Predictors of overall survival in esophageal cancer patients with pathologic complete response after neoadjuvant therapy and surgery

Esophageal cancer recurrence occurs even in those who have a pathologic complete response (pCR) following neoadjuvant therapy and esophagectomy. The purpose of this study is to identify predictors of overall survival in patients with pCR. Using the National Cancer Database, a retrospective analysis of all adult patients with ypT0N0 esophageal cancer following neoadjuvant chemotherapy and radiation between 2012 and 2020 was performed. The variables analyzed were age, gender, ethnicity, insurance, Charlson-Deyo comorbidity score, clinical stage, and facility type. Cox proportional hazards regression was used to identify predictors of overall survival. Wilcoxon rank sum and chi-square tests were used for continuous and categorical variables, respectively, with a significance level of P<0.05. There were 2767 patients that met the inclusion criteria, with the mean age of 63; 78% were male and 92% were White. Median survival was 6.6 years (95% confidence interval [CI]: 6.21-7.12). In multivariable analysis, older age (hazard ratio [HR] 2.7 per year, P<0.0001), male gender (HR 3.3, P = 0.02), Charlson-Deyo score ≥ 2 (HR 3.9, P = 0.01), and advanced clinical stage (Stage IV vs. Stage I, HR 21.93, P<0.001) predicted worse overall survival. Among patients who achieved pCR, advanced age, male gender, comorbidities, and clinical stage significantly influenced survival. Tumor- and treatment-related factors that impacted overall survival are advanced clinical stage and treatment at community facilities. These findings suggest that patients with advanced-stage esophageal cancer who achieve pCR remain at higher risk for recurrence and future studies should investigate this population further.