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

Malcolm D Mason, Wendy R Parulekar, Matthew R Sydes, Michael Brundage, Peter Kirkbride, Mary Gospodarowicz, Richard Cowan, Edmund C Kostashuk, John Anderson, Gregory Swanson, Mahesh K B Parmar, Charles Hayter, Gordana Jovic, Andrea Hiltz, John Hetherington, Jinka Sathya, James B P Barber, Michael McKenzie, Salah El-Sharkawi, Luis Souhami, P D John Hardman, Bingshu E Chen, Padraig Warde, Malcolm D Mason, Wendy R Parulekar, Matthew R Sydes, Michael Brundage, Peter Kirkbride, Mary Gospodarowicz, Richard Cowan, Edmund C Kostashuk, John Anderson, Gregory Swanson, Mahesh K B Parmar, Charles Hayter, Gordana Jovic, Andrea Hiltz, John Hetherington, Jinka Sathya, James B P Barber, Michael McKenzie, Salah El-Sharkawi, Luis Souhami, P D John Hardman, Bingshu E Chen, Padraig Warde

Abstract

Purpose: We 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 methods: NCIC 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.

Results: One 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.

Conclusion: This 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.

Trial registration: ClinicalTrials.gov NCT00002633.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2015 by American Society of Clinical Oncology.

Figures

Fig 1.
Fig 1.
CONSORT diagram. ADT, androgen-deprivation therapy; RT, radiotherapy.
Fig 2.
Fig 2.
Overall survival (OS). ADT, androgen-deprivation therapy; HR, hazard ratio; RT, radiotherapy.
Fig 3.
Fig 3.
Deaths from prostate cancer. ADT, androgen-deprivation therapy; RT, radiotherapy.
Fig 4.
Fig 4.
Time to disease progression (TTP; A) using prespecified definition of biochemical progression and (B) using American Society for Radiation Oncology Phoenix definition of biochemical progression. ADT, androgen-deprivation therapy; RT, radiotherapy.

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