Introduction: Neoadjuvant chemotherapy (NAC) ± radiation (NRT) is the “gold standard” approach for locally advanced esophageal cancer (EC). However, the benefits of RT on overall survival (OS) in patients with resectable EC undergoing neoadjuvant therapy followed by esophagectomy remain controversial. Methods: The National Cancer Data Base was queried for patients with nonmetastatic EC between 2004 and 2014. Kaplan–Meier, log-rank, and Cox multivariable regression analysis were performed to analyze OS. Logistic regression analyzed factors associated with 90-day mortality, lymph node involvement, and complete pathological response (pCR). Results: A total of 12,238 EC patients who underwent neoadjuvant therapy [neoadjuvant chemoradiation (NACR), 92.1% and NAC, 7.9%] followed by esophagectomy were included. OS was similar in patients undergoing NAC ± RT (35.9 vs. 37.6 mo, respectively, p = 0.393). pCR rate was 18.1% (19.2%, NACR vs. 6.3%, NAC, p < 0.001). NRT was an independent predictor for increased pCR (HR 2.593, p < 0.001). Patients with pCR had increased survival compared with those without pCR (62.3 vs. 34.4 mo, p < 0.001); however, no difference was found between NACR and NAC (61.7 mo vs. median not reached, p = 0.745) in pCR patients. In non-pCR patients, NAC had improved OS compared with NACR (37.3 vs. 30.8 mo, p = 0.002). NRT was associated with worse 90-day mortality (8.2% vs. 7.7%, HR1.872, p = 0.036) In Cox regression, NRT was an independent predictor of worse OS (HR 1.561, p < 0.001). Conclusions: Neoadjuvant RT is associated with improved pCR rates; however, it had deleterious effects in short- and long-term survival. Also, patients who did not achieve pCR had worse OS after neoadjuvant RT.
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