ctDNA detects residual disease after neoadjuvant chemoradiotherapy and guides adjuvant therapy in esophageal squamous cell carcinoma
Zhichao Liu, Guoqiang Wang, Yang Yang, Yuchen Su, Hong Zhang, Jun Liu, Peng Cui, Xuning Fan, Jinyu Yang, Zhihong Zhang, Xing Gao, Yin‐Kai Chao, Bianca Mostert, J.J.B. van Lanschot, Bas P. L. Wijnhoven, Simon Law, Chunguang Li, Shangli Cai, Zhigang Li
Abstract
The diagnostic accuracy of circulating tumor DNA (ctDNA) for detecting molecular residual disease (MRD) after multimodal treatment remains unclear. In a prospective cohort of 132 patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT) followed by clinical response evaluation and surgery, tumor-informed personalized-panel and fixed-panel ctDNA assays are applied to serial blood samples. Personalized ctDNA assay demonstrates a superior baseline detection rate (99.2%) and outperforms fixed panels in diagnosing post-nCRT residual disease. Integrating personalized ctDNA with conventional clinical diagnostic methods increases sensitivity for predicting non-pathological complete response (non-pCR) from 78.4%-80.7% to 92.0%-93.2%. Patients with detectable MRD post-nCRT and/or post-surgery exhibit worse survival outcomes. In non-pCR patients, adjuvant immunotherapy improves disease-free survival in post-surgery MRD-positive cases, whereas MRD-negative patients derive no benefit. These findings support incorporating ctDNA into response assessment to guide organ-sparing strategies and adjuvant therapy decisions in ESCC. This study is registered at ClinicalTrials.gov (NCT03937362).