Predictive Role of Ctdna in Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Immunotherapy and Chemotherapy: A Prospective Cohort Study

Background The integration of anti-PD-1 antibody therapy with chemotherapy (Immunochemotherapy, ICT) has shown promising results in the neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma (ESCC). Conventional imaging may not fully capture immunotherapy effects due to unconventional response patterns like pseudoprogression. This study seeks to evaluate the potential of ctDNA as a predictive marker for pathological complete response (pCR) and pathological lymph node metastasis(pN) in patients with localized ESCC undergoing neoadjuvant ICT. Methods In this study, the main objective is to determine the concordance between ctDNA status and pCR and pN. Exploratory objectives of the research involved examining the predictive value of tissue-specific tumor mutational burden (TMB) regarding pCR and pN. Results The analysis of 44 blood and 38 tissue samples from 23 patients revealed that ctDNA level dynamics significantly correlated with pCR rates and pN status. Decreasing ctDNA levels during neoadjuvant ICT were linked to higher pCR rates (p < 0.05), whereas detectable post-neoadjuvant ICT ctDNA levels indicated a greater risk of pN+ (p < 0.01). Tissue TMB showed no association with pCR or pN. These results highlight ctDNA as a reliable biomarker for monitoring neoadjuvant ICT efficacy and predicting pathological outcomes in ESCC, particularly in identifying pseudoprogression. The study also explored ctDNA dynamics in relation to the tumor’s immune microenvironment, uncovering underlying molecular mechanisms. Conclusion This study is the first to explore the dynamic changes of ctDNA during neoadjuvant ICT in monitoring pCR and pN in ESCC patients. Our results indicate that ctDNA holds promise as a predictive biomarker for evaluating treatment efficacy in patients with ESCC undergoing neoadjuvant ICT. Further research could elucidate the specific ctDNA signatures that correlate with therapeutic efficacy and metastatic spread, enhancing personalized treatment strategies for ESCC.