Local Regrowth After Neoadjuvant Chemoradiotherapy and Active Surveillance for Esophageal Cancer: An Analysis of Surgical Specimens From the SANO Trial.

OBJECTIVE: To assess pattern of regrowth after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This may inform optimization of response evaluations and explore the possibility for endoscopic treatment of cancer regrowth. SUMMARY BACKGROUND DATA: Active surveillance is a treatment approach for patients with locally advanced esophageal cancer but the timely detection of regrowth remains challenging. METHODS: A retrospective cohort study was conducted in patients with complete clinical response 3 months after nCRT who underwent active surveillance. Patients with cancer regrowth that underwent surgery were included. Resection specimens were reviewed by 2 pathologists. The primary outcome was the anatomic layer(s) of regrowth within the esophageal wall. RESULTS: In total, 75 resection specimens were available 6-36 months after nCRT. Cancer cells were seen in the mucosal layer in 68 of 75 (91%) patients. In 4/75 (5%) patients the tumor was confined to the mucosa. In 13/75 patients (17%), tumor was seen in the mucosa and submucosa but 4 patients also had lymph node involvement. Overall, tumor was present in the submucosa in 88%, proper muscle layer in 71%, and surrounding stroma in 61% of specimens. The majority of regrowth occurred in all layers and this pattern did not change over time. CONCLUSIONS: Detected regrowth after nCRT predominantly involves the mucosa and submucosa in the majority of patients and its temporal regrowth pattern support endoscopy as a diagnostic tool. Given the risk of undetected nodal disease and the current limitations of staging after nCRT, surgery remains the recommended treatment for regrowth.