Cautionary Tale in Long-Term Surveillance of Prostate Cancer

Nick Mulcahy

February 24, 2015

The hopeful idea that active surveillance can be used to manage intermediate-risk prostate cancer got deflated a bit yesterday during a presscast that precedes the Genitourinary Cancers Symposium (GUCS) 2015 being held later this week in Orlando, Florida.

In a single-center cohort study, 213 intermediate-risk patients had a 3.75 times higher chance of dying of prostate cancer compared with 708 low-risk patients (11.5% vs 3.7% at 15 years; P = .01), according to D. Andrew Loblaw, MD, a radiation oncologist at Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada.

Median follow-up was 6.4 years for the low-risk group and 6.9 years for the intermediate-risk group.

The groundbreaking Toronto data are the first long-term outcomes of patients with intermediate-risk prostate cancer managed on active surveillance (defined as having prostate-specific antigen levels higher than 10 ng/mL, Gleason score 7, or clinical stage T2b/2c).

The greater risk for death from prostate cancer "surprised" Dr Loblaw and colleagues, who have been active surveillance pioneers, because the team expected — and found — that overall survival was worse for the intermediate-risk patients, who had more comorbidities and a shorter life expectancy compared with patients with low-risk disease.

Active surveillance is used in these patients because they will likely die of something other than prostate cancer, which has a protracted mortality timeline, Dr Loblaw explained.

But that was not the case.

"Some patients with intermediate-risk disease do in fact die of prostate cancer — that's important," said urologist Charles Ryan, MD, from the University of California, San Francisco, who moderated the presscast.

Should active surveillance be abandoned in intermediate-risk patients?

Dr Loblaw said that "more research is needed to identify suitable patients."

The new data are a "cautionary tale," said the authors in their meeting abstract.

Furthermore, "extreme caution" is needed when using active surveillance in men with intermediate-risk disease, they conclude.

The Toronto investigators plan to further analyze their cohort data, including data from patients who have "favorable" and "unfavorable" intermediate risk, among other variables, Dr Loblaw commented. This risk stratification was used in a recent American study, published last week in JAMA Oncology, which concluded that favorable risk patients are, in fact, candidates for active surveillance.

Dr Ryan believes more markers, either clinical or molecular, are needed to stratify risk.

Another expert endorsed active surveillance, but in a restricted group of men.

"I think there is a role for active surveillance in intermediate-risk disease," said Timothy E. Schultheiss, PhD, a radiation physicist at City of Hope in Duarte, California, who also participated in the presscast during the question-and-answer session.

Men managed with this strategy should be limited to those with less than 10 years' life expectancy, "because that is when the survival curves start to separate," Dr Schultheiss said, referring to the point in the study when the difference in prostate cancer–specific survival between the low- and intermediate-risk groups started to emerge.

The 10-year prostate cancer–specific survival was 95.5% for the intermediate-risk group and 98.2% for the low-risk group (P = .01).

Notably, about 40% of the men in the intermediate-risk group were younger than 70 years, which is not typical. Typically, men with intermediate-risk disease who are managed with active surveillance tend to be older than age 70 years, said Dr Lablow.

The study's prostate cancer death data, which were first published online in the Journal of Clinical Oncology in December (2015;33:272-277), "garnered a little bit of concern from the other [active surveillance] groups around the world," he also said. But the 15-year prostate cancer–specific survival results in the low-risk group were confirmatory evidence that active surveillance is "safe and appropriate" in these low-risk men, said Dr Lablow.

In the intermediate-risk group, about one third (36%) of the patients went on to receive treatment (mainly radiotherapy).

The median treatment-free interval for intermediate-risk patients was 12.3 years. Overall, 33 intermediate-risk patients developed biochemical failure.

In addition, 17 patients developed metastatic disease (11 with intermediate-risk [4.6%] and six with low-risk [0.8%] disease).

This study received funding from Prostate Cancer Canada and Sunnybrook Health Sciences Centre. Dr Loblaw has financial ties with GlaxoSmithKline, Merck, Bristol-Myers Squibb, Novartis, Roche, Amgen, Astellas Pharma, Sanofi, Janssen Oncology, Paladin, Janssen Oncology, Amgen, Elekta, and Paladin. Dr Ryan reports financial ties to Astellas Pharma, Janssen Oncology, Bayer, Millennium, BIND Karyopharm, and Novartis. Dr Schultheiss has disclosed no relevant financial relationships.

Genitourinary Cancers Symposium (GUCS) 2015: Abstract 163. To be presented February 26.


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