Adding radiotherapy to androgen-deprivation therapy for locally advanced prostate cancer improves overall survival 30% in the long term, according to a report published online Feb. 17 in the Journal of Clinical Oncology.
Radiotherapy also improves disease-specific outcomes when added to androgen-deprivation therapy (ADT), and its benefits “are achieved without major detriment in terms of long-term toxicity,” said Dr. Malcolm D. Mason of Cardiff University and Velindre Hospital, Wales, and his associates.
Dr. Malcolm Mason
These long-term results from this international randomized, controlled trial confirm that the previously reported short-term survival benefits are maintained for a median follow-up of 8 years and “firmly establish the role of radiotherapy” for locally advanced prostate cancer, they said.
“Recent data suggest that some men with T3-4 disease are still being managed with ADT alone. Although there are undoubtedly patients for whom [radiotherapy] or indeed any curative therapy would be inappropriate because of age, comorbidity, or other factors, we conclude that patients with clinically node-negative, locally advanced prostate cancer who are suitable for additional radiotherapy should be offered that option – an opinion shared by European and North American guidelines,” Dr. Mason and his associates noted.
The trial, which the investigators described as the largest to compare the two approaches to prostate cancer, enrolled 1,205 patients during 1995-2005 and followed them through the end of 2010. The median patient age at baseline was 70 years. There were 465 deaths.
A total of 260 deaths occurred with ADT alone, compared with 205 with ADT plus radiotherapy. Median overall survival time was 9.7 years for ADT alone, compared with 10.9 years for ADT plus radiotherapy. Ten-year overall survival was 49% for ADT alone, compared with 55% for ADT plus radiotherapy.
Prostate cancer–specific mortality also declined markedly with the addition of radiotherapy to ADT (hazard ratio, 0.46). Time to disease progression was extended with radiotherapy. And the rate of progression-free survival at 10 years was 46% with ADT alone, compared with 74% when radiotherapy was added, Dr. Mason and his associates said (J. Clin. Oncol. 2015 Feb. 17 [doi:10.1200/JCO.2014.57.7510]).
“The radiotherapy technique used in our trial reflects the prevailing treatment philosophies of the time. The study predated outcome data from randomized trials of dose-escalated radiotherapy, and the radiotherapy doses used here are modest by modern standards,” they noted.
The addition of radiotherapy had “a detectable, although modest” impact on toxicity, with small increases in the number of patients who experienced impotence, urinary frequency, ischemia, or hypertension. Bowel-related adverse effects were more frequent with the addition of radiotherapy, but most were grade 1 or 2. Any toxic effects of grade 3 or higher were of short duration, “and we would suggest that the toxicity of radiotherapy should not be regarded as a barrier to its routine use in this patient population,” the researchers said.
The National Cancer Institute, the Canadian Cancer Society Research Institute, the United Kingdom Medical Research Council, and the United Kingdom National Cancer Research Network supported the study. Dr. Mason disclosed ties to Sanofi and Dendreon; his associates reported ties to MIOT Institute Chennai, BiPar/Sanofi-Aventis, Novartis, Pfizer, Janssen Pharmaceuticals, Astellas Pharma, and B&C.