Background: RTOG 9902 was a randomized controlled trial of the addition of adjuvant chemotherapy (CT; paclitaxel, oral etoposide, and estramustine x4 cycles) to 24 mo of androgen suppression (AS) and radiation (RT) for patients (pts) with high-risk CaP., beginning with an initial 4 mo of AS; RT began after 2 mo. 9902 accrued 397 pts and closed early due to excess toxicity. At a median follow-up of 9.2 years, there was no benefit to CT, but it is hypothesized that a subset analysis by post-RT PSA identifies pts that benefit from treatment intensification with CT. Methods: Post-RT PSA status was dichotomized at > 0.2 ng/mL within 1 mo of RT. Landmark analysis redefined starting times for disease-free survival (DFS), time to distant metastasis (TDM) and overall survival (OS) at 16 weeks post-RT (36 weeks post-randomization) when CT was planned to complete. Pts were excluded if they did not get RT or assigned CT, or experienced DFS events/lost to follow-up < 36 wks post-randomization. Hazard ratios (HR), 95% confidence intervals (CI), and PSA-by-treatment interaction were estimated by Cox or competing-risks regression. Results: 333 pts were analyzed: 190 without and 143 with CT. 37% of pts had a post-RT PSA ≤0.2, 34% > 0.2, and 29% no recorded PSA in the defined interval. CT was associated with improved DFS for pts with PSA > 0.2 (HR 0.59, 0.38-0.91), but not for those with PSA ≤0.2 (HR 0.94, 0.60-1.46; interaction p = 0.13). This association, for those with PSA > 0.2, persisted in those pts who received the full course of CT and trended in the same direction for pts receiving 1-3 cycles. CT was associated with a trend toward improved TDM in the PSA > 0.2 group (HR 0.56, 0.23-1.35) and not in the PSA≤0.2 group (HR 1.31, 0.36-4.70), based on 32 pts with metastases. OS did not show the same pattern (PSA > 0.2: HR 0.98, 0.55-1.77; PSA≤0.2: HR 0.57, 0.29-1.13). Conclusions: This analysis suggests that men with high-risk CaP and suboptimal response to AS+RT, as identified by post-RT PSA > 0.2, may benefit from adjuvant CT. Prospective trials using contemporary CT (e.g. docetaxel) will help optimize treatment for these men. NRG-GU002, recently activated, is addressing this issue.