Serious complications of biopsies include infection and hospitalization
•  Overtreatment- 75% of Gleason 6 indolent cancers at prostate biopsy are
confirmed at radical prostatectomy
•  Recommendation by USPSTF to stop PSA screening misses an opportunity to
detect and treat men with high grade (Gleason ≥7), the aggressive form of
prostate cancer
The 4Kscore Test
•  The only blood test that accurately identifies risk for aggressive
prostate cancer
•  Aggressive prostate cancer is defined by both high-grade disease and
long term clinical outcomes (rate of prostate cancer metastases)
•  Based on 10 years of work by scientists at Memorial Sloan-Kettering
Cancer Center and evaluated in over 21,000 men in 11 peer-reviewed
papers on clinical studies including a prospective, blinded prebiopsy
study of 1012 men in US (October 2013 to April 2014)
What is the 4Kscore Test?
Components
Results
Total PSA
Proprietary
to OPKO
{
Free PSA
Intact PSA
hK2
+ Age, DRE, and
prior biopsy status
OPKO ALGORITHM
% risk of having
aggressive prostate
cancer for an
individual patient
Prostate cancer tests
When to use the 4Kscore Test ?
Prior to 1st
biopsy
After previous
negative biopsy
*Not indicated in men who
•  Have a diagnosis of prostate cancer
•  Are taking 5-alpha reductase inhibitors within the last 6 months
•  Have undergone a prostate procedure within the last 6 months
The biomarkers in the 4Kscore Test are based on 10 years of clinical research conducted by
Memorial Sloan Kettering Cancer Center and leading international cancer centers
Study
Cohort
4Kscore/Endpoint
Subjects
AUC
Reference
ERSPC
Unscreened
Biopsy
740
0.90
BMC?Med.?2008;?6(1):?19
ERSPC
Unscreened
Biopsy
262
0.87
BMC?Cancer?2010;?10(1):?635
ERSPC
Unscreened
Biopsy
2914
0.84
ProtecT
Unscreened
Biopsy
6129
0.82
ERSPC
Screened
Biopsy
1501
0.80
ERSPC
Screened
Biopsy
1241
0.83
US?Validation?
Study
Screened
Biopsy
1012
0.82
ERSPC
Prior?Biopsy
Biopsy
925
0.87
ERSPC
Post?RP
RP
392
0.84
MDC
Unscreened
Metastasis
792
0.82
VIP
Unscreened
Metastasis
5360
GG
Total/Subjects/Studied
21,268
J?Clin?Oncol.?2010;?28(15):?
2493–2498
J?Natl?Cancer?Inst?2015;?107(7):?
djv095
Clin?Cancer?Res.?2010;?16(12):?
3232–3239
Cancer?2010;?116(11):?2612G
2620
Eur?Urol.?2014;?in?press;?doi:?
10.1016/j.eururo.2014.10.021
Br?J?Cancer?2010;?103(5):?
708–714
Eur?Urol.?2013;?64(5):?693G699
Cancer?Epidemiol?Biomarkers?
Prev.?2011;?20(2):?255G61
Eur?Urol.?2015;?in?press;?doi:?
10.1016/j.eururo.2015.01.009
11/PeerDReviewed/Publications
Prospective, blinded, multicenter US study
validates 4Kscore Test
• 
• 
• 
• 
• 
• 
1012 patients enrolled in 26 academic
and community practices
Referred for biopsy regardless of age,
PSA, clinical findings or prior biopsy status
Minimum of 10 core TRUS-guided
biopsies performed
The 4Kscore Test was performed at
OPKO Lab, Nashville, TN
Pathology conducted according to the
established practice at each center
Presented in the 2014 AUA Plenary Session
and published in European Urology
(http://dx.doi.org/10.1016/j.eururo.
2014.10.021) Epub Ahead of Print
26 Clinical study sites
Gleason score distribution in prospective US Study
Gleason Grade
N
% All
Cancers
N = 470
Negative
542
--
% All
Patients
N = 1,012
53.6%
Summary
77.2%
6
239
50.9%
23.6%
7 (3+4)
108
23.0%
10.7%
7 (4+3)
59
12.6%
5.8%
8
35
7.4%
3.5%
9
26
5.5%
2.6%
10
3
0.6%
0.3%
22.8%
Negative
or Gleason
6
Negative
or
prostate
cancer
Gleason
6
Aggressive
High-Grade
(Gleason
≥ 7)
prostate cancer
The 4Kscore Test has the greatest accuracy for predicting aggressive
prostate cancer
Sensitivity
4Kscore
AUC = 0.82 1
AUC = area under the curve
Larger AUC = better
accuracy for predicting
aggressive prostate cancer
AUC of other tests when
applied to aggressive disease
PSA
AUC = 0.69 1
AUC = 0.5
PHI = 0.72, 0.67 2,3
PCA3 = 0.68 4
1 - Specificity
1. 
2. 
Parekh, D et al. http://dx.doi.org/10.1016/j.eururo.2014.10.021(Epub Ahead of Print)
Catalona et al. J Urol. 185:1650 2011
3.
4.
Wang, W et al. Scientific Reports 4:1-8 2014
Chevli, K et al. J Urol 191:1743 2014
1.0
The risk of aggressive prostate cancer predicted by the
4Kscore Test is confirmed by prostate biopsy
Legend:
0.6
0.4
95% confidence
interval
0.2
Perfect correlation
n=1012
0.0
231 aggressive
prostate cancers
detected in 1,012
subjects
Actual biopsy result
0.8
Actual percentage
of aggressive
prostate cancer
detected by biopsy
0.0
0.2
0.4
0.6
0.8
Predicted by 4Kscore Test
1.0
4Kscore Test is more accurate than total PSA alone in predicting
aggressive prostate cancer in subset of men with PSA 16-20ng/mL
Total PSA
DRE
4Kscore Test Result
Biopsy Result
16.1
Normal
69%
7
16.4
Normal
1%
Negative
16.4
Normal
8%
Negative
16.6
Normal
50%
6
17.1
Normal
80%
9
17.3
Normal
89%
7
17.5
Normal
87%
8
17.6
Abnormal
98%
8
18.1
Abnormal
88%
9
18.4
Abnormal
87%
7
18.5
Normal
14%
Negative
18.5
Abnormal
94%
7
19.0
Normal
3%
Negative
19.5
Normal
0%
Negative
19.7
Abnormal
96%
7
19.8
Abnormal
83%
8
20.0
Abnormal
98%
9
PSA ≥3.0 ng/ml at age 60
(n=2432)
15
4Kscore
> 7.5%
4Kscore Test Biomarkers
> 7.5% (N =1510, 62%)
= 2.4%
= 5.6%
= 9.9%
= 16.4%
10
5 year
10 year
15 year
20 year
all men PSA ≥ 3
5
all men
PSA ≥ 3
4Kscore Test Biomarkers
≤ 7.5% (N = 922, 38%)
4Kscore
≤ 7.5%
0
% of patients with distant metastases
20
The 4Kscore Test predicts the probability of distant metastases
within 20 years
0
5
10
15
20
5 year
10 year
15 year
20 year
=
=
=
=
0%
0.2%
1.0%
1.8%
Time from baseline (years)
Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers:
A Nested Case–Control Study Stattin, P et al. http://dx.doi.org/10.1016/j.eururo.2015.01.009(Epub Ahead of Print)
Based on your 4Kscore Test result, your probability for having a high-grade cancer
is 5%. This means that if 100 men with your same 4Kscore Test result were to
have a prostate biopsy, 5 out of the 100 men would have a finding of high-grade
prostate cancer upon biopsy.
Clear result reporting for informed decision making
The patient’s 4Kscore Test result is 5%
At a 4Kscore
Test result of 5%, about 1 in 20 men biopsied would have high-grade prostate cancer.
95% chance that
= the biopsy does not
find a high-grade
prostate cancer.
4Kscore Test Result
≤1%
5%
≥100
20
10%
15%
20%
25%
30%
40%
10
6.7
5
4
3.3
2.5
50% 60% 70% 80% 90% ≥ 95%
2
<2
Number of men to biopsy to find one high-grade prostate cancer
4Kscore =
Personal Positive Predictive Value
5% chance that
= the biopsy finds a
high-grade prostate
cancer.
4Kscore as a reflex test for abnormal PSA and/or DRE
Features
4Kscore- Detection & Prognosis
Components
tPSA, fPSA, Intact PSA, and hK2
Integrates clinical information
Yes- Age, prior negative prostate biopsy (Y/N), and DRE status
Commercial
Indication
CLIA accredited LDT
Any PSA level, age, or DRE, and to distinguish risk of aggressive
prostate cancer from indolent or no cancer
Predicts high grade cancer on Bx
Yes, AUC = 0.80 – 0.90
Reported as individual patient % risk for aggressive prostate cancer
(PPV)
Predicts high grade disease in danger zone
(PSA ≥ 1.5 and ≤ 4ng/mL)
Yes
Predicts aggressive prostate cancer at RP
Yes
Predicts long term risk of metastases
Yes, up to 15-20 years clinical outcomes data in 2 large studies