AUTHOR=Wei Shuang , Li Zuoji , Liu Tingting , Sun Guizhen , Sun Hongfu , Huang Wei 

TITLE=Immunotherapy in advanced esophageal squamous cell cancer: earlier or later?

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1524176

DOI=10.3389/fmed.2025.1524176

ISSN=2296-858X

ABSTRACT=Background and objectiveSeveral large-scale phase III clinical trials have confirmed the survival benefit of immunotherapy in patients with locally advanced or metastatic esophageal cancer (EC). The study aimed to investigate whether early use of immunotherapy can improve long-term survival.MethodsPatients with locally advanced or metastatic esophageal squamous cell cancer (ESCC) diagnosed from January 2018 to December 2021 were retrospectively analyzed. According to the time of immunotherapy, patients were divided into the early immunotherapy group (EIT group, first-line immunotherapy) and the late immunotherapy group (LIT group, second-line immunotherapy). A 1:1 propensity score matching (PSM) was applied to balance the observable potential confounding factors between the two groups. The primary outcome was overall survival (OS).ResultsA total of 359 patients were enrolled; after propensity score matching, the clinical features were well balanced between the two groups, including 107 patients. The median OS was 15.7 months (95%CI: 12.81–18.59) in the EIT group and 17.7 months (95%CI: 14.89–20.57) in the LIT group, respectively (p = 0.185, HR = 1.25). The PFS1 of patients was 8.7 months (95%CI: 7.53–9.87) and 7.6 months (95%CI: 5.90–9.30), respectively, and the difference was statistically significant (p = 0.032, HR = 0.72). The PFS2 of patients was 12.97 months (95%CI: 11.37–14.58) and 12.93 months (95%CI: 11.65–14.21), respectively, and the difference was statistically significant (p = 0.045, HR = 0.73). Subgroup analysis showed that male patients with middle thoracic EC, younger than 65 years old, with only one site of metastasis, only lymph node progression, no combined radiotherapy after progression, and TP (paclitaxel + platinum) regimen chemotherapy may have greater benefits. The COX multivariate analysis showed that the EIT group and the differentiation degree of the tumor had an impact on OS (P: 0.03, 0.04; HR: 0.73, 0.70).ConclusionEarly immunotherapy can improve PFS without affecting OS for patients with locally advanced or metastatic ESCC.