Panel Encourages Broader Use of Surveillance in Some Men with Prostate Cancer
An independent panel of experts met December 5–7 at an NIH-sponsored state-of-the-science conference on the role of active surveillance in the management of men with localized prostate cancer.
An independent panel of experts has endorsed delaying treatment, at least for a time, for many men who are diagnosed with forms of prostate cancer that likely pose no risk to long-term health.
Forgoing immediate treatment with surgery or radiation, both of which can have serious side effects, and instead actively monitoring the disease is a "viable option" for many men diagnosed with low-risk prostate cancer, the panel concluded in a draft statement from the NIH-sponsored state-of-the-science conference.
The large majority of men diagnosed each year with low-risk prostate cancer opt for immediate treatment with surgery or radiation. Both treatments can produce side effects that can seriously impair a man's quality of life, including erectile dysfunction and incontinence. Even so, in the United States only about 10 percent of men diagnosed with low-risk prostate cancer choose some form of observation.
The prognosis for men diagnosed with low-risk prostate cancer is so good, the panel concluded, that "strong consideration should be given to removing the anxiety-provoking term 'cancer' for this condition." Avoiding the term in these cases could encourage fewer men to pursue immediate treatment, several panel members suggested.
NIH convened the conference to assess data supporting active surveillance, the observation-first approach most commonly used in the United States for selected men with low-risk prostate cancer. Due to widespread screening with the prostate-specific antigen (PSA) test, low-risk prostate cancers now account for the majority of diagnosed cases. Active surveillance involves monitoring the cancer with PSA testing, digital rectal examination, and biopsies at routine intervals and initiating treatment with curative intent only if and when these monitoring techniques indicate that the disease may be progressing.
Defining Prostate Cancer Risk
The most recent clinical guidelines on prostate cancer from the National Comprehensive Cancer Network define very-low risk and low-risk disease as follows:
- Clinical stage T1c (no palpable disease, biopsy recommended based on abnormal PSA)
- Gleason score of 6 or less
- PSA density (ratio of PSA level to prostate gland size) of 0.15 ng/mL/cc or less
- Two or fewer biopsy cores in which cancer is present, and less than 50 percent cancer present in any involved core
- Clinical stage T1-T2a
- Gleason score 2-6
- PSA < 10 ng/mL
Based on studies showing similar survival outcomes compared with immediate treatment, active surveillance has been recommended for men with low-risk or very low-risk prostate cancer, depending on their life expectancy. Categorizations such as low-risk disease are based on the PSA score at diagnosis, the grade of the tumor's aggressiveness (Gleason score), and to what extent tumor cells are found in needle biopsy samples taken from the prostate.
"We estimate that more than 100,000 men diagnosed with prostate cancer each year in the United States would be candidates for active monitoring rather than immediate treatment," said the panel chair, Dr. Patricia Ganz of UCLA's Jonsson Comprehensive Cancer Center.
The conference covered a wide range of topics, such as how evolving pathology practices have affected tumor grading and the potential economic implications if more men diagnosed with prostate cancer were to pursue an observation-first approach.
A number of important questions remain about active monitoring approaches, the panel wrote. It's still unclear, for example, how best to carry out these observation-first protocols, including the frequency of biopsies, which carry their own risks. Effective approaches are still needed to improve the process by which patients interact with physicians to reach treatment decisions, panel members said, including informed discussions about options such as active surveillance.
Assessing the Evidence
Only two clinical trials comparing an observation-first approach with immediate treatment have been completed and both involved watchful waiting—that is, no routine monitoring and only initiating treatment to alleviate symptoms. The studies supporting active surveillance, on the other hand, have been observational.
The clinical trials presented at the conference produced conflicting results. The first, a Swedish trial, found that immediate treatment reduced the risk of prostate cancer death. But many men in the trial, only about 5 percent of whom were diagnosed by screening, had higher-risk disease than men considered to be candidates for observation-first approaches in the United States, acknowledged the trial's lead investigator, Dr. Lars Holmberg of King's College School of Medicine in London.
In a yet-to-be published U.S. trial, the Prostate Intervention Versus Observation Trial (PIVOT), however, overall and prostate-cancer specific mortality were very similar for low-risk men whether treated with watchful waiting or immediate surgery. About half of the men in this trial had their cancer diagnosed following a PSA screening test, and 40 percent were categorized as having low-risk disease.
"These are the men being treated in the United States today," said PIVOT's lead investigator, Dr. Timothy Wilt of the Veterans Affairs Center for Chronic Disease Outcomes Research in Minneapolis, MN. "Our data suggest that observation is the preferred option in men with low-risk disease."
Several large active surveillance programs are under way in North America, and although the programs are similar in most respects, they vary somewhat with regard to monitoring procedures and treatment triggers.
Despite the differences, very few prostate cancer deaths have occurred across these programs. For example, of the more than 650 men who have participated in the University of California, San Francisco's active surveillance program, none have died from prostate cancer, said the program's leader, Dr. Peter Carroll. Sixty-four percent of participants have lived at least 5 years without switching to active treatment. While most of the men in the program have low-risk disease, a small percentage of men have higher-risk disease.
Although some men will never require treatment, Dr. Carroll stressed that the aim of active surveillance is to delay treatment—and its potential side effects—as long as possible. "It's not treatment versus no treatment," he said. "That's important."
A modest proportion of men in the large active surveillance programs drop out, choosing to have surgery or radiation despite no evidence that their cancer is progressing. To understand why men make these decisions, research is needed on the role of factors such as anxiety and family pressures, the panel concluded. Future studies should compare the effectiveness of different active surveillance protocols, the panel recommended.
Several studies suggest that physician recommendation is perhaps the strongest factor driving men's treatment decisions. But a patient's role, and his reaction to a cancer diagnosis, shouldn't be discounted, said panel member Dr. Barry Kogan, chair of the Division of Urology at Albany Medical College.
"The word 'cancer' tends to set off an emotional response in patients," Dr. Kogan said, "that encourages them to pursue what they perceive to be the most effective treatment regimen."
A videocast of the conference is available online