Abiraterone±enzalutamide (AR pathway inhibition) + ADT: early PSA ≤0.2ng/mL flags long-tail OS in STAMPEDE

This post-hoc landmark analysis pooled five randomized Phase 3 STAMPEDE comparisons in metastatic or very high-risk non-metastatic prostate adenocarcinoma (n=7129; recruited Oct 5, 2005–Sept 2, 2016) testing standard-of-care ADT (±docetaxel, depending on the specific STAMPEDE comparison) versus intensification with ADT+docetaxel±zoledronic acid, ADT+abiraterone acetate±enzalutamide (androgen receptor pathway inhibitors), or ADT+prostate radiotherapy (mHSPC only). PSA at 6/12/24 weeks after randomization stratified overall survival most strongly at 24 weeks, and PSA subcategories (≤0.2, >0.2–1.0, >1.0–3.0, >3.0ng/mL) separated outcomes differently by metastatic volume and (in non-metastatic disease) nodal status; notably, PSA ≤0.2ng/mL at any timepoint tracked with favorable prognosis and was similarly informative even when achieved early. In the abiraterone±enzalutamide groups, 96-month OS among men with PSA ≤0.2ng/mL at 24 weeks still varied substantially by disease extent—low-volume metastatic 64.1% (95% CI 57.8–69.8) vs high-volume metastatic 44.6% (37.1–51.9), while non-metastatic node-positive reached 79.4% (73.8–83.9) and non-metastatic node-negative was highest at 82.8% (78.7–86.1); for orientation, abiraterone+ADT improved OS versus ADT alone in STAMPEDE (HR 0.62) and docetaxel+ADT improved OS mainly in high-volume mHSPC in CHAARTED (HR 0.63), while prostate RT benefits OS in low-burden metastatic disease in STAMPEDE (HR 0.68).