Real-World Management of High-Risk Prostate Cancer Post-Radical Prostatectomy: Insights from a Regional Quality Collaborative

Background/Objectives: Data from clinical trials showing the non-inferiority of early salvage radiotherapy were recently incorporated into societal guideline statements. However, questions remain regarding ideal prostate-specific antigen (PSA) criteria for salvage, and how to apply these findings to pathologic lymph node-positive (pN+) disease. We investigated variance in management of clinically localized prostate cancer found to have high-risk features after radical prostatectomy. Methods: We retrospectively identified patients from May 2015 to January 2024 utilizing a multi-institutional, regional collaborative database. The primary outcome was identifying factors associated with the receipt of adjuvant versus salvage therapy. Factors associated with secondary treatment were assessed via multivariable logistic regression. Results: In total, 230 (38%) patients received adjuvant and 375 (62%) received salvage therapy. Rates of adjuvant versus salvage therapy differed by practice setting (p < 0.001). A higher percentage of patients received salvage (38.9%) over adjuvant (13.5%) therapy in or after 2020 (p < 0.001). In our model, patients with preoperative PSA ≥ 10 ng/mL (OR: 2.15, CI: 1.31–3.53) and treatment in or after 2020 (OR: 3.41, CI: 1.75–6.66) had higher odds, while patients with persistent detectable postoperative PSA ≥ 0.1 ng/mL had lower odds (OR: 0.39, CI: 0.20–0.74) of undergoing salvage therapy. Among pN+ patients, 51% received adjuvant and 49% received salvage therapy. Conclusions: The management of high-risk prostate cancer remains varied. In our regional cohort, rates of salvage versus adjuvant therapy increased after publication of level-one evidence. Further work is warranted to better delineate who will most benefit from adjuvant versus early salvage therapy.