Type of publication:
Randomised controlled trial
Parker CC; James ND; Brawley CD; Clarke NW; Ali A; Amos CL; Attard G; Chowdhury S; Cook A; Cross W; Dearnaley DP; Douis H; Gilbert DC; Gilson C; Gillessen S; Hoyle A; Jones RJ; Langley RE; Malik ZI; Mason MD; Matheson D; Millman R; Rauchenberger M; Rush H; Russell JM; Sweeney H; Bahl A; Birtle A; Capaldi L; Din O; Ford D; Gale J; Henry A; Hoskin P; Kagzi M; Lydon A; O'Sullivan JM; Paisey SA; Parikh O; Pudney D; Ramani V; Robson P; *Srihari NN; Tanguay J; Parmar MKB; Sydes MR; STAMPEDE Trial Collaborative Group
PLoS Medicine, 2022 Jun 07; Vol. 19 (6), pp. e1003998
Background: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL).Methods and Findings: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively.Conclusions: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC.Trial Registration: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.
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