Watchful waiting has downsides, but physicians acknowledge overtreatment
Part One in a series
A general consensus exists in the prostate cancer field that “we diagnose more people than we need to diagnose, and we cure more people than we need to cure,” says Howard Parnes, MD, chief of the prostate and urologic cancer research group in the Division of Cancer Prevention for the National Cancer Institute in Bethesda, Maryland. “About 95% of men with a Gleason score of 6 are treated with radiation or surgery— we know that represents overtreatment,” Dr. Parnes says, adding that it is important to “consider the big picture.”
He notes that in the United States, a man's lifetime risk of being diagnosed with prostate cancer is 16%, while his lifetime risk of dying from the disease is 3%.
“Do we need to diagnose prostate cancer in 1 in 6 men?” Dr. Parnes asks. “The data strongly suggest that we do not. A recent estimate from the European Randomized Prostate Cancer Screening Trial (ERSPC) is that 48 men would have to undergo radical surgery or radiation to avert a single prostate cancer death. This provides a window into the magnitude of overtreatment.”
Pros and Perils of Watchful Waiting
One alternative to surgery and radiation is watchful waiting, which involves waiting for symptoms to develop after a prostate cancer diagnosis and treating those symptoms as they occur. Another alternative that has gained favor in recent years is active surveillance, which entails closely monitoring for changes in tumor biology, including frequent prostate-specific antigen (PSA) testing, digital rectal exams, and annual biopsies. Any significant changes in these measures would lead physicians to recommend curative treatment.
Although the medical community has become more accepting of both watchful waiting and active surveillance options for low-risk prostate cancer in recent years, many questions remain, such as which men can afford to wait?
“When you select someone for active surveillance, you presume you have all the information, but if you're wrong that's a problem,” says Badrinath Konety, MD, associate professor of urology and vice chairman of the department of urology at the University of California, San Francisco.“ It may be that they already had the disease but you didn't find it, or that the cancer changes in its biology, or a new cancer develops.”
Despite persistent questions about the relative merits of all types of prostate cancer treatments, however, very few randomized studies have been conducted comparing them. It is difficult to accrue patients for such trials, notes Dr. Parnes, because “it's not generally acceptable to patients or their doctors to either delay definitive therapy or to have the treatment modality chosen by random chance in a study.”
At the same time, given the very long natural history of prostate cancer, these studies require many years of follow up. Canadian and European researchers have done better at recruiting patients to studies comparing immediate therapy to expectant management with curative intent (active surveillance) because they seem more willing to question whether immediate treatment with its attendant side effects is definitely the best option, Dr. Parnes speculates.
The Scandinavian Prostate Cancer Group (SPCG) Study Number 4 was the first, large, randomized study to address surgery versus watchful waiting; it included data from695 patients. Final results, published in the Journal of the National Cancer Institute in 2008, showed that among men younger than age 65 years whose prostate cancer was detected in methods other than PSA testing, cure with surgery is possible.1 Results were less certain for men older than 65 years. The study concluded that after 12 years of follow up, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer—a difference of 5.4%. In addition, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases, a difference of 6.7%. No benefits were seen in overall survival, however.
The majority of patients participating in the SPCG study, however, were diagnosed by methods other than PSA testing, which is how most men in the United States are now diagnosed. How the study's results would apply to men in the United States with earlier diagnosed disease is not known.
Examining Treatment Options
Three studies currently underway are expected to provide additional information and may well change how low-risk prostate cancer is treated. The first, the US Prostate Cancer Intervention Versus Observation Trial (PIVOT), is expected to publish results next year. PIVOT began in 1992 and will compare radical prostatectomy to watchful waiting in 731 patients from 50 medical centers nationwide—primarily from US Veterans Affairs (VA) centers and the National Cancer Institute. PIVOT will expand on the SPCG-4 study by including three-quarters of patients whose tumors were detected by PSA and one-third who are African American.
The study will examine overall mortality, prostate-specific survival, and quality of life, including common side effects such as urinary incontinence, bowel problems, and sexual dysfunction.
“When we first started the study, there was concern over whether it could or should be done,” says PIVOT's chairperson, Timothy J. Wilt, MD, MPH, professor of medicine and staff physician at the Minneapolis VA Center for Chronic Disease Outcomes Research in Minneapolis, Minnesota.“ We've demonstrated both, and hopefully this will lead to other studies, such as comparing brachytherapy to surgery.”
Dr. Wilt believes the study will provide critically important information to help patients understand the risks and potential benefits of treatment versus watchful waiting and help improve their decision-making process on quality- of-life issues. “On average, the men in PIVOT had higher PSAs than those being diagnosed today,” he says. “That should be reassuring to men today that they have time to consider all their options.”
1Prostate cancer experts agree that patient overtreatment exists.
2Several current studies are trying to determine benefits of treatment versus watchful waiting and active surveillance.
3SPCG Study Number 4 showed some benefit to surgery versus watchful waiting in men younger than 65 years.
4Results from PIVOT are expected in 2010. It is a larger study than SPCG Number 4 and, unlike that study, included mostly men who were diagnosed by PSA screening (at earlier stages in their disease).
Dr. Wilt adds that PIVOT researchers have spent much time considering how to get their study's scientific information to patients in a user-friendly fashion after the study is completed. They have worked closely with the US Agency for Healthcare Research and Quality, which distributes to providers and patients information on making informed decisions. Two other current studies, which are looking at active surveillance rather than watchful waiting, are ProtecT in the United Kingdom and START in Canada. The next issue of “CancerScope”will look at these 2 trials.