Observation as Good as Surgery for Some Men with Prostate Cancer

Adapted from the NCI Cancer Bulletin.

Many men diagnosed with early-stage prostate cancer could forego radical prostatectomy and live as long as men who have immediate surgery, according to long-awaited results from a clinical trial published July 19, 2012, in the New England Journal of Medicine (NEJM).

The results of the trial, called PIVOT, were initially presented in May 2011 at the American Urological Association annual meeting. But many researchers and clinicians have been anxious to see the published paper so they can delve into the trial’s details and better gauge how the results will affect clinical practice.

The trial took place from 1994 to 2002, when screening for prostate cancer with the prostate-specific antigen (PSA) test was becoming widespread. The 731 men in the trial, whose median age was 67, were diagnosed with localized prostate cancer based on PSA test results and a biopsy. They were then randomly assigned to undergo either a radical prostatectomy or observation, sometimes called “watchful waiting.”

Overall, after follow-up for as long as 15 years (median of 10 years), the percentage of men who died from any cause was similar in both groups: 47 percent in men assigned to surgery versus 49.9 percent in men who underwent observation, a difference that was not statistically significant. The absolute difference in the risk of dying from prostate cancer was very similar, 5.8 percent versus 8.4 percent, and was also not statistically significant.

The data suggested, however, that men in the surgery group whose PSA level was above 10 ng/mL had a lower risk of dying from any cause including prostate cancer, Timothy Wilt, M.D., of the Veterans Affairs Center for Chronic Disease Outcomes Research in Minneapolis, MN, and his colleagues reported. A similar, but not statistically significant, trend was seen among men whose cancer was considered to be at intermediate or high risk of progressing.

“Our findings add to evidence supporting observation, and possibly active surveillance, for most men who receive a diagnosis of localized prostate cancer, especially those with a low PSA value or low-risk disease,” they wrote.

The trial is “not necessarily definitive,” said Barry Kramer, M.D., M.P.H., director of NCI’s Division of Cancer Prevention. But the results, he continued, “are important findings that men can incorporate into the decision-making process” as they consider their options.

Dr. Kramer cautioned against extrapolating too much from the subset analyses that suggested a benefit from surgery for men with a PSA score above 10 ng/mL or high-risk disease. When the overall results of a study are not statistically significant, subgroup analyses “can give you variable and conflicting results,” he said. “You have to be careful in interpreting those findings.”

In an accompanying editorial in NEJM, Ian Thompson, M.D., of the University of Texas Health Science Center and Catherine Tangen, Dr.P.H., of the Fred Hutchinson Cancer Research Center argued that the trial’s size likely affected its results. PIVOT was originally designed to enroll 2,000 patients, but, due to difficulties in recruiting patients, the design was altered. In the end, Drs. Thompson and Tangen wrote, there were too few patients to provide the necessary statistical power to show whether surgery could reduce mortality.

The finding that men with low-risk cancer who underwent surgery had no reduction in the risk of dying is consistent with other studies of active surveillance, the editorialists continued, and “strongly supports this approach” for those men. “On the other hand, high-grade, aggressive prostate cancers usually have a lethal course if left untreated,” wrote Drs. Thompson and Tangen. “It is these men who are at greatest risk for death from cancer and who are most likely to benefit from therapy but whom we must treat effectively.”           

Although PIVOT compared surgery with watchful waiting, active surveillance appears to be a more commonly used approach than watchful waiting. A number of cancer centers have established active surveillance programs, said Ethan Basch, M.D., of Memorial Sloan-Kettering Cancer Center in New York. Dr. Basch chaired a panel assembled by the American Society of Clinical Oncology (ASCO) that issued recommendations on PSA screening for prostate cancer 2 days before the publication of the PIVOT results.

“When you put all of the available data together, you can begin to piece together a vision of a screening strategy” for prostate cancer, Dr. Basch said. Younger men who opt for PSA screening and are diagnosed with intermediate- or high-grade cancer would discuss potential treatments, while men diagnosed with low-grade disease would go into a surveillance program, he continued.

“That could potentially lead to a very different risk-benefit ratio for many men,” said Dr. Basch, one with a greater likelihood of benefit and a smaller risk of harms. He cautioned, however, that such a strategy needs to be tested prospectively in clinical trials.