Systematic Review of Time to Definitive Treatment for Intermediate-Risk and High-Risk Prostate Cancer: Are Delays Associated with Worse Outcomes?

Nguyen, David-Dan; Haeuser, Lorine; Paciotti, Marco; Reitblat, Chanan; Cellini, Jacqueline; Lipsitz, Stuart R; Kibel, Adam S; Choudhury, Atish D; Cone, Eugene B; Trinh, Quoc-Dien

PURPOSE Prostate cancer (PCa) is most commonly 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. Since treatment delay for intermediate-risk and high-risk disease is more controversial, we sought to determine if delays for these disease states negatively impacted oncological outcomes. MATERIALS AND 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 surgical (CSS), and overall survival (OS). 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 result of delays identified a higher risk of BCR and worse pathological outcomes, but not worse cancer-specific or OS. 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 there is a higher risk of BCR and worse pathological outcomes associated with delays beyond 6-9 months. To date, there are no reports of worse CSS or OS as a result of delayed treatment for intermediate-risk and high-risk PCa.