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Prostate radiotherapy in low-volume metastatic hormone-sensitive prostate cancer: A network meta-analysis

  • Soumyajit Roy,
  • Gagan Fervaha,
  • Daniel E. Spratt,
  • Yilun Sun,
  • Yilun Sun,
  • Andrew Loblaw,
  • Shawn Malone,
  • Michael Ong,
  • Fred Saad,
  • Fred Saad,
  • Scott C. Morgan

Background and objective

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.

Key findings and limitations

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).

Conclusions and clinical implications

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.

Commentary by Dr. Constance Thibault

Previous studies (STAMPEDE, HORRAD) highlighted the potential benefit of prostate radiotherapy (RT) in low-volume metastatic hormone-sensitive prostate cancer (mHSPC), particularly in improving overall survival (OS) in men with low-volume metastatic disease. However, in these studies, the systemic treatment was androgen deprivation therapy (ADT) alone, questioning whether the addition of RT retains its benefit when patients received also androgen receptor pathway inhibitors (ARPIs) +/- docetaxel. PEACE-1 is the only randomised controlled study to evaluate prostate RT in patients treated with ADT + docetaxel with or without abiraterone. A progression-free survival (PFS) benefit was observed for patients with low volume disease but no OS  benefit was present. There remains uncertainty about the benefit of performing prostate RT in patients with de novo low-volume mHSPC in the era of intensified treatments.


A network meta-analysis has been recently published in European Urology investigating the efficacy of adding prostate RT to systemic therapy in patients with mHSPC under intensified systemic regimens, including ADT and ARPIs.


The analysis involved a thorough search of bibliographic databases and meeting proceedings up to July 2023, focusing on randomised controlled trials (RCTs) that explored the combination of ADT, ARPIs, and RT in varying configurations. The primary outcome was OS, assessed through a network meta-analysis employing a fixed-effects Bayesian model, ensuring robust comparison across treatment modalities.


The meta-analysis included data from ten RCTs involving 4423 patients, segmented into four treatment groups: SOC (standard of care), SOC + ARPI, SOC + RT, and SOC + ARPI + RT. The findings indicated a hierarchy in treatment efficacy, with SOC + ARPI + RT demonstrating the highest potential for reducing mortality, as evidenced by the highest Surface Under the Cumulative Ranking (SUCRA) scores. The comparative effectiveness was notably significant against SOC + ARPI and SOC alone, suggesting an added benefit of RT in conjunction with ARPIs. These results suggest a paradigm shift in treating low-volume mHSPC, positioning SOC + ARPI + RT as a potentially superior strategy that could redefine treatment benchmarks. This combination not only aligns with the intensification trend but also promises enhanced survival benefits, meriting consideration for routine clinical practice. However, the study acknowledges the need for further confirmation through RCTs or individual patient data meta-analyses, given the limitations of trial-level aggregate data.


The network meta-analysis furnishes compelling evidence supporting the integration of prostate RT with ADT and ARPIs in the treatment of men with low-volume mHSPC, advocating for its adoption in clinical settings pending further validation. This approach could significantly impact clinical outcomes for this patient cohort, underscoring the need for ongoing research and adaptation of clinical guidelines based on emerging evidence.