Associations between etiologic factors and mortality after endometrial cancer diagnosis: the NRG Oncology/Gynecologic Oncology Group 210 trial.
BACKGROUND
Few 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.


METHODS
Prior 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.


RESULTS
Median follow-up was 60months after enrollment (range: 1day-118months). 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).


CONCLUSIONS
Several 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.
Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: Felix.20@osu.edu.
Ashley S
AS
Felix
Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK, USA.
D
D
Scott McMeekin
Washington University School of Medicine, St. Louis, MO, USA.
David
D
Mutch
Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK, USA.
Joan L
JL
Walker
Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, USA.
William T
WT
Creasman
Division of Gynecologic Oncology, The Ohio State University College of Medicine, Columbus, OH, USA.
David E
DE
Cohn
NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, USA.
Shamshad
S
Ali
Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital/Brown University, Providence, RI, USA.
Richard G
RG
Moore
Gynecologic Oncology, University of Minnesota, Minneapolis, MN, USA.
Levi S
LS
Downs
Anatomical Pathology, University of Maryland, College Park, MD, USA.
Olga B
OB
Ioffe
Surgical Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kay J
KJ
Park
Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
Mark E
ME
Sherman
Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Louise A
LA
Brinton
D000367:Age Factors; D018269:Carcinoma, Endometrioid / Q000209:etiology / Q000401:mortality / Q000473:pathology; D016889:Endometrial Neoplasms / Q000209:etiology* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D009765:Obesity / Q000150:complications / Q000453:epidemiology
Endometrial cancer; Etiologic factors; GOG; NRG; Prognosis