Effectiveness of androgen-deprivation therapy and radiotherapy for older men with locally advanced prostate cancer

Purpose: We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods: We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age > 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age ≥ 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results: In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score-adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score-adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score - adjusted methods. Conclusion: Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival.