Sex Disparities After Induction Chemoradiotherapy and Esophagogastrectomy for Esophageal Cancer

Background The impact of sex on the outcomes of treatment for locally advanced esophageal carcinoma is unclear. This study analyzed the impact of sex on response to neoadjuvant chemoradiotherapy (nCRT), tumor recurrence, and survival. Methods From January 1990 through December 2013, female patients who received nCRT followed by esophagogastrectomy at 3 affiliated centers were compared with control male patients based on age, pretreatment clinical stage, histologic type, and surgical era. Only patients staged preoperatively with computed tomographic scans and endoscopic ultrasonography (EUS) were included. Results There were 366 patients (145 women and 221 men). The median female age was 64 years (range, 22–81 years), whereas male patients were 61 years (range, 33–82 years). The histologic type was adenocarcinoma in 105 (72%) women and 192 (87%) men, and it was squamous cell carcinoma in 40 (28%) women and 29 (13%) men (p = 0.005). Women were more likely to attain either a complete pathologic (CP) response or a nearly complete pathologic (NCP) response to induction therapy (84 [58%]) compared with men (103 [47%]; p = 0.034). Men had an 80% increased risk of recurrence (hazard ratio [HR], 1.80; 95% CI, 1.15–2.68; p = 0.008). There was no sex association with risk of death (p = 0.538). Irrespective of sex, a partial responder (relative to a complete or nearly complete responder) was 3 times more likely to have recurrence (HR, 2.96; 95% CI, 1.98–4.43; p < 0.001) and 2.5 times more likely to die (HR, 2.56; 95% CI, 1.88-3.48; p < 0.001). Conclusions Female sex correlated with improved rates of achieving either a CP response or an NCP response after neoadjuvant chemotherapy and a smaller likelihood of experiencing tumor recurrence. Future efforts should be directed at understanding determinants of this sex disparity.