Duration of Androgen Suppression with Postoperative Radiotherapy (DADSPORT) for Nonmetastatic Prostate Cancer: A Collaborative Systematic Review and Meta-analysis of Aggregate Data
Sarah Burdett, David J. Fisher, Jayne F. Tierney, Adrian Cook, Daniel E. Spratt, James J. Dignam, Wendy Seiferheld, Amar U. Kishan, Yilun Sun, Sylvie Chabaud, Jason A. Efstathiou, Christopher Parker, Alan Pollack, Paul Sargos, I. Latorzeff, Meryem Brihoum, Charles Catton, Noel W. Clarke, Felix Y. Feng, Theodore Karrison, P. Pommier, Howard M. Sandler, Matthew R. Sydes, Claire L. Vale
Abstract
BACKGROUND AND OBJECTIVE: To better understand the role of hormone therapy (HT) with postoperative radiotherapy (RT) for nonmetastatic prostate cancer, the DADSPORT Collaboration planned a systematic review and meta-analysis of aggregate data from randomised controlled trials (RCTs). METHODS: RCTs evaluating HT with postoperative RT in people with nonmetastatic prostate cancer were identified. Methods were prespecified prior to results of recent trials being known (CRD42022325769). The primary outcome was overall survival (OS); metastasis-free survival (MFS) and prostate cancer-specific survival (PCSS) were the secondary outcomes. Summary results, including those by prespecified participant subgroups, were obtained from investigators and combined across trials using a fixed-effect meta-analysis. Sensitivity and network meta-analyses evaluated the consistency of findings. KEY FINDINGS AND LIMITATIONS: Five RCTs (six trial comparisons, 4411 participants; 96% of all eligible) were included in the primary analysis. There was no clear evidence that OS was improved with HT (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.74-1.00, p = 0.057; absolute effect 2% [0-3.5%] at 8 yr) or that effects varied by HT duration (p = 0.6). Any benefit of HT on OS appears to be confined to people with higher pre-RT prostate specific antigen levels (p = 0.07) and CAPRA-S scores (p = 0.09). HT significantly improved MFS (HR = 0.78, 95% CI = 0.69-0.88, p < 0.001) and PCSS (HR = 0.61, 95% CI = 0.47-0.79, p < 0.001), with 4% absolute improvements for both outcomes at 8 yr. CONCLUSION AND CLINICAL IMPLICATIONS: Short- or long-course HT after postoperative RT improves MFS and PCSS. Observed improvements in OS are small and may be limited to people with higher-risk factors.