Survival benefit of combined immunotherapy and chemoradiotherapy in locally advanced unresectable esophageal cancer: an analysis based on the SEER database

Background While simultaneous chemoradiotherapy remains the established therapeutic modality for patients afflicted with locally advanced esophageal cancer, the effectiveness of this radical approach falls short of the desired outcome. Numerous investigations have illuminated the prospect of enhancing therapeutic efficacy through the amalgamation of chemoradiotherapy and immunotherapeutic interventions. Consequently, we embarked on an examination to scrutinize the potential survival advantages conferred by the confluence of chemoradiotherapy and immunotherapy in relation to locally advanced unresectable esophageal carcinoma, drawing upon the extensive SEER database for our analysis. Methods We extracted clinicopathological attributes and survival statistics of patients afflicted with locally advanced unresectable esophageal carcinoma, diagnosed within the temporal span encompassing the years 2004-2014 and 2019-2020, from the extensive SEER database. To discern disparities in both overall survival (OS) and cancer-specific survival (CSS) between the cohorts subjected to chemoradiotherapy combined with immunotherapy and chemoradiotherapy alone, we employed analytical tools such as Kaplan-Meier analysis, the Log-rank test, the Cox regression proportional risk model, and propensity-matched score (PSM) methodology. Results A total of 7,758 eligible patients were encompassed in this research, with 6,395 individuals having undergone chemoradiotherapy alone, while 1,363 patients received the combined treatment of chemoradiotherapy and immunotherapy. After 1:4 propensity score matching, 6,447 patients were successfully harmonized, yielding a well-balanced cohort. The Kaplan-Meier curves demonstrated a substantial enhancement in OS (P = 0.0091) and CSS (P < 0.001) for the group subjected to chemoradiotherapy combined with immunotherapy as compared to chemoradiotherapy alone. Further multivariable analysis with PSM confirmed that chemoradiotherapy combined with immunotherapy benefits OS(HR=0.89, 95% CI 0.81-0.98) and CSS (HR=0.68, 95% CI 0.61-0.76). In addition, Univariable and multivariable Cox regression analyses of the matched patient groups unveiled several independent prognostic factors for OS and CSS, including sex, age, marital status, tumor location, tumor size, pathologic grade, SEER historic staging, and treatment modality. Among these factors, being female, married, and receiving chemoradiotherapy combined with immunotherapy emerged as independent protective factors, while age exceeding 75 years, non-superior segment tumor location, tumor size greater than 6 cm, Grade 3-4 pathology, and regional SEER historic staging were all found to be independent risk factors. The survival advantage of the chemoradiotherapy combined with the immunotherapy group over the chemoradiotherapy alone group was substantial. Conclusions This investigation furnishes compelling evidence that the integration of immunotherapy with chemoradiotherapy confers a noteworthy survival advantage when contrasted with conventional chemoradiotherapy for individuals grappling with locally advanced unresectable esophageal carcinoma.