Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysis

Abstract

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 We obtained prepublication, unpublished, and harmonised results from investigators.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 3yr. 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.

Keywords: Androgen deprivation therapy; Meta-analysis; Metastases; Prostate cancer; Radiotherapy; Standard of care; Systematic review.

Fig. 1

Effect of adding prostate radiotherapy to ADT on (A) survival, (B) progression-free survival, (C) biochemical progression, and (D) failure-free survival in men with mHSPC. Each filled square denotes the HR for that trial comparison, with the horizontal lines showing the 95% confidence interval (CI). The size of the square is directly proportional to the amount of information contributed by a trial. The diamond represents a (fixed-effect) meta-analysis of the trial HRs, with the centre of this diamond indicating the HR and the extremities the 95% CI. ADT = androgen deprivation therapy; HR = hazard ratio; RT = radiotherapy.

Fig. 2

Effect of adding prostate radiotherapy to ADT on survival by patient age at randomisation, performance status, clinical T stage, and Gleason sum score. Each filled square denotes the HR for each subgroup of men defined by, age at randomisation, performance status, clinical T stage, and Gleason sum score within each trial, with the horizontal lines showing the 95% confidence interval (CI). The size of the square is directly proportional to the amount of information contributed by a subgroup. Each filled circle denotes the HR for the interaction between the effect of radiotherapy and these subgroups for each trial, with the horizontal lines showing the 95% CI. The size of each circle is directly proportional to the amount of information contributed by a trial. The open circle represents a (fixed-effect) meta-analysis of the interaction HRs, with the horizontal line showing the 95% CI. ADT = androgen deprivation therapy; HR = hazard ratio; RT = radiotherapy.

Fig. 3

Effect of adding prostate radiotherapy to ADT on survival, progression-free survival, and failure-free survival (exploratory) by the number of bone metastases. ADT = androgen deprivation therapy; HR = hazard ratio; RT = radiotherapy.