Hormone therapy use and duration with post-operative radiotherapy for recurrent prostate cancer: An individual patient data meta-analysis.

Abstract

305 Background: Addition of hormonal therapy (HT) to definitive radiotherapy (RT) in localized prostate cancer improves overall survival (OS). However, the effect of HT on OS when added to post-operative RT (PORT) after radical prostatectomy is less clear. Herein, we report an individual patient data (IPD) meta-analysis of randomized trials to quantify the benefit of adding HT to PORT. Methods: The POSEIDON meta-analysis was an IPD meta-analysis of randomized phase 3 trials of PORT±HT utilizing IPD from the MARCAP consortium. The primary outcome was OS. Meta-analyses evaluated the benefit of HT to PORT, addition of short-term HT (ST-HT, 4-6 months), or addition of long-term HT (LT-HT, 24 months) to PORT. Tests for interaction based on pre-PORT PSA and duration of HT were evaluated and non-linear associations between pre-PORT PSA and OS were modeled with cubic splines. Results: Six phase 3 trials were eligible for inclusion in our analysis and had IPD available (6057 patients, median follow-up of 9.02 years). The addition of HT to RT did not improve OS (HR 0.87, 95%CI 0.76-1.01, p=0.06). There was no significant interaction between duration of HT and this effect (p-interaction 0.25), though there was a significant interaction based on pre-PORT PSA >0.5 ng/mL vs. ≤0.5 ng/mL (p-interaction 0.02). For all pre-PORT PSA values, the upper bounds of the 95% CI of the hazard ratio for OS crossed 1 for patients randomized to ±ST-HT (n=3938). For patients randomized to ±LT-HT (n=1088), the upper bounds of the 95% CI for OS fell below 1.0 at PSA >1.6 ng/mL. Conclusions: Our findings provide the strongest level of evidence to date to suggest there is no meaningful OS benefit to adding HT, either ST- or LT-HT, to PORT for PSA <0.5 ng/mL in biomarker unselected patients, with no apparent difference in efficacy for ST-HT versus LT-HT.