Associations between etiologic factors and mortality after endometrial cancer diagnosis: The NRG Oncology/Gynecologic Oncology Group 210 trial

• Non-endometrioid histologic subtype, advanced stage and older age are associated with worse endometrial carcinoma prognosis.
• Obesity is related to higher mortality among low-grade endometrioid cases.
• Parity is associated with lower mortality in serous cases but higher mortality in carcinosarcoma cases.

BackgroundFew studies have analyzed relationships between risk factors for endometrial cancer, especially with regard to aggressive (non-endometrioid) histologic subtypes, and prognosis. We examined these relationships in the prospective NRG Oncology/Gynecologic Oncology Group 210 trial.MethodsPrior to surgery, participants completed a questionnaire assessing risk factors for gynecologic cancers. Pathology data were derived from clinical reports and central review. We used the Fine and Gray subdistribution hazards model to estimate subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations between etiologic factors and cause-specific subhazards in the presence of competing risks. These models were stratified by tumor subtype and adjusted for stage and socioeconomic status indicators.ResultsMedian follow-up was 60 months after enrollment (range: 1 day–118 months). Among 4609 participants, a total of 854 deaths occurred, of which, 582 deaths were attributed to endometrial carcinoma. Among low-grade endometrioid cases, endometrial carcinoma-specific subhazards were significantly associated with age at diagnosis (HR = 1.04, 95% CI = 1.01–1.06 per year, P-trend) and BMI (class II obesity vs. normal BMI: HR = 2.29, 95% CI = 1.06–4.98, P-trend = 0.01). Among high-grade endometrioid cases, endometrial carcinoma-specific subhazards were associated with age at diagnosis (HR = 1.05, 95% CI = 1.02–1.07 per year, P-trend < 0.001). Among non-endometrioid cases, endometrial carcinoma-specific subhazards were associated with parity relative to nulliparity among serous (HR = 0.55, 95% CI = 0.36–0.82) and carcinosarcoma cases (HR = 2.01, 95% CI = 1.00–4.05).DiscussionSeveral endometrial carcinoma risk factors are associated with prognosis, which occurs in a tumor-subtype specific context. If confirmed, these results would suggest that factors beyond histopathologic features and stage are related to prognosis.ClinicalTrials.gov Identifier: NCT00340808.