Nodal Clearance as a Predictor of Oncologic Outcomes in Esophageal and Gastroesophageal Junction Malignancies Receiving Trimodality Therapy.

Purpose/Objective(s) Standard of care for surgical candidates with locally advanced esophageal/gastroesophageal junction (E/GEJ) cancers is trimodality therapy. Similar to other groups, we have previously demonstrated the strong prognostic significance of pathological complete response (pCR) at the time of esophagectomy. Little is known about the prognostic significance of nodal clearance alone, however. We sought to determine the prognostic significance of nodal clearance in the subgroup of node positive E/GEJ (N+ E/GEJ), hypothesizing that nodal clearance drives the improved outcomes seen in patients with pCR as the primary tumor is more completely removed at esophagectomy. Materials/Methods Patients undergoing TMT for a primary N+ E/GEJ cancer from 1993-2020 within a single institution were retrospectively analyzed. All patients had either clinically involved nodal disease prior to nCRT and/or pathologically confirmed residual nodal disease at time of esophagectomy. Cancer and demographic features were collected. Direct comparisons were made between pCR versus no pCR and nodal clearance (ypN0) versus persistent nodal disease (ypN+) using the Kaplan-Meier method to estimate progression free survival (PFS) and overall survival (OS). Results One hundred eighty-one patients with median follow up of 140 months were included for analysis. Median age at diagnosis was 60.1 years (30.1-80.9), 142 (78.5%) were adenocarcinomas, 102 (56.4%) were AJCC stage IIIA. Fifty-one (28.2%) had pCR, 103 (56.9%) had ypN0 (including 52 [28.7%] with nodal clearance and residual tumor) and 78 (43.1%) had ypN+. Median OS and PFS for the entire cohort were 26.4 (95% CI, 20.5-32.3) and 18.0 months (95% CI, 12.7-23.4), respectively; 2-year local control rate was 87.4% (95% CI, 84.6-90.2). When comparing ypN0 to ypN+, there were statistically significant improvements in OS and PFS. In contrast, there were no significant differences in OS and PFS when comparing patients with pCR to no pCR (Table 1). Conclusion While pCR is a known prognostic factor in E/GEJ regardless of nodal status, in the high-risk subset of N+ E/GEJ patients, nodal clearance was associated with significantly improved OS and PFS regardless of primary tumor response. This is a novel observation and warrants similar hypothesis testing in other data sets and may have implications for therapy in node positive patients.