The utility of prostate radiotherapy (RT) is unclear in men with metastatic hormone-sensitive prostate cancer (mHSPC) receiving intensified systemic therapy with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs). We performed a network meta-analysis of randomized controlled trials (RCTs) to investigate the role of prostate RT in low-volume mHSPC.
Bibliographic databases and conference proceedings were searched through July 2023 for RCTs evaluating the addition of ARPIs or prostate RT to standard of care (SOC) systemic therapy, defined as ADT or ADT plus docetaxel, for the initial treatment of mHSPC. We focused exclusively on aggregate data from the low-volume mHSPC subpopulation in these trials. We pooled the treatment arms into four groups: SOC, SOC plus ARPI, SOC plus RT, and SOC plus ARPI plus RT. The primary outcome was overall survival (OS). To compare treatment strategies, a fixed-effects Bayesian network meta-analysis was undertaken, while a Bayesian network meta-regression was performed to account for across-trial differences in docetaxel use as part of SOC and in proportions of patients with de novo presentation.
Ten RCTs comprising 4423 patients were eligible. The Surface Under the Cumulative Ranking Curve scores were 0.0006, 0.45, 0.62, and 0.94 for SOC, SOC plus RT, SOC plus ARPI, and SOC plus ARPI plus RT, respectively. On a meta-regression, in a population with de novo mHSPC and no docetaxel use, we did not find sufficient evidence of a difference in OS between SOC plus ARPI plus RT versus SOC plus ARPI (hazard ratio [HR]: 0.76; 95% credible interval: 0.51-1.16) and SOC plus RT versus SOC plus ARPI (HR: 1.10; 95% credible interval: 0.92-1.42).
There was some evidence that SOC plus ARPI plus RT reduced mortality compared with the next best strategy of SOC plus ARPI in patients with low-volume de novo mHSPC. A meta-analysis with individual patient data or an RCT is needed to confirm these findings.
European urology. 2024 Apr 02 [Epub ahead of print]
Soumyajit Roy, Gagan Fervaha, Daniel E Spratt, Yilun Sun, Amar U Kishan, Andrew Loblaw, Shawn Malone, Michael Ong, Fred Saad, Christopher J D Wallis, Scott C Morgan
Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA., Division of Urology, University of Toronto, Toronto, ON, Canada., Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, USA., Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA., Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA., Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada., Department of Radiology, Radiation Oncology and Medical Physics, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada., Division of Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada., Department of Surgery, Université de Montréal, Montreal, QC, Canada., Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, USA; Department of Urology, Mount Sinai Hospital and University Health Network, University of Toronto, Toronto, ON, Canada., Department of Radiology, Radiation Oncology and Medical Physics, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada. Electronic address: .