Background: Novel hormonal therapy (NHT) i.e. novel androgen receptor or androgen synthesis inhibitors have been approved for treatment of pts with mCSPC and mCRPC based on improved OS. However, OS of patients after progression on first-line NHT for mCSPC is not well characterized. It is currently unknown whether the OS in pts “after” progression on first-line NHT in mCSPC versus mCRPC is significantly different. Herein, our objective was to assess OS after disease progression on NHT given as the first-line therapy in the mCSPC vs first-line therapy in mCRPC setting. Methods: In this IRB-approved study, patient-level data were collected retrospectively, only those treated with NHT as first-line therapy for mCSPC or mCRPC were included. For patients receiving NHT in the mCRPC setting, no prior NHT was allowed in the mCSPC setting. Median overall survival and hazard ratios were determined by Kaplan-Meier analysis. Results: A total of 173 pts (45 mCSPC and 128 mCRPC) were eligible and included in the analysis. Median OS in the mCSPC versus mCRPC were similar: 23 vs. 17 months, hazard ratio: 0.9855, (95% CI: 0.6225 – 1.560, P=0.951). See the table. Conclusions: These results suggest median OS is similar after progression on one NHT whether given in the first-line mCSPC or first-line mCRPC setting. These data have implications on patient counseling and prognostication as well as the design of clinical trials in patients experiencing disease progression on an NHT. These hypothesis generating data need external validation.