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 (ΔAIC) 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 (ΔAIC 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 (ΔAIC 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.

OBJECTIVE:We aimed to determine pretreatment pathological tumor extent in the resection specimen after neoadjuvant chemoradiotherapy (nCRT) and to assess its prognostic value in patients with esophageal cancer. METHODS:Patients with esophageal cancer, treated with nCRT plus surgery were included (2003-2011). Pretreatment pathological T-stage (prepT-stage) and N-stage (prepN-stage) were estimated based on the extent of regressional changes and residual tumor cells in the resection specimen. Interobserver agreement was determined between 3 pathologists. The prognostic performance of prepT-stage and prepN-stage was scored using the difference in Akaike information criterion (ΔAIC). PrepN-stage and posttreatment pathological N-stage (ypN-stage) were combined to determine the effect of nodal sterilization on prognosis. RESULTS:Overall concordance for prepT-stage and prepN-stage was 0.69 and 0.84, respectively. Prognostic strength of prepT-stage was similar to clinical T-stage and worse compared with ypT-stage (ΔAIC 1.3 versus 2.0 and 8.9, respectively). In contrast, prognostic strength of prepN-stage was better than cN-stage and similar to ypN-stage (ΔAIC 17.9 versus 6.2 and 17.2, respectively). PrepN+ patients who become ypN0 after nCRT have a worse survival compared with prepN0 patients, with a five year overall survival of 51% versus 68%, P = 0.019, respectively. CONCLUSIONS:PrepT-stage and prepN-stage can be estimated reproducibly. Prognostic strength of prepT-stage is comparable with clinical T-stage, whereas prepN-stage is better than cN-stage. PrepN+ patients who become ypN0 after nCRT have a worse survival compared with prepN0 patients. Pretreatment pathological staging should be considered useful as a new staging parameter for esophageal cancer and could also be of interest for other tumor types.