Influence of Adverse Pathologic Features on Potential Benefit of Hormone Therapy Use with Postoperative Radiotherapy in Recurrent Prostate Cancer: An Individual Patient Data Meta-analysis.

Abstract

A recent individual patient data (IPD) meta-analysis of randomized trials found a limited overall survival (OS) and metastasis-free survival (MFS) benefit to the addition of hormonal therapy (HT) to postoperative radiotherapy for prostate cancer in patients with pre-radiotherapy prostate-specific antigen (PSA) ≤0.5 ng/ml. We evaluated whether the OS and MFS benefits of adding HT might be significantly modified by an increasing count of adverse pathological features (adverse feature count [AFC]). We obtained IPD from five randomized phase 3 trials of postoperative radiotherapy ± HT. AFC was prospectively defined as the sum (0-4) of grade group 4-5 disease, seminal vesicle invasion, positive surgical margins, and extracapsular extension. Intention-to-treat one-stage meta-analytical models were used. We also evaluated the interaction of the benefit of HT with a restricted score comprising only GG4-5 and seminal vesicle invasion (range 0-2), as a pre-specified sensitivity analysis. We included IPD from 4781 patients with a median follow-up of 9.1 yr. AFC was independently prognostic for OS and MFS. However, AFC did not significantly modify the OS benefit of HT (interaction hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.79-1.10; p = 0.4) or MFS benefit (interaction HR, 0.88; 95% CI, 0.77-1.01; p = 0.08). Results were similar when AFC was analyzed categorically and in high-risk subsets, and when the restricted AFC score was used. Overall, the data suggest that although adverse pathological features are prognostic, they do not appear predictive of HT benefit after postoperative radiotherapy, which is relevant for patients with a PSA ≤0.5 ng/ml before radiation.