Simon Chapman, professor of public health at the University of Sydney, writes:
Last week’s publication of my book, Let Sleeping Dogs Lie? What men should know before getting tested for prostate cancer (free download here), has provoked a stream of testimonials from men who had their prostate cancer found via a PSA test, had it treated (mostly by prostatectomy to surgically remove the prostate, or by various forms of radiotherapy), and now live to tell the tale.
The tale is basically “Thanks to the test, we found the cancer early. Obviously I’m still alive. Ergo, the test and the early detection saved my life. Every man should be tested annually.”
Prostate cancer survivor Treasurer Wayne Swan is perhaps the most prominent Australian man who strongly advocates for the test, in 2003 telling the then head of Cancer Council Australia, the PSA test refusnik Prof Alan Coates, that his public position would “condemn many young men in this country to death.”
But, just as interviewing lottery winners is not a sensible way of making informed judgements about the odds of winning, so is it unwise to use the “I’m alive” testimony of post-treatment survivors as a guide to the value of the test.
The simplest way of explaining the odds of having a PSA test save your life is to look at the results obtained from a long-running Europe-wide randomised controlled trial of PSA screening.
It found that for every 1000 men aged 55-69 who were allocated to the screening arm of the trial and were then followed for 10 years, 93 had prostate cancer diagnosed and treated and three died from the disease over the following ten years. In 1000 unscreened men allocated to the “control” arm of the trial, 55 (who would have mostly been tested following noticing symptoms) were found to have the disease and four died over the same period. So, PSA screening finds cancer, and yes it prevents deaths from prostate cancer, but to a soberingly small degree.
A more recent Swedish trial reported better outcomes, but commentators in The Lancet and from the US National Cancer Institute have both suggested there are few lessons in the Swedish results for nations like the USA and Australia where de facto PSA screening has been occurring since the late 1980s.
Most of those who remain alive after treatment are convinced that they would be otherwise dead. Some would be, but the widespread occurrence of “indolent”, non-life threatening cancer shows that there is much over-treatment.
In our book from page 34 we show complete Australian data on age standardised prostate cancer deaths and incidence rates (the rate of prostate cancer per 100,000 men). In the 39 years 1968-2007, the age standardised death rate from prostate cancer has varied very little, with an average of 35.8/100,000 men and a range of 32.2 to 43.7. The most recent rate in 2007 (31/100,000) was very similar to the death rate at the beginning of this 38 year series in 1968 (35.6/100,000). In between there was a rise in the death rate (in the early to mid 1990s) which has now reversed back to rates seen in the early 1970s, a decade before the PSA test became available.
However, when you look at the data on prostate cancer incidence, the same basically flat trend we see for deaths is not apparent. Instead there is a dramatic leap in the incidence of the disease from the early 1990s. This change has been largely sustained ever since, resulting in a startling difference in the risk of men being diagnosed with prostate cancer before the 1990s (approximately 1 in 22 men in their lifetime) to nearly three times that today (1 in 8).
The massive rise in finding prostate cancer has not been matched by any remotely comparable fall in the rate of prostate cancer deaths. Lots of cancer is being found that would not have killed the men with it. And lots of that cancer is being unnecessarily tested. The big problem is that current diagnostic tools are poor at differentiating the nasty, fatal cancers from those which are indolent.
When you are diagnosed with prostate cancer, you are henceforth “on the bus” of treatment. Many will have radical surgery or radiotherapy and we know from statewide data in NSW that long-term impotency rates average 77% and incontinence rates 12% in treated men. Quality of life is dramatically altered in most men.
To this, the president of the Urological Society Dr David Malouf says: “There is no evidence that we are over-diagnosing or over-treating prostate cancer.”
Many men who have survived prostate cancer have enduring sexual and incontinence problems.
Here’s what one (John) wrote to a discussion board this week.
I was screened 12 years ago and 32 PSA … I had no symptoms .. the discovery of my high PSA resulted in me losing my female partner. Decided to scale down house so sold my impressive 4 bed for a 2 bed flat. My turning down a high profiled job offer managing a shopping mall. God only knows how much stress. Radiotherapy that virtually nuked my sex life, etc etc. Here I am 12 years later, still no symptoms. New female partner decides to leave (now a pattern with prostate cancer). Total wipe out of sex ability. Almost made incontinent, but thankfully now sorted. Intense stress levels. Employer now alerted to my vulnerability, etc etc. so career prejudiced etc. So from my point of view whilst I value of course all the treatment and care I have received, I have never had any symptoms and wonder where I would be now if I had not taken this PCa medical course. I’d certainly be in a happy relationship, have a better job, look younger and be far less cynical.
Less than 3% of prostate cancer deaths are in men aged less than 60 and more than half occur in men aged over 80, which exceeds average life expectancy today. No international expert group outside of urology has ever promoted mass testing.
• This article first appeared in today’s Crikey bulletin
Well said Simon. Even the Americans who are traditionally quite aggressive in their cancer treatment are starting to question their approach to early-stage prostate cancer, This robust article by a leading urologist appeared in this month’s ASCO post, the monthly newsletter with opinion pieces from the American Society of Clinical Oncology. The treatment decisions about patients with early stage prostate cancer should no longer be left solely to urologists. It is time for a national rethink in Australia on our approach to this disease.
How Do We Eliminate Unnecessary Treatment for Prostate Cancer?
By Richard J. Boxer, MD November 2010, Volume 1, Issue 6
Page last updated at Monday, November 01, 2010, 10:05 AM
Prostate cancer was diagnosed in nearly 200,000 American men in 2009. Approximately 50% to 62% of the men who were diagnosed have low-risk prostate cancer defined as: (1) prostate-specific antigen (PSA) of 10 ng/mL or less; (2) Gleason histologic score of the primary and secondary microscopic patterns each assigned a value of 1 to 5 (an indication of the tumor’s potential aggressiveness) and less than a total of 7 (with no patterns of 4 or 5 in biopsies); and (3) no more than 10% to 50% cancer (various opinions) found in no more than 2 of 12 biopsy cores.
Over the past 30 years, nearly 1 million American men have received radiation therapy and/or radical prostatectomy for prostate cancer that would have a very low risk of ever leading to their death. These men, however, have been subjected to the attendant morbidity associated with therapy-morbidity that may have resulted in a decline of their quality of life.1
Willet F. Whitmore, Jr, Chairman of the Urology Service at Memorial Sloan-Kettering Cancer Center for more than 30 years, said of prostate cancer in 1990, “Is cure possible? Is cure necessary? Is cure possible only when it is not necessary?”2 It may be that nothing has fundamentally changed in the past 20 years.
Surgical or radiation treatment for early-stage disease cures 98% of men at 10 years. Those men who receive no treatment for low-risk prostate cancer have a 98% survival rate. What has been accomplished? It is time to rethink our approach to this disease.
Concerning Data
Annually, 30 million men are screened using PSA criteria. But two recent U.S. studies1,3 have thus far not shown any reduction in the death rate from prostate cancer. And European investigators reported4 that only 1 death could be prevented for every 1,400 men screened and 48 treated. Also, studies have shown that for patients with low-risk prostate cancer, a 10-year delay occurs between the time the cancer is detected by PSA and the time there would be physical evidence of the disease.5,6
Radical prostatectomy was performed nearly 60,000 times last year.7 Approximately 80% of surgeons performed fewer than 10 procedures per year, and 25% of men who underwent surgery had a surgeon who performed only a single such procedure in a year. This paucity of experience has been found to translate into poorer outcomes,8 higher complication rates, and a higher risk of postoperative incontinence and impotence. At least 30% of men given curative treatment for prostate cancer experience negative quality-of-life consequences.
In 2009, radiation therapy was used to treat approximately 85,000 patients with prostate cancer (55,000 by external-beam radiation therapy and 30,000 by brachytherapy), the majority with low-risk disease. Radiation therapy and surgery are associated with equivalent 10-year outcome data, but radiotherapy avoids the potential risks associated with anesthesia. Nevertheless, this modality has not produced a significant reduction in the death rate in patients with low-risk prostate cancer.
Relative Treatment Outcomes
Active surveillance or “watchful waiting” offers an option for some men with low-risk prostate cancer,9 in avoiding the potential adverse quality-of-life consequences from treatment. In several large studies of active surveillance, only 2% to 5% of patients had tumor progression and 16% to 25% had a significant rise in PSA.10 This approach has resulted in very few men requiring further therapy, no change in mortality, and of course no complications from surgery or radiation therapy. Thus, no treatment has the same effect on outcome as aggressive therapy.
Yet NCI’s Surveillance, Epidemiology and End Results (SEER) data demonstrate that over the past 20 years, marked increases in the use of radiation therapy and radical prostatectomy (compared to no therapy) have been observed. This may be because more men are being screened for elevated PSA. In addition, improvements in both surgical and radiation therapy and overmarketing by the health-care industry have given the public the perception that the treatments today have a greater success rate and fewer complications.
In support of surgical treatment, Holmberg and colleagues reported a randomized Swedish trial designed to determine whether radical prostatectomy reduces the risk of death due to prostate cancer. They observed a statistically significant difference in the risk of death due to prostate cancer after radical prostatectomy, as compared with watchful waiting, but no significant difference between the two groups in the overall survival rate.11
Finding Treatment Criteria
It has been widely reported that prostate cancer deaths have been reduced recently, but this is a reflection of the increased number of men diagnosed because of PSA screening. Actually, it is the proportion of men with prostate cancer who die that has decreased. The percentage of men who die with prostate cancer has declined because the number of men who have been diagnosed through screening has massively increased. In other words, the numerator (deaths) has stayed the same while the denominator (incidence) has risen. In 1975, 1993, and 2005, respectively, approximately 90, 240, and 170 American men per 100,000 were diagnosed with prostate cancer. The number of Americans per 100,000 dying of prostate cancer today is actually higher (~25) than it was in 1930 (~18).12 Wholesale screening results in earlier detection and treatment of a disease that would never cause harm. This is not progress; it is overtreatment13 due to overscreening.
Histologic Grade Determines Treatment
The histologic grade should determine whether the patient is treated. A Gleason grade totaling 6 or less for the primary and secondary areas commonly indicates that the disease will not cause the patient’s death. However, when the pattern results in a score of 7 or greater, the cancer has a much more aggressive course. For every one-level increase in histologic grade of either the primary or secondary pattern, there is a reduction in survival of 20% to 50% in every age range over 5, 10, and 15 years. These data are substantially true regardless of treatment.14
Does this imply that the patient’s survival is determined at the time of the diagnosis? Should patients who are diagnosed with a Gleason score of 7 to 10 be treated but have a higher expectation of prostate cancer leading to their death, and those with Gleason 6 or less be left untreated? Perhaps. What is absolutely certain is that there are tens of thousands of men who are needlessly or inappropriately treated (any treatment, wrong treatment, or treatment by an inexperienced doctor), either because they have low-risk prostate cancer, an expected survival of less than 10 years, or advanced disease.
Need for Research
Billions of dollars are expended annually in overscreening, overdiagnosis, and treatment of tens of thousands of American men,15 resulting in loss of quality of life. Only a tiny fraction of desperately needed money is focused on research.
Recent studies in genetics at the University of Michigan,16 Memorial Sloan-Kettering,17 Texas Southwestern,18 and Harvard19 have identified DNA signatures that are more prevalent in aggressive tumors. This type of critical basic research could lead to an understanding of which patients should be observed and which should be offered curative therapy.
Basic research must be expanded to determine which patients need treatment; medical decision-making must be based upon evidence and outcomes; and men should be treated by experienced doctors only if there is the likelihood that prostate cancer may cause their death. ■
References
1. Welch HG, Albertsen PC: Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986-2005. J Natl Cancer Inst 101:1325-1329, 2009.
2. Whitmore WF Jr: Natural history of low-stage prostate cancer and impact of early detection. Urol Clin North Am 17:689-697, 1990.
3. Andriole GL, Crawford ED, Grubb RL 3rd, et al: Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 360:1310-1319, 2009.
4. Schröder F, Hugosson J, Roobol SJ, et al: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 360:1320-1328, 2009.
5. Draisma G, Boer R, Otto SJ, et al: Lead times and over detection due to PSA screening: Estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst 95:868-878, 2003.
6. Tornblom M, Eriksson H, Franzen S, et al: Lead time associated screening for prostate cancer. Int J Cancer 108:122-129, 2004.
7. Blum RH, Scholz M: Invasion of the Prostate Snatchers. New York, Other Press, 2010.
8. Savage CJ, Vickers A: Low annual caseloads in US surgeons conducting radical prostatectomy. J Urol 182:2677-2679, 2009.
9. Klotz L: Active surveillance for favorable risk prostate cancer: What are the results, and how safe is it? Los Angeles, Prostate Cancer Research Institute. Available at http://www.prostate-cancer.org/education/localdis/klotz_activesurveillance.html.
10. NCI Cancer Bulletin, January 12, 2010. Available at http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/011210/page2. Accessed October 4, 2010.
11. Holmberg L, Bill-Axelson A, Helgesen F, et al: A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med 347:781-789, 2002.
12. Jemal A, Siegel R, Jiaquan Xu, et al: Cancer statistics, 2010. CA Cancer J Clin 60:277-300, 2010.
13. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Prostate cancer. V.3.2010. Available at http://www.nccn.org. Accessed October 4, 2010.
14. Albertsen PC, Hanley JA, Gleason DF, et al: Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. JAMA 280:975-980, 1998.
15. Saigal CS, Litwin MS: The economic costs of early stage prostate cancer. Pharmacoeconomics 20:869-878, 2002.
16. Palanisamy N, Ateeq B, Kalyana-Suldaram S, et al: Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma. Nat Med 16:793-798, 2010.
17. Taylor BS, Schultz N, Hieronymous H, et al: Integrative genomic profiling of human prostate cancer. Cancer Cell 18:11-22, 2010.
18. Kong Z, Xie D, Boike T, et al: Downregulation of human DAB2IP gene expression in prostate cancer cells results in resistance to ionizing radiation. Cancer Res 70:2829-2839, 2010.
19. Min J, Zaslavsky A, Fedele G, et al: An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-κB. Nat Med 16:286-294, 2010.
Dr. Boxer is Professor of Clinical Urology at the University of Miami and Clinical Professor at the University of Wisconsin, Madison, and the Medical College of Wisconsin.
Let Sleeping Dogs Lie is an important an valuable contribution to a man’s education about prostate cancer risk. Please see our comments about it on The “New” Prostate Cancer InfoLink. However, there are also dogs that are all to wide awake, and they can bite!
The fundamental issue is the need to be able to distinguish between risk for biologically evident prostate cancer (i.e., having some prostate cancer cells in one’s prostate, normally some time after age 40) and risk for clinically significant prostate cancer (i.e., prostate cancer that may metastasize in the near future).
We have NO test today that can accurately help any doctor or his male patients make that distinction. Finding genes that predispose some men to prostate cancer will not be enough to solve that problem, either, because genetic predisposition does not necessarily lead to clinical effect.
There is a massive need for high quality research into identification of the triggers that lead to prostate cancer cell growth and metastasis. Until we know more in this field, controversy will continue over the appropriate and inappropriate uses of the PSA test and other tests curently available … and these tests are simply not sufficiently sophisticated to do the job we ask of them.