Lesion-level comparison of primary and secondary tumors after neoadjuvant immunochemotherapy in multifocal esophageal squamous cell carcinoma: a single-center retrospective study.

Background: Neoadjuvant immunochemotherapy (NIC) has emerged as a promising treatment strategy for locally advanced esophageal squamous cell carcinoma (ESCC). However, its clinical benefit in multifocal esophageal carcinoma (MEC) remains poorly understood. Given the potential biological heterogeneity between primary and secondary lesions, discordant responses to NIC may be observed between lesions. Therefore, assessing response consistency and its clinical relevance in MEC after NIC is essential. In this study, radiological and pathological assessments were performed to compare treatment responses between primary and secondary lesions, while the efficacy and safety of NIC were simultaneously evaluated. Methods: We retrospectively analyzed 14 patients with MEC (including 28 lesions) treated at the First Affiliated Hospital of Zhengzhou University between 2019 and 2024. Eligible patients had two pathologically confirmed squamous cell carcinomas, defined as primary and secondary lesions based on tumor size. Cross-sectional areas were measured through thin-slice contrast-enhanced computed tomography (CT) before and after NIC to calculate the tumor regression rate (TRR). In patients undergoing surgery, pathological response was evaluated by the College of American Pathologists (CAP) tumor regression grade system. Key clinical variables were extracted from medical records. Results: A total of 14 patients with MEC were included (11 males, median age 64 years). The median TRR was 31.26% (range, -58.00% to 66.28%) for primary lesions and 21.91% (range, -5.00% to 41.70%) for secondary lesions. Although primary lesions showed numerically greater regression, paired analysis demonstrated no statistically significant difference (Z=-1.503, P=0.13). Among 12 patients who underwent surgery, pathological complete response (pCR) was achieved in 16.7% of both primary and secondary lesions, with complete concordance between paired tumors. Major pathological response (MPR) occurred in 33.3% of primary lesions and 25.0% of secondary lesions, with a concordance rate of 91.7%; no significant difference was observed (P=0.32). Treatment-related adverse events occurred in 71.4% of patients, predominantly grade I-II. Twelve patients (85.7%) underwent esophagectomy, and postoperative complications were generally manageable. Conclusions: No significant differences were observed between primary and secondary lesions in radiological regression or pathological response following NIC. However, NIC demonstrated an acceptable efficacy and safety profile in this small cohort, supporting its feasibility in this rare clinical subset. Larger prospective studies are needed to clarify these observations.