A fifteen-year study of men with prostate cancer compared so-called watchful waiting to radical prostatectomy or radiation treatment (New England Journal of Medicine, March 11, 2023). The researchers screened over 82,000 men for PSA levels between 1999 and 2009. Of that total, 2664 were diagnosed with localized prostate cancer. 545 underwent radiation therapy, 545 were randomized to active surveillance (watchful waiting) and 553 underwent radical prostatectomy. Did the outcome of this long-term trial suggest we are overtreating prostate cancer?
The Results of the “ProtecT” Trial:
The researchers called their 15-year study the “Prostate Testing for Cancer and Treatment (ProtecT) trial.” The goal was to evaluate:
“…the effectiveness of conventional treatments in clinically localized prostate cancer that was detected on prostate-specific antigen (PSA) testing.”
And the envelope please!
The results were somewhat surprising. Some experts might conclude we are overtreating prostate cancer:
“After median follow-up of 15 years, 45 patients (2.7%) had died of prostate cancer: 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group. No significant difference in prostate cancer mortality was found among the trial groups.”
The authors concluded that:
“After 15 years of follow-up, prostate cancer–specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer.”
More aggressive treatment did reduce the spread of the disease, but it did not change survival statistics.
Should Men With Prostate Cancer Delay Treatment?
Some commentators have concluded that men with a new diagnosis of prostate cancer could delay surgery or radiation therapy and instead participate in active surveillance. Others, however, point out that some of the strategies employed in this long-running trial are no longer the norm.
Modern testing, such as MRI prostate imaging, targeted biopsies and whole-body scans, have revolutionized diagnosis. There are also newer treatments that are more effective and less invasive.
The lead author of the study published in the New England Journal of Medicine told CNN that:
“The good news is that if you’re diagnosed with prostate cancer, don’t panic, and take your time to make a decision.”
CNN also quoted Dr. Bruce Trock, a professor of urology, epidemiology and oncology at Johns Hopkins University:
“When men are carefully evaluated and their risk assessed, you can delay or avoid treatment without missing the chance to cure in a large fraction of patients.”
Regardless of the decision, active surveillance is essential. That means regular checkups, PSA testing and careful followup with a knowledgeable health professional.
Another Study Also Asked If We Are Overtreating Prostate Cancer:
A study published in the Journal of the National Cancer Institute (July 17, 2013) created a firestorm of controversy within the urology community. Researchers performed autopsies on men who died between 2008 and 2011 from causes other than prostate cancer in Moscow, Russia, and Tokyo, Japan. During the autopsies the prostate glands were removed and prepared for pathology analysis. One experienced uropathologist analyzed all the slides using standard techniques.
Of the 320 prostates that were collected and analyzed, 37.3% of the Caucasian men (mean age 62.5 years old) had prostate cancer. So did 35.0% of the Asian men (mean age 68.5 years old). Roughly 40% of the men over 60 had identifiable prostate cancer and 60% of the men over 80 had prostate cancer.
Most fascinating of all, nearly one third of all the cancers were scored Gleason 7 or greater, meaning that they would be considered aggressive, requiring surgery or some other invasive treatment. Over half the Asian men had a Gleason score of 7 or greater. [The Gleason score is a way of characterizing the severity or aggressiveness of the tumor. A Gleason 6 is considered mildly aggressive, whereas a 7 is often described as moderately aggressive and frequently leads to treatment.]
Making Sense of Confusing Data:
OK, before your eyes glaze over, let’s cut to the chase. We need to reemphasize that the men in this study did NOT die from prostate cancer. Most probably did not even know that they had prostate cancer. They may have died from heart attacks, strokes, accidents or some other cause.
When their prostate glands were examined, a high proportion had high-grade cancers. That is what is so astonishing about this study. Had these guys been living in the U.S. and getting screened with a PSA test, many would have been biopsied and nearly half of the detected tumors would have been considered so serious that they would have required prompt treatment (surgery, radiation, anti-androgen drug therapy, etc).
Overtreating Prostate Cancer?
What are we to make of this research? The lead author, Dr. Alexandre Zlotta, is director of Uro-oncology at Mount Sinai Hospital in New York City. He and his colleagues introduce their research with this overview:
“The widespread use of prostate-specific antigen (PSA) testing has dramatically changed the prostate cancer (PCa) landscape, enhancing PCa detection at a more curable stage. The perverse effects of PSA testing have included the diagnosis of a considerable proportion of cancers that are probably indolent [slow to develop], carrying a low probability of progressing to clinically significant, lethal PCa. The lifetime risk for men in North America to be diagnosed with PCa is almost 17%, but the risk of dying from PCa is 3.4%.
“Although men with apparent indolent disease may be offered active surveillance, data suggest overtreatment of low-risk disease is a problem, with less than 10% of men electing active surveillance in the United States. As a result, men may suffer debilitating side effects such as sexual impotence and urinary incontinence.”
Dr. Zlotta was quoted by Reuters:
“The study suggests that the progression of early prostate cancer, including some more aggressive forms of the disease, is far from inevitable within a man’s lifetime as many such tumors are found in men who died from other causes when their prostate is analyzed on autopsy…The study concludes that it is probably worth re-examining our current definitions of clinically unimportant and clinically significant prostate cancer.” In the paper, Dr. Zlotta and his colleagues point out that “a large proportion of tumors are not destined to become life-threatening.”
When most men are told that they have prostate cancer and that a biopsy reveals it is “aggressive” because of a Gleason score of 7, they are easily convinced they need immediate treatment. What the latest study reveals, however, is that the story is far more nuanced and complicated.
Urologists do not know which cancers, even those with a Gleason score of 7, will remain “indolent,” not causing any worrisome disease and which will become a problem or lead to death. That leaves millions of men in a terrible bind. We encourage active surveillance, regardless of the decision.
You may find our interviews on prostate cancer worth listening to:
Prostate Cancer Puzzle (Free bonus interview with Dr. Katz)
How To Reduce Your Risk of Breast or Prostate Cancer (with Dr. Susan Love and Dr. Charles “Snuffy” Myers)
We would like to get your feedback on the latest study. What do you make of it? How do the results affect your understanding of prostate cancer? Will it change your communication with your doctor? Please share your own experiences with prostate cancer below in the comment section.