Survival after neoadjuvant approaches to gastroesophageal junction cancer

Background Gastroesophageal junction (GEJ) cancers can be treated with equipoise using neoadjuvant chemoradiation (NACRT) or chemotherapy alone (NAC), but the comparative outcomes are unclear. Methods Patients with non-metastatic T2-4 or N1-3 GEJ adenocarcinoma who underwent definitive surgery and NAC or NACRT were selected from the National Cancer Database. The primary outcome was overall survival (OS). Multivariable regression and propensity score analysis were used to adjust for age, comorbidity, and other characteristics. Results We identified 2435 patients treated with NACRT and 648 patients treated with NAC. OS was not significantly different between NACRT and NAC (51% versus 54% at 3 years, respectively, P = 0.11). Extent of pathological downstaging (complete, partial/mixed, none) after NACRT or NAC was highly prognostic of survival. Patients with no response did equally poorly after either preoperative regimen, and NAC was significantly less likely than NACRT to produce any response (adjusted odds ratio 0.62, P < 0.0001). Rate of adjuvant chemotherapy usage was significantly lower after NACRT than after NAC (12% versus 34%, P < 0.0001). In patients with residual tumor and nodal disease, adjuvant chemotherapy was associated with higher OS after NACRT (adjusted hazard ratio 0.81, P = 0.05), but not after NAC. These results were further validated by propensity score analysis. Conclusions NACRT had similar survival to NAC despite superior pathological downstaging. Adjuvant chemotherapy is relatively underused after NACRT and warrants further study as a risk-adapted means to improve survival, especially in patients with larger burden of residual disease.