Proper prognostic classification of histopathologic response to neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma

Abstract

Abstract Background Accurate restaging and histological assessment of esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT) provide valuable prognostic information. We aimed to elucidate proper classification methods to discriminate and predict prognosis in ESCC patients who received nCRT followed by surgery and in the recurrent subgroup. Methods We included 309 patients with ESCC who underwent nCRT followed by complete resection for analysis of overall survival (OS). Among them, 304 patients were eligible for recurrence-free survival (RFS) analysis, and OS analysis was also separately performed on 98 recurrent patients. Tumor regression grade (TRG) was assessed using the modified Ryan scheme and ypTNM was recorded based on the 8th edition of the AJCC TNM classification. The combination of TRG and lymph node status resulted in two ypTN systems: ypTN (four categories) and ypTN (three categories). In the ypTN (four categories) system, the categories were ypT-N-, ypT + N-, ypT-N+, and ypT + N+. When considering ypT + N- and ypT-N + as one category, it produced the ypTN (three categories) system. We plotted Kaplan-Meier survival curves based on various classification methods. The log-rank test was used to examine differences in survival rates and calculate P values. The selected classification methods underwent univariable and multivariable Cox regression analyses. Results The mean follow-up period was 39.2 months (range, 0.6–70.4). Compared to classification methods of TRG, ypT, ypN, ypTNM, and ypTN (four categories), ypTN (three categories) performed the best ability to distinguish and predict OS and RFS in overall population with P < 0.001 for overall models and significant differences between adjacent groups. In the recurrent population, we found the binary classification of ypN was a good predictor of OS (ypN- vs. ypN+, HR: 1.819, 95%CI: 1.150–2.878, P = 0.011). The reliability of these classification methods in both the overall population and the recurrent population was confirmed by univariable and multivariable Cox regression analyses. Conclusions The prognosis of ESCC patients who received nCRT followed by surgery can be distinguished and predicted by ypTN (three categories) system. Lymph node status was an ideal prognostic classification for the recurrent subgroup.