Survival outcomes in metastatic castration-resistant prostate cancer in the up-front treatment era.

Abstract

336 Background: Several studies have shown that the survival outcome of patients with metastatic prostate cancer after progression to metastatic castration-resistant prostate cancer (mCRPC) appears to be independent of a variety of prognostic factors, suggesting that prolonged time-to-CRPC is important for overall survival. However, the findings of these studies are based on data before the clinical application of up-front therapies such as docetaxel, abiraterone, enzalutamide, and apalutamide for hormone-sensitive metastatic prostate cancer (mHSPC), and the survival of patients with mCRPC with disease progression on up-front treatment has not been fully investigated. Methods: We retrospectively identified 318 patients diagnosed with treatment-naïve mHSPC between March 2014 and January 2022 from our database of 13 affiliated institutions. The patients included in this study were those who received the first-line treatment for mHSPC and progressed to mCRPC and received a second-line treatment. We defined the up-front group as patients who received abiraterone, apalutamide, or enzalutamide in addition to androgen deprivation therapy (ADT) as the first-line treatment for mHSPC, and the vintage group as patients who received ADT alone or bicalutamide or flutamide in addition to ADT. We compared the time-to-CRPC in each group, i.e., the time from diagnosis of mHSPC to progression to mCRPC. We also compared the overall survival (OS) after CRPC and the progression-free survival (PFS) after CRPC, calculated from the diagnosis of castration resistance, between the up-front group and the vintage group. To minimize selection bias, we performed propensity score matching between the up-front group and vintage group and adjusted for covariates such as age, metastatic burden, and Gleason score. Results: Of the 318 patients, 100 were in the up-front group and 218 in the vintage group. Fifteen of the up-front group and 205 of the vintage group progressed to mCRPC within the observation period and received second-line treatment. Fourteen patients from each group were extracted for the analysis of survival after CRPC by propensity score matching, and the clinicopathologic variables in each group were well balanced. In the analysis of the propensity score-matched cohort, time-to-CRPC was significantly prolonged in the up-front group compared to the vintage group (median, not-reached vs. 10.7 months; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.12-0.28; p<0.001), while OS after CRPC (median, 18.2 months vs. not-reached; HR, 13.80; 95% CI, 1.52-125.10; p=0.019) and PFS after CRPC (median, 4.7 months vs. not-reached; HR, 7.73; 95% CI, 2.05-229.19; p=0.003) were significantly shortened in the up-front group. Conclusions: Although overall survival of mHSPC has improved in the up-front therapy era compared to the vintage hormonal therapy era, survival after disease progression to mCRPC may be shortened.