OBJECTIVES: In the era of personalized medicine, oncologists seek to tailor treatments for their patients based on indicators of differential response to treatment. The objective of this study was to estimate the survival benefit associated with androgen deprivation therapy (ADT) receipt in elderly Medicare patients newly diagnosed with Stage 4 metastatic (S4M1) prostate cancer across patient subgroups defined by Gleason score and age. METHODS: We analyzed elderly men diagnosed with S4M1 prostate cancer between 2004-2009 in the SEER-Medicare datasets and followed through 2010 or until loss to follow-up. An inverse probability weighted Cox proportional hazards model with ADT-by-age and ADT-by-Gleason score interaction terms was used to estimate overall survival (OS) and prostate cancer-specific survival (PCSS). RESULTS: Among 4,691 patients, 3,426 (73%) men received ADT within the first 6 months of diagnosis and 1,265 (27%) men did not receive any form of ADT (median follow-up: 17 months). There were 3,173 total deaths in the cohort, 1,923 (61%) deaths of which were due to prostate cancer. Compared to the non-ADT group, ADT users had a 52%, 39%, 59%, and 62% relative reduction in the risk of all-cause death in men aged 66-70, 71-75, 76-80, and 80+, respectively (statistically significant; based on stratified hazard ratios from the Cox model). A similar trend was observed for PCSS for the age subgroups. Compared to the non-ADT group, ADT users had a 54% and 57% relative reduction in the risk of all-cause deaths and prostate cancer-specific deaths in men with Gleason 8-10, respectively. However, the startified hazard ratios for Gleason <8 showed no OS benefit (Gleason 2-6: [1.4 (0.79-2.44)] and Gleason 7: [0.88 (0.68-1.14)] or PCSS benefit (Gleason 2-6: [1.09 (0.53-2.20)]; Gleason 7: [1.05 (0.72-1.51)]. CONCLUSIONS: ADT was beneficial in terms of OS and PCSS for all age and Gleason score subgroups except men with Gleason score 2-6 and 7.