A B S T R A C T PurposeThe prognostic value of sex for esophageal cancer survival is currently unclear, and growing data suggest that hormonal influences may account for incidence disparities between men and women. Therefore, moving from the hypothesis that hormones could affect the prognosis of patients with esophageal cancer, we investigated the primary hypothesis that sex is associated with survival and the secondary hypotheses that the relationship between sex and survival depends, at least in part, on age, histology, and race/ethnicity. Patients and MethodsBy using the SEER databases from 1973 to 2007, we identified 13,603 patients (34%) with metastatic esophageal cancer (MEC) and 26,848 patients (66%) with locoregional esophageal cancer (LEC). Cox proportional hazards model for competing risks were used for analyses. ResultsIn the multivariate analysis, women had longer esophageal cancer-specific survival (ECSS) than men in both MEC (hazard ratio [HR], 0.949; 95% CI, 0.905 to 0.995; P ϭ .029) and LEC (HR, 0.920; 95% CI, 0.886 to 0.955; P Ͻ .001) cohorts. When age and histology were accounted for, there was no difference for ECSS between men and women with adenocarcinoma. In contrast, women younger than age 55 years (HR, 0.896; 95% CI, 0.792 to 1.014; P ϭ .081) and those age 55 years or older (HR, 0.905; 95% CI, 0.862 to 0.950; P Ͻ .001) with squamous cell LEC had longer ECSS than men. In the squamous cell MEC cohort, only women younger than age 55 years had longer ECSS (HR, 0.823; 95% CI, 0.708 to 0.957; P ϭ .011) than men. ConclusionSex is an independent prognostic factor for patients with LEC or MEC. As secondary hypotheses, in comparison with men, women age 55 years or older with squamous cell LEC and women younger than age 55 years with squamous cell MEC have a significantly better outcome. These last two findings need further validation.

4541 Background: The American Cancer Society estimated that during 2008 approximately 16,470 new esophageal cancer cases would be diagnosed in the United States. Previous studies indicate that the incidence of esophageal cancer is more in males than females; however the influence of sex in the progression of esophageal cancer is not clearly understood. In vitro and in vivo models showed that administration of estradiol significantly inhibited the growth of ER-positive and AR-positive KSE-1 tumors in both males and females in conjunction with an increase in the estradiol levels and a decrease in the DHT levels in the serum. Thus we tested the clinical significance of sex in the overall survival of esophageal cancer using SEER data. Methods: A total of 21,584 patients with localized and metastatic esophageal cancer from 1988–2004 were screened using the SEER registry. The patients were divided into age at diagnosis, sex and ethnicity. The analysis for overall survival was based on the Cox proportional hazards model adjusted for marital status, site of primary tumor, treatment, histology and tumor grade and stratified by year of diagnosis and SEER registry site. Pairwise interactions (age and sex, age and race, and sex and race) were also examined. Results: Females with localized esophageal cancer had significantly longer overall survival compared to males (p<0.001). In metastatic esophageal cancer, females seemed to have longer overall survival than males (p=0.054). Overall survival decreased with increasing age (p<0.001). African Americans with localized esophageal cancer have worse median overall survival compared to Caucasians (p<0.001). No significant difference was noted with respect to ethnicity in metastatic esophageal cancer (p=0.22). Also pairwise interactions did not have significant difference. Conclusions: This is the first and largest study showing gender as an independent prognostic factor in patients with localized and metastatic esophageal cancer. Females had a significant better overall survival than males in esophageal cancer suggesting that sex hormone pathways may have a potential impact on tumor progression. These data warrant further studies to explore the role of these pathways in the diagnosis and treatment of esophageal cancer. No significant financial relationships to disclose.