Population-based assessment of treatment patterns for high-risk localized prostate cancer.

349 Background: Patients diagnosed with high- or very high risk (H/vHR) prostate cancer (PCa) are at substantial risk of disease recurrence, metastasis, and death after treatment. Historically, treatment paradigms for these patients have been similar to those with intermediate-risk (IR) disease [radiotherapy (RT) with androgen deprivation therapy (ADT) and radical prostatectomy (RP)] though there is a growing body of evidence supporting intensified systemic therapy in this group. To contextualize this emerging trial data, we characterized real world treatment patterns for these patients. Methods: We performed a retrospective population-based cohort study using province-wide linked administrative data in Ontario, Canada. We descriptively characterized initial treatment patterns (within 1 year of diagnosis) for men with H/vHR PCa and compared them to a concurrent cohort of patients with IR disease to assess differences in management. Results: We identified 13,206 patients diagnosed with H/vHR PCa from 2010-2021 who were compared to 18,365 with IR disease. Most patients received active treatment, though rates were statistically significantly higher in the H/vHR (n=12,606, 95.5%) than IR cohort (n=14,995, 81.6%; p<0.001; standardized diff 0.44). 6207 (47%) of patients in the H/vHR cohort and 7286 (40%) of patients in the IR cohort underwent RP (p<0.001; standardized difference 0.148). Median time to RP was 98 days in the HR cohort and 105 days in the IR cohort (Median time (Q1-Q3); p<0.003; standardized difference 0.11). 6321 (47.9%) of those with H/vHR disease and 7427 (40.4%) of those with IR disease underwent radiotherapy (p<0.001; standardized difference 0.150). Very few patients received intensified systemic therapy: 77 patients (0.2%) received chemotherapy and 49 (0.2%) received androgen receptor pathway inhibitors. While treatment patterns were similar, patients with H/vHR disease were more likely to progress to metastasis (46% vs 30%, p<0.001) and more rapidly (2.6 vs 4.3 years, p<0.001), with similar patterns observed for CRPC, mCRPC treatment, prostate cancer events, and death. Conclusions: Despite higher rates of treatment, patients with H/vHR localized disease experience significantly worse clinical outcomes than those with IR. These data highlight the need for therapies which can improve clinical outcomes in this patient population, such as the potential use of intensified systemic therapies including Androgen Receptor Pathway Inhibitors (ARPIs).