Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer

Abstract
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.