Clinical significance of combining circulating tumor DNA and endoscopic response evaluation for esophageal squamous cell carcinoma.

BACKGROUND: We previously demonstrated the usefulness of circulating tumor DNA (ctDNA) in blood for assessing tumor burden for esophageal squamous cell carcinoma (ESCC). We also found that endoscopic response evaluation predicted the prognosis of ESCC patients. In this study, we determined whether the combination of post-NAC ctDNA with endoscopic evaluation can improve the prediction of the prognosis in ESCC patients. METHODS: Thirty-one patients with ESCC treated with neoadjuvant chemotherapy (NAC) and surgery at Keio University Hospital between 2019 and 2024 were reviewed. Blood samples for ctDNA analysis were collected before and after NAC. An endoscopic responder (ER) was defined based on the endoscopic findings. Patients were classified into three groups by post-NAC ctDNA and ER status: (A) ctDNA-negative and ER, (B) ctDNA-negative and non-ER, and (C) ctDNA-positive. Recurrence-free survival (RFS) and pathological lymph node status were investigated. RESULTS: Sixty blood samples were collected from 31 patients. Of these patients, 29 were ctDNA-positive before NAC, and 13 became negative after NAC. ER was observed in 10 patients. Three-year RFS was significantly higher in ctDNA-negative than in ctDNA-positive (74% vs. 12%, p = 0.001). When combining ctDNA and ER, group A had no recurrences during follow-up. Three-year RFS rates for groups A, B, and C were 100, 53, and 12%, respectively (p = 0.004). 80% of group A patients showed no lymph node metastasis. CONCLUSIONS: The combination of post-NAC ctDNA and ER predicts the prognosis more accurately. These indicators will individualize ESCC treatment.