Analysis of data from 58,172 patients identified from Surveillance, Epidemiology, and End Results (SEER) registries as having stage I or II endometrial adenocarcinoma found that pelvic radiotherapy and lymphadenectomy were associated with statistically significantly reduced noncancer mortality, particularly among those with intermediate-and high-risk disease. Among low-risk stage I patients, however, both treatments were associated with statistically significant increased endometrial cancer–specific mortality.
Pelvic radiotherapy was also associated with increased cancer-specific mortality in stage II patients, whereas lymphadenectomy was associated with decreased endometrial cancer mortality in stage II patients.
Interpretation of Data
There was no evidence that whole-pelvic radiotherapy was associated with statistically improved endometrial cancer–specific mortality in any risk category. “On the whole, we interpret these findings as evidence that the associations between [whole-pelvic radiotherapy] and lymphadenectomy and improved overall survival reported in other SEER studies [are] largely due to the selection of healthier patients with higher-risk disease for these interventions, rather than effects of the treatments per se,” Loren K. Mell, MD, and colleagues from the University of California San Diego in La Jolla wrote in the Journal of the National Cancer Institute.
The number of deaths totaled 2,589 from endometrial cancer, 3,019 from secondary malignancies, and 8,015 from other causes. The median times to death were 31 months for endometrial cancer, 57 months for secondary malignancy, and 78 months for noncancer causes.
“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),” the researchers reported.
“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),” they added.
The authors noted that while radiotherapy and lymphadenectomy have been associated with improved survival in population-based studies of endometrial cancer, randomized trials and meta-analysis of controlled trials have not found evidence that these interventions improve survival.
“It is important to reconcile findings from both population-based studies and randomized trials because the latter cannot always be relied on to resolve every controversy. Patients represented on randomized trials are not drawn randomly from the population, so the degree to which the findings from clinical trials strictly represent the population to which their findings are applied may be questionable,” the investigators stated.
“Moreover, because of the costs of conducting clinical trials, their power to estimate primary, secondary, and subgroup effects is nearly always constrained. It is often assumed that benefits of more aggressive treatment may be underestimated in observational studies because of selective application of these treatments in patients with higher-risk disease. However, our findings indicate that, conversely, their benefits can be overestimated as well because of selective application in patients at low risk of competing mortality.” ■
Mell LK, et al: J Natl Cancer Inst 105:1656–1666, 2013.