Is There a Benefit to Prolonging the Interval Between Neoadjuvant Chemoradiation and Esophagectomy in Esophageal Cancer?

Abstract

Evidence suggests that delaying surgical procedures may increase the rate of pathologic complete response (pCR) and that pCR is associated with improved overall survival (OS). In this study, the National Cancer Data Base (NCDB) was analyzed to evaluate this relationship in a large hospital-based registry. We identified patients diagnosed with esophageal adenocarcinoma or squamous cell carcinoma who received neoadjuvant chemoradiation (CRT) followed by esophagectomy from 2003 to 2012. Patients were stratified into quartiles based on the interval between the completion of CRT to operative treatment (≤40 days, 41-50 days, 51-63 days, and ≥64 days), and those with pT0N0M0 were classified as having pCR. Multivariate logistic regression was used to assess the impact of covariates on pCR, and multivariate Cox regression was used to assess their impact on OS. The study population included 5,393 patients. Increasing the time interval to the surgical procedure was associated with an increased pCR rate (12.3% for ≤40 days to 18.3% for ≥64 days; p < 0.001). On multivariate analysis, a time interval greater than or equal to 51 days was associated with an increased likelihood of pCR (p = 0.009 for 51-63 days; p < 0.001 for ≥64 days), as was an increased radiation dose ≥50 Gy (p = 0.046 for 50-50.4 Gy; p = 0.02 for >50.4 Gy). Increasing the time interval was not associated with an improvement in OS for any quartile on multivariate analysis. In addition, OS was worse for those who underwent operation ≥64 days after completion of radiation therapy (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.33; p = 0.03). Although increasing the time interval from CRT to surgical intervention was associated with a higher pCR rate, there was no improvement in survival.