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

Objectives: The prognostic value of tumor regression scores (TRS) in patients with esophageal adenocarcinoma (EAC) 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 EAC after neoadjuvant CROSS protocol between 2016 and 2020 were evaluated. TRS was grouped according to the modified Ryan score; metabolic response, according to the PERCIST criteria. Variables from endoscopic ultrasound, endoscopic biopsies, and positron emission tomography (primary and regional lymph node standardized uptake values [SUVs]) were collected. Results: The study population comprised 277 patients. A TRS of 0 (complete response) was identified in 66 patients (23.8 % ). Seventy-eight patients (28.1 % ) had TRS 1 (partial response), 97 (35 % ) had TRS 2 (poor response), and 36 (13 % ) had TRS 3 (no response). On survival analysis for overall survival (OS), patients with TRS 0 had longer survival compared to those with TRS 1, 2, or 3 ( P = .010, P < .001, and P = .005, respectively). On multivariable logistic regression, the presence of signet ring cell features on endoscopic biopsy (odds ratio [OR], 7.54; P = .012) and greater SUV uptake at regional lymph nodes (OR, 1.42; P = .007) were significantly associated with residual tumor at pathology (TRS 1, 2, or 3). On multivariate Cox regression for predictors of OS, higher SUVmax at the most metabolically active nodal station (hazard ratio [HR], 1.08; P = .005) was independently associated with decreased OS, whereas pathologic complete response (HR, 0.61; P = .021) was independently associated with higher OS. Conclusions: Patients with pathologic complete response had prolonged OS, whereas no difference in survival was detected among other TRS categories. At initial staging, the presence of signet ring cells and greater SUV uptake at regional lymph nodes predicted residual disease at pathology and shorter OS, suggesting the need for new treatment strategies for these patients.