Locoregional Residual Esophageal Cancer after Neo-adjuvant Chemoradiotherapy and Surgery Regarding Anatomic Site and Radiation Target Fields A Histopathologic Evaluation Study

Objective: Neoadjuvant chemoradiotherapy followed by surgery establishes a considerable pathologic complete response (pCR) in EC. The aim was to determine site of residual tumor and its prognostic impact. Summary Background Data: High rates of residual tumor in the adventitial region even inside the radiation fields will influence current decision-making. Methods: We evaluated resection specimens with marked target fields from 151 consecutive EC patients treated with carboplatin/paclitaxel and 41.4Gy between 2009 and 2018. Results: In radically resected (R0) specimens 19.8% (27/136) had a pCR (ypT0N0) and 14% nearly no response (tumor regression grade: tumor regression grade 4-5). Residual tumor commonly extended in or restricted to the adventitia (43.1%; 47/109), whereas 7.3% was in the mucosa (ypT1a), 16.5% in the submucosa (ypT1b) and 6.4% only in lymph nodes (ypT0N+). Macroscopic residues in R0-specimens of partial responders (tumor regression grade 2-3: N = 90) were found in- and outside the gross tumor volume (GTV) in 33.3% and 8.9%, and only microscopic in- and outside the clinical target volume in 58.9% and 1.1%, respectively. Residual nodal disease was observed proximally and distally to the clinical target volume in 2 and 5 patients, respectively. Disease Free Survival decreased significantly if macroscopic tumor was outside the GTV and in ypT2-4aN+. Conclusions: After neoadjuvant chemoradiotherapy, pCR and ypT1aN0 were seen in a limited number of R0 resected specimens (19.8% and 7.3%, respectively), whereas 6.4% had only nodal disease (yT0N+). Disease Free Survival decreased significantly if macroscopic residue was outside the GTV and in responders with only nodal disease. Therefore, we should be cautious in applying wait and see strategies.