Absolute PSA value after androgen deprivation (AD) is a strong independent predictor of survival in new metastatic (D2) prostate cancer (PCa): Data from Southwest Oncology Group Trial 9346 (INT-0162)

4517 Background: PSA is a biomarker for monitoring disease activity in PCa. It is not well established if absolute PSA values achieved after AD is prognostic in patients (pts) with new D2 PCa. Methods: Hormone naive D2 pts with baseline PSA ≥ 5ng/mL are treated with 7 months (ms) AD induction. Pts achieving PSA-n (PSA ≤ 4.0 ng/ml that is stable or declining on ms 6 and 7) are randomized to continuous vs. intermittent AD on month 8. To be eligible for this analysis (approved by Data Safety Monitoring Committee), pts had to have a prestudy PSA with at least 2 subsequent PSAs during induction and be registered at least 1 year prior to analysis date. Survival was defined from 8 months to death due to any cause. Associations were evaluated by proportional hazards regression models. P≤0.05 was statistically significant. Results: Of the first 1,395 registered pts, 1345 were eligible for this analysis. Median age was 70 years, median baseline PSA 76.1 ng/mL, 38% had bone pain (BP) and 47 % had Gleason sum (GS) > 7. Median number of on-study PSAs during induction was 5 (range: 2 -18). Of the 1,345 pts, 1134 achieved PSA-n with 965 maintaining PSA-n at end of induction. Of those achieving PSA-n, 604 (45% of all pts) had an undetectable PSA (PSA-u, ≤ 0.2 ng/mL) at end of induction. In multivariate analysis, 4 significant independent risk factors were associated with post-induction survival: Performance status, GS, BP, and being randomized. After adjustment for these factors, pts who had a PSA-n at the end of induction but not PSA-u had less than half the risk of death (RoD) as those who did not have PSA-n (HR: 0.41; 95% CI 0.32, 0.54, p < 0.001), and pts with PSA-u had about one-quarter the RoD as pts with no PSA-n (HR: 0.26; 95% CI 0.20, 0.35, p < 0.001). After adjustment for covariates, pts with PSA-u had significantly better survival than those with only PSA-n at end of induction (p < 0.001). The median overall survival was 13 ms for the 383 not normalized (95% CI: 11 to 16 ms), 44 ms for the 360 pts normalized but not undetectable (95% CI: 39 to 55 ms), and 75 ms for the 602 pts with PSA-u (95% CI: 62, 91 ms). Conclusion: Achieving a PSA-n or PSA-u after 7 ms of AD is a strong predictor of survival and should be used to tailor future trial design in new D2 pts. [Table: see text]