Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial

• Published in: The Lancet (British edition) Vol. 378; no. 9809; pp. 2104 - 2111
• Main Authors: Warde, Padraig, Dr, Mason, Malcolm, MB, Ding, Keyue, PhD, Kirkbride, Peter, MB, Brundage, Michael, MD, Cowan, Richard, MB, Gospodarowicz, Mary, MD, Sanders, Karen, BSc, Kostashuk, Edmund, MD, Swanson, Greg, MD, Barber, Jim, MB, Hiltz, Andrea, MSc, Parmar, Mahesh KB, PhD, Sathya, Jinka, MB, Anderson, John, MB, Hayter, Charles, MD, Hetherington, John, MB, Sydes, Matthew R, CStat, Parulekar, Wendy, MD
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 17.12.2011; Elsevier; Elsevier Limited; Lancet Publishing Group
• Subjects: Adenocarcinoma - mortality; Adenocarcinoma - radiotherapy; Adenocarcinoma - therapy; Aged, 80 and over; Androgen Antagonists - adverse effects; Androgen Antagonists - therapeutic use; Androgens; Biological and medical sciences; biomedical research; Cancer therapies; Clinical trials; Combined Modality Therapy; diarrhea; gastrointestinal system; General aspects; Gonadotropin-Releasing Hormone - agonists; Gynecology. Andrology. Obstetrics; hemorrhage; Humans; Internal Medicine; Male; Male genital diseases; Medical sciences; men; Nephrology. Urinary tract diseases; Orchiectomy; patients; Prostate cancer; prostate-specific antigen; prostatic neoplasms; Prostatic Neoplasms - mortality; Prostatic Neoplasms - radiotherapy; Prostatic Neoplasms - therapy; Quality of Life; Radiation therapy; radiotherapy; Radiotherapy - adverse effects; seminal vesicles; Survival Rate; Toxicity; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; United States; United Kingdom; British Isles; Phase III trial; Urinary system disease; Androgen deprivation therapy; Prostate disease; Malignant tumor; Radiotherapy; Medicine; Randomization; Clinical trial; Combined treatment; Locally advanced stage; Male genital diseases; Prostate cancer; Cancer
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(11)61095-7

Summary Background Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Methods Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65–69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Results Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4–8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70; hazard ratio [HR] 0·77, 95% CI 0·61–0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). Interpretation The benefits of combined modality treatment—ADT and RT—should be discussed with all patients with locally advanced prostate cancer. Funding Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council.