Neoadjuvant Immunotherapy and Chemoradiation Followed by Esophagectomy for Esophageal Cancer

ABSTRACT Background Treatment of locally advanced esophageal cancer includes neoadjuvant chemoradiation (chemoRT) and esophagectomy. We evaluated perioperative and oncologic outcomes among patients who received neoadjuvant chemoRT and immunotherapy (I/O). Methods Adults who underwent esophagectomy following neoadjuvant chemoRT or chemoRT+I/O for T1-4, N0-3, M0 esophageal cancer were identified from the National Cancer Database (2012-2020). Unadjusted, propensity score-matched, and Cox proportional hazards analyses compared perioperative outcomes and three-year overall survival (OS) between neoadjuvant chemoRT versus chemoRT+I/O cohorts. Results Among 17,937 patients, 261 (1.5%) received neoadjuvant chemoRT+I/O. ChemoRT+I/O patients were younger (62 versus 64 years, p=0.002) and had a longer interval between chemotherapy and surgery (104.5 versus 97.0 days, p<0.001) compared with chemoRT patients. Among the chemoRT+I/O cohort, there were more undifferentiated tumors (46.4% versus 34.3%, p<0.001) with adenocarcinoma histology (93.9% versus 81.2%, p<0.001) compared with the chemoRT cohort. On unadjusted analysis, there were no significant differences regarding margin positivity, 30-day readmission, 30-day mortality, or 90-day mortality. ChemoRT+I/O patients had higher 3-year OS (61.4% 95%CI [54.2-67.7] versus 55.1% [54.3-55.9], p=0.02), more lymph nodes resected (median 17.0 IQR [11.0-25.0] versus 15.0 [10.0-22.0], p=0.007), and less pathologic nodal downstaging from N2 to N1/N0 (36.8% vs 48.4%, p<0.001) than chemoRT patients. Propensity score-matched analyses (n=217) revealed no differences in perioperative outcomes and 3-year OS (65.0% 95%CI [57.1-71.8] versus 56.0% [48.0-63.3], p=0.11) between the chemoRT+I/O and chemoRT cohort. Conclusions There were similar perioperative outcomes and 3-year OS between patients who received neoadjuvant chemoRT+I/O and chemoRT, supporting the feasibility of adding immunotherapy to neoadjuvant regimens.