The CHAARTED study showed that adding docetaxel (Doc) to androgen deprivation therapy (ADT) in men initiating treatment for metastatic hormone-sensitive prostate cancer (mHSPC) prolongs survival, particularly in high-volume disease. Androgens drive both mHSPC and metastatic castration-resistant prostate cancer (mCRPC). Lower nadir serum testosterone concentrations are associated with better outcomes in men treated with ADT for biochemical relapse, while higher androgens at mCRPC are associated with better prognosis and increased benefit from abiraterone. We evaluated the association of serum steroids at 24 weeks with overall survival (OS) and time to CRPC (TTCRPC) in 588 men with available samples from the CHAARTED study. Steroid concentrations were measured using mass spectrometry. The median testosterone concentration at 24 weeks was 8 ng/dL and did not differ in ADT alone vs ADT plus Doc arm. Achieving nadir testosterone below 20 ng/dL was not associated with OS or TTCRPC in either arm. In high-volume disease, Doc conferred an OS and TTCRPC benefit regardless of steroid concentrations. In low-volume disease, steroid concentrations in the lowest quartile at 24 weeks identified a subset of men with poor survival outcomes more like high-volume disease, and in whom Doc was also associated with improved OS and TTCRPC. The known OS benefit of Doc in high-volume mHSPC is not modified by serum steroid concentrations achieved on treatment. In low-volume disease, steroid concentrations in the lowest quartile may identify a poor prognosis subset in whom Doc also confers OS benefit.
Keywords: E3805; chemohormonal therapy; docetaxel; hormone sensitive; prostate cancer; steroid levels.