Researchers analyzing clinical and pathological outcomes in men with low- and intermediate-risk prostate cancer under “active surveillance” found that — despite close monitoring —   metastatic disease develops in about 3 percent of these patients, and can rise to as high as 10 percent in those at the upper limits of intermediate risk. The study, “Metastatic Prostate Cancer in Men Initially Treated with Active Surveillance,” was published in The Journal of Urology, with data also presented at the 2015 Annual Meeting of American Urological Association in New Orleans.

Prostate specific antigen (PSA) testing has improved early diagnosis of prostate cancer. About 40 percent of new cases are determined to be lower-risk cancers, defined by a Gleason score (GS) of 6 or less with PSA levels of 10 ng/ml or less. Because prostate cancer treatment often includes radical therapies, such as surgery and radiation, active surveillance has been increasingly accepted as an effective approach in men with clinically insignificant disease and lower risk of cancer spread, so as to minimize aggressive treatments and their side effects. However, a small subset of patients are known to progress to metastatic disease.

Researchers, from Sunnybrook Health Sciences Centre at the University of Toronto, initiated an analysis in 1995 to understand how active surveillance correlates with pathological outcomes, assessing metastasis risk. The study included 980 patients, of whom 211 (21.5%) were classified as intermediate risk, 109 (11.1%) had baseline PSA values greater than 10 ng/ml, and 133 (13.6%) had GS 7 disease. Thirty of these men eventually developed metastases, including 18 people who developed metastases in the bones, and 13 in the lymph nodes.

Analyses confirmed for the researches that active surveillance appears to be a safe approach in low-risk patients and in select intermediate-risk patients, particularly those with GS 6 and PSA greater than 10 ng/ml, according to a press release.

“This is a detailed analysis of thirty patients initially treated with surveillance for what was thought to be favorable disease, but which eventually progressed to metastatic disease,” Laurence Klotz, MD, FRCS(C), professor of Surgery at the University of Toronto, said in the release. “We previously reported on five such patients. The current report represents a considerably larger group with longer follow-up, which presented an opportunity for risk analysis.”

The team also determined independent predictors of metastatic disease, namely PSA doubling in less than three years and a Gleason score of 7. “The presence of Gleason pattern 4 on diagnostic biopsy conferred a threefold to fourfold increased risk of metastatic disease,” Dr. Klotz said. “Such patients should be offered surveillance with caution. Further evaluation with magnetic resonance imaging and/or genetic biomarkers should be strongly encouraged if surveillance is elected as an option in these patients.”

But others were stronger in warnings against active surveillance of intermediate-risk based on these results. “The researchers may be overly optimistic about the safety of surveillance, particularly in patients with Gleason 7 disease,” said Michael O. Koch, MD, chairman of the Department of Urology at Indiana University School of Medicine. “Since median follow-up was only 6.3 years, the number of patients with Gleason 7 disease in whom metastases develop will grow even further. As of now active surveillance would appear to be ill-advised in this group of patients.”

Researchers acknowledged that the 3 percent figure is a best-case scenario, and emphasized the importance of proper disease classification to correctly determine which men with prostate cancer should be on active surveillance.