Cause-Specific Effects of Radiotherapy and Lymphadenectomy in Stage III Endometrial Cancer: A Population-Based Study

Radiotherapy and lymphadenectomy have been associated with improved survival in population-based studies of endometrial cancer, which is in contrast with findings from randomized trials and meta-analyses. The primary study aim was to estimate the cause-specific effects of adjuvant radiotherapy and lymphadenectomy on competing causes of mortality. We analyzed Surveillance, Epidemiology, and End Results (SEER) data from 1988 to 2006. The sample comprised 58172 patients with stage I and II endometrial adenocarcinoma. Patients were risk stratified by stage, grade, and age. Cumulative incidences and cause-specific hazards of competing causes of mortality were estimated according to treatment. All statistical tests were two-sided. Pelvic radiotherapy was associated with statistically significantly increased endometrial cancer mortality (hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.52 to 1.82) in all stage I and II patients and decreased noncancer mortality in intermediate and high-risk stage I and II patients (HR 0.82; 95% CI 0.77 to 0.89). Lymphadenectomy was associated with increased endometrial cancer mortality in stage I patients (HR 1.27; 95% CI 1.16 to 1.39), decreased endometrial cancer mortality in stage II patients (HR 0.61; 95% CI 0.52 to 0.72), and decreased noncancer mortality in both stage I and II patients (HR 0.84; 95% CI 0.80 to 0.88). Effects of radiotherapy and lymphadenectomy on second cancer mortality varied according to risk strata. Radiotherapy and lymphadenectomy are associated with statistically significantly reduced noncancer mortality in stage I and II endometrial cancer. The improved overall survival associated with these treatments reported from SEER studies is largely attributable to their selective application in healthier patients rather than their effects on endometrial cancer.