Metastasis and Mortality in Men With Low- and Intermediate-Risk Prostate Cancer on Active Surveillance

Abstract

Background: Active surveillance (AS) is a safe treatment option for men with low-risk, localized prostate cancer. However, the safety of AS for patients with intermediate-risk prostate cancer remains unclear. Patients and Methods: We identified men with NCCN-classified low-risk and favorable and unfavorable intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration. We analyzed progression to definitive treatment, metastasis, prostate cancer–specific mortality (PCSM), and all-cause mortality using cumulative incidences and multivariable competing-risks regression. Results: The cohort included 9,733 men, of whom 1,007 (10.3%) had intermediate-risk disease (773 [76.8%] favorable, 234 [23.2%] unfavorable), followed for a median of 7.6 years. The 10-year cumulative incidence of metastasis was significantly higher for patients with favorable (9.6%; 95% CI, 7.1%–12.5%; P<.001) and unfavorable intermediate-risk disease (19.2%; 95% CI, 13.4%–25.9%; P<.001) than for those with low-risk disease (1.5%; 95% CI, 1.2%–1.9%). The 10-year cumulative incidence of PCSM was also significantly higher for patients with favorable (3.7%; 95% CI, 2.3%–5.7%; P<.001) and unfavorable intermediate-risk disease (11.8%; 95% CI, 6.8%–18.4%; P<.001) than for those with low-risk disease (1.1%; 95% CI, 0.8%–1.4%). In multivariable competing-risks regression, favorable and unfavorable intermediate-risk patients had significantly increased risks of metastasis and PCSM compared with low-risk patients (all P<.001). Conclusions: Compared with low-risk patients, those with favorable and unfavorable intermediate-risk prostate cancer managed with AS are at increased risk of metastasis and PCSM. AS may be an appropriate option for carefully selected patients with favorable intermediate-risk prostate cancer, though identification of appropriate candidates and AS protocols should be tested in future prospective studies.