Pathological Outcomes After Uncertain Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Background: The Surgery As Needed for Oesophageal cancer(SANO) trial showed that one third of patients with resectable, locally advanced esophageal carcinoma achieved complete clinical response (CCR) after neoadjuvant chemoradiotherapy (nCRT) and were eligible for active surveillance. However, determining CCR remains challenging, and the optimal approach for patients with uncertain tumor response at restaging after nCRT has not been established. This study investigated the pathological outcomes of these patients. Methods: Patients from the SANO cohort with non-traversable lesions, high-grade dysplasia (HGD) or clinical suspicion of residual tumor without (cyto-)histological confirmation at clinical response evaluations 4-12 weeks after nCRT were included. The primary endpoint was the complete pathological response rate after resection. Results: A total of 272 patients had an uncertain tumor response at restaging: 94 with non-traversable lesions, 50 with HGD, and 128 with clinical suspicion of residual tumor. Of these, 205 underwent esophagectomy, and 15% (95%CI 10-20) had a complete pathological response. The complete pathological response rates were 26% (19/73, 95%CI 17-37) for the non-traversable lesions group, 10% (4/42, 95%CI 4-22) for the HGD group, and 8% (7/90, 95%CI 4-15) for the clinical suspicion group. The highest rate of complete pathological response was observed in patients with squamous cell carcinoma and non-traversable lesions (33%, 14/42, 95%CI 21-48). Conclusion: Esophagectomy should be advised for most patients with an uncertain tumor response after nCRT, as 85% have residual disease. One-third of patients with squamous cell carcinoma and non-traversable lesions on endoscopic assessment achieved a complete pathological response, which should be considered in shared decision-making following restaging.