Prognostic Impact of Postoperative Lymph Node Metastases After Neoadjuvant Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophagus: From the Results of NEOCRTEC5010, a Randomized Multicenter Study

OBJECTIVE:To determine the prognostic impact of pathologic lymph node (LN) status and investigate risk factors of recurrence in esophageal squamous cell carcinoma (ESCC) patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT). SUMMARY BACKGROUND DATA:There are no large-scale prospective study data regarding ypN status and recurrence after pCR in ESCC patients receiving NCRT. METHODS:The NEOCRTEC5010 trial was a prospective multicenter trial that compared the survival and safety of NCRT plus surgery (S) with S in patients with locally advanced ESCC. The relationships between survival and cN, pN, and ypN status were assessed. Potential prognostic factors in patients with ypN+ and pCR were identified. RESULTS:A total of 389 ESCC patients (NCRT182; S207) were included. Patients with pN+ in the S group and ypN+ in the NCRT group had decreased overall survival (OS) and disease-free survival (DFS) compared with pN0 and ypN0 patients, respectively. Partial response at the primary site [hazard ratio (HR), 2.09] and stable disease in the LNs (HR, 3.26) were independent risk factors for lower DFS, but not OS. For patients with pCR, the recurrence rate was 13.9%. Patients with distant LN metastasis had a median OS and DFS of 16.1 months and 14.4 months, respectively. Failure to achieve the median total dose of chemotherapy was a significant risk factor of recurrence and metastasis after pCR (HR, 44.27). CONCLUSIONS:Persistent pathologic LN metastasis after NCRT is a strong poor prognostic factor in ESCC. Additionally, pCR does not guarantee a cure; patients with pCR should undergo an active strategy of surveillance and adjuvant therapy.