How Long Should Active Surveillance Last?

 Men with low-risk prostate cancer who go on active surveillance rather than treatment are best followed-up for more than 15 years — and perhaps indefinitely — according one of the longest studies to date to look at the issue. 

Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years "suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed," said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. "These data are crucial, given the long current life expectancy" of men in otherwise good health. 

Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.

At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.

Long-Life Expectancy Justifies Extending

The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL. 

In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.

In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.

Treatment-Free Survival Falls to 31% 

The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers. 

While Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%. 

"These are non-negligible numbers," said Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.

Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.

The low rate of deaths from prostate cancer over the extended period is reassuring, Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered "safe."

Based on these data, "men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years," Palmstedt said.

Active Surveillance Now More Common

Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, a professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.

"The window of opportunity for cure is typically very wide," Cooperberg said. Although many men "will never need treatment…long-term surveillance is definitely important" for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed. 

"Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis," he explained.

Palmstedt reported no potential conflicts of interest. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health. 

https://www.medscape.com/viewarticle/how-long-should-active-surveillance-last-2024a10007kb