Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC).
To systematically review trials of prostate radiotherapy.
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 We obtained prepublication, unpublished, and harmonised results from investigators.
We included trials that randomised men to prostate radiotherapy and androgen deprivation therapy (ADT) or ADT only.
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.
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.
Prostate radiotherapy should be considered for men with mHSPC with a low metastatic burden.
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.
European urology. 2019 Feb 27 [Epub ahead of print]
Sarah Burdett, Liselotte M Boevé, Fiona C Ingleby, David J Fisher, Larysa H Rydzewska, Claire L Vale, George van Andel, Noel W Clarke, Maarten C Hulshof, Nicholas D James, Christopher C Parker, Mahesh K Parmar, Christopher J Sweeney, Matthew R Sydes, Bertrand Tombal, Paul C Verhagen, Jayne F Tierney, STOPCAP M1 Radiotherapy Collaborators
Meta-analysis Group, MRC Clinical Trials Unit at UCL, London, UK. Electronic address: ., Department of Urology, OLVG, Amsterdam, The Netherlands; Department of Urology, Amsterdam UMC (VU), Amsterdam, The Netherlands., MRC Clinical Trials Unit at UCL, London, UK., Meta-analysis Group, MRC Clinical Trials Unit at UCL, London, UK., Department of Urology, Amsterdam UMC (VU), Amsterdam, The Netherlands., The Christie and Salford Royal Hospitals, Manchester, UK., Department of Radiotherapy, Amsterdam UMC (AMC), Amsterdam, The Netherlands., Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, UK., Royal Marsden Hospital, Sutton, Institute of Cancer Research, Sutton, UK., Dana-Faber Cancer Institute, Boston, MA, USA., Department of Urology, Cliniques Universitaires Saint Luc, Brussels, Belgium., Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands.