Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

Abstract

PurposeWe have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial.Patients and MethodsNCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables.ResultsOne thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT.ConclusionThis analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.

EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

“…The combination is clearly better than EBRT or ADT monotherapy [72]. In both high-risk localised and locally advanced disease, upfront combination with docetaxel only improves relapse free survival, with no survival benefit at 9 years [73].…”

The Re-Emerging Role of Elective Pelvic Nodal Irradiation in High-Risk Node Negative Prostate Cancer

“…Interestingly in the ADT alone group, 10% received delayed RT for local progression, suggesting that these results may underestimate the benefit of RT. Although patient on ADT + RT reported a higher frequency of adverse events related to bowel toxicity, these were manageable with only two of 589 patients reporting grade 3 or greater diarrhoea at 24 months after RT [13].…”

Radiotherapy for Prostate Cancer: is it ‘what you do’ or ‘the way that you do it’? A UK Perspective on Technique and Quality Assurance

“…The SPCG-7 and intergroup MRC PR3/PR07 studies randomised men with predominantly localised (SPCG) or predominantly locally advanced (MRC) disease to hormone therapy alone, or to hormone therapy plus radiotherapy. In both trials, men who received radiotherapy had significantly better overall survival than men treated with hormone therapy alone [3,22]. Thus, at least in the context of locally advanced disease, radical radiotherapy prolongs survival and conceivably might cure some men.…”

“…This is inevitable, given that the ProtecT trial is unique in comparing three prostate treatment modalities, probably was only achievable when it was done and in the UK -and so will never be repeated. There have been a several other landmark trials in the UK of radiotherapy for prostate cancer, including the Medical Research Council (MRC) RT01 and PR07 trials, the Cancer Research UK/NIHR Cancer Research Network CHHIP trial, and exploratory data from the MRC STAMPEDE trial [2][3][4][5]. This article aims to put these radiotherapy trials into their historical context as a backdrop when the first results of the ProtecT trial are unveiled in 2016.…”