Impact of advances in therapy on survival in patients with de novo metastatic prostate cancer.
Authors: Adekolujo Orimisan Samuel , Akanbi Maxwell Oluwole , Wahab Ahsan , Mosalem Osama , Adekolujo Oyebimpe O , Wang Ling , Hrinczenko Borys , Isaac Dan 
Published: June 2022

e17052 Background: The approval of newer therapies including novel androgen pathway inhibitors (abiraterone [2011], enzalutamide [2012], apalutamide [2018]), and radium 223 dichloride [2013]) in the past decade has expanded the therapeutic landscape for patients with metastatic prostate cancer (mPCa). Such therapies have demonstrated a consistent benefit on survival in clinical trials including highly selected patients. However, the benefit on survival at the population level is unknown. This study aims to evaluate the impact of therapeutic advancements in the past decade on survival in patients with de novo mPCa using the SEER database. Methods: We included males with de novo mPCa ≥18 years of age in the SEER database from 2000 to 2018. Patients with missing survival data and those diagnosed at autopsy were excluded. Using the year of diagnosis, patients were categorized into two therapeutic periods: 2000-2010 (period A) and 2011-2018 (period B). The period 2011 to 2018 corresponds to the timeline of approval for novel antiandrogens and radium 223. Kaplan-Meier was used to estimate prostate cancer-specific survival (pCS) and overall survival (OS). Log-rank test was used to compare pCS and OS between the two periods. Univariate and multivariate cox regression models were performed to determine the significant covariates for pCS and OS. Results: A total of 33,969 patients were included in the analysis; 15,433 in period A (45.4%) and 18,536 in period B (54.6%). The mean age was 70.9(SD:10.5) and 61% were Caucasian. No significant difference was noted in the clinicopathologic and socioeconomic characteristics in both periods. The median pCS (36 vs. 30 months, p < 0.001) and OS (30 vs. 25 months, p < 0.001) were longer in period B compared to period A. In the multivariate model for pCS, diagnosis during period B was associated with a significantly decreased hazard of death from prostate cancer (HR:0.89, CI: 0.85-0.94, p < 0.001). Age > 80 years (HR:1.6, p < 0.001), PSA > 50 ng/mL (HR:1.3, p < 0.001), and poorly differentiated histology (HR:2.0, p < 0.001) were significant predictors of worse pCS. Hispanic origin (HR:0.94, p = 0.02) and median household income > $75000 (HR:0.86, p = 0.007) were associated with better pCS. In the multivariate model for OS, diagnosis in period B was associated with a decreased hazard of death from any cause (HR:0.89, CI:0.85-0.93, p < 0.001). Age > 65 years (HR:1.26, p < 0.001), PSA > 50 ng/mL (HR:1.30, p < 0.001), and poorly differentiated histology (HR:1.6, p < 0.001) were associated with worse OS. Hispanic origin (HR:0.94, p = 0.01) and median household income > $75000 (HR:0.81, p < 0.001) were associated with better OS. Conclusions: The diagnosis of de novo mPCa during the period of the therapeutic advancement (2011-2018) was associated with improved pCS and OS. However, the observed 11% reduction in the risk of death from any cause in this population-based study was smaller than the reported 20 to 38% in clinical trials.