Enhancing survival in locally advanced esophageal cancer: a comparative analysis of neoadjuvant immunotherapy versus conventional neoadjuvant therapies using the SEER database.

Background: Neoadjuvant immune checkpoint inhibitors (ICIs) for locally advanced esophageal cancer have drawn significant research interest. We used the Surveillance, Epidemiology, and End Results (SEER) database to explore survival benefits of neoadjuvant immunotherapy (NAI) in this group. Methods: A comprehensive analysis was conducted utilizing the SEER database to assess the efficacy of NAI in conjunction with surgery compared to traditional neoadjuvant therapy. The study encompassed clinical and pathological characteristics as well as survival statistics of patients diagnosed with locally advanced resectable esophageal cancer between 2004 and 2014, and from 2019 to 2020. Patient data were categorized into NAI group and conventional neoadjuvant therapy (CNAT) group. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analysis, Cox regression models, propensity score matching (PSM), and inverse probability of treatment weighting (IPTW). Results: A total of 3,708 eligible patients were included in this study, among whom 944 received NAI and 2,764 received CNAT. Kaplan-Meier curves demonstrated a significant improvement in OS and CSS in the NAI group compared to CNAT group (P<0.05). Further Cox regression analysis revealed sex, age, tumor size, grade, SEER summary stage, and treatment modality as independent prognostic factors (P<0.05). Specifically, female and receipt of NAI were associated with better prognosis, while age over 65 years, tumor size exceeding 60 mm, grade III-IV, and "regional" summary stage were considered as risk factors. Subsequent subgroup analyses and interaction assessments revealed that, compared to "unmarried and others" patients and those with tumor sizes ≤60 mm, "married" patients and those with tumor sizes >60 mm experienced significantly greater survival benefits from NAI (interaction P values <0.05). The external validation cohort included 157 patients with locally advanced esophageal squamous cell carcinoma, of which 108 received neoadjuvant chemoimmunotherapy (nICT) group and 49 received neoadjuvant chemotherapy (nCT group). Univariate and multivariate Cox regression analyses identified treatment group [hazard ratio (HR): 0.466, 95% confidence interval (CI): 0.225-0.962, P=0.04] as an independent predictor of OS. Conclusions: The combination of NAI with surgical intervention significantly improved survival outcomes in patients with locally advanced esophageal cancer. These findings support the integration of immunotherapeutic agents into neoadjuvant treatment, offering promising directions for future clinical strategies and research in the management of esophageal cancer.