1. In a retrospective review of over 30 000 prostate cancer patients, adding radiotherapy to androgen deprivation therapy (ADT) was associated with lower cancer-specific and all-cause mortality compared to ADT alone.
2. The survival benefit of radiotherapy plus ADT remained in elderly patients (>75 years of age) as well as in patients with screen-detected high-risk prostate cancer.
Evidence Rating Level: 3 (Average)
Study Rundown: Locally advanced prostate cancer is defined by extension of the tumor beyond the prostate gland and is associated with significantly higher mortality compared to localized prostate cancer, with ten-year cause specific mortality of approximately 25%. Two recent randomized controlled trials (RCT) have demonstrated that the addition of radiotherapy (RT) to androgen deprivation therapy (ADT) significantly increases survival in this patient population compared to ADT alone. However, these randomized trails excluded men over 75 years of age and patients with screen-detected high-risk prostate cancer. The purpose of this trial was to determine whether the benefit of adding RT to ADT persists within these excluded groups. The authors retrospectively analyzed the patient outcome data of over 30 000 prostate cancer patients within the United States and stratified patients to 3 groups: patients demonstrating similar baseline characteristics as previous RCTs, elderly patients, and patients with screen-detected high-risk prostate cancer. At the conclusion of the trial, the addition of RT to ADT was associated with reduced cause-specific and all-cause mortality for all 3 subgroups. The results of this study support the hypothesis that the combination RT and ADT may be beneficial to these additional patient populations. The main limitation of the trial was the retrospective study design; additional prospective trials within the older population and patients with screen-detected high risk prostate cancer are needed to confirm this observed association.
Relevant Reading: Androgen Deprivation Therapy and Competing Risks
In-Depth [retrospective cohort]: In this study, patient data was abstracted from the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare database to compare ADT alone versus ADT plus RT in 3 populations: men aged 65 to 75 years with clinical stage T2-T3 and moderately to poorly differentiated prostate cancer (the original RCT cohort), men aged 76 to 85 years with the same disease characteristics (elderly cohort), and men aged 65 to 85 years with screen-detected high-risk prostate cancer (screen-detected cohort). In the RCT cohort, 4642 patients were in the ADT arm and 8282 patients were in the ADT plus RT arm. In the elderly cohort, 8694 patients were in the ADT arm and 5646 patients were in the ADT plus RT arm. In the screen-detected cohort, 2017 patients were in the ADT arm and 2260 patients were in the ADT plus RT arm. Comparisons were made using Cox proportional hazard models with propensity scores to adjust for multiple confounders. In the RCT cohort, adding RT to ADT was associated with decreased cause-specific mortality (HR= 0.43; 95% CI: 0.37-0.49) and overall mortality (HR: 0.63; 95% CI: 0.45-0.96). Similarly in the elderly cohort, adding RT to ADT was associated with decreased cause-specific mortality (HR: 0.51; 95% CI= 0.44-0.59) and overall mortality (HR: 0.63: 95% CI: 0.59-0.67). Finally in the screen-detected cohort, adding RT to ADT was associated with decreased cause-specific mortality (HR: 0.25; 95% CI: 0.19-0.33) and overall mortality (HR: 0.50; 95% CI: 0.45-0.55).
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