External Validation of Pretreatment Pathological Tumor Extent in Patients with Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer

Abstract

Background. This study was conducted to validate a pretreatment (i.e. prior to neoadjuvant chemoradiotherapy) pathological staging system in the resection specimen after neoadjuvant chemoradiotherapy for esophageal cancer. The study investigated the prognostic value of pretreatment pathological T and N categories (prepT and prepN categories) in both an independent and a combined patient cohort. Methods. Patients with esophageal cancer treated with neoadjuvant chemotherapy and esophagectomy between 2012 and 2015 were included. PrepT and prepN categories were estimated based on the extent of tumor regression and regressional changes of lymph nodes in the resection specimen. The difference in Akaike's information criterion (DAIC) was used to assess prognostic performance. PrepN and ypN categories were combined to determine the effect of nodal sterilization on prognosis. A multivariable Cox regression model was used to identify combined prepN and ypN categories as independent prognostic factors. Results. The prognostic strength of the prepT category was better than the cT and ypT categories (DAIC 7.7 vs. 3.0 and 2.9, respectively), and the prognostic strength of the prepN category was better than the cN category and similar to the ypN category (DAIC 29.2 vs. -1.0 and 27.9, respectively). PrepN ? patients who became ypN0 had significantly worse survival than prepN0 patients (2-year overall survival 69% vs. 86% in 137 patients; p = 0.044). Similar results were found in a combined cohort of 317 patients (2-year overall survival 62% vs. 85%; p = 0.002). Combined prepN/ypN stage was independently associated with overall survival. Conclusions. These results independently confirm the prognostic value of prepTNM staging. PrepTNM staging is of additional prognostic value to cTNM and ypTNM. PrepN0/ypN0 patients have a better survival than prepN ?/ ypN0 patients.Potentially curative treatment for esophageal cancer consists of neoadjuvant chemo(radio)therapy followed by surgery. After neoadjuvant therapy, the percentage of residual tumor cells and lymph node regression is of prognostic value. Several studies investigated the impact of tumor regression and classified histopathological response to neoadjuvant therapy and its correlation to prognosis.

Shrinkage versus fragmentation response in neoadjuvantly treated oesophageal adenocarcinoma: significant prognostic relevance

“…Moreover, recognition and early clinical evaluation of these patterns of response correlated to (future) imaging modalities may contribute to improved patient selection for further treatment. New pathological approaches focusing upon tumour response to predict patient survival have been recently explored, 29,30 exemplifying the applicability and reliance of these data. These studies in particular aimed to assess the clinical relevance of regression changes such as fibrosis, mucinous lakes, keratin pearls and foreign-body giant cell reactions, as well as the presence of tumour remnants.…”

Collaborative multidisciplinary management and expertise of cT2–3 locally advanced operable esophageal squamous cell carcinoma: a report of two cases

“…Earlier, our study group investigated a new classification system depending on regressional changes in the resection specimen. We proved that pretreatment pathological prep-N staging was more accurate than conventional N-staging ( 30 , 31 ).…”

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet‐ring cells, and/or poorly cohesive cells

“…Hazard ratios (HRs) in models based on pre‐treatment histopathological factors were adjusted for variables as known pre‐treatment: age, gender, cT stage (cT3–4 versus cT1–2) and cN stage (cN+ versus cN0). HRs in models based on post‐treatment histopathological factors were adjusted for variables as available post‐treatment: age, gender, prepT stage (prepT3–4 versus prepT1–2), prepN stage (prepN+ versus prepN0) [ 21 , 22 ], ypT stage (ypT3–4 versus ypT1–2), ypN stage (ypN+ versus ypN0), TRG (TRG 3–4 versus TRG 2), and resection margin status (R1 versus R0).…”