Systematic review of active surveillance for clinically localized prostate cancer to develop recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and surveillance repeat biopsy strategy

Context: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring and reclassification in active surveillance (AS) protocols for localized prostate cancer (PCa).

Objective: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy.

Evidence acquisition: A protocol-driven, PRISMA-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per-protocol and/or triggered). Clinical effectiveness data were not assessed.

Evidence synthesis: Of 17,011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264,852 patients were included. Only a minority of protocols included use of MRI for recruitment (n=17), follow-up
(n=47) and reclassification (n=26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with >3positive cores, and 39% of protocols excluded patients with core involvement (CI) >50%/core. ≥80% of protocols mandated a confirmatory TRUS biopsy. 72% (n=189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually, and 25% every 2 years. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy.

Conclusions: For AS protocols in which use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume ISUP 2 (≤3 positive cores and cancer involvement ≤50% CI/core) or another single element of intermediate-risk disease; patients with ISUP 3 should be excluded; (2) Per-protocol confirmatory prostate biopsies should be performed within 2 years, and per-protocol surveillance repeat biopsies should be performed at least once every 3 years for the first 10 years; and (3) For patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal >3 positive cores or maximum CI>50%/core, they should be monitored closely for evidence of adverse features (e.g. upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified.

Patient summary: We examined the literature to issue new recommendations on active surveillance (AS) for managing localized prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), thresholds for close monitoring of men with low-risk but more extensive disease, and when to perform repeat biopsies (within 2 years and 3 yearly thereafter).