Background
Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC).
Objective
To systematically review trials of prostate radiotherapy.
Design, setting, and participants
Using a prospective framework (framework for adaptive meta-analysis [FAME]), we prespecified methods before any trial results were known. We searched extensively for eligible trials and asked investigators when results would be available. We could then anticipate that a definitive meta-analysis of the effects of prostate radiotherapy was possible. We obtained prepublication, unpublished, and harmonised results from investigators.
Intervention
We included trials that randomised men to prostate radiotherapy and androgen deprivation therapy (ADT) or ADT only.
Outcome measurements and statistical analysis
Hazard ratios (HRs) for the effects of prostate radiotherapy on survival, progression-free survival (PFS), failure-free survival (FFS), biochemical progression, and subgroup interactions were combined using fixed-effect meta-analysis.
Results and limitations
We identified one ongoing (PEACE-1) and two completed (HORRAD and STAMPEDE) eligible trials. Pooled results of the latter (2126 men; 90% of those eligible) showed no overall improvement in survival (HR = 0.92, 95% confidence interval [CI] 0.81–1.04,
p
= 0.195) or PFS (HR = 0.94, 95% CI 0.84–1.05,
p
= 0.238) with prostate radiotherapy. There was an overall improvement in biochemical progression (HR = 0.74, 95% CI 0.67–0.82,
p
= 0.94 × 10
−8
) and FFS (HR = 0.76, 95% CI 0.69–0.84,
p
= 0.64 × 10
−7
), equivalent to ∼10% benefit at 3 yr. The effect of prostate radiotherapy varied by metastatic burden—a pattern consistent across trials and outcome measures, including survival (<5, ≥5; interaction HR = 1.47, 95% CI 1.11–1.94,
p
= 0.007). There was 7% improvement in 3-yr survival in men with fewer than five bone metastases.
Conclusions
Prostate radiotherapy should be considered for men with mHSPC with a low metastatic burden.
Patient summary
Prostate cancer that has spread to other parts of the body (metastases) is usually treated with hormone therapy. In men with fewer than five bone metastases, addition of prostate radiotherapy helped them live longer and should be considered.
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