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 dis-ease 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.(c) 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Automated summary

This systematic review and meta-analysis highlight the need to optimize patient selection for those with intermediate-risk (IR) features. The findings demonstrate that unselected IR patients have higher risks of metastasis and cancer mortality compared to patients with low-risk features, underscoring the importance of optimizing the selection of patients with IR features.