Prostate Cancer Metastasis Risk Higher in Some AS Patients

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Study points to a need for caution in using active surveillance for men with Gleason 7 disease.

Metastases develop in a small proportion of patients placed on active surveillance (AS) for prostate cancer (PCa), but the risk is significantly higher in some men than others, such as those with Gleason 7 tumors, a new study found.

In a study of 980 men placed on AS—769 with low-risk and 211 with intermediate-risk PCa—a team led by Laurence Klotz, MD, of Sunnybrook Health Sciences Centre in Toronto found that 30 men (3%) progressed to metastatic disease at a median of 6.3 year after diagnosis, according to study findings published in The Journal of Urology (2016;195:1409-1414). Metastases developed in 13 (10%) of 133 patients with Gleason 7 disease.

Metastases occurred in 16 low-risk and 14 intermediate-risk patients, and developed in bone in 18 patients and lymph nodes in 13. Of the 30 men, 15 died from PCa, 4 died of other causes, and 11 are alive with metastases.

Patients with intermediate-risk disease were at higher risk for metastasis, but those with Gleason score 6 and PSA level greater than 10 ng/mL were not at increased risk.

In multivariate analysis, a PSA doubling time less than 3 years versus greater than 3 years was associated with a 3.7-fold increased risk of metastasis. Gleason score 7 compared with 6 was associated with a 3-fold increased risk. The presence of 3 or more positive biopsy cores was associated with a 2.7-fold increased risk compared with fewer positive cores.

The authors concluded that AS appears safe in patients at low risk and in select patients at intermediate risk, particularly those with Gleason score 6 and PSA levels greater than 10 ng/mL. The presence of Gleason pattern 4 on diagnostic biopsy was associated with a 3-fold to 4-fold increased risk of metastasis. Patients with Gleason pattern 4 should be offered active surveillance with caution, according to the investigators.

In editorial comments accompanying the new report, Michael O. Koch, MD, of the Indiana University School of Medicine in Indianapolis, said Dr. Klotz and his colleagues contribute to the growing body of knowledge of the usefulness of AS for managing PCa, but observed: “While the authors have highlighted the risk factors for developing metastases in patients treated with AS, they may be overly optimistic about the safety of this management strategy, particularly in patients with Gleason 7 disease.”

Dr. Koch pointed out that the median follow-up was only 6.3 years, so the number of patients with Gleason 7 disease in whom metastases will develop will grow even more. “As of now AS would appear to be ill-advised in this group of patients,” he noted.