Predicting outcomes in esophageal adenocarcinoma following neoadjuvant chemoradiation: interactions between tumor response and survival

Objectives The prognostic value of tumor regression scores (TRS) among patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation remains unclear. We sought to investigate the prognostic value of pathologic and metabolic treatment response among EAC patients undergoing neoadjuvant chemoradiation. Methods Patients who underwent esophagectomy for esophageal adenocarcinoma after neoadjuvant CROSS protocol from 2016-2020 were evaluated. TRS was grouped per modified Ryan score, metabolic response per PERCIST criteria. Variables from endoscopic ultrasound, endoscopic biopsies, and positron-emitting tomography (primary and regional lymph node SUVs) were collected. Results The study population consisted of 277 patients. TRS=0 (complete response) was identified in 66 (23.8%) patients, TSR=1 (partial response) in 78 (28.1%), TRS=2 (poor response) in 97 (35%), and TRS=3 (no response) in 36 (13%). On survival analysis for OS, patients with TRS=0 had longer survival compared to TRS=1, 2, and 3 patients (p=0.010, p<0.001, and p=0.005, respectively). On multivariable logistic regression, presence of signet ring cell features on endoscopic biopsy (OR 7.54, p=0.012) and higher SUV uptake at regional lymph nodes (OR=1.42, p=0.007) were significantly associated with residual tumor at pathology (TRS=1,2,3). On multivariate Cox regression for predictors of OS, higher SUVmax at the most metabolically active nodal station (HR 1.08, p=0.005) was independently associated with decreased OS, while pathologic complete response (HR 0.61, p=0.021) was independently associated with higher OS. Conclusions Patients with pathologic complete response had prolonged OS, while no difference in survival was detected among other TRS categories. At initial staging, presence of signet ring cells and higher SUV uptake at regional lymph nodes predicted residual disease at pathology and shorter OS, suggesting the need for new treatment strategies for these patients.