6 PCRI Insights • www.PCRI.org
Updated Information and Insight
for Some Common Questions…
Grace Lu-Yao, Ph.D. and Siu-Long Yao, M.D.
Treatment Choices
for Early (Localized)
Prostate Cancer
Over the last two decades, prostate specific antigen (PSA) testing has
been able to diagnose prostate cancer at a much earlier stage, and we
have witnessed tremendous changes in the characteristics of prostate
cancer. This phenomenon was discussed in detail in the November, 2009
issue of Insights entitled, The Great Prostate Cancer Stage Migration (1). PSA
testing may find prostate cancer 6-12 years earlier than previous methods
(2, 3). This fact raises the possibility that previous data based on men
diagnosed at a later stage of cancer, through means other than PSA testing,
may not be applicable to patients who are diagnosed today. Using outdated
information may limit the accuracy and appropriateness of subsequent
decisions. Below are some common questions about this issue.
There seems to be a lot of controversy about whether to treat prostate
cancer that has not spread beyond the prostate (i.e., localized disease).
Some doctors and organizations say that this type of cancer should be
treated, while others say it should be monitored closely, and treated only if
needed. What is the basis of this controversy?
Because of screening, most prostate cancers diagnosed today (~93%) are
found at early stage and have not spread to other parts of the body (4). In
addition, we have known for a long time that this early type of prostate
cancer is extremely common. For example, in autopsy studies, approximately
50% of men in their 50s and more than 75% of men in their 80s have been
found to have early prostate cancer (5, 6).
No one would have known about this cancer if an autopsy had not been performed. These men all died of something other than prostate cancer, so treating their prostate cancer would not have been beneficial.
If so many men have prostate cancer (about 1 of every 6 men will be
diagnosed with prostate cancer), but relatively few die of prostate
cancer (about 1 of every 30 men will die of prostate cancer), who
should be getting treated, and who should be monitored closely?
Several studies (7, 
have shown that men with low-risk disease
characterized by a Gleason score <7 (the Gleason score is a measure of
the aggressiveness of a cancer and ranges from 2 – 10, with 10 being
the most aggressive), who delay treatment until it is necessary, live
as long as men without prostate cancer. This makes some sense
because about 29 – 84% of prostate cancers would never have been
discovered (and would never bother or hurt these men) in the
absence of contemporary screening (e.g., PSA and rectal exam) (9-11).
When considering treatment, surgery (radical prostatectomy)
is one of the most common approaches, and the approach for
which much of the data exists. One of the best studies of surgery was
the Scandinavian Prostate Cancer Group 4 study (SPCG-4) which
randomly assigned men with early prostate cancer to surgery or no
surgery (12). In this study, surgery reduced overall deaths from 30%
to 24%, and deaths due to prostate cancer from 15% to 10% (12).
However, these survival benefits did not seem to occur in patients
over age 65 years. In addition, most of the patients in the study
(~95%) had disease that was somewhat more advanced than
that currently diagnosed through contemporary screening (12).
This is important because cancer diagnosed through contemporary
screening is much less likely to cause death in a patient compared
to disease diagnosed in earlier eras (such as the era when the SPCG-4
trial was conducted).
The Table below shows that prostate cancer diagnosed in the contemporary era (and treated only when necessary) has more favorable survival experience (about 94%- 98% survival at 10-year after diagnosis) than the same cancer diagnosed in earlier eras before the advent of PSA screening (about 77% – 85% survival at 10-year after
diagnosis).
Table.
Ten-Year Risk of Dying of Prostate Cancer according to
Cancer Risk Group for Men under 70 Years of age without Initial
Attempted Curative Therapy Author Year of Diagnosis
Risk Group 10-Year Risk of Death Due to Prostate Cancer Contemporary PSA Era
Stattin (13) 1997 – 2002 One lobe of prostate affected & PSA <10 & Gleason score <7
2% Stattin( 13) 1997 – 2002 Both lobes of prostate affected or PSA ≥10 or Gleason score ≥7 5%
Lu-Yao (8) 1992 – 2002 One lobe of prostate affected
2%
Lu-Yao (8) 1992 – 2002 One or two lobes of prostate affected
6%
Pre-PSA Era Albertsen (14) 1971 – 1984 One or two lobes of prostate
affected
21%
Johansson (15) 1977 – 1984 One or two lobes of prostate affected
15%
Lu-Yao (7) 1983 – 1992 One or two lobes of prostate affected
23%
Because early-stage low-risk disease is less likely to harm a patient, the risk of unnecessary treatment correspondingly increases. Taken together, this information suggests that there may not be reasonable proof of benefit from surgery in cancers
with Gleason score <7, or men who are >65 years of age. Information about the potential benefits of other treatment approaches is more difficult to find. For example, thereare no definitive studies (i.e., randomized trials) that have evaluated
primary androgen deprivation (hormonal therapy), radiation therapy,
brachytherapy (seeds), cryotherapy (freezing), robotic radical prostatectomy,
photon-beam or intensitymodulated radiation therapy compared to delaying treatment until it is necessary (16).
All cancer therapies are associated with substantial side effects. For example, urinary leakage is more common with radical prostatectomy (35%) than with radiation
therapy (12%) or androgen deprivation (11%) (16). Erectile dysfunction (ability to maintain an erection) occurs frequently after all treatments (radical prostatectomy,
58%; radiation therapy, 43%; androgen deprivation, 86%) (16, 17). Adjuvant hormone therapy was associated with worse outcomes across multiple qualityof-
life domains among patients receiving brachytherapy or radiotherapy (18). Patients treated with brachytherapy often report having long-lasting urinary system
irritation, bowel and sexual symptoms, and transient problems with vitality or hormonal function (18).
Many of these treatment-related adverse events are worsened by obesity, a large prostate size, a high PSA value, and older age (18).
In summary, the choice of treatment approach is truly a personal matter. Cancer doctors like to see the good, even in very challenging situations. We like to say that the glass is half full. Others can look at the same situation and say that the
glass is half empty. Each person’s focus will be different depending on whether he feels that he needs to fight the cancer and risk side effects from treatment, or whether living with the cancer (and its side effects if it progresses) will be OK. We have
entered a new era and it is safe to say that many patients can now live with their cancer just like patients with diabetes or heart disease or other chronic diseases can live with their ailments. People do die of these diseases, but many more can
make peace, and live with them.
Should I get a second opinion to help me with my treatment decision?
Yes. Second opinion and multidisplinary approach may provide different perspectives and more comprehensive information. As researchers, healthcare providers, and scientists, we try to provide clear and objective information. However, each of us believes strongly in what we do, and each of us anxiously
wants to help. Sometimes, during all the confusion following a new diagnosis of cancer, both healthcare providers and patients can inadvertently mix up fact and
opinion.
Siu-Long Yao, MD
Executive Director, Oncology Clinical Research
Merck Research Laboratories
Clinical Assistant Professor
Medical Oncology
Cancer Institute of New Jersey
Dr. Yao is responsible for Phase I-III clinical development of numerous
oncology drugs and biologics at Merck Research Laboratories. He is also a
clinical assistant professor at the Cancer Institute of New Jersey where he specializes in genitourinary oncology.
Dr. Yao holds a B.A. in chemistry and a B.A. in biochemistry, both from the University of Pennsylvania. He attended Yale University School of Medicine and completed Internal Medicine internship and residencies at Dartmouth-
Hitchcock Medical Center in Hanover, NH. Following residency, Dr. Yao completed subspecialty fellowship training in hematology, and oncology, both at Johns Hopkins. He is a Board certified internist, hematologist, and oncologist.
For example, although specialists may present various options, most overwhelmingly “recommend” the therapy that they themselves deliver (19). In a national survey of physicians, 93% of urologists chose radical prostatectomy as the preferred
treatment option, while 72% of radiation oncologists believed surgery and external beam radiotherapy were equivalent treatments (19). In addition, healthcare professionals tend to recommend particular types of treatment in specific regions of
the country (20, 21). For example, in the late 1980s and early 1990s, the
rate of radical prostatectomy in the Northwest region was more than five times that in the Northeast region (20). Getting a second opinion can help. Hearing things a second
time, after the initial shock of the diagnosis, can help you make that distinction. A different specialist may have a different preference, and you can hear another side of the story. Don’t be dismayed if you hear something different each time you talk to someone else. I often tell my patients that doctors in the US are amongst the most tested in the world. We have to constantly pass a test every few years to get, and
maintain, licensure and certification.
If there was a single correct answer for everyone, we would have had to provide that same answer over and over again on each test, and each patient would get the same answer every time the situation arose. The fact is, though, that there is no one
correct answers. The art of medicine is finding the answer that is best for
each patient.
References
1. Cavanagh WA. The great prostate cancer stage migration.
In: Insights. Los Angeles, CA: Prostate Cancer Research
Institute; 2009. p. 12-15.
2. Draisma G, Boer R, Otto SJ, van der Cruijsen IW, Damhuis
RAM, Schroder FH, et al. Lead Times and Overdetection
Due to Prostate-Specific Antigen Screening: Estimates From
the European Randomized Study of Screening for Prostate
Cancer. J Natl Cancer Inst 2003;95(12):868-878.
3. Brawley OW. Prostate cancer screening: Clinical
applications and challenges. Urol Oncol 2004;22(4):353-7.
4. Shao YH, Demissie K, Shih W, Mehta AR, Stein MN, Roberts
CB, et al. Contemporary Risk Profile of Prostate Cancer in
the United States. J Natl Cancer Inst 2009.
5. Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD. The
frequency of carcinoma and intraepithelial neoplasia of
the prostate in young male patients [see comments]. J Urol
1993;150(2 Pt 1):379-85.
6. Gronberg H. Prostate cancer epidemiology. Lancet
2003;361(9360):859-64.
7. Lu-Yao GL, Yao SL. Population-based study of long-term
survival in patients with clinically localised prostate cancer
[see comments]. Lancet 1997;349(9056):906-10.
8. Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola
RS, et al. Outcomes of localized prostate cancer following
conservative management. Jama 2009;302(11):1202-9.
9. Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E,
Gulati R, et al. Lead time and overdiagnosis in prostatespecific
antigen screening: importance of methods and
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10. Schroder FH, Hugosson J, Roobol MJ, Tammela TLJ,
Ciatto S, Nelen V, et al. Screening and Prostate-Cancer
Mortality in a Randomized European Study. N Engl J Med
2009:NEJMoa0810084.
11. McGregor M, Hanley JA, Boivin JF, McLean RG. Screening
for prostate cancer: estimating the magnitude of
overdetection. CMAJ 1998;159(11):1368-72.
12. Bill-Axelson A, Holmberg L, Ruutu M, Haggman M,
Andersson SO, Bratell S, et al. Radical prostatectomy versus
watchful waiting in early prostate cancer. N Engl J Med
2005;352(19):1977-84.
13. Stattin P, Holmberg E, Johansson J-E, Holmberg L, Adolfsson
J, Hugosson J, et al. Outcomes in Localized Prostate Cancer:
National Prostate Cancer Register of Sweden Follow-up
Study. J. Natl. Cancer Inst. 2010:djq154.
14. Albertsen PC, Hanley JA, Fine J. 20-year outcomes following
conservative management of clinically localized prostate
cancer. Jama 2005;293(17):2095-101.
15. Johansson J-E, Andren O, Andersson S-O, Dickman PW,
Holmberg L, Magnuson A, et al. Natural History of Early,
Localized Prostate Cancer. JAMA 2004;291(22):2713-2719.
16. Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC,
Kane RL. Systematic Review: Comparative Effectiveness
and Harms of Treatments for Clinically Localized Prostate
Cancer. Ann Intern Med 2008;148(6):435-448.
17. Stanford JL, Feng Z, Hamilton AS, Gilliland FD, Stephenson
RA, Eley JW, et al. Urinary and sexual function after radical
prostatectomy for clinically localized prostate cancer: the
Prostate Cancer Outcomes Study. Jama 2000;283(3):354-60.
18. Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse
L, Hembroff L, et al. Quality of Life and Satisfaction with
Outcome among Prostate-Cancer Survivors. N Engl J Med
2008;358(12):1250-1261.
19. Fowler FJ, Jr., McNaughton Collins M, Albertsen
PC, Zietman A, Elliott DB, Barry MJ. Comparison of
recommendations by urologists and radiation oncologists
for treatment of clinically localized prostate cancer. JAMA
2000;283(24):3217-22.
20. Lu-Yao GL, McLerran D, Wasson J, Wennberg JE. An
assessment of radical prostatectomy. Time trends,
geographic variation, and outcomes. The Prostate Patient
Outcomes Research Team. Jama 1993;269(20):2633-6.
21. Potosky AL, Harlan LC, Stanford JL, Gilliland FD, Hamilton
AS, Albertsen PC, et al. Prostate Cancer Practice Patterns
and Quality of Life: the Prostate Cancer Outcomes Study. J
Natl Cancer Inst 1999;91(20):1719-1724
Dr. Grace Lu-Yao is a cancer epidemiologist whose primary research
interest includes study of the epidemiology of prostate cancer and
outcomes assessment of prostate cancer therapies. She received her
graduate training in health services research and epidemiology at
Yale University. After her doctoral training, Dr. Lu-Yao received a
faculty appointment at Dartmouth Medical School and worked with
Dr. John E. Wennberg, the founding father of outcomes research and
evidence-based medicine. Many of her research findings have been incorporated in guidelines and
featured in highly respected medical journals with wide media coverage.
Grace Lu-Tao, Ph.D.
Cancer Institute of New Jersey
Robert Wood Johnson Medical School
