Use With Caution: Active Surveillance in Patients With Intermediate-Risk Prostate Cancer

D. Andrew Loblaw, MD

The risk of dying from prostate cancer increased fourfold when active surveillance was used to monitor men with intermediate-risk disease compared with low-risk prostate cancer patients, according to results of a new study, the first to examine long-term outcomes of patients with low- versus intermediate-risk prostate cancer who have been managed with this conservative approach to care.

Results were presented February 23 at a presscast held in advance of the 2015 Genitourinary Cancers Symposium, and they suggest that while overtreatment of low-risk prostate cancer remains a concern, when it comes to intermediate-risk patients more information is needed to determine who can safely be managed with active surveillance.

Active surveillance is recognized globally as standard care for low-risk and some intermediate-risk patients with prostate cancer. Patients on active surveillance undergo physical and digital rectal examinations, PSA measurements, and repeat tumor biopsies.

However, the overall utility of this approach for patients with intermediate-risk disease is unknown due to a lack of mature data. To glean a better understanding of its impact among intermediate-risk patients, researchers prospectively analyzed overall (OS) and cause-specific (CSS) survival data from 945 patients receiving active surveillance for their prostate cancer between 1995 and 2013.

Of the total, 732 had low-risk disease, and 213 had intermediate-risk disease, defined as either Gleason score ≥7, PSA >10 ng/mL, or clinical stage T2b/2c. Patients in the two cohorts were followed for a median of 6.4 and 6.9 years, respectively, and 61.5% of men in the intermediate-risk group were aged >70 years.

“When we looked at the low- and intermediate-risk groups, we did see a difference in overall survival, represented by a hazard ratio of 2.1—meaning an approximately twofold higher risk of dying from any cause for patients in the intermediate-risk group,” noted study coauthor Andrew Loblaw, MD, a radiation oncologist at Sunnybrook Health Sciences Centre in Canada where the patient data were collected. At 10 years, OS for patients with low-risk disease was 84.2% versus 67.3% in the intermediate-risk group. OS at 15 years was 66.7% and 50.8%, respectively.

“What surprised us,” Loblaw continued, “was that there actually seemed to be a greater risk of dying from prostate cancer for patients with intermediate-risk disease. The hazard ratio [for CSS] was 3.7, so almost a fourfold increase, and that was statistically significant.” At 15 years, 96.7% of men were free of prostate cancer death in the low-risk group versus 88.5% in the intermediate-risk group.

Loblaw said these data confirm that for patients with low-risk prostate cancer, active surveillance remains “a very safe, reasonable, and appropriate approach that aligns with guideline recommendations.”

He cautioned, however, that “despite the selection factors that we used in our clinic for intermediate-risk patients, we’re still seeing, at least in this analysis, a greater risk of dying from prostate cancer, and we believe that more research is needed to better identify the group of intermediate-risk patients who may be watched conservatively.”

“We think there is a group out there, but we want to be able to reproducibly identify these individuals so that we can do so safely.”

Presscast moderator Charles J. Ryan, MD, of the UCSF Helen Diller Family Comprehensive Cancer Center, concurred with this assessment. He noted the need to identify further markers of risk, including genomic and other biomarkers that are being studied and integrated into patient care.

Timothy Schultheiss, PhD, FASTRO, of City of Hope National Medical Center, believes there is a role for active surveillance in intermediate disease, and candidates for this approach include patients with a relatively short life expectancy. “Clearly, this can be defined as less than 10 years, because that is when the survival curves start to separate.”

“Overtreatment essentially is defined as treating patients who are very unlikely ever to die of prostate cancer. I think that is where active surveillance is an appropriate alternative,” said Schultheiss.

Musunuru HB, Klotz L, Vespirini D, et al. Cautionary tale of active surveillance in intermediate risk patients: overall cause-specific survival in the Sunnybrook experience. Presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL. Abstract 163.

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