Relationships of Tubal Ligation to Endometrial Carcinoma Stage and Mortality in the NRG Oncology/Gynecologic Oncology Group 210 Trial

摘要

Stage is the strongest prognostic factor among patients with endometrial cancer, irrespective of histology or grade. Patterns of metastasis, however, vary by tumor subtype suggesting that characterizing routes of metastasis may help improve staging procedures and lead to better management. Metastasis of endometrial cancer occurs via lymphatics, blood vessels, invasion through the uterine wall, or passage through the fallopian tube into the peritoneum. The importance of the fallopian tube as a conduit for the spread of endometrial carcinoma into peritoneal cavity is ill defined. Assessment of the tube's role in metastasis of this cancer could have implications for staging, management, and understanding of its pathogenesis. The present study was designed to test the hypothesis that tubal ligation (TL), which should impede transtubal passage of tumor cells, is associated with lower endometrial carcinoma stage at presentation and, consequently, lower mortality. Associations between TL, cancer stage, extrauterine metastasis, and mortality in patients with endometrial cancer were examined. Participants in the NRG Oncology/Gynecologic Oncology Group (GOG) 210 Trial were women with presurgical diagnoses of endometrial carcinoma (carcinoma or carcinosarcoma) who were eligible for surgery. None had undergone prior retroperitoneal surgery or pelvic/abdominal radiation. Four thousand four hundred eighty nine eligible patients from 62 US institutions were available for analysis. Cases were oversampled for aggressive tumor types. After exclusions, patients completed a risk factor questionnaire that included TL history. Twenty-eight percent of the subjects reported a previous TL at a median age of 32 years. Pathology data derived from clinical reports and central review were examined. Tumor subtypes, including high-grade endometrioid, serous, and clear cell carcinomas, were examined as an effect modifier of relationships between TL, stage, and peritoneal metastasis. Logistic regression models were used to assess associations between TL with stage and peritoneal metastasis, overall and by tumor subtype. Cox proportional hazards regression models were used to assess the relationship between TL and mortality. All statistical tests (P values) were 2-sided. There was an inverse relationship between TL and both stage III (odds ratio [OR], 63; 95% confidence interval [CI], 0.52-0.78) and stage IV carcinomas (OR, 0.14; 95% CI, 0.08-0.24) overall and among individual tumor subtypes compared with stage I. Tubal ligation was also inversely associated with peritoneal metastasis overall (OR, 0.39; 95% CI; 0.22-0.68) and among serous carcinoma cases (OR, 0.28; 95% CI, 0.11-0.68). Cox multivariable models adjusted for covariates except stage showed an inverse association between TL and endometrial carcinoma-specific mortality; the hazard ratio was 0.74, with a 95% CI of 0.61 to 0.91. After adjustment for stage, however, this survival advantage was eliminated. Similar relationships were observed with all-cause mortality. These findings provide evidence that transtubal spread is an important mechanism for metastasis of aggressive histological types of endometrial carcinoma. The association of TL with lower stage and mortality among women with aggressive endometrial carcinomas may have prognostic implications.