PROSTATE DISEASE Perspectives on Harvard Medical

Transcription

Perspectives on
PROSTATE DISEASE
CONTENTS
SPRING 2007 | Volume 1 Number 2
1Confronting controversies, suggesting solutions
A message from Editor in Chief Marc B. Garnick, M.D., about why lack of consensus exists on the use of complementary therapies and other topics of great interest to patients—
and how to find your own solutions
H a rva r d
M e dic a l
School
3Complementary therapies for prostate disease: What works and what doesn’t
Harvard experts discuss issues that patients may want to consider when using complementary therapies, and assess how well these therapies work for benign prostatic
hyperplasia, erectile dysfunction, prostate cancer, and prostatitis
15How to handle a relapse after treatment for prostate cancer
What it means to experience biochemical recurrence following radical prostatectomy or radiation therapy, knowing when to act, and exploring your options; includes an interview with a couple struggling with the emotional impact of a rising PSA
26 A patient’s story: Overcoming incontinence
How one man persisted for almost two years in an effort to remedy one of the most bothersome possible side effects of prostate cancer treatment, and what men facing therapeutic decisions can learn from his experience
33 New options for treating erectile dysfunction
What penile rehabilitation after prostate cancer treatment involves, what the studies show, and why you may want to consider it; just be aware that this remains a controversial area, and not all experts are convinced it is effective
37Harvardexperts discuss surgical options for benign prostatic hyperplasia
Three Harvard experts describe the available surgical options for treating BPH, and which ones they find patients prefer; the second part in a series which began in the last issue of
Perspectives
44 Searching PubMed in five easy steps
A guide to finding the studies cited in this publication, so you can evaluate the evidence on your own
45Glossary Definitions of medical terms used in this issue
IN THE NEXT ISSUE:
The latest advice about treating prostatitis
What you need to know about hormone therapy
How one man maintained his sex life during and after prostate cancer treatment
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P e r sp e c t i v e s o n P r o stat e D i s e a s e | S p r i n g 2 0 0 7
Advisory and Editorial Board
Marc B. Garnick, M.D., Editor in Chief
Perspectives on
Prostate Disease
Editor in Chief
Marc B. Garnick, M.D.
Clinical Professor of Medicine,
Physician, Hematology/
Oncology Division, Beth Israel
Deaconess Medical Center
Editor
Ann MacDonald
Illustrator
Scott Leighton
Art Director
Heather Derocher
Production Editors
George V.H. Allen
Charmian Lessis
Published by
Anthony L. Komaroff, M.D.
Editor in Chief
Edward Coburn
Publishing Director
Perspectives on Prostate Disease
is supported in part by a charitable
nonprofit family foundation.
Copyright ©2007 by the President and
Fellows of Harvard College
For corporate sales and licensing, please
e-mail: [email protected]
Dr. Garnick is an internationally renowned expert in medical oncology and urologic cancer. A clinical
professor of medicine at Harvard Medical School, he also maintains an active clinical practice at Beth
Israel Deaconess Medical Center, and has dedicated his career to the development of new therapies for the
treatment of prostate cancer. The concept for developing Perspectives on Prostate Disease emerged from
Dr. Garnick’s keen interest in helping explain issues of medical importance to patients and their families
in order to help them select appropriate treatment choices. He has authored numerous scientific articles
and reviews on clinical research, drug development, and cancer biology and has written or edited six
books, including A Patient’s Guide to Prostate Cancer. In addition to his academic affiliations, Dr. Garnick
founded the Hershey Family Foundation for Prostate Cancer Research at Beth Israel Deaconess Medical
Center, serves as medical advisor to World Book Encyclopedia, and serves on the boards of trustees of
Bowdoin College and the University of Pennsylvania School of Medicine.
Per-Anders Abrahamsson, M.D., Ph.D., is an
internationally respected leader in urology who since
2004 has served as Adjunct Secretary General of the
European Association of Urology, where he leads the
organization’s research activities. He is Chairman of the
Department of Urology at Malmo University Hospital,
Lund University, in Sweden, and an Adjunct Professor
in the Department of Urology, University of Rochester
Medical Center, in New York. The author of numerous
scientific publications, including book chapters and
books, he serves on the editorial boards of several scientific journals. He has received a number of national and
international awards and is the organizer of international
conferences that bring physicians together from multiple
disciplines.
William C. DeWolf, M.D., is a Professor of Surgery
(Urology) at Harvard Medical School and Chief of the
Division of Urology at Beth Israel Deaconess Medical
Center in Boston. He is a member of numerous professional societies and the author of numerous original
reports, abstracts, and review articles published in peerreviewed journals. A member of the American Urologic
Association Program Committee for Basic Research in
Prostate Cancer, Dr. DeWolf ’s own research interests
include the identification of urinary biomarkers for prostate cancer and a better understanding of the molecular
biology of prostate cancer.
Carolyn C. Lamb, M.D., is an Instructor in Radiology
at Harvard Medical School and a radiation oncologist at
Mt. Auburn Hospital in Cambridge. She is a member of
several professional societies, including the American
Society for Therapeutic Radiation and Oncology and the
American Medical Women’s Association. She has published a number of scientific papers on the treatment of
prostate cancer, including the implantation of radioactive
seeds and treatment of genito-urinary complications of
cancer treatment. Her clinical interests include developing more precise methods of delivering radiation therapy,
in order to target tumors while sparing healthy tissue.
Kevin R. Loughlin, M.D., M.B.A., is a Professor
of Surgery (Urology) at Harvard Medical School and
Director of Urologic Research at Brigham and Women’s
Hospital. He is also staff urologist at the Harvard University Health Service, a large university health program
that serves the needs of Harvard students, faculty,
employees, and their families. His clinical interests
include urologic oncology and urologic incontinence.
In addition to publishing numerous scientific articles
on prostate disease, he is the author of several books,
including 100 Questions and Answers about Benign
Prostate Disease and The Clinical Guide to Prostate
Specific Antigen.
Abraham Morgentaler, M.D., is an Associate Clinical
Professor of Surgery (Urology) at Harvard Medical School
and Director of Men’s Health Boston, where he specializes in treating a range of prostate diseases and male
sexual and reproductive difficulties. Dr. Morgentaler
has developed a particular expertise in treating erectile
dysfunction, low testosterone levels, and benign prostatic hyperplasia. He has published numerous scientific
articles, especially on the issues of erectile dysfunction
and testosterone replacement therapy. He is also the
author of several articles and books for the lay public,
including The Viagra Myth: The Surprising Impact on
Love and Relationships.
David S. Rosenthal, M.D., a past President of the
American Cancer Society, is currently a Professor of
Medicine at Harvard Medical School and Director and
Chief Executive Officer of Harvard University Health
Service, coordinating the care and management of
35,000 members of the Harvard University community.
Dr. Rosenthal is also the Medical Director of the Leonard P.
Zakim Center for Integrative Therapies at Dana-Farber
Cancer Institute, which seeks to integrate complementary therapies with conventional cancer treatments. He is
the author of numerous scientific articles as well as several publications for laypeople, including The American
Cancer Society’s Guide to Complementary and Alternative
Cancer Methods.
Harvey B. Simon, M.D., is an Associate Professor of
Medicine at Harvard Medical School, a member of the
Health Sciences Technology Faculty at Massachusetts
Institute of Technology, and a primary care internist at
Massachusetts General Hospital in Boston. In addition
to authoring numerous scientific articles and textbook
chapters, he is the founding editor of the monthly
newsletter Harvard Men’s Health Watch, where he writes
frequently about prostate disease and erectile dysfunction. He is also the author of six consumer health books,
including The Harvard Medical School Guide to Men’s
Health and The No Sweat Exercise Plan: Lose Weight,
Get Healthy, and Live Longer.
James A. Talcott, M.D., is an Associate Professor of
Medicine at Harvard Medical School. He is also Director
of the Center for Outcomes Research at Massachusetts
General Hospital, which focuses on evaluating the impact
of cancer and its treatment on patients, improving the
delivery of cancer care, and assessing cancer care technology. Using qualitative and quantitative research tools,
Dr. Talcott and his colleagues have developed validated
instruments to better understand the quality-of-life impact
of treatment, particularly as it is expressed by patients
themselves. The ultimate goal of this research is to better
determine what information is needed by patients so that
they can make informed treatment decisions.
Confronting controversies, suggesting
solutions
A message from Editor in Chief Marc B. Garnick, M.D.
The positive response to the inaugural issue of Perspectives on Prostate Disease
has been gratifying and indicates that we are on target in providing the type of
unique, compassionate, and unbiased information that readers are looking for.
In this second issue of Perspectives, we continue our examination of the thorniest problems facing men with prostate disease. In particular, we examine three
controversial topics that are of great interest to patients, but where no consensus yet exists about the best medical advice or treatments.
• Complementary therapies. Our lead article explores alternative and complementary therapies for various types of prostate disease. This topic is of
obvious interest, as many men with prostate disease use such therapies.
(Surveys indicate, for example, that at least one-third of men with prostate cancer do so.) We assembled a panel of Harvard experts, each with a
unique perspective on this issue, to provide a frank and no-nonsense discussion about which therapies work, which do not, and what you should
think about before trying anything. In this article, you will learn the views
of an epidemiologist who studies population trends of disease and correlates them with intake of food, vitamins, and other nutrients; an oncologist
specializing in integrative medicine, who provides cancer patients with
advice about complementary therapies; and a primary care physician who
has been in practice more than 30 years, who provides a common-sense
approach to choosing and using complementary therapies.
• Biochemical recurrence. Anywhere from 15% to 30% of men treated for
prostate cancer will experience biochemical recurrence—meaning that a
follow-up PSA test indicates that their prostate cancer has returned. The
news can be terrifying. If you find yourself in this position, what are your
options and when should you undergo additional treatment? This article
explores the controversies about what really constitutes a biochemical recurrence, what factors your doctor weighs in making a recommendation
about whether to undergo a second (salvage) therapy, and what to consider
when deciding among treatments.
• Erectile dysfunction. Researchers are continually trying to find new ways
to address the problem of erectile dysfunction, which can occur both as a
consequence of prostate disease and as a side effect of treatment. To augment the information provided in Sex and the Prostate, a supplementary
publication that was sent to all new subscribers, in this issue of Perspectives
Ha rva r d M e d i c a l s c h o o l
w w w. he a lt h . har v ard. e du
we provide the latest information about the controversial topic of penile
rehabilitation. Although a number of hospitals are advertising penile rehabilitation programs aggressively—and the research looks promising—the
jury is still out about how effective it is. This article explains what you
should know about the timing of interventions, the choices available, and
what, realistically, your chances of success are.
But prostate disease is about more than just controversy. Other articles
suggest solutions to common and vexing challenges in prostate disease. This
issue of Perspectives includes the second part of our Harvard experts’ discussion about the best treatment for benign prostatic hyperplasia, this time focusing on options in surgical management. Our panel not only discusses medical
factors to think about but also delves into financial considerations that may
influence a doctor’s recommendation. This is information doctors usually don’t
volunteer, and the type that you are unlikely to read about anywhere else.
This issue also includes an in-depth interview with a patient who talks
about the huge physical and emotional impact of incontinence following prostatectomy. This patient discusses his almost two-year search for a solution
for urinary incontinence, which provides important lessons and guidance for
readers facing the same problem.
As I write this, we are busily preparing our summer issue of Perspectives,
which will include reports of many new advances in prostate disease treatment.
Between now and then, many international medical organizations will convene
to discuss various types of prostate disease, including prostate cancer, erectile
dysfunction, and benign prostatic hyperplasia. These include the European Association of Urology, which meets in Berlin in March, the American Urological
Association in Anaheim, Calif., in May, and the American Society of Clinical
Oncology in Chicago in June. Thousands of physicians and other health care
professionals attend and participate in these three meetings, many of whom
are dedicating their career to the study and furthering of knowledge related
to prostate disorders. In the next issue of Perspectives, we will summarize the
most important findings reported at these meetings and discuss areas of research that are emerging.
In the meantime, we deeply appreciate your continued support and will
uphold our pledge to present unbiased, evidence-based information in these
pages. That way, you can make your own decisions about where you stand on
controversial topics and which solutions are best for you.
Editor in Chief, Perspectives on Prostate Disease
Complementary therapies for prostate
disease: What works and what doesn’t
Harvard experts discuss issues that patients may want to consider
If you have been diagnosed with prostate disease, chances are that you’ve
thought about trying some type of complementary therapy in addition to conventional medical treatment from a physician. If you have, you are not alone.
Various studies have found that anywhere from 27% to 43% of American men
with prostate cancer use at least one form of complementary therapy. Similar
findings have been reported in Canada and Europe. Although statistics are
harder to find for how many men use complementary therapies for benign
prostatic hyperplasia (BPH), erectile dysfunction, or prostatitis, it is likely that
the practice is common.
Unfortunately, the issue of complementary therapies doesn’t often come up
during a visit to the physician. Patients tend not to mention the complementary therapies they are using, while doctors may not ask about them. Often this
is a function of time: A man and his doctor may have only 10 or 15 minutes
together in a typical office visit.
To learn more about what physicians think about various complementary
therapies—and about specific lifestyle changes—the editors of Perspectives on
Prostate Disease invited three Harvard experts to participate in a roundtable
discussion on this important topic. The panel consisted of these experts:
Weighing the evidence
The tables referenced below
review commonly used
complementary therapies by
particular disease and provide an
assessment of what works and
what doesn’t, based on evidence
published in scientific journals:
BPH
Table 1, page 10
Erectile dysfunction
Table 2, pages 10–11
Prostate cancer
Table 3, pages 11–14
Prostatitis
Table 4, page 14
• Dr. Edward Giovannucci, a professor of nutrition and epidemiology at
the Harvard School of Public Health whose research has focused on
how lifestyle factors such as diet and physical activity contribute to the
development of cancer, particularly colon cancer and prostate cancer.
Dr. Giovannucci is considered one of the nation’s pre-eminent experts
on nutrition and prostate cancer.
• Dr. David S. Rosenthal, a professor of medicine at Harvard Medical
School, director and chief executive officer of Harvard University Health
Service, and medical director of the Leonard P. Zakim Center for Integrative Therapies at Dana-Farber Cancer Institute. In addition to serving on
the editorial board of Perspectives, he is the author of numerous scientific
articles and several publications for laypeople.
• Dr. Harvey B. Simon, an associate professor of medicine at Harvard
Medical School, a member of the Health Sciences Technology Faculty at
Massachusetts Institute of Technology, and a primary care physician at
Massachusetts General Hospital. A member of the editorial board of
Perspectives, he has authored numerous scientific articles and textbook
Metabolic syndrome
Anyone with three or more of the
following attributes meets the
diagnostic criteria for metabolic
syndrome, which increases the
risk of diabetes or heart disease:
• waist size greater than
40 inches in men, or
35 inches in women
• blood pressure of 130/85 mm
Hg or more
• HDL cholesterol less than
40 mg/dl in men and
less than 50 mg/dl in women
• triglyceride level of 150 mg/dl
or more
• fasting blood glucose level of
110 mg/dl or more
chapters and is the founding editor of the monthly newsletter Harvard
Men’s Health Watch.
• Dr. Marc B. Garnick, editor in chief of Perspectives, moderated the discussion.
In the following pages, you will learn what these experts had to say about
the issue of complementary therapies in general, as well as their interpretation
of what the published evidence shows about the effectiveness of specific foods,
herbs, and other complementary remedies.
But first, a brief explanation of the terminology used in this article. The
panel agreed to use the language as defined by the National Center for Complementary and Alternative Medicine (NCCAM), a division of the National
Institutes of Health. NCCAM defines alternative medicine as therapies used
in place of conventional medicine, while complementary medicine consists of
therapies used together with conventional medicine. Although an even newer
term, integrative medicine, is becoming popular with physicians and patients
who want to fully integrate both conventional and complementary practices,
for the sake of simplicity this article will use “complementary” to underscore
a point our experts all agreed on: Any unconventional therapy patients
choose is best used along with—rather than as a substitute for—conventional
medical therapy.
POPD: How do you advise your patients when they ask about complementary
therapies?
ROSENTHAL: The major role of a physician is to provide advice about two areas,
efficacy and safety. I tend to divide these therapies into three categories based
on safety and efficacy: the first category consists of those that are both safe and
have evidence of effectiveness; the second includes those that are safe but lack
evidence of efficacy; and the third consists of those that are unsafe and have
been proven ineffective. The middle category is by far the largest. It includes
herbs such as saw palmetto, which some men take for BPH. These herbs and
botanicals are probably safe when used alone. But in many cases there is no
evidence that they actually have any effect, or the only evidence has come from
small pilot studies rather than from randomized clinical trials. So the evidence
is suggestive, not conclusive.
SIMON: I think it’s also important that a patient have a frank conversation with his
physician about any complementary therapies the patient is taking. Of course,
how to do all that in the allotted 10-minute office visit is another matter.
(Laughs.) That’s exactly why I started doing integrative medicine
consultations, which take up to 45 minutes to an hour.
ROSENTHAL:
Another issue that both patients and physicians need to be aware of is
that herbs can interact with other herbs, and with drugs that we prescribe.
SIMON:
ROSENTHAL:
One of the most common interactions involves herbs and
botanicals that affect the liver, by acting on cytochrome P450 enzymes (see
below). Many herbs, such as St. John’s wort, affect this system. So it’s important
that patients understand that some herbs can enhance the effects of medications, or sometimes negate any beneficial effect.
When I do integrative medicine consultations, I advise people not to try
too many supplements at one time. Try one herb or botanical first, and see if
you tolerate it without any side effects before adding anything else. That’s exactly the same thing we do when we prescribe any medication.
POPD: When
it comes to vitamins and antioxidants, is it better for people to get
these in food or take them as supplements?
SIMON: In studies done in adults, a finding that high blood levels of antioxidants correlate with a good health outcome doesn’t mean at all that people will
get the same good effect by taking a pill or a vitamin.
GIOVANNUCCI: That’s generally correct. Blood levels of particular carotenoids
usually reflect a diet consistently high in fruits and vegetables, rather than any
benefit from taking a supplement.
And I always warn patients that nothing is standardized with respect to over-the-counter substances. The PC SPES story is a glaring example
of what can happen because there is no standardization (see “PC SPES:
A cautionary tale,” page 7). Patients lost faith. And clinical researchers lost
a great deal of time and energy.
ROSENTHAL:
Exactly! PC SPES was heavily promoted as a treatment for prostate
cancer. But it turns out that the product contained not only the eight Chinese
herbs listed on the bottle, but also a little estrogen and some other contaminants. And the real problem is that there’s no federal oversight over the quality
of these products. We can’t verify what ingredients are in a particular bottle.
So unless there’s a pretty good reason to think that something may be useful,
I tell my patients, “Caveat emptor: Buyer beware.”
SIMON:
Cytochrome P450 enzymes
Cytochrome P450 enzymes, most often found in
the liver, help people metabolize drugs and herbs.
But health problems may occur when you are
taking a drug metabolized by cytochrome P450
and then take another drug or herb that interferes
with this process. Some drugs and herbs inhibit
the function of cytochrome P450 enzymes, which
can lead to increased effect of a drug and possibly
toxic side effects. Other drugs and herbs stimulate
cytochrome P450, so that any other drugs you are
taking may be metabolized so quickly that they
have little or no beneficial effect.
*
Assessing the evidence:
Prostatitis
For more information, see
Table 4
Capodice JL, Bemis DL, Buttyan R, et al.
Complementary and Alternative Medicine
for Chronic Prostatitis/Chronic Pelvic Pain
Syndrome. Evidence-based Complementary
and Alternative Medicine 2005;2:495–501.
PMID: 16322807.
Shoskes DA, Manickam K. Herbal and
Complementary Medicine in Chronic
Prostatitis. World Journal of Urology
2003;21:109–13. PMID: 12720037.
Shoskes DA, Zeitlin SI, Shahed A, Rajfer J.
Quercetin in Men with Category III Chronic
Prostatitis: A Preliminary Prospective,
Double-Blind, Placebo-Controlled Trial.
Urology 1999;54:960–3. PMID: 10604689.
* Whenever this icon appears, see “Searching
PubMed in five easy steps,” page 44.
A partial list of drugs, herbs, and foods that affect
cytochrome P450 follows, but you should check
with your own doctor to avoid problems.
Antidepressants
Other medications
Fluoxetine (Prozac)
Sertraline (Zoloft)
Cimetidine (Tagamet)
Omeprazole (Prilosec)
Antifungals
Foods and herbs
Ketoconazole (Nizoral)
Itraconazole (Sporanox)
Garlic
Ginseng
Grapefruit juice
Charcoal-broiled meat
POPD: Let’s
What may work for BPH
Table 1
Bent S, Kane C, Shinohara K, et al. Saw
Palmetto for Benign Prostatic Hyperplasia.
New England Journal of Medicine
2006;354:557–66. PMID: 16467543.
Wilt TJ, Ishani A, Stark G, et al. Saw Palmetto
Extracts for Treatment of Benign Prostatic
Hyperplasia: A Systematic Review. Journal
of the American Medical Association
1998;280:1604–9. PMID: 9820264.
Wilt TJ, MacDonald R, Ishani A. BetaSitosterol for the Treatment of Benign
Prostatic Hyperplasia: A Systematic Review.
BJU International 1999;83:976–83. PMID:
10368239.
See page 44.
look at particular prostate diseases. What does the research show in
terms of what men can do to help themselves?
GIOVANNUCCI: My research focuses on lifestyle factors, which include nutrition,
physical activity, and body weight. The studies show that these basic lifestyle
factors actually have a lot of impact on the risk of developing various types of
prostate disease. For example, there’s more and more evidence that cardiovascular disease contributes to erectile dysfunction. To lower risk for developing
erectile dysfunction, or even to alleviate it, the best advice is to start exercising
more, maintain a normal body weight, and avoid smoking. And some of this
advice is probably also important for prostate cancer and BPH.
SIMON: We also need to educate physicians about the importance of lifestyle
issues for prevention. Erectile dysfunction is the best example, since it’s basically
a manifestation of atherosclerosis, which is a highly preventable disease.
GIOVANNUCCI: There is also some evidence that metabolic syndrome might be a fac-
tor in prostate cancer progression (see “Metabolic syndrome,” page 4). And you
can prevent or ameliorate metabolic syndrome by following the same basic advice:
more exercise, a better diet. I know that’s going to sound like the same old boring
message, but following this advice can have a huge benefit on overall health and
on prostate diseases in particular. So patients don’t have to go searching for exotic
herbs, especially when there is essentially no evidence that they are beneficial.
POPD: What
do the studies say about the impact of lifestyle factors on prostate
cancer? Is there any way for a man to adjust his diet to reduce the risk of prostate
cancer or slow its progression?
GIOVANNUCCI: Unfortunately, not all of the answers are in for preventing prostate cancer, and there’s even less evidence about how to stop its progression.
Again, what seems to be most important is reducing body weight or keeping
body weight normal. There’s a little bit of evidence that physical activity may
be helpful, but probably only at a fairly high level. Walking is probably not sufficient to reduce risk.
In terms of specific foods, there is reason to believe that fish, selenium, and tomatoes might all be important in reducing risk of developing prostate cancer (see
Table 3). But there’s almost no evidence that changing your diet after diagnosis will
have any impact on prostate cancer progression. Of course, eating a healthy diet,
and including some of these specific foods, won’t do harm and would improve
overall health, which would help men going through treatment for prostate cancer.
SIMON: The
studies done to date on this issue are preliminary, and they don’t
produce solid evidence that something really will slow the progression of prostate cancer. But I’m all for giving patients a ray of hope. An example is that I
now advise my patients to consider selenium and possibly pomegranate juice.
They’re not going to hurt you, and a small study suggests pomegranate juice
might slow progression. But I also advise them not to expect too much from it.
PC SPES: A cautionary tale
PC SPES is now off the market, but in the 1990s this herbal product was promoted as being good for
“prostate health.” After anecdotal reports and preliminary laboratory studies indicated that PC SPES
might help men with advanced prostate cancer, the National Center for Complementary and Alternative
Medicine (NCCAM) funded four research studies—including one in patients—to determine its efficacy,
safety, and mechanism of action.
The research ended abruptly in 2002, however, when the FDA issued a warning about PC SPES, based on
reports that men taking the supplement developed blood clots; some patients died. Shortly after the FDA
warning, NCCAM halted all four studies (although it eventually restarted the laboratory trials). The U.S.
distributor issued a voluntary recall and eventually went out of business.
Researchers analyzed samples of PC SPES to determine what went wrong and discovered that some
batches were contaminated with DES, an estrogen. This helped explain a puzzling side effect many
patients had experienced while taking PC SPES—breast enlargement and soreness that could result from
taking female hormones. Scientists discovered that other batches of PC SPES contained indomethacin, a
pain reliever, and warfarin, a blood thinner.
Harvard’s Osher Institute, which conducts research into complementary therapies, is currently trying to
develop a research “bank” of purified, standardized herbs so that future studies can avoid these problems.
I agree. And just one further point is that for prostate cancer,
especially in men who may have a relatively good prognosis, such as localized
cancer, it’s much more likely that a man will die of something else, possibly
heart disease, before he dies of prostate cancer. So I think that it’s probably
worth putting more energy into the basics, such as diet and lifestyle, to prevent
conditions like heart disease.
Assessing the evidence:
Erectile dysfunction
Table 2
Moyad MA, Barada JH, Lue TF, et al.
Prevention and Treatment of Erectile
Dysfunction Using Lifestyle Changes and
Dietary Supplements: What Works and What
is Worthless, Part 2. Urologic Clinics of North
America 2004;31:259–73. PMID: 15123406.
See page 44.
GIOVANNUCCI:
POPD: What
is the current thinking about lycopene, which has certainly received a
lot of attention in the press?
GIOVANNUCCI: The evidence is still mainly from epidemiological studies, so it’s
suggestive, not definitive. But the important point is that even if you go by the
epidemiologic evidence, the benefits are really based on tomato consumption,
and tomatoes contain many nutrients besides lycopene. So I would probably
recommend slightly or somewhat increasing consumption of tomatoes or
tomato products, such as tomato sauce.
POPD: What
about the issue of cooked versus uncooked tomatoes?
GIOVANNUCCI: The epidemiologic data provide good evidence that cooked tomatoes enhance absorption of lycopene. There’s also evidence that oil enhances
absorption of lycopene—but that doesn’t mean people should eat fatty pizza.
You just need a little bit of oil.
SELECT study
SELECT (Selenium and Vitamin E
Cancer Prevention Trial) is the
largest prostate cancer prevention
study ever undertaken, with more
than 35,000 men participating.
Participants have been randomly
assigned to take 200 mcg of
selenium or 400 IU of vitamin E—
or the two in combination, or a
placebo—and will be followed for
a minimum of seven years and a
maximum of 12 years. By that time
it should become clear whether
taking selenium or vitamin E, or
both together, will reduce the risk
of prostate cancer.
SIMON: I’ve
found that when I tell patients to eat more tomatoes, they’re not
impressed. But if someone else tells them to go to the health food store and
buy some lycopene pills, they dash right over. And the data suggest that eating
tomatoes can help reduce risk of prostate cancer, but the evidence is not there
for lycopene supplements.
GIOVANNUCCI: Another
problem is that we have no idea how much of the
lycopene contained in a supplement is absorbed by the body.
What may work for
prostate cancer
Table 3
Chan JM, Gann PH, Giovannucci EL. Role of
Diet in Prostate Cancer Development and
Progression. Journal of Clinical Oncology
2005;23:8152–60. PMID: 16278466.
Chan JM, Holick CN, Leitzmann MF, et al.
Diet after Diagnosis and the Risk of Prostate
Cancer Progression, Recurrence, and Death
(United States). Cancer Causes and Control
2006;17:199–208. PMID: 16425098.
Clark LC, Combs GF, Turnbull BW, et al. Effects
of Selenium Supplementation for Cancer
Prevention in Patients with Carcinoma of
the Skin. Journal of the American Medical
Association 1996;276:1957–63. PMID:
8971064.
Duffield-Lillico AJ, Dalkin BL, Reid ME, et
al. Selenium Supplementation, Baseline
Plasma Selenium Status and Incidence
of Prostate Cancer: An Analysis of the
Complete Treatment Period of the Nutritional
Prevention of Cancer Trial. BJU International
2003;91:608–12. PMID: 12699469.
Giovannucci E, Rimm EB, Liu Y, et al.
A Prospective Study of Tomato Products,
Lycopene, and Prostate Cancer Risk.
Journal of the National Cancer Institute
2002;94:391–8. PMID: 11880478.
Pantuck AJ, Leppert JT, Zomorodian N, et
al. Phase II S tudy of Pomegranate Juice
for Men with Rising Prostate-Specific
Antigen Following Surgery or Radiation
for Prostate Cancer. Clinical Cancer Research
2006;12:4018–26. PMID: 16818701.
See page 44.
We advise patients that, because of the unknown nature of over-thecounter supplements, the best way to get all of the vitamins and antioxidants
you need is to eat healthy foods.
ROSENTHAL:
GIOVANNUCCI: I
think that definitely makes sense because lycopene is not the
only dietary factor to think about. Studies show that you may also be able to
reduce your risk of prostate cancer by eating more fatty fish, which are full of
omega-3 fatty acids and also contain vitamin D. There’s also some evidence
that cruciferous vegetables, such as broccoli, may have a modest benefit.
Whole grains have also shown some potential benefit for preventing
prostate cancer, perhaps because they contain selenium. But we don’t know
for sure.
SIMON:
Right. And if patients want to take selenium supplements, it’s
important not to overdo it.
GIOVANNUCCI:
SIMON: Taking
a daily multivitamin is probably good insurance for all men. For
the most part, it’s a way to ensure that you get adequate daily requirements of
vitamins without overdoing it. But there are three possible exceptions to be
aware of. The first is selenium, since most multivitamins contain less than the
200 mcg that appears protective in the Nutritional Prevention of Cancer Trial
(see “What may work for prostate cancer,” left). Second, most multivitamins
contain 400 IU of vitamin D, but many experts now recommend 600–800 IU
a day. Finally, multivitamins don’t contain any fish oil, but men with coronary
artery disease, or with major risk factors for heart disease, may benefit from
1,000 mg of omega-3 fatty acids a day, and would be wise to take a supplement
if they don’t get that amount in their diet.
ROSENTHAL: I think another important piece of advice for patients is that they
should not go on a diet while undergoing treatment for cancer. It’s not healthy
to lose significant amounts of weight, which a lot of fad diets will cause.
SIMON: Although
if someone is obese and has prostate cancer, it might be a
good idea to shed some body weight.
ROSENTHAL: That’s true, but once you’ve been diagnosed with prostate cancer it’s
important not to go on a crash diet, but instead adopt a healthy one.
POPD: How
should our readers react when they read about something new in the
paper, whether it’s about pomegranate juice or some new herb or botanical?
SIMON: The answer is simple: React with caution. As physicians, I think we first
have to point out that medicine is science, that therapies can be evaluated, and
that there are big bucks involved in the selling of herbs and other unregulated
remedies, where people are making extravagant claims. If something sounds
too good to be true, it is.
ROSENTHAL: I think that we should obviously also advise people to be skeptical of
anything touted as a cure for cancer. And yet there are still some people out there
who are going to prey on patients’ hope that something is going to work, and
encourage them to use an alternative therapy instead of proven medical therapy.
Maybe people get tired of hearing the same old message, but the
fact is, we do know a lot about prevention of various diseases, and I think
people get distracted. They are confronted every day with news about something that’s different, and may, in fact, have promise down the road. But even
if it does, its effect may be relatively modest compared to what we know is
effective—diet and physical activity.
GIOVANNUCCI:
POPD: What
large studies on complementary therapies for prostate disease should
our readers be aware of?
ROSENTHAL: The SELECT study is the big one, which everyone is waiting for,
because it will help determine whether taking selenium and vitamin E might
reduce the risk of prostate cancer (see “SELECT study,” page 7). But the results
aren’t going to be known for years.
Reliable online resources
More and more men with prostate disease are going online to find information about health topics, including complementary
therapies. Our Harvard experts recommend the following Web sites:
Free access
National Cancer Institute
Office of Cancer Complementary and Alternative Medicine
www.cancer.gov/cam
Offers information about particular types of cancer as well as
clinical trials and research evaluating complementary therapies.
Features information from the Best Case Series Program, an
independent review of medical records of patients treated with
complementary therapies for cancer, to determine which ones
hold promise.
National Institutes of Health
National Center for Complementary and Alternative Medicine
www.nccam.nih.gov
Provides general information about complementary therapies, as
well as a list of clinical studies that are recruiting patients. Posts
fact sheets about particular herbs and supplements and diseases—
although not yet on prostate disease or prostate cancer.
Subscription required
ConsumerLab.com, LLC
www.consumerlab.com
Reviews herbs and supplements a bit like Consumer Reports
reviews cars and other consumer products—with rankings
and grades. Provides in-depth information about products,
recalls and warnings, and summaries by particular medical
condition. Web access costs $27 per year.
Natural Medicines Comprehensive Database
www.naturaldatabase.com
Posts information that is medically reviewed and contains
references to particular studies. Search by product name
or medical condition and see drug/herb interactions. Web
access costs $9.97 per month, or $92 per year.
Table 1. Complementary therapies for benign prostatic hyperplasia (BPH)
To read more about the studies cited in this table, see “What may work for BPH,” page 6.
Substances that may work
Substance and possible mechanism of action
Assessment
Beta-sitosterol
Mixture of several extracts of plants containing
substances that mimic cholesterol; not clear how it
alleviates BPH symptoms.
One review of four randomized trials involving a total
of 519 men, published in 1999 in BJU International,
concluded that beta-sitosterol improves urinary
symptoms, but cautioned that long-term safety and
effectiveness were unknown.
Pygeum
Derived from the bark of an African evergreen tree;
not clear how it works, but some researchers have
proposed that it reduces inflammation or slows
prostate growth.
One study, involving 263 men recruited at eight sites
in Europe, found that participants who took pygeum
experienced improvement in urinary symptoms. (The
study is available only in German, so a citation is not
provided here.)
Saw palmetto
Derived from the berry of the saw palmetto tree; not
clear how it works, although a leading theory is that it
affects male hormones.
Safety considerations: May increase the risk of
bleeding when taken with herbs and drugs that also
have this effect (such as garlic, aspirin, anticoagulants,
antiplatelet medications, NSAIDs); should not be taken
with drugs that affect levels of male hormones.
Probably the best studied herb for BPH treatment, but
studies are conflicting.
A review of 18 studies involving 2,939 men, published
in 1998 in the Journal of the American Medical
Association, concluded that saw palmetto supplements
improved urinary symptoms about as much as the
medication finasteride (Proscar). But a randomized
trial involving 225 men who took saw palmetto for a
year, published in 2006 in the New England Journal
of Medicine, found no evidence that saw palmetto
was any better at improving urinary symptoms than
placebo.
Table 2. Complementary therapies for erectile dysfunction
To read more about the substances discussed in this table, see “Assessing the evidence: Erectile dysfunction,” page 7.
Substances that may work
10
Assessment
Korean red ginseng
Derived from a plant root; not clear how it may help
alleviate erectile dysfunction, but one theory is that it
increases levels of nitric oxide, a chemical that occurs
naturally in the body and contributes to erections.
Safety considerations: Some formulations may
lower blood sugar levels and alter the effects of
blood pressure or heart medications; may affect the
cytochrome P450 system (see page 5).
Three small studies suggest that this herb may
improve ability to have an erection, but further study is
necessary.
L-arginine
A precursor to nitric oxide; may help erectile function
by increasing blood levels of this substance.
Safety considerations: May increase risk of bleeding
when used with anticoagulants or antiplatelet drugs,
or with herbs such as ginkgo biloba, garlic, or saw
palmetto; when used with nitroglycerin or erectile
dysfunction drugs, may cause blood pressure to drop;
may increase blood sugar levels.
Three small preliminary studies indicate that this
substance may benefit men with low levels of nitric
oxide, but larger studies are needed. Men at risk for
heart disease should avoid taking this substance, as a
study of possible benefits of taking L-arginine to treat
heart attack survivors was stopped early when six
volunteers taking this substance died.
Vitamin supplements
May have a synergistic effect when used with erectile
dysfunction medication.
A small study of men who did not respond to
medication alone found that erectile function and
patient satisfaction improved in many who took daily
folic acid and vitamin E supplements in addition to
sildenafil (Viagra).
Table 3. Complementary therapies for prostate cancer
Many complementary therapies used for prostate cancer, such as vitamins and particular nutrients, are found
naturally in food. Our panel of Harvard experts agreed that men seeking to reduce their risk of developing prostate
cancer—or of having it progress, if it’s already been diagnosed—should eat a healthy diet and engage in regular
physical activity. These “lifestyle” habits offer the best all-around protection because they reduce the risk of the
number 1 threat to men—heart disease.
Nevertheless, epidemiologic studies (which follow large groups over time) have identified a number of specific
dietary factors that appear to affect risk of prostate cancer development. Data are limited, however, about whether
dietary changes made after diagnosis will have any impact on cancer progression. To learn more about the studies
cited in this table, see “What may work for prostate cancer,” page 8.
Substances that may reduce risk
Substance and possible mechanism
of action
Impact on prostate cancer risk
Impact on prostate cancer
progression
Fish
Not clear why fish may be
protective; one theory is that
omega-3 fatty acids contained in
fatty fish may inhibit a particular
molecular pathway involved in
cancer development.
Fair to good evidence exists
that eating fish may reduce risk
of prostate cancer. Two large
prospective studies, for example,
found that men who ate fish were
less likely to develop prostate
cancer or die from it.
May reduce progression, but less
data are available. A 2006 study
found that men with the highest
intake of fish after diagnosis were
27% less likely to have their cancer
progress than men with the lowest
consumption.
Selenium
May inhibit several biological
pathways that encourage cancer
growth, such as cell proliferation
and angiogenesis.
Safety considerations: Taking
too much can cause nausea and
vomiting; consult with your doctor
if you are undergoing radiation
treatment, as this supplement (and
any antioxidant) may interfere with
treatment.
Strong evidence exists that
selenium reduces risk. A 2003
randomized controlled study found
that men who took selenium
supplements were 50% less likely to
develop prostate cancer than those
who took placebo pills. Several
other studies reported similar
findings.
Insufficient evidence exists
regarding impact on progression.
11
Tomatoes
Contain a number of nutrients;
it remains unclear whether the
antioxidant lycopene, some other
nutrient, or combinations of
nutrients underlie protective effect.
Good evidence that consumption
of cooked tomatoes may reduce
risk. A 2002 study found that men
who regularly consumed two or
more servings of tomato sauce
per week could reduce their risk
of developing prostate cancer by
35% compared with men who
ate tomato sauce less than once
a month. A review of 21 studies
found anywhere from a 10% to
20% reduction in risk among men
with the highest intake of tomatoes,
with cooked tomatoes offering the
most protection.
Increasing consumption after
diagnosis may reduce progression
but data are more limited. A 2006
study found that increased intake
of tomato sauce after diagnosis
might reduce risk of prostate cancer
progression by 30% to 40%. Other
studies reporting a protective
effect from increased tomato
consumption after treatment have
been small or poorly designed.
Vitamin E
Has antioxidant effects that may be
helpful; supplements contain alphatocopherol, a form of vitamin E.
Safety considerations: May
increase risk of bleeding if you are
taking anticoagulants or antiplatelet
medications; may interfere with
treatment if you are undergoing
radiation therapy (ask your doctor).
Good evidence that this may
reduce risk, but the benefit is seen
only in men who smoke. The AlphaTocopherol Beta-Carotene study, for
example, reported that men who
smoked and took 50-IU vitamin
E supplements a day reduced risk
of prostate cancer by 30% to 40%.
Other studies have confirmed a
protective effect for smokers.
Limited data exist regarding impact
on progression.
Substances that may be protective, but evidence is limited
12
Substance and possible mechanism
of action
progression
Carotenoids
(Other than lycopene; see
“Tomatoes,” above)
Occur naturally in plants; may have
antioxidant properties.
Some evidence of reduced risk, but
data are limited and findings have
been mixed. One study reported
that men with higher blood levels of
particular antioxidants—lutein, betacryptoxanthin, and zeaxanthin—had
a 70% to 80% reduced risk of prostate
cancer. But a randomized clinical
trial found that men who took
beta carotene supplements had an
increased risk of prostate cancer if
they already had high blood levels of
this antioxidant.
Limited data exist regarding impact
on progression.
Melatonin
Inhibits prostate cancer cell growth
in test tubes.
Safety considerations: Avoid if
you are taking anticoagulants
or antiplatelet medications; may
increase or decrease blood pressure,
and may increase blood sugar
levels in people with diabetes.
Insufficient evidence, although
some studies have suggested that
men with prostate cancer have
lower levels of melatonin than
other men.
A small study involving 14 men
with advanced prostate cancer who
were not responding to hormone
therapy alone found that taking
melatonin supplements in addition
to hormone therapy improved
response. PSA levels decreased by
more than half in eight men, and
nine lived longer than one year.
Pomegranate juice
Contains a variety of antioxidants
and flavonoids, which may inhibit
cancer growth.
Insufficient evidence regarding
impact on developing prostate
cancer.
A small 2006 study suggests that
men whose PSA is rising after
cancer treatment may be able
to slow the rate at which PSA
increases by drinking 8 ounces of
pomegranate juice every day. The
study involved 50 men who were
followed until their PSA doubled.
Investigators found that average
PSA doubling time slowed from an
average of 15 months before the
study began to an average of 54
months afterward.
Soy
Contains isoflavones, nutrients that
can inhibit cell growth and affect
hormones that may fuel the growth
of prostate cancer.
Safety considerations: May interact
with warfarin (Coumadin); check
with your doctor for advice.
Limited data exist, but suggest that
higher soy intake may reduce risk.
No evidence exists regarding
impact on progression.
Vitamin D
May inhibit growth of prostate
cancer cells.
Epidemiologic studies have
produced mixed results.
Limited evidence regarding impact
on progression.
Substance
progression
Calcium and dairy products
Good evidence that higher intake
increases risk. One study found
that men who consumed more
than 2,000 mg of calcium daily
were five times as likely to develop
metastatic prostate cancer as
those who consumed less than
500 mg of calcium per day. A large
epidemiologic study found that
intake of more than 1,500 mg of
calcium per day might increase the
risk of aggressive and fatal prostate
cancer, but not the risk of less
aggressive, localized cancer.
Studies suggest that high calcium
intake may increase the likelihood
of progression. One theory is
that calcium has different effects,
depending on the stage of cancer
development or progression.
Meat consumption
A number of studies have found
that increased consumption of meat,
especially red meat, increases risk of
developing prostate cancer, possibly
because of high fat content or the
way the meat is cooked.
Insufficient evidence regarding
Substances that may increase risk
13
Zinc
Because zinc contributes to many
bodily functions, including healthy
immune functioning and wound
healing, zinc supplements have
sometimes been touted as a
cure for various prostate diseases.
However, there is no evidence that
zinc supplements help—and in
prostate cancer, such supplements
may cause harm.
Limited evidence that zinc
supplements may increase risk. One
study found that men who took
100-mg zinc supplements daily
were more than twice as likely to
develop advanced prostate cancer
as men who did not take the
supplements.
No data are available regarding
Table 4. Complementary therapies for prostatitis
To learn more about complementary therapies for prostatitis, see “Assessing the evidence: Prostatitis,” page 5.
Substance that may work
14
Assessment
Quercetin
A bioflavonoid, a chemical that contributes to color in
plants; its antioxidant and anti-inflammatory effects
may explain how it works.
One small randomized controlled study has evaluated
quercetin for the treatment of chronic nonbacterial
prostatitis (chronic pelvic pain syndrome). The study
involved 30 men who took quercetin for a month.
Investigators reported in 1999 in Urology that 67%
of men taking quercetin reported improvement of
symptoms, compared with 20% of men taking placebo.
How to handle a relapse after treatment
for prostate cancer
Editor in Chief Marc B. Garnick, M.D., discusses what biochemical
recurrence means and what your options are
“Am I going to die?” This is the first question a patient usually asks me when a
follow-up blood test reveals that his prostate-specific antigen (PSA) level has
risen after he has already undergone treatment for prostate cancer (usually a
radical prostatectomy or radiation therapy). The fear is understandable: When
PSA levels rise to a certain threshold after prostate cancer treatment, the
patient has suffered what is known technically as a biochemical recurrence,
sometimes also referred to as a biochemical relapse or stage D1.5 disease.
Whatever term is used, it means that prostate cancer remains within the prostate after radiation therapy, that it survived outside the excised area after radical prostatectomy, or that it has reappeared in metastatic form in other tissues
and organs. In most cases the cancer remains at a microscopic level, and many
years will pass before any physical evidence of it is detectable on a clinical
exam or any abnormalities are seen on a bone scan or CT scan.
That’s usually of small comfort to the patient whose PSA has risen. It’s
emotionally traumatic to go through treatment for prostate cancer, thinking
it is cured, and then learn that it might have come back. For many men, it’s as
if they’re dealing with another diagnosis of cancer, except this time it’s much
worse because there is less likelihood of getting cured. A man’s confidence and
sense of safety may be shattered, especially because the popular misconception
is that when prostate cancer recurs, it is deadly.
Which brings me back to my patient’s question: “Am I going to die?”
The simple answer is yes, eventually—we all do—but you may not die from
prostate cancer. Of course, with prostate cancer, nothing is simple. This may be
one disease, but it can appear in multiple forms, so every diagnosis or recurrence requires individualized assessment and intervention. To start thinking
about the salient issues, see “Four key questions,” right.
In practical terms, biochemical recurrence means that you are now dealing
with a chronic disease, like diabetes, so that your clinical monitoring will have to
increase and you may need to choose or adjust treatment to meet new challenges.
Unfortunately, we don’t yet have sufficient research to provide clear guidance
about when a second therapy (referred to as salvage therapy) should be considered after biochemical recurrence, and which type of salvage therapy is most
effective in particular circumstances. (Salvage therapy is a terrible term, but I use
it in this article because it is the standard name for follow-up therapy.)
For those who have already suffered a biochemical recurrence after being
Four key questions
If your PSA rises after prostate
cancer treatment, answering four
key questions will help you and
your doctor determine next steps:
• What were your risk
characteristics, such as Gleason
score, PSA, and cancer stage,
at the time of diagnosis? (See
Table 5.)
• What type of treatment did you
have? That will help determine
your next treatment options.
• How long has it been since
you underwent initial therapy
for prostate cancer? This helps
indicate how aggressive followup treatment needs to be.
• How fast is your PSA rising,
as determined from several
evaluations?
15
treated for prostate cancer—or dread each follow-up blood test because it
might signal such a recurrence—this article explains what a rising PSA after
treatment really means and what your treatment options are.
Table 5. Predictors of biochemical recurrence at time of diagnosis
Although a number of clinical factors contribute to your risk of relapse after treatment
(see “Assessing your personal risk,” page 18), the parameters below provide a simpler
assessment of your chances of biochemical recurrence, based on your clinical profile at
the time of diagnosis. For more sophisticated estimates, based on specific risk factors,
see Figures 1 through 3, or consult “The Guide to Due Diligence in Early-Stage Prostate
Cancer,” a publication sent with the Winter issue of Perspectives.
Low risk (33% chance of biochemical
recurrence within five years)
Gleason score less than or equal to 6
and
PSA less than or equal to 10 ng/ml
and
Cancer stage T1c or T2a
Intermediate risk (50% chance of
biochemical recurrence within five years)
Gleason score of 7 (if 3+4)
and/or
PSA greater than 10 but no greater than 20 ng/ml
and/or
Cancer stage T2b
High risk (85% chance of biochemical
recurrence within five years)
Gleason score of 7 (if 4+3), or 8 or more
and/or
PSA greater than 20 ng/ml
and/or
Cancer stage T2c or more
Defining biochemical recurrence
As you are probably aware, both normal prostate cells and prostate cancer cells
manufacture PSA. That is why the PSA level should fall to undetectable levels
in men treated with radical prostatectomy, in which the prostate is removed,
but is not likely to drop to zero in men treated with radiation therapy, even
when treatment is successful. This is because after radiation therapy the prostate gland remains intact and can recover some function. This is also true if
you received hormone therapy as part of your radiation treatment: As you
recover, testosterone levels rise, and so does your PSA.
The real challenge is defining what constitutes a biochemical recurrence
after a particular type of therapy. There is no consensus on this issue, but the
working guidelines are summarized in Table 6.
Further muddying the water, it is not clear what PSA levels should be in
men who have undergone neoadjuvant hormone therapy in addition to radiation therapy. Hormone therapy suppresses levels of testosterone; once the
therapy is stopped, testosterone levels rise, and PSA generally increases
rapidly until the hormonal environment stabilizes.
Moreover, some men who have undergone external beam radiation
16
therapy or implantation of radioactive seeds (brachytherapy) experience a phenomenon known as PSA bounce, a temporary spike in PSA that does not necessarily indicate recurrence. Studies offer varying conclusions about how common
this phenomenon is, probably because they use different definitions of what
constitutes a “bounce.” (The latest thinking about how to differentiate the two will
be explored in a later issue of Perspectives.) Until more is known, if you have had
some form of radiation therapy for prostate cancer and experience a spike in your
PSA level, it is wise to ask your physician whether this could be a PSA bounce.
Table 6. Guidelines for determining biochemical recurrence
Initial therapy
PSA threshold
Comments
Radical prostatectomy
0.2 ng/ml on at least two
successive tests
Some physicians continue
to use a higher threshold of
0.4 ng/ml or greater
Radiation therapy (external
beam or brachytherapy)
Three successive
elevations in PSA
compared to nadir (low
point), regardless of actual
reading, according to
the American Society for
Therapeutic Radiology
and Oncology
Many oncologists use a
working definition that
biochemical recurrence
has occurred if PSA levels
are greater than 1–2 ng/ml
12 to 18 months following
initial treatment.
Ideally, post-treatment PSA
levels should be less than 0.5
ng/ml, but this is rare; levels
of 0.6–1.4 ng/ml may occur.
Neoadjuvant hormone
therapy and radiation therapy
Unknown
A common challenge
Rising PSA after initial treatment often comes as a shock to the person affected,
but it’s actually a common problem. Studies indicate that biochemical recurrence affects roughly 15%–30% of men initially thought to be curable with
localized treatment of prostate cancer. Certainly if you find yourself in this
situation, you are not alone.
For example, a study published in the Journal of Urology, which followed
3,478 men who underwent radical prostatectomy for prostate cancer, found
that 32% were likely to suffer a biochemical recurrence within 10 years. (The
study actually followed patients an average of a little more than five years, but
used actuarial tables to predict outcome at 10 years.) Another study, published
in the Journal of the American Medical Association, examined the outcomes
for 1,997 men who underwent radical prostatectomy and were followed for
an average of a little more than five years, and found that 15% experienced
biochemical recurrence in that time. (For further details about these studies,
see “Biochemical recurrence after surgery,” page 18.)
17
Biochemical recurrence
after surgery
Pound CR, Partin AW, Eisenberger MA, et
al. Natural History of Progression after PSA
Elevation Following Radical Prostatectomy.
Journal of the American Medical Association,
1999;281:1591–7. PMID: 10235151.
Roehl KA, Han M, Ramos CG, et al.
Cancer Progression and Survival Rates
Following Anatomical Radical Retropubic
Prostatectomy in 3,478 Consecutive Patients:
Long-Term Results. Journal of Urology,
2004;172:910–14. PMID: 15310996.
See page 44.
18
Other studies indicate that a similar (or perhaps slightly higher) percentage
of men treated with radiation therapy will experience a biochemical recurrence
(see “Biochemical recurrence after radiation therapy,” page 19). For example, a
study of 1,449 men with prostate cancer treated with brachytherapy, published
in the Journal of Urology, found that anywhere from 19% to 26% experienced
biochemical recurrence within 12 years, depending on the definition of recurrence. It should be noted that nearly half the men were also treated with either
neoadjuvant hormone therapy or a combination of brachytherapy and external
beam radiation therapy, which may have increased the success of treatment or
delayed recurrence. And a study comparing the outcomes of 393 men who
received different doses of external beam radiation therapy for prostate cancer,
published in the Journal of the American Medical Association, found that
19.6% of those who underwent high-dose radiation therapy experienced biochemical recurrence within five years, while 38.6% of those who underwent
conventional-dose radiation therapy did.
Assessing your personal risk
Several factors contribute to your risk profile. One important factor is whether
you have localized or more advanced disease at the time of biochemical recurrence. As indicated in Table 5, your pretreatment numbers such as Gleason
score and pathological cancer stage will provide some indication of whether
the recurrence is local or metastatic. Also important is how much the PSA
increased within a given time period (known as the PSA velocity) before
treatment, and how long it takes for PSA to double in value (known as PSA
doubling time) after treatment.
For example, two studies that looked at the relationship between PSA
velocity and post-treatment outcomes in men treated for early-stage prostate
cancer found that men with a PSA velocity of 2 ng/ml or less in the year before
diagnosis had a much better prognosis than those whose PSA velocity was
greater than 2 ng/ml per year (see “PSA velocity and prognosis,” page 20).
In a study of 1,095 men treated with surgery, published in the New England
Journal of Medicine, investigators found that men with a PSA velocity greater
than 2 ng/ml in the year preceding diagnosis were 50% more likely to experience biochemical recurrence than the men whose PSA velocity was less than
that. These men were also likely to experience biochemical recurrence faster
and faced a greater likelihood of dying from prostate cancer than the other
men. In the second study, involving 358 men treated with external beam radiation therapy, published in the Journal of the American Medical Association,
researchers found that men with a PSA velocity greater than 2 ng/ml in the
year preceding diagnosis were 80% more likely to experience biochemical
recurrence than the others, and less likely to survive (see Table 7). Similarly,
post-treatment PSA doubling time can also be used to assess the likelihood
that disease is local or metastatic and provide insight into prognosis.
Table 7. PSA velocity before diagnosis and estimated chances of survival
An analysis of PSA velocity in the year preceding diagnosis reveals that it can predict the
likelihood of survival seven years after external beam radiation therapy. (Similar findings
have been reported for an analysis of men who underwent radical prostatectomy.)
Overall risk profile
(based on PSA, Gleason
score, cancer stage)
When PSA velocity is less
than or equal to 2 ng/ml
per year
When PSA velocity is greater
than 2 ng/ml per year
Low risk
100%
81%
High risk
96%
76%
Biochemical recurrence
after radiation therapy
Potters L, Morgenstern C, Calugara E, et al.
12-Year Outcomes Following Permanent
Prostate Brachytherapy in Patients with
Clinically Localized Prostate Cancer. Journal
of Urology 2005;173:1562–6. PMID:
15821486.
Source: Journal of the American Medical Association, July 27, 2005.
When the post-treatment PSA level doubles in less than six months, for example, and certainly when it doubles in less than three months, the cancer has
most likely spread and therefore requires systemic treatment (see “Metastatic
disease: Hormone therapy,” page 24). Research has also shown that the length
of time it takes PSA to double can be used to estimate likelihood of whether
disease will become clinically evident (detected by symptoms and scans) following biochemical recurrence (see Table 8).
Zietman AL, DeSilvio ML, Slater JD, et
al. Comparison of Conventional-Dose vs
High-Dose Conformal Radiation Therapy in
Clinically Localized Adenocarcinoma of the
Prostate: A Randomized Controlled Trial.
Journal of the American Medical Association
2005;294:1233–9. PMID: 16160131.
See page 44.
Table 8. PSA doubling time and outcome five years after biochemical recurrence
A study involving 2,809 men who were treated with surgery and subsequently experienced
biochemical recurrence (defined as a PSA of 0.4 ng/ml or more) found a clear relationship
between PSA doubling time and eventual clinical outcomes.
PSA doubling time
Percentage of men without prostate cancer*
Less than 6 months
38%
6–11 months
46%
12 months–9 years, 11 months
62%
10 years or more
87%
* No clinical indication of local or systemic disease, based on digital rectal examination,
transrectal ultrasonography, biopsy, or bone scan.
Source: Mayo Clinical Proceedings, June 2001.
Of course, estimates of average likelihood of progression are simply that—
estimates—and may not indicate what is going on in your own case. So to
better determine whether your cancer recurrence is localized to the prostate
or has spread elsewhere, your doctor will not only look at your pretreatment
numbers, but also restage the disease by repeating some of the tests you had at
the time of your initial diagnosis. You will likely undergo a bone scan and an
abdominal pelvic CT scan. You may also undergo a ProstaScint scan, which
uses monoclonal antibodies tagged with a radioisotope to identify metastatic
19
prostate cancer in lymph nodes and other areas in the pelvis. It’s important to
note, however, that not all doctors recommend such tests because in most men
who experience rising PSA, these scans will usually not reveal any clinical
evidence of metastases.
PSA velocity and
prognosis
D’Amico AV, Chen MH, Roehl KA, Catalona
WJ. Preoperative PSA Velocity and the
Risk of Death from Prostate Cancer After
Radical Prostatectomy. New England Journal
of Medicine 2004;351:125–35. PMID:
15247353.
D’Amico AV, Renshaw AA, Sussman B, Chen
MH. Pretreatment PSA Velocity and Risk
of Death from Prostate Cancer Following
External Beam Radiation Therapy. Journal
of the American Medical Association
2005;294:440–7. PMID: 16046650.
See page 44.
20
Knowing whether and when to act
If your PSA indicates that biochemical recurrence has occurred—or if you are
tracking your PSA closely, to determine whether you may need to consider
treatment—you probably want to know what your options are. But as you
evaluate options, consider not only what to do, but whether and when to act.
Unfortunately, experts don’t agree about when salvage treatment for recurrent prostate cancer should begin, or which salvage treatments are best. Of
course, if you experience biochemical recurrence and the cancer appears aggressive—as indicated by your pretreatment risk profile (see Table 5) or a PSA
doubling time of less than six months (see “Assessing your personal risk,” page
18)—your physician is likely to recommend immediate treatment, probably
with hormone therapy, to delay metastases.
But many other men will find themselves in a gray area, with clinical
profiles and PSA doubling times that are not sufficient to trigger immediate
salvage therapy. If you are in this category, your physician may recommend
waiting to treat until your PSA rises to a particular level. That means you may
have more frequent PSA testing, which can be nerve-racking but is necessary
to detect progression earlier. (For more insight into what this feels like, see
“A couple’s story: Tracking PSA,” page 25.)
Although many men diagnosed with biochemical recurrence will want to
take immediate action to stop the cancer, going ahead with therapy for the sake
of simply doing something may cause more harm than good. The risks and complications of surgery or radiation, already high when delivered after an initial
diagnosis of prostate cancer, may become even greater when these therapies are
delivered as salvage after biochemical recurrence. Data are sparse on the side effects of salvage therapy, simply because not many studies have been done on the
topic, but I always advise patients in this situation to consider that any complications of the initial therapy may be increased if their abdominal and pelvic areas
are subjected to a second therapy. For example, some research indicates that the
likelihood of developing urinary incontinence after prostatectomy is greater
following salvage treatment (where it may affect 20%–60% of men) than when
it is the first mode of treatment (where it may affect 2%–15% of men).
It’s also wise to consider the impact of further treatment if you have other
diseases besides prostate cancer, such as diabetes, cardiovascular disease, or a
pulmonary disease such as emphysema. If you do, it is likely that you are on
medications for these disorders, and are already dealing with significant health
challenges and risks. Undergoing additional treatment for prostate cancer may
add to these risks, or may require that you readjust medications you are taking.
Options for men who had surgery
How long after treatment it took for the PSA to rise and how quickly it rose
provide important clues to whether it’s likely that your cancer is localized or
metastatic. Generally speaking, the prognosis is worse for men whose PSA
never becomes undetectable after surgery, or rises quickly a short time after
treatment. Prognosis is better for men whose PSA rises slowly and begins to
rise a long time after treatment. A few scenarios will help clarify what the
options are in each situation.
Some men learn right away that they have residual disease. The surgeon
sends any tissue excised during the operation to a pathologist for analysis. If
the pathologist finds positive margins—meaning that he found cancer cells at
the borders, or margins, of the excised tissue—this means that you may need to
undergo radiation treatment to eradicate the cells remaining in the prostate area.
Figure 1. Preoperative
PSA level and freedom
from relapse
Percentage of men expected to avoid
cancer progression in 10 years
100
90
80
91%
78%
74%
70
60
49%
50
40
30
20
10
0
<2.6 2.6–4.0 4.1–10 >10
ng/ml ng/ml ng/ml ng/ml
Preoperative PSA levels
Source: Journal of Urology, 2004
Figure 2. Gleason score
and freedom from
metastases
100
Percentage of men free of metastases
in 10 years
Finally, remember that you have time to make an informed decision about
whether and when to undergo additional treatment for prostate cancer following
biochemical recurrence. The evidence shows that you can expect to live for many
more years. For example, the Journal of the American Medical Association study
cited earlier, which reported that 15% of men experienced biochemical recurrence in a little over five years, also analyzed what happened to the men afterward. The authors found that it took an average of eight years for the cancer to
metastasize to the bones, and the men survived another five years after that—
for a total of 13 years, on average, after biochemical recurrence.
Remember that average survival times are based on studies of men treated
in the past, and sometimes as long as 10 or 20 years ago. What’s more, some of
these studies (including the Journal of the American Medical Association study
cited above) included men who did not undergo further treatment after biochemical recurrence occurred. It’s likely that these men would have survived
for a longer time if they had received additional treatment after biochemical
recurrence was detected (although longer survival would come at the cost of
treatment side effects). For these reasons, the “average” chances may be much
better for a man treated today.
And such averages can never predict what will happen in your particular
case. That’s why, when I talk with patients about studies like this one, I encourage them to make decisions based on their own risk profile. As shown in Figures 1 through 3, your particular risk will vary, depending on factors such as
PSA level at diagnosis, PSA doubling time, and Gleason score.
Finally, when it comes to evaluating your options, much will depend on
whether you were treated initially with surgery or radiation therapy, with or
without hormone therapy.
90
80
70
60
40
30
20%
20
10
0
55%
50
5–7
8–10
Gleason score
Source: Journal of the American Medical
Association, 1999
Scenario 1. Sometimes the PSA level never becomes undetectable after a
prostatectomy. This situation, which is fortunately rare but among the most
challenging to treat, means either that some cancer cells remained in the pros-
21
tatic fossa (tissue left behind during surgery in the area once occupied by the
prostate gland), or—more likely—that micrometastases had already spread
beyond the prostate. A man in this situation may need additional therapy right
away. The options offered may be radiation or hormone therapy, or both, or an
investigational therapy.
Figure 3. PSA doubling
time and freedom from
metastases
Percentage of men free of metastases
in 10 years
100
90
80
70
60
50
40
30
26%
20
10
0
53%
≥10 months <10 months
PSA doubling time
Source: Journal of the American Medical
Association, 1999
Scenario 2. Sometimes the PSA falls to undetectable levels for several months
following radical prostatectomy, and then begins to creep up. Typically, a man
in this situation learns during one of his follow-up tests that he has experienced a biochemical recurrence. If the PSA level rises within the first year after
surgery, it usually indicates metastatic disease. The treatment option most
often offered is hormone therapy (either intermittent or continuous).
Scenario 3. The PSA does not begin to rise until a year or more after surgery.
This is more likely to indicate localized disease, although it is possible that
the disease has spread. Your treatment options depend on the PSA doubling
time—how quickly PSA is increasing. If your PSA doubles in less than six
months, and certainly less than three months, your doctor may recommend
treating the area again, but this time with radiation or hormone therapy,
in order to eradicate the disease.
Scenario 4. The PSA rises a year or more after surgery, but the doubling time is
slow (a year or longer). This is probably the best scenario of all, as it indicates
that the cancer may be localized and not aggressive. In this situation, you may
opt for active surveillance—monitoring PSA and periodically having other
tests, but not necessarily choosing an active intervention right away.
Salvage options after radical prostatectomy
Most men who experience a biochemical recurrence after prostatectomy and
decide to undergo treatment have three options. The best strategy depends on
your risk profile and comfort with side effects.
Radiation therapy
Many men opt to undergo salvage radiation therapy. Although few studies
have been done to evaluate long-term results, many men do respond to salvage
treatment. One study involving 368 men who had initially undergone radical
prostatectomy, for example, found that five years after undergoing salvage
radiation therapy, 46% remained free of biochemical recurrence, and 92%
were still alive; at eight years, 35% remained free of biochemical recurrence,
and 80% were still alive. Other studies have reported that salvage radiation
therapy is likely to be most effective in men whose Gleason score, PSA level
and doubling time, and other clinical features indicate less aggressive disease
(see “For more information: Salvage radiation therapy,” page 23).
Side effects. Be aware that radiation therapy delivered after a prostatectomy
markedly increases the likelihood of impotence and may increase the likelihood
22
of incontinence. If you are already incontinent after surgery, then having radiation therapy is likely to make the problem permanent. For that reason, most men
who become incontinent after surgery will wait until they regain control over
their bladder or rectum before undergoing postoperative radiation therapy.
Radiation with hormone therapy
Another option is to undergo hormone treatment while undergoing salvage radiation therapy, because this may increase the effectiveness of radiation therapy.
Hormone therapy
If the PSA doubling time is less than six months, indicating that the cancer is
aggressive, radiation therapy may not be adequate, as it is likely the cancer has
already spread. In that case, a better option is a full course of hormone therapy,
which can delay the time of onset to bone metastasis.
But other considerations also come into play. If you are sexually active and
want to remain so, hormone therapy may not be the right option for you. Or
you can opt for erectile-sparing hormone therapy, which involves a single agent
like bicalutamide (Casodex), or bicalutamide and finasteride (Proscar) (see “For
more information: Erectile-sparing hormone therapy,” page 24). Another option
is to go on intermittent hormone therapy, in effect taking occasional “holidays”
from treatment. This allows men to recover some quality of life while at the same
time reducing levels of testosterone, which fuels the cancer. (These options will
be discussed in greater detail in the next issue of Perspectives.)
If you are elderly (defined as having less than 10 years of life expectancy),
you may not want the full spectrum of hormone therapy because it causes
other complications.
For more information:
Salvage radiation therapy
Buskirk SJ, Pisansky TM, Schild SE, et al.
Salvage Radiotherapy for Isolated Prostate
Specific Antigen Increase after Radical
Prostatectomy: Evaluation of Prognostic
Factors and Creation of Prognostic Scoring
System. Journal of Urology 2006;176:
985–90. PMID: 16890677.
Sengupta S, Christensen CM, Zincke H, et
al. Detectable Prostate Specific Antigen
Between 60 and 120 Days Following Radical
Prostatectomy for Prostate Cancer: Natural
History and Prognostic Significance.
Journal of Urology 2006;176:559–63.
PMID: 16813889.
Stephenson AJ, Shariat SF, Zelefsky MJ,
et al. Salvage Radiotherapy for Recurrent
Prostate Cancer after Radical Prostatectomy.
Journal of the American Medical Association
2004;291:1325–32. PMID: 15026399.
See page 44.
Salvage options after radiation therapy
If your initial cancer treatment was radiation therapy and you experience a
biochemical recurrence, the salvage treatment you choose depends on whether
you received external beam radiation therapy or brachytherapy, as well as
whether you also received hormone therapy.
Salvage prostatectomy
When one of my patients experiences biochemical recurrence following radiation therapy, the first question I expect to hear is, “Can we just go in and take
it out?” Salvage prostatectomy is a possibility for some men, but it is not used
often, simply because it’s such a difficult operation. Radiation therapy causes
scar formation and the development of fibrous tissue in the treated area, so
that a surgeon may be unable to distinguish among different types of tissue.
It may be difficult, for example, to distinguish the specific boundaries of the
rectum and the bladder because of prior radiation scarring. Some highly
skilled surgeons can perform a salvage prostatectomy, but the larger consideration is whether it is worth doing at all.
23
Erectile-sparing hormone
therapy
Boccardo F, Rubagotti A, Barichello M, et al.
Bicalutamide Monotherapy Versus Flutamide
Plus Goserelin in Prostate Cancer Patients.
Journal of Clinical Oncology 1999;17:
2027–38. PMID: 10561254.
One could make a strong argument that in most cases, rising PSA after
radiation therapy indicates systemic disease, and any type of local therapy—
even salvage prostatectomy—is not going to solve the larger problem of cancer
cells that have metastasized elsewhere. For those cells, you need hormone
therapy (see “Metastatic disease: Hormone therapy,” below).
Salvage radiation therapy
In certain unusual circumstances, if recurrent cancer is found only in a limited
part of the prostate gland, it may be possible to place radioactive seeds in the
area to eradicate the cancer. The techniques for performing this are still under
investigation, and long-term data on effectiveness are not yet available. Be
aware that it is not known whether this additional radiation will increase the
risk of other types of cancers.
See page 44.
Cryotherapy
Another option, also appropriate only when a localized area of cancer is found,
is cryotherapy. This freezes the prostate gland to kill any remaining cancer cells.
This highly specialized treatment is not practiced widely, and substantial complications have been reported.
Metastatic disease: Hormone therapy
If your doctor determines that you have a metastatic rather than a localized
recurrence, hormone therapy is your best option—and it is appropriate
whether you initially underwent a radical prostatectomy or radiation therapy.
Before a man who has experienced biochemical recurrence decides to have
hormone therapy, however, the first question is whether he has had it before.
Some men who were at intermediate or high risk of relapse (see Table 5) and
decided to have radiation therapy initially probably also had hormone therapy
beforehand because this increases the chances that initial therapy will succeed.
If the patient had a hard time of it, in terms of side effects, he may not want
to consider hormone therapy again.
Hormone therapy works by reducing testosterone levels. Because testos
terone fuels the growth and development of prostate cancer, reducing levels of
this fuel helps stop cancer from progressing—or at least slows the rate of progression. This topic will be explored in greater detail in the summer issue
of Perspectives.
Hope for the future
Experiencing biochemical recurrence can be emotionally devastating—there’s
no doubt about it. But research continues about how best to treat men who
experience a relapse following initial therapy for prostate cancer, and it is likely
that new therapies will emerge in the coming years. In the meantime, stay informed about your treatment options and work with your doctor to determine
whether it’s time to consider some type of salvage therapy.
24
A couple’s story: Tracking PSA
Joe and Patricia Shields* have been married nearly 25 years. Mr. Shields received a diagnosis of prostate
cancer in 2001, at age 57, and underwent a radical prostatectomy. In the summer of 2004, a routine
blood test revealed that Mr. Shields’ PSA had doubled, from 0.02 ng/ml to 0.04 ng/ml. It held steady
for the next few months, then jumped to 0.1 ng/ml, where it’s remained for more than 15 months. Mr.
Shields has not experienced a biochemical recurrence (see Table 6). Even so, the Shields are concerned
about the fact that the PSA level has increased at all, and find themselves living in a gray area, where
medical science can offer little guidance.
Joe Shields: I mostly put it out of my mind. The day I go in to have the test done is hard. The day I
need to call in for my results is hard. But otherwise I try not to worry about it. It’s not that I’m cavalier
about risk. But I could spend the next 10 years worrying about dying of cancer, and then die in a car crash.
Patricia Shields: I think there’s a gender difference in how we cope. Joe says, “This is the hand I
was dealt, I can’t worry about it, I just need to get up and get on with life.” Meanwhile, I have a female,
“protect the nest” outlook. There isn’t a day that goes by when I don’t think about it.
In some ways, learning Joe’s PSA increased was much worse than the initial diagnosis. The first time
around, you’re in shock. Then you think it’s behind you. But now it feels like something hanging over us
all the time.
Joe Shields: One aspect of this that has been difficult is the ambiguity. When I was evaluating my
options the first time around, there were guidelines. I felt like I could make an intelligent choice. But with
PSA elevation after surgery, there are no clear treatment recommendations.
* Editor’s Note: Names and some biographical details have been changed to protect this couple’s privacy.
All medical details are as reported.
25
A patient’s story: Overcoming
incontinence
Christopher Miller* is a real estate agent who is married and has two sons.
About five years ago, at age 56, Mr. Miller was diagnosed with prostate cancer.
After a great deal of research and consultations with five doctors, Mr. Miller
decided to have a radical prostatectomy.
Although he considers the operation a success, in that it has apparently
eradicated the cancer, Mr. Miller struggled for almost two years to overcome
persistent urinary incontinence. For much of that time, he felt ill-served by the
medical community. The story of how he eventually overcame this problem
may be helpful to other men in the same situation.
Can you share with our readers what was going through your mind when you
learned you had prostate cancer?
Like anyone else, I was surprised. You never think it’s going to happen to you.
The biggest fear, of course, is that it might be life-threatening. Even though I
knew this is generally a disease that takes a long time to grow, I still wondered
how much longer I might have to live. So I thought of things like: Is my family
provided for? Are my financial affairs in order? Will my children be secure?
Will I ever meet my grandchildren?
Of course, I was very concerned about my wife. We’d been married 32 years
at that point, and I worried about what impact this would have on her. She’s a
very strong and good person, and she remained at my side every moment of
the time. And that support proved to be invaluable.
How many physicians did you see before making a treatment decision?
As I recall, I saw two oncologists and three surgeons. They were all the best
doctors, all highly recommended.
* Editor’s note:The name
of this patient and certain
biographical details have
been changed to preserve
his privacy. All medical
details are as he reported
them.
26
Why did you decide on a radical prostatectomy?
We had a meeting with a radiation oncologist at a major teaching hospital.
He looked at my medical history, then he looked me in the eye, and he said,
“I know I can cure you, but the research is not on my side. The data more strongly
support your having surgery.” He said this in front of a room full of doctors.
Here was a man who was a radiation oncologist, who was saying, “Maybe you
should have surgery.” So even though I had talked to other people, I think that was
really the convincing moment. My wife and I were looking for a cure, and all of the
information we were getting was that, given my set of circumstances, surgery was
best. So then it was a question of who was going to perform the surgery.
Did anyone mention active surveillance as an option?
They did, but they frowned on it. Of course, this was four or five years ago.
And all the information I was getting was, “Get this thing out of you.” Another
factor was that I was young enough that people were saying, “Look, you’ve got
a long life to live. If you were in your 70s, it might be a different story.”
Did the doctors advise you about possible complications from surgery?
They all explained that I might develop impotence or incontinence afterward. One
reason that I finally chose the surgeon I did was because the complication rates he
quoted were lower than the others’. He really believed that there was less than a 1%
chance that I’d have an incontinence issue, and a 30% chance of impotence.
Editor’s note: See Table 9 for
a more accurate assessment
of the risks of complications.
And was that a deciding factor in your selection?
Absolutely. I mean, here were all the big guns in town, and his numbers
seemed like the best. I also asked around. And the feedback was, “He’s got great
hands.” We knew that his bedside manner left a lot to be desired, but I thought,
“Who needs bedside manner? Let’s just get the best person, with the best
hands, and let’s get it done.” And that’s how we selected him.
Table 9. Impotence and incontinence
The reported statistics on the likelihood of developing impotence or incontinence after
prostate cancer treatment vary widely, as shown by the ranges below.
Procedure
Percentage of men who
may develop impotence
Percentage of men who
may develop incontinence
Radical prostatectomy
30%–70%
2%–15%
External beam radiation
therapy
30%–70%
1%–2%
Brachytherapy
30%–50%
2%
How did the operation go? And when did it become apparent that you might take
longer to recover than you had been led to believe?
The operation went fine. I went back to work very quickly, and in most respects I
felt fine. I was incontinent immediately after surgery, but I was led to believe that
the problem would straighten itself out within a few weeks or months. But it didn’t.
Did you share your concerns about incontinence with your surgeon?
I did, during follow-up visits after the surgery. I probably visited him three to
four times during the first six months after surgery. He told me the problem
would get better, and for the first month or two, I believed that. But as time
went on, nothing was getting any better.
And he didn’t seem to care. In a typical visit, I waited a half hour or an hour
to see him for literally five minutes, and then he moved on to the next person.
So I finally gave up on him.
27
Kegel exercises
The strength and proper action
of your pelvic floor muscles
are important in maintaining
continence. Here’s how to do basic
pelvic muscle exercises, named for
Arnold Kegel, the physician who
first developed them:
1.Pretend you are trying to avoid
passing gas. You will feel a
contraction more in the back
than the front, like you are
pulling the anal area in.
2.Practice both short contractions
and releases and longer ones
(gradually increasing the
strength of the contraction and
holding it at your maximum for
up to 10 seconds).
3.Repeat multiple times, several
times a day.
Could you tell our readers more about the problems you were experiencing?
I had no problem at night, and I think for most people that’s the case. But
when I got up, I was going through anywhere from four to five pads a day. I
used a high-absorbency pad that tied around my hips on both sides, and I’d
change it throughout the day. I tried doing Kegel exercises, to control the flow,
but nothing worked. I was in trouble. I’m an active person. It was embarrassing, and it was the last thing I wanted to deal with. (Editor’s note: For more
information, see “Kegel exercises,” left.)
Was impotence an issue?
Forget about sex! That was the last thing on my mind during this period.
I knew I had to deal with the incontinence issue first.
So what did you do?
After about a year of waiting for this to get better, I consulted with another surgeon. He recommended a sling procedure. I decided I would try this to see if it
would make a difference. That was my second mistake. It was a very difficult
operation, more difficult than the radical prostatectomy.
Did the second operation alleviate your incontinence?
No, everything was basically the same. That was a disappointment. After I told
a friend about all my mishaps, he suggested I ask about having an artifical
sphincter inserted. He’d heard it was very successful. I did consult one surgeon
about it, but he hadn’t done many of these operations.
So I was at a dinner, about a year and a half after I first developed incontinence, and I was talking to a woman whose husband was a prostate surgeon
who had passed away. And I told her about my dilemma. She gave me the
name and number of one of her husband’s colleagues, and told me to use her
name when I called him. So I did.
When I met with him, he explained the artificial sphincter procedure to me
and my wife. I was immediately comfortable with him. He performed the operation. And I must say it has changed my whole life for the better. I still wear a very
tiny pad, just in case there’s a leak when I bend a certain way, or lift something, just
for protection more than anything else. And I’m very happy with it.
Could you explain exactly how this works?
The surgeon inserts a small pump in the scrotum, which is attached to a
sphincter cuff and a small balloon located near the belly button (see Figure 4).
When I feel the need to urinate, I go to the toilet, and I squeeze the pump in
my scrotum with one hand. By pressing the pump, I deflate this cuff, and the
pressure comes off the urethra. So at that point I’m able to urinate. Then probably 35 to 40 seconds later, the balloon fills back up. By then I’ve finished
urinating, or if I haven’t, I do it again.
28
Table 10. Surgical options for incontinence after radical prostatectomy
If you’ve experienced persistent and bothersome urinary incontinence following radical prostatectomy, even after 6 to 12
months of trying conservative measures like Kegel exercises, it may be time to consider surgery. Current options and success
rates are summarized below, based on a recent review article in Current Opinion in Urology (see “For more information: Urinary
incontinence,” page 31). Be aware that many of the studies cited involved small numbers of men.
Type of procedure
Success rates
Comments
Artificial sphincter
The surgeon places a fluid-filled
cuff around the urethra and a small
pump in the scrotum. The cuff
prevents urine from escaping until a
man squeezes the pump, releasing
pressure on the urethra and
allowing urine to flow (see Figure 4).
• In a study involving 47 men who were
followed for an average of three years,
87% reported regaining continence.
• In the same study, 95.7% of men said
they were satisfied with the operation.
• 23.4% of men developed some type of
complication, most often mechanical
failure or infection.
• 25.5% of men required some type of
follow-up surgery to adjust the device
within five years.
• Considered the gold standard of
therapy for severe urinary incontinence
following prostate cancer surgery.
• It may take 4 to 6 weeks to heal from
surgery, during which the pump
cannot be activated.
• Possible complications include infection,
erosion of tissue around the implants,
and malfunctioning of the device.
• Additional adjustment surgeries may be
necessary.
Bulking agents
A bulking agent is injected into the
tissue around the urethra, so that it’s
narrower and closes more readily.
• 17% of men became completely
continent in one long-term study, and
remained so for an average of about 11
months.
• Other patients in this study enjoyed
some degree of relief for an average of
six months.
• In another small study, evaluating
injection of carbon microspheres in
eight men, none of them became
completely continent.
• Collagen is most often used as a
bulking agent.
• This procedure can be performed on an
outpatient basis.
• After the injection, you may experience
irritation for a day or two whenever you
urinate.
• Success may diminish over time as
bulking agents (especially collagen) are
absorbed into the body.
• This may be best viewed as a temporary
measure or as an option for men who
cannot undergo invasive surgery.
Bulbourethral sling surgery
The surgeon makes an incision
between the scrotum and the
rectum and installs a supportive
sling under and around the urethra,
anchoring it to each side of the
pelvic bone. By placing pressure on
the urethra, the sling helps retain
urine until the bladder fills.
• In one study involving 71 men who
responded to questionnaires following
surgery, 36% regained continence
(as indicated by not having to use an
absorbent pad), while 68% used one or
two pads a day.
• Another study, involving 36 men
followed for a year, compared two types
of slings. It found that 56% of men
who received a pigskin sling regained
continence, while 87% of those who
received a silicone-mesh sling did.
• A third study, involving a Dacron or
polypropylene-mesh sling, involved 30
men and found that 66.7% regained
continence.
• Several types of sling procedures exist,
but this remains the most common.
• Slings are made of different types of
materials, such as collagen or silicone
mesh.
• Surgery is challenging and may involve
transplantation of the patient’s own
tissue to support the sling, adding
to postsurgical discomfort and
complications.
• Complications can include infection,
discomfort, and a shift from
incontinence to difficulty urinating.
Source: Current Opinion in Urology, March 2006.
29
Figure 4. Artificial sphincter
A
Pressure regulation balloon
Bladder
Inflatable cuff
B
Scrotum
Pump
An artificial sphincter is a surgically implanted device with three major components. An inflatable
cuff surrounds the urethra; when inflated, it prevents urine from leaking out of the bladder (see A). A
pressure regulation balloon implanted in the lower abdomen ensures that the cuff remains inflated until
it is time to urinate. At that point, a man squeezes a pump located in the scrotum, which deflates the
cuff enough so that urine can flow (see B). The cuff then reinflates on its own.
Are you aware of this material in your scrotum when you’re not using it?
Not unless I feel it with my hand. I can walk around, exercise, do everything
I normally do, and I don’t feel it. One challenge is riding a bike, because you
need a flat seat so that your weight is better distributed, rather than concentrated in the middle. So I have to get another seat for my bike. But I can go out
now and play football with my boys. I can do anything I want to do.
What was the recovery from this operation like, compared to the others you had?
It was probably a quarter as hard as the other two. It was nothing. I went in.
I think I stayed overnight. And then I was back at work in a day or two.
30
What about potency? We haven’t talked about that yet.
Once I dealt with the incontinence issue, when I felt that I was 98% back to
normal, then I could really focus on the sexual part. I couldn’t up to that point.
I’m not totally impotent. There are times when I can have intercourse without the aid of any chemical. But, I must say, it does help.
You’ve tried an erectile dysfunction drug?
Yes, but I’m not a “druggie” kind of person. If we want to go that route, which
is very helpful in terms of creating more firmness, it means taking a pill and
planning ahead. Sex is no longer spur-of-the-moment.
For me, the biggest change is that dealing with all of this enabled my wife and
me to readdress our sexual life. And I think, as a man, you sort of think it’s all
about being hard and being up, and I think what has happened is that I’m now
able to focus more on the other person, which I might not have been doing as well
prior to this operation. It’s made our sexual relationship deeper and stronger.
Because it gave you an opportunity to talk about things?
Yes. And sometimes the way we’ve been doing things is not necessarily the best
way. So it’s given me time to reflect about how to make it different and be more
thoughtful, and I think that plays out well for my wife.
Knowing what you do now, what advice can you provide to people who are going
to be reading this story?
I think you have to find a doctor who will give you the right information. The hurt
for me was not necessarily that I developed incontinence. I just wished my original
surgeon had been more honest with me. And I’d advise other men that they really
need to question the numbers about side effects. And if they know going into surgery that the likelihood of complications is high, then they’re prepared.
What I can’t understand, because surgeons have been performing prostatectomies for years, is why the information about incontinence and impotence
isn’t more accurate. There is information that is available, but it’s not real. It’s a
shame. It’s not right.
Urinary incontinence
Begg CB, Riedel ER, Bach PB, et al. Variations
in Morbidity after Radical Prostatectomy.
New England Journal of Medicine
2002;346:1138–44. PMID: 11948274.
Klingler HC, Marberger M. Incontinence after
Radical Prostatectomy: Surgical Treatment
Options. Current Opinion in Urology
2006;16:60–4. PMID: 16479205.
Potosky AL, David WW, Hoffman RM, et al.
Five-Year Outcomes after Prostatectomy
or Radiotherapy for Prostate Cancer: The
Prostate Cancer Outcomes Study. Journal of
the National Cancer Institute 2004;96:
1358–67. PMID: 15367568.
Stanford JL, Feng Z, Hamilton AS, et al.
Urinary and Sexual Function after Radical
Prostatectomy for Clinically Localized
Prostate Cancer: The Prostate Cancer
Outcomes Study. Journal of the American
Medical Association 2000;283:354–60.
PMID: 10647798.
Talcott JA, Rieker P, Clark JA, et al. PatientReported Symptoms after Primary Therapy
for Early Prostate Cancer: Results of a
Prospective Cohort Study. Journal of Clinical
Oncology 1998;16:275–83. PMID: 9440753.
See page 44.
Of course, in a typical office visit, sometimes the doctor can’t address all these issues.
But my surgeon didn’t even ask. And where do I end up on his statistical map?
I think urologists need to start dealing with this issue.
31
Urinary incontinence: Common and persistent
Although most reported statistics on the incidence of urinary incontinence following
radical prostatectomy for prostate cancer indicate that the problem affects 2%–15% of men
(see Table 9), this is likely understating the problem. Men are often reluctant to mention
the problem to their doctors or, as in Mr. Miller’s case, find that their doctors don’t ask
about it. Another problem is that relatively few studies have examined how long urinary
incontinence persists and what proportion of men affected seek out interventions, as Mr. Miller did.
One study that sent periodic surveys to 279 patients to proactively seek their responses
both before and after treatment for prostate cancer, which was published in the Journal of
Clinical Oncology, found that at three months after surgery, 58% of men reported wearing
an absorbent pad in the previous week, and at 12 months after surgery, 35% reported
using a pad in the previous week. The investigators also asked about urinary leakage,
assuming some men were using absorbent pads as a protective measure but might not
be leaking urine on a regular basis. They found that at three months after surgery, 24% of
men reported leaking urine “a lot” in the previous week, and at 12 months, 11% were still
experiencing the problem. These results confirmed earlier studies, done on a retrospective
basis (asking men to recall a problem, rather than report it as it occurred), which found that
31% to 40% of men either wore protective pads or experienced urinary leakage.
Larger studies, reported more recently, indicate that the problem of urinary incontinence
often persists after surgery for prostate cancer. For example, an analysis of the outcomes of
1,291 men who underwent radical prostatectomy, published in the Journal of the American
Medical Association, found that 8.4% remained incontinent 18 months or longer after
surgery. Another study of 901 men treated with surgery, published in the Journal of the
National Cancer Institute, found that 14% to 16% were incontinent five years after treatment.
Finally, an analysis of the Medicare claims records of 11,522 men who underwent radical
prostatectomy, published in the New England Journal of Medicine, found that, depending on
age, anywhere from 18% to 24% of men continued to experience incontinence more than
one year after surgery, and 7% to 9% sought out some type of corrective procedure, such as
the placement of an artificial sphincter.
The flip side is that the majority of men who undergo treatment for prostate cancer
regain continence. And even men who become incontinent are willing to accept that
consequence as they weigh all the risks and benefits of cancer treatment. To read these
studies yourself, see “For more information: Urinary incontinence,” page 31.
32
New options for treating erectile
dysfunction
Penile rehabilitation after treatment for prostate cancer
Studies indicate that anywhere from 30% to 70% of men who undergo radical prostatectomy or external beam radiation therapy, and 30% to 50% of men
who opt for brachytherapy, will develop impotence after treatment. Recent insights into why this happens have led to a whole new approach in treating men
who are interested in preserving their sexual function. The new therapies are
often referred to collectively as penile rehabilitation, a concept first introduced
by European physicians in 1997. Since then, penile rehabilitation has gradually
evolved and is now being offered at a number of major teaching hospitals; it
is less likely to be offered in the community setting. Although exact regimens
vary, penile rehabilitation typically consists of oral or injected medications,
alone or in combination with other interventions, to restore and preserve erectile function before any long-term damage occurs.
But this therapy remains controversial. Although preliminary results look
promising, only a handful of reliable studies evaluating various types of penile
rehabilitation have been published—and these have used different types of
interventions, for different periods, so it is difficult to compare one method
with another. Moreover, no consensus yet exists about which approach is best
for a particular patient. Even so, penile rehabilitation may be something worth
asking your doctor about if you have just been diagnosed with prostate cancer
or are currently undergoing treatment. This article briefly reviews options in
penile rehabilitation and the limited scientific evidence.
New insights into erectile dysfunction
When erectile function becomes impaired following radical prostatectomy,
the problem has traditionally been attributed to nerve damage. The nerves that
trigger erections may become damaged during surgery (even during so-called
nerve-sparing surgery), leading to a problem known as neuropraxia—a temporary loss of function that theoretically should recover in time. The problem
is that it can take as long as two years for the nerves to recover sufficiently to
enable a man to have a spontaneous erection, and by then other damage may
have occurred.
Recent research suggests that when the penis is flaccid for long periods of
time, and therefore deprived of a lot of oxygen-rich blood, the low oxygen level
causes some muscle cells in the columns of erectile tissue (corpora cavernosa)
to lose their flexibility and gradually change into something akin to scar tissue.
This scar tissue, moreover, seems to interfere with the penis’s ability to expand
33
when it’s filled with blood. In fact, imaging studies indicate that blood may
drain away from the penis rather than fill it.
Less research has been done about impotence after radiation therapy, but it
appears that the underlying cascade of damaging events is similar to what occurs
after radical prostatectomy. Radiation damages the lining of the small blood
vessels, but this damage may take months or even years to manifest itself.
What all this means is that the traditional advice given to men—essentially
to wait for erectile function to return on its own—may not be adequate. Simply
put, erections seem to work on a use-it-or-lose-it basis. To prevent the secondary damage that may occur if the penis remains flaccid for a prolonged period,
researchers now think that a better approach is to intervene soon after treatment
to restore erectile function. (For more information about the studies mentioned
below, see “For more information: Penile rehabilitation,” page 36.)
Options after radical prostatectomy
Preliminary studies indicate that penile rehabilitation for men who undergo
radical prostatectomy is most effective when it begins soon after surgery and
involves a combination of therapies.
A study published in 2005 in the Journal of Sexual Medicine, for example,
reported the results of 132 men who were followed for 18 months after radical
prostatectomy. A total of 58 men enrolled in a penile rehabilitation program
within six months of surgery and took sildenafil (Viagra) or penile injections
(see Figure 5) to achieve erections three times a week. When investigators followed up 18 months later, 52% of the men in the penile rehabilitation group
said they could have spontaneous erections firm enough for intercourse, compared with 19% of the men who did not seek intervention. A larger proportion
of men who underwent penile rehabilitation also said they responded to sildenafil when they needed to take it: 64% of the rehabilitation group responded
versus 24% of the untreated group.
Figure 5. Injection therapy
Using a small needle (about half an inch long,
the same size as those used to inject insulin), a
man can inject one or more prescription drugs
into the side of the penis. The injected drugs
all work by relaxing the smooth muscle tissue
of the penis and allowing blood to flow into
the erectile tissue.
34
Figure 6. Vacuum device
This technique creates an erection by way
of a vacuum pump. A man lubricates his
penis and puts it into an airtight plastic
cylinder attached to a hand-held pump.
Air is pumped out of the cylinder to
create a vacuum, which increases blood
flow to the penis and causes an erection.
An elastic band placed at the base of the
penis maintains the erection.
Although the study was not randomized—and thus its results could be
influenced by patient self-selection or investigator bias—it confirmed the results
of an earlier small study conducted by the European team that first pioneered
the concept of penile rehabilitation. In 1997, researchers from Italy reported in
the Journal of Urology that they had followed 30 men who underwent nervesparing radical prostatectomy, who were then randomized either to an observation group or to one that received penile injections three times a week,
starting within a month after surgery. When investigators assessed the men at
a six-month follow-up exam, they found that 67% of those who completed the
entire schedule of injections reported spontaneous erections firm enough for
intercourse, compared with 20% of men who did not receive injections. Imaging
studies with ultrasound also indicated that the men who did not receive penile
therapy had developed nerve, tissue, and vascular damage that may have contributed to their higher rates of erectile dysfunction.
Although both studies were small, they provide evidence that early intervention to restore erectile function may be important. Exactly when treatment
should begin, though, is still an open question. One small study has looked
at various intervention points. As reported in the Journal of Urology in 2003,
investigators enrolled 73 men who underwent radical prostatectomy and randomly assigned them to receive injections at various times (within a month,
2–3 months, 4–6 months, or 7–12 months) after surgery. A total of 36 men
received injections within the first three months, while 37 received injections
between months 4 and 12. When the men were examined 5, 10, and 20 minutes after receiving the injection, the investigators found that 70% of the men
who received an injection within the first three months after surgery could
achieve erections firm enough for intercourse, compared with 40% of men
receiving an injection after three months.
The results of this study are sometimes used to support the opinion that
penile rehabilitation is most effective for men following radical prostatectomy
if it begins within three months of surgery. However, it’s important to point
35
Penile rehabilitation
Gontero P, Fontana F, Bagnasacco A, et al.
Is There an Optimal Time for Intracavernous
Prostaglandin E1 Rehabilitation Following
Nonnerve Sparing Radical Prostatectomy?
PMID: 12771740.
Montorsi F, Guazzoni G, Strambi LF, et al.
Recovery of Spontaneous Erectile Function
after Nerve-Sparing Radical Retropubic
Prostatectomy with and without Early
Intracavernous Injections of Alprostadil.
PMID: 9302132.
Mulhall J, Land S, Parker M, et al. The Use of
an Erectogenic Pharmacotherapy Regimen
Following Radical Prostatectomy Improves
Recovery of Spontaneous Erectile Function.
Journal of Sexual Medicine 2005;2:532–40.
PMID: 16422848.
Ohebshalom M, Parker M, Guhring P,
Mulhall JP. The Efficacy of Sildenafil Citrate
Following Radiation Therapy for Prostate
Cancer: Temporal Considerations. Journal
of Urology 2005;174:258–62. PMID:
15947650.
Raina R, Agarwal A, Allamaneni SS, et al.
Sildenafil Citrate and Vacuum Constriction
Device Combination Enhances Sexual
Satisfaction in Erectile Dysfunction
after Radical Prostatectomy. Urology
2005;65:360–4. PMID: 15708053.
See page 44.
out that the study involved only a single injection given within particular time
frames after surgery; it’s not clear that the men would continue to respond so
dramatically later on.
In addition to looking at the timing of treatment, investigators are conducting studies to determine the best mode of treatment. So far, the results indicate
that a combination of therapies is probably best. For example, in 2005, investigators reported in Urology that men who had undergone radical prostatectomy
and were not able to obtain erectile function after trying a vacuum constriction
device (see Figure 6) might benefit by taking sildenafil before using the device.
The study involved 31 men who began taking 100 mg of sildenafil an hour or
two before using the vacuum device. At an 18-month follow-up, researchers
found that seven men did not benefit from treatment, but 24 said that by using
this combination therapy, they were able to have erections again.
Options after radiation therapy
The use of penile rehabilitation after radiation therapy has been less frequently
studied, but one report in the Journal of Urology bears mention. In this study,
110 men who had developed erectile dysfunction after undergoing some form
of radiation therapy were followed after they began taking sildenafil, at an average of eight months following cancer treatment. Investigators then checked
in with them at three different times.
The investigators found that men who underwent brachytherapy had better
results than those who underwent external beam radiation therapy. In the first
year of penile rehabilitation treatment, 76% of men who underwent brachytherapy responded to sildenafil, and 60% reported erections firm enough for
intercourse, compared with a 68% response rate among men who underwent
external beam radiation therapy, with 50% reporting erections firm enough for
intercourse. By the third year of treatment, however, response rates had fallen
in both groups: Only 44% of the men who received brachytherapy were still responding to sildenafil, compared with 38% of men who received external beam
radiation therapy. Likewise, only 26% of the men who received brachytherapy
reported erections firm enough for intercourse, compared with 19% of those
who received external beam radiation therapy.
What you can do now
Research continues in an effort to find new modalities for restoring erectile
function following prostate cancer treatment. Some investigators are experimenting with ways to encourage nerves to regenerate faster, for example.
In the meantime, although the evidence isn’t perfect, you may want to ask your
doctor about options for penile rehabilitation while you are discussing treatments. Although the field is still in its infancy, penile rehabilitation may help
increase the odds that you will regain erectile function.
36
Harvard experts discuss surgical options
for benign prostatic hyperplasia (Part 1 of 2)
Benign prostatic hyperplasia (BPH) is one of the most common disorders
affecting men as they grow older. Yet there is much confusion about the best
way to treat this disorder surgically, in part because it seems that every year,
a new surgical option is introduced.
The editors of Perspectives on Prostate Disease invited three Harvard experts
to participate in a roundtable discussion to share their thoughts about the relative benefits and risks of current surgical treatments for BPH. The first issue of
Perspectives presented their thoughts about the best drug treatments for BPH
(see Perspectives, Winter 2007).
The panel consisted of these experts:
• Dr. Kevin R. Loughlin, professor of surgery (urology) at Harvard
Medical School, who is senior surgeon and director of urologic research at
Brigham and Women’s Hospital and staff urologist at Harvard University
Health Services, a large university health program that serves the needs of
Harvard students, faculty, employees, and their families.
• Dr. Abraham Morgentaler, associate clinical professor of surgery
(urology) at Harvard Medical School and director of Men’s Health Boston.
Dr. Morgentaler specializes in diseases of the prostate and has a particular
interest in treating erectile dysfunction, low testosterone levels, and BPH.
He has published widely on the issue of erectile dysfunction.
Editor’s note: Men who
decide to undergo surgery
to relieve BPH symptoms
have multiple options
to choose from. Our
panel of Harvard experts
discusses the most common
options, which are briefly
defined below. See Table
13 for a comparison of
recovery rates and other
considerations.
• Dr. Martin G. Sanda, associate professor of surgery (urology) at Harvard
Medical School and director of the Prostate Care Center at Beth Israel
Deaconess Hospital. Dr. Sanda has extensive experience in prostate cancer
and BPH and has devoted much of his professional research to evaluating
prostate-related treatment outcomes and developing new therapies.
• Dr. Marc B. Garnick, editor in chief of Perspectives, moderated the
discussion.
Transurethral resection of the prostate (TURP). Still the most common
form of surgery, TURP is often inelegantly referred to as the “Roto-Rooter”
technique. This procedure takes place in an operating room under general or
spinal anesthesia. During the procedure, the surgeon uses an instrument called
a resectoscope to view the prostate (see Figure 7). The surgeon threads the
resectoscope through the penis to the prostate, then uses the electrical loop to
cut away the overgrown tissue that’s pressing against the urethra.
37
Transurethral microwave thermotherapy (TUMT). This is one of several
techniques that use heat to destroy prostate tissue. In TUMT, the doctor guides
a thin catheter carrying a miniature microwave generator through the penis to
the prostate. There, microwaves destroy some of the prostate tissue and relieve
pressure on the urethra. A cooling jacket around the generator protects the
urethra. The procedure can be performed on an outpatient basis.
Transurethral needle ablation (TUNA). This is a newer thermal approach
that uses low-level radio waves delivered through twin needles to heat and kill
obstructing prostate cells. Shields protect the urethra from damage. This can
also be performed on an outpatient basis.
Photoselective vaporization of the prostate (PVP). Although several options
in laser surgery exist, our Harvard experts most often use the PVP laser
technique, also known as the GreenLight laser. This uses a high-energy laser
Figure 7. TURP
A
B
C
During transurethral resection of the penis (TURP), which is performed under general or spinal anesthesia,
the surgeon inserts a thin tube known as a resectoscope into the urethra and threads it up into the enlarged
prostate (A). The resectoscope contains a tiny camera, enabling the surgeon to view the prostate as the
operation proceeds, and an electric loop. Using one type of electrical current, the surgeon uses the loop
to chip away at the overgrown prostate tissue (B). The surgeon then applies a different electrical current
to cauterize the tissue and reduce bleeding. The area is then flushed with a sterile solution to remove bits
of tissue, and a catheter is inserted temporarily into the urethra and bladder until the area recovers. After
surgery, the newly enlarged passageway enables urine to flow more easily (C).
38
Figure 8. GreenLight procedure
A
B
C
When prostate enlargement obstructs the flow of urine (A), a relatively new laser technique may be used instead of TURP. In a photoselective
vaporization of the prostate (PVP), or GreenLight, procedure, the surgeon threads a thin tube known as a cystoscope into the urethra and
up into the enlarged prostate. The surgeon then threads a fiber-optic device through the cystoscope to generate high-intensity pulses of
light, which simultaneously vaporize the obstructing tissue and cauterize it to reduce bleeding (B). After surgery, a catheter may be inserted
temporarily to allow urine to flow while the area is healing. This technique creates an enlarged, uniform channel for urine to flow through (C).
to vaporize prostate tissue that is obstructing the flow of urine through the
urethra (see Figure 8).
POPD: When
is it time to consider surgery for BPH?
MORGENTALER: For the most part, it really comes down to patient choice about
how to handle the symptoms of BPH. The only situations that are major indications for treatment include acute urinary retention, bladder stones, maybe recurrent urinary tract infections, or a high post-void residual. (Editor’s note: For
definitions, see “Glossary,” page 45.)
SANDA: Surgery is also worth considering if a man isn’t responding well enough
to any of the drugs used to treat BPH, or if he can’t tolerate the side effects. In
the past, patients really had only two options when it came to surgery for BPH.
If the patient had a reasonable-sized prostate, he could undergo a TURP, and
if he had an especially large prostate, then perhaps an open prostatectomy. But
today a man considering surgery has many more options (see “TURP use
declines,” page 40).
POPD: Which
surgical procedures do you recommend to your own patients?
SANDA: One trend in BPH management that really has changed in the last few
years is the emergence of a later generation of laser therapy that seems to be
more effective than earlier alternatives. I’m referring to the GreenLight laser,*
which comes close to TURP in terms of removing obstructive prostate tissue
and releasing pressure on the urethra, but it’s less likely to cause bleeding and
other complications.
* Editor’s note: A firstgeneration GreenLight
laser is discussed in
this article; a second
generation, more
powerful laser, which
can treat larger glands
with shorter duration
times for the procedure,
has recently become
available.
39
LOUGHLIN: I
TURP use declines
As less invasive surgical
procedures for BPH have emerged,
use of those that require hospital
stays, such as TURP, have declined.
In 1994, about 136,000 TURP
procedures were performed in the
United States; by 2004, fewer than
90,000 were performed.
share Marty’s enthusiasm for the GreenLight laser. I think people
need to understand that a TURP is done in an operating room, with spinal or
general anesthesia, and it involves a hospital stay. Treatment with the GreenLight laser is also done in an operating room, but it’s day surgery, usually with
spinal anesthesia, although general anesthesia is sometimes used. There is no
blood loss, and the patient either goes home with a catheter inserted overnight,
or stays in the hospital overnight. Some doctors are even sending people home
without a catheter, although I have not done so and would not recommend it.
MORGENTALER: I’ve
become a fan of the newer heat treatments, such as microwave and TUNA, even though I started off as a complete skeptic. I think that
there’s an important role for heat treatments in the surgical management of
BPH, although I think it’s also important to recognize that these techniques
absolutely do not replace TURP or the GreenLight laser.
POPD: Can
you tell our readers more about why you’re enthusiastic about the
heat-based techniques?
MORGENTALER: The nice thing about the heat-based treatments is that they’re
done in the office. A lot of patients with BPH are treated for symptoms of
bother, such as frequency and urgency of urination. In practical terms, they
may be getting up multiple times in the night to urinate. Yet many of the men
I treat are otherwise relatively healthy. They’re leading busy lives, and the last
thing they want to think about is going into an operating room and undergoing general or spinal anesthesia. That’s always been a real stumbling block in
terms of getting people to undergo surgical treatment for BPH.
POPD: How
are the heat-based treatments a better alternative, in such cases?
MORGENTALER: Most men tolerate these procedures well, and when they come
back for a follow-up exam four to six weeks later, they are usually quite satisfied with the results. In fact, I’ve never seen any man I treat who is as happy
with a medication as he’s been with one of these heat-based treatments. Now,
I should point out that I’ve seen men just as happy with the results of TURP.
But for men who don’t want an operation, for whatever reason, microwave or
TUNA are good options.
POPD: How
long have you been offering these treatments?
MORGENTALER: For a year. Although the numbers of cases aren’t huge, I can say
that for the majority of men I’ve treated, these treatments have produced nice
results.
LOUGHLIN: One
issue we haven’t discussed, but should, concerns the likelihood
of having to undergo a repeat procedure. The 2003 Medicare data on BPH surgery reoperation rates indicate that TURP and GreenLight laser are basically
equivalent, and if anything, the GreenLight laser seems to have a slight edge, at
least in terms of the need for a repeat procedure. But the data also indicate that
40
the repeat operation rate for people who have microwave therapy or TUNA
is much higher. So essentially a person who undergoes one of the heat-based
therapies is six or seven times as likely to need a second operation as someone
undergoing a TURP or GreenLight laser procedure (see Table 11).
Table 11. Reoperation rates
The federal Medicare program tracks data on the need to have a repeat operation for BPH
within 24 months after a first procedure. This provides one indicator of how effective the
procedures are. The figures below are based on Medicare data for 2003.
Procedure
Percentage of men who required another
operation within 24 months
TURP
2.2%
TUMT
11.9%
TUNA
14%
PVP laser
2.05%
MORGENTALER: I’m not saying that microwave and TUNA are equivalent to TURP
or the GreenLight laser. They’re not. But I think a heat-based treatment can be
viewed as an intermediate intervention—more effective than medication for
BPH, but not as effective as TURP or GreenLight. So I think heat-based treatments are actually a wonderful advance, in that they can be performed in a
doctor’s office, involve less fear on the patient’s part, and have nice results, in
my experience.
LOUGHLIN: I
agree that a patient needs to understand that a TURP is going to
require that he be in an operating room. It also involves longer recovery than
microwave or TUNA. But, to me, the 2003 Medicare data are extremely persuasive, in that you’re looking at a 2% reoperation rate versus a 12% to 14%
reoperation rate.
POPD: What
other factors might influence a patient’s choice of surgery for BPH?
Or the recommendation that you make as doctors?
LOUGHLIN: A real dilemma for urologists is that if you look at reimbursement
rates, there’s about a seven-to-one financial advantage in doing an office-based
procedure. If a doctor recommends a TURP or GreenLight laser, it’s done in
the operating room. That means the urologist gets about $500 in reimbursement, to use a ballpark figure. If the urologist does a TUNA or a microwave in
his office, he’ll get a lot more. That’s a real issue sometimes.
POPD: Good
point. The Journal of Urology included a study three years ago about
the way reimbursement rates affected treatment recommendations for BPH as
well as for other conditions (see Table 12).
41
Table 12. Reimbursement matters
Medicare is the nation’s largest health insurance provider, serving roughly 40 million
Americans (mainly those 65 and older). As such, changes in Medicare coverage and
reimbursement policies have an enormous impact on the practice of medicine.
A 2004 study in the Journal of Urology found that Medicare reforms implemented in the
1990s significantly reduced reimbursement rates to urologists for surgical procedures done
on an inpatient basis, while increasing rates for outpatient procedures. For example, in 1986,
Medicare reimbursed urologists $998 to $1,830 per TURP, depending on their geographic
location; in 2004, the reimbursement had fallen to $704, regardless of geography.
Medicare also reimburses particular procedures differently, depending on whether they
are performed in a physician’s office or in an operating room, as shown in the chart
below.
BPH surgical procedure
Medicare reimbursement
Performed in operating
room
Performed in physician’s
office
Transurethral
thermotherapy (another
name for microwave
treatment, or TUMT)
$552
$4,272 (gross)*
Transurethral needle
ablation (TUNA)
$585
$4,098 (gross)*
* This does not cover the cost of disposable items, which can be more than $1,000 per
procedure, and other overhead costs, so net reimbursement is less.
Source: Lotan Y, Cadeddu JA, Roehrborn CG, Stage KH. The Value of Your Time: Evaluation
of Effects of Changes in Medicare Reimbursement Rates on the Practice of Urology.
Journal of Urology 2004;172:1958–62. PMID: 15540765.
POPD: Are
there any questions we should have asked about surgical treatments
for BPH that we have not asked and that you think are important to convey to
our potential readership?
MORGENTALER: I think an important issue is, what happens if somebody
doesn’t want to undergo treatment for BPH?
POPD: Excellent
question. What’s your answer to that?
MORGENTALER: The studies suggest that for many men, the urinary symptoms
and overall bother of BPH really wax and wane over time. One review found
that one-third of men who forgo treatment eventually report feeling better, and
if there is an improvement it usually occurs in the first six months. So if some
men choose to put off treatment, I think that’s a valid option.
LOUGHLIN: Some
men may want to avoid surgery because they’re too frail to
risk blood loss, side effects from anesthesia, or complications. If a patient is
that brittle, the best option may be to manage his symptoms with medication
and with a catheter if necessary.
42
Table 13. BPH surgical procedures compared
Procedure
What’s involved
Success rates
Side effects
Transurethral resection
of the prostate (TURP)
• Performed in operating
room
Provides symptom relief in
70%–85% of men treated
• 6% or fewer men will
experience erectile
dysfunction
• Requires general or
spinal anesthesia
• May cause ejaculatory
problems
• May spend one to two
days in hospital, with
catheter inserted to
enable urination
• Blood loss, urinary
incontinence,
infections, and
complications from
anesthesia are less
common but do occur
• Heavy physical activity
may be restricted for
two weeks or more to
prevent bleeding
• Full recovery may take
four to six weeks
Photoselective
vaporization of the
prostate (PVP or
GreenLight)
• Most patients treated in
outpatient setting
Improvement in symptom
relief similar to TURP
• Catheter remains in
place at least overnight
for most patients
• Less bleeding than
TURP
• Urinary frequency
or urgency in first
month may be
more troublesome
(temporarily) than after
TURP
• Can resume light
activity and return to
work within two to
three days
• Can resume vigorous
activity in four to six
weeks
Transurethral microwave
thermotherapy (TUMT)
• Performed on
outpatient basis in
doctor’s office
More effective than
medication but less
effective than TURP
• Some urinary side
effects, such as frequent
urination or discomfort
during urination, that
can last for several
weeks
More effective than
medication but less
effective than TURP
• Some urinary side
effects, such as frequent
urination or discomfort
during urination, that
can last for several
weeks
• Procedure takes about
one hour
Transurethral needle
ablation (TUNA)
• Done on an outpatient
basis
• Ejaculatory problems
similar to TURP
• More discomfort if
done in doctor’s office
than for procedures
such as TURP or
GreenLight
43
Searching PubMed in five easy steps
You can find and read the studies that are referenced in the pages of Perspectives on Prostate
Disease by searching PubMed, a resource of the National Library of Medicine. The abstracts
(short summaries) of the studies are available for free, but in most cases you will have to pay to obtain the full report.
Here’s how to access an abstract:
1. Open up your browser’s window while connected to the Internet. Type www.pubmed.gov
and hit return.
2. This brings you to the PubMed welcome page. You will see the following:
3. In the space after “For,” type the PMID (short for “PubMed ID”) number that appears with the
reference you want. For example, for the study by Capodice and colleagues, published in
2005 (see first entry under “Assessing the Evidence: Prostatitis,” page 5), the PMID is 16322807.
Search PubMed
for
Go Clear
4. Click on “Go” or press the enter key. PubMed will retrieve the abstract, which will appear on
your screen.
5. To purchase an article (if this option is available), change “Display” from “Abstract plus” to
“abstract” (click on the arrow to pull down the menu). If the journal provides a link for
purchase—or if a link is provided for a free copy of the article—click on the icon and follow
the instructions.
44
Glossary
acute urinary retention: An inability to urinate, in spite of a full
bladder.
alternative medicine: A therapy used in place of conventional
medicine.
benign prostatic hyperplasia (BPH): Enlargement of the prostate
gland, usually developing with age. It may be associated with an
elevated PSA, but there is no cancer present in the gland.
metabolic syndrome: A cluster of attributes that increase the risk
of developing diabetes and heart disease. See “Metabolic syndrome,”
page 4, for parameters.
metastatic: When used alone or with the term cancer, refers to
cancer that has spread throughout the body, beyond the organ or
tissue in which it originated.
biochemical recurrence: A post-treatment increase in PSA level,
indicating that prostate cancer has recurred or spread.
micrometastases: Cancer cells outside the primary tumor, such as
in the lymph nodes, that are still too small to be detected by CT or
bone scan or by physical examination.
brachytherapy: A type of radiation therapy in which small seeds of
radioactive material are placed in the prostate gland.
neoadjuvant hormone therapy: The use of hormone therapy
before prostatectomy or radiation therapy.
cancer: The presence of abnormal or malignant cells that have lost
normal regulatory controls of growth; cancer cells may also spread to
other parts of the body and grow.
penile rehabilitation: Therapy to increase the chances that erectile
function will recover following treatment for prostate cancer.
complementary medicine: Therapies used in conjunction with
conventional medicine. Sometimes also referred to as integrative
medicine.
post-void residual: The amount of urine left in the bladder after
urinating.
digital rectal examination (DRE): A part of the physical
examination in which the physician puts a gloved finger into the
rectum and examines the prostate gland and rectum for abnormalities
that can be detected by touch.
placebo: A pill with no active ingredients, or a “dummy” treatment.
prognosis: The prediction of how well the patient is likely to do with
or without treatment of the disease, as estimated from symptoms,
pathology, and other diagnostic information.
erectile dysfunction: A more specific term for impotence.
progression: The increase in symptoms of a disease, such as BPH,
or the growth and spread of cancer, either by direct extension or
metastases.
external beam radiation therapy: A type of radiation therapy
that uses an external source of radiation aimed at the cancer.
prostate gland: A walnut-shaped gland at the base of the bladder
in males involved in reproductive functioning.
Gleason score: A system of identifying and grading the appearance
of prostate cancer, as viewed under the microscope. Scores range from
2 to 10.
prostate-specific antigen (PSA): A substance secreted by the
prostate gland, some of which passes into the bloodstream. It can
be abnormally elevated in patients with prostate cancer, benign
enlargement of the prostate (BPH), prostatitis, or other conditions.
gynecomastia: Breast enlargement occurring in men.
hormone therapy: Treatment intended to reduce or eliminate the
supply of male hormones to the prostate and its metastases, causing
cell death and slowing cancer growth.
prostatitis: An infection of the prostate gland, usually by bacteria;
this noncancerous condition can raise the PSA level.
impotence: The inability to obtain or maintain an erection sufficient
for sexual intercourse; also called erectile dysfunction.
salvage therapy: A second procedure (such as radiation therapy or
surgery) used following the failure of the initial treatment to control
or cure the cancer.
localized: When used with the term cancer, refers to cancer that
is limited to a specific gland, without any distant spread; an organconfined cancer.
stage of cancer: The level of advancement of cancer. The three
general stages are localized, regional, or disseminated (or metastatic).
Specific stages may be identified by number (I, II, III) or letter (A, B, C, D).
margin: In reference to the prostate gland, the outermost surface of
the gland, which is removed at the time of radical prostatectomy.
testosterone: An androgen; a male hormone involved in the growth
and development of the prostate gland and prostate cancer.
45
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PROSTATE DISEASE Perspectives on Harvard Medical

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