Background: Chemohormonal therapy with androgen deprivation therapy and docetaxel (ADT+D) improves overall survival (OS) and quality of life (QOL) at 12 months compared to ADT alone in metastatic hormone sensitive prostate cancer (mHSPC). However, the prognostic relationship between QOL, disease characteristics, and OS has not been described in this population. Methods: In this post-hoc exploratory analysis of the CHAARTED trial, the QOL instrument Functional Assessment of Cancer Therapy-Prostate (FACT-P) was completed by patients treated with ADT and ADT+D. Log-rank test and Cox proportional hazards models were used to test the association between QOL and OS by clinical and disease characteristics. Results: 790 men were included in the study (ADT+D, n = 397; ADT, n = 393). Baseline higher QOL by FACT-P (n = 790) was associated with better OS in univariate regression (HR 0.70 [0.55,0.90], p = 0.005), however the association was not significant in multivariate analysis (HR 0.80 [0.62-1.04], p = 0.09). There was a trend towards improved survival for patients with the lowest baseline QOL (lowest quartile) treated with ADT+D compared to ADT (HR 0.75 [0.53, 1.05], p = 0.09). In contrast, patients with the highest baseline QOL (highest quartile, 63% high volume disease) had similar survival regardless of treatment arm (HR 0.92 [0.63-1.36], p=0.69). Higher 3-month QOL by FACT-P (n = 654) was associated with survival in the multivariate analysis independently of treatment arm (HR 0.76 [0.58, 1.0], p = 0.05). Patients with the highest 3-month QOL had comparable survival regardless of treatment arm (HR 1.11 [0.73, 1.67], p = 0.63), while patients with the lowest 3-month QOL experienced a survival benefit with ADT+D compared to ADT (HR 0.69 [0.48, 0.99], p = 0.047). Conclusions: In this analysis, 3-month QOL by FACT-P was significantly associated with survival for patients with mHSPC. Patients with the poorest QOL ("most symptomatic”) appeared to experience survival benefit from ADT+D regardless of disease volume. Conversely, patients reporting the highest QOL (“least symptomatic”) did not seem to benefit from ADT+D despite a predominance of patients with high volume disease in that cohort. These findings suggest that consideration of QOL may enhance decision making and patient selection when considering chemohormonal treatment for mHSPC.

* Adjusting for treatment arm, performance status, disease volume, Gleason score, and prior local therapy.