Systematic review of time to definitive treatment for intermediate-risk and high-risk prostate cancer: Are delays associated with worse outcomes?

233 Background: Prostate cancer (PCa) is an indolent disease, especially when detected at a localized stage. Unlike other tumors that may benefit from timely receipt of definitive therapy, it is generally accepted that treatment delays for localized PCa are acceptable, especially for low-risk PCa. We sought to determine if treatment delays for intermediate-risk and high-risk PCa negatively impacted oncological outcomes. Methods: We conducted a systematic review of the literature with searches of Medline, EMBASE, and the Cochrane Database of Systematic Reviews, from inception to June 30, 2020. General study characteristics as well as study population and delay information were collected. The outcomes of interest extracted included biochemical recurrence (BCR), pathological features (positive surgical margins, upgrading, extracapsular extension, and other pathological features), cancer-specific survival, and overall survival. Due to significant heterogeneity between studies, a meta-analysis was not possible. Results: After identifying 1793 unique references, 24 manuscripts met criteria for data extraction, 15 of which were published after 2013. Based on our review, delays up to 3 months are safe for all PCa and are not associated with worse oncological outcomes. Some studies identified worse oncological outcomes as a result of delays beyond 6 to 9 months. However, these studies are counterbalanced by others finding no statistically significant association with delays up to 12 months. Studies that did find worse outcomes as a result of delays identified a higher risk of BCR and pathological findings, but not worse survival. Conclusions: Definitive treatment for intermediate-risk and high-risk PCa can be delayed up to 3 months without any oncological consequences. Some evidence suggests that delays beyond 6-9 months are associated with a higher risk of BCR and varying worse pathological findings; as such, care should be given to provide definitive treatment within 9 months. To date, there is no evidence of worse cancer-specific or overall survival as a result of delayed treatment for intermediate-risk and high-risk PCa.