Clinicopathological and Perioperative Factors Associated with Overall Survival and 90-Day Mortality Following Esophagectomy for Esophageal Cancer

Background/Objectives: Esophageal cancer (EC) is an aggressive malignancy, and outcomes following esophagectomy are influenced by both oncological and perioperative factors. This study aimed to identify clinicopathological and perioperative factors associated with overall survival (OS) after esophagectomy for EC and, secondarily, to evaluate factors associated with 90-day mortality. Methods: A total of 101 patients who underwent radical esophagectomy with two-field lymphadenectomy between April 2016 and April 2023 were retrospectively evaluated. The primary outcome was OS, defined as the time from esophagectomy to death from any cause or the date of last follow-up. The secondary outcome was 90-day postoperative mortality. OS was evaluated using Kaplan–Meier and Cox proportional hazards analyses, whereas 90-day mortality was assessed using Firth penalized-likelihood logistic regression because of the limited number of events. Results: During follow-up, 74 patients (73.3%) died, including 11 deaths within 90 days after esophagectomy. The estimated 1-, 3-, and 5-year OS rates were 80.1%, 44.8%, and 38.0%, respectively. In the whole-cohort multivariable Cox model, stratified by surgical approach, lymph node positivity was associated with poorer OS (HR 10.57, 95% CI 4.78–23.38; p < 0.001). Among patients receiving neoadjuvant chemotherapy (n = 76), lymph node positivity (HR 6.34, 95% CI 2.60–15.45; p < 0.001) and pathological non-response (HR 2.96, 95% CI 1.13–7.73; p = 0.027) were associated with poorer OS. In exploratory Firth regression analysis, lymph node positivity (OR 103.11, 95% CI 7.40 –> 1000; p < 0.001) and intraoperative complications (OR 75.58, 95% CI 7.42 –> 1000; p < 0.001) were strongly associated with 90-day mortality. Conclusions: Lymph node positivity was consistently associated with poorer OS both in the entire cohort and among patients receiving neoadjuvant chemotherapy. Pathological non-response was additionally associated with poorer OS in the neoadjuvant chemotherapy subgroup, while lymph node positivity and intraoperative complications were strongly associated with 90-day mortality.