title: Relationships of Tubal Ligation to Endometrial Carcinoma Stage and Mortality in the NRG Oncology/ Gynecologic Oncology Group 210 Trial.
abstract: BACKGROUND
  Stage is a critical determinant of treatment among endometrial carcinoma patients; understanding patterns of tumor spread may suggest approaches to improve staging. Specifically, the importance of exfoliation of endometrial carcinoma cells through the fallopian tubes into the peritoneum is ill defined. We assessed the hypothesis that tubal ligation (TL), which should impede transtubal passage of cells, is associated with lower endometrial carcinoma stage at presentation and, consequently, lower mortality.
  
  
  METHODS
  The NRG Oncology/Gynecologic Oncology Group (GOG) 210 Trial included 4489 endometrial carcinoma patients who completed a risk factor questionnaire that included TL history. Pathology data were derived from clinical reports and central review. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between TL with stage and peritoneal metastasis, overall and by tumor subtype. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals for TL and mortality. All statistical tests were two-sided.
  
  
  RESULTS
  Compared with stage I, TL was inversely associated with stage III (OR = 0.63, 95% CI = 0.52 to 0.78) and stage IV carcinomas (OR = 0.14, 95% CI = 0.08 to 0.24) overall and among individual tumor subtypes. TL was inversely related to peritoneal metastasis overall (OR = 0.39, 95% CI = 0.22 to 0.68) and among serous carcinomas (OR = 0.28, 95% CI = 0.11 to 0.68). In multivariable models unadjusted for stage, TL was associated with lower endometrial carcinoma-specific mortality (HR = 0.74, 95% CI = 0.61 to 0.91); however, adjustment for stage eliminated the survival advantage. Similar relationships with all-cause mortality were observed.
  
  
  CONCLUSIONS
  TL is associated with lower stage and mortality among women with aggressive endometrial carcinomas, suggesting transtubal spread is clinically important. Future studies should evaluate whether detection of intraluminal tumor cells is prognostically relevant.
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES). ashley.felix@nih.gov.
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Felix
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: D Scott
authors.initials: DS
authors.lastname: McMeekin
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: William T
authors.initials: WT
authors.lastname: Creasman
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: David
authors.initials: D
authors.lastname: Mutch
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: David E
authors.initials: DE
authors.lastname: Cohn
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: Richard G
authors.initials: RG
authors.lastname: Moore
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: Levi S
authors.initials: LS
authors.lastname: Downs
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: Richard
authors.initials: R
authors.lastname: Zaino
authors.affiliation: : Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics (ASF, LAB) and Cancer Prevention Fellowship Program, Division of Cancer Prevention (ASF), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK (SM, JLW); Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC (WTC); Washington University School of Medicine, St. Louis, MO (DM); Division of Gynecologic Oncology, Ohio State University College of Medicine, Columbus, OH (DEC); Women and Infants Hospital/Brown University, Providence, RI (RGM); University of Minnesota, Minneapolis, MN (LSD); Memorial Sloan Kettering Cancer Center, New York, NY (RAS); Anatomic Pathology, Penn State Milton S. Hersey Medical Center, Hershey, PA (RZ); Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (MES).
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000401:mortality* / Q000556:secondary* / Q000601:surgery; D018284:Cystadenocarcinoma, Serous / Q000401:mortality / Q000556:secondary; D016889:Endometrial Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D010534:Peritoneal Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013246:Sterilization, Tubal; D011795:Surveys and Questionnaires