Active Surveillance for Intermediate-risk Prostate Cancer: A Systematic Review, Meta-analysis, and Metaregression

Context: Active surveillance (AS) is increasingly selected among patients with localized, intermediate-risk (IR) prostate cancer (PCa). However, the safety and optimal candidate selection for those with IR PCa remain uncertain. Objective: To evaluate treatment-free survival and oncologic outcomes in patients with IR PCa managed with AS and to compare with AS outcomes in low-risk (LR) PCa patients. Evidence acquisition: A literature search was conducted through February 2022 using PubMed/Medline, Embase, and Web of Science databases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed to identify eligible studies. The coprimary outcomes were treatment-free, metastasis-free, cancer-specific, and overall survival. A subgroup analysis was planned a priori to explore AS outcomes when limiting inclusion to IR patients with a Gleason grade (GG) of ≤2. Evidence synthesis: A total of 25 studies including 29 673 unselected IR patients met our inclusion criteria. The 10-yr treatment-free, metastasis-free, cancer-specific, and overall survival ranged from 19.4% to 69%, 80.8% to 99%, 88.2% to 99%, and 59.4% to 83.9%, respectively. IR patients had similar treatment-free survival to LR patients (risk ratio [RR] 1.16, 95% confidence interval (CI), 0.99-1.36, p = 0.07), but significantly higher risks of metastasis (RR 5.79, 95% CI, 4.61-7.29, p < 0.001), death from PCa (RR 3.93, 95% CI, 2.93-5.27, p < 0.001), and all-cause death (RR 1.44, 95% CI, 1.11-1.86, p = 0.005). In a subgroup analysis of studies including patients with GG ≤2 only (n = 4), treatment-free survival (RR 1.03, 95% CI, 0.62-1.71, p = 0.91) and metastasis-free survival (RR 2.09, 95% CI, 0.75-5.82, p = 0.16) were similar between LR and IR patients. Treatment-free survival was significantly reduced in subgroups of patients with unfavorable IR disease and increased cancer length on biopsy. Conclusions: The present systematic review and meta-analysis highlight the need to optimize patient selection for those with IR features. Our findings support limiting the inclusion of IR patients in AS to those with low-volume GG 2 tumor. Patient summary: Active surveillance is increasingly used in patients with localized, intermediate-risk (IR) prostate cancer. In this population, we have reported higher risks of metastasis and cancer mortality in unselected patients than in patients with low-risk features, underscoring the need to optimize the selection of patients with IR features.