This article by Lee and colleagues [1Lee A. Wong A.T. Schwartz D. et al.Is there a benefit to prolonging the interval between neoadjuvant chemoradiation and esophagectomy in esophageal cancer?.Ann Thorac Surg. 2016; 102: 433-439Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar] is provocative. Their analysis of the National Cancer Database evaluated the relationship between a pathologic complete response (pCR) rate and overall survival when “delaying” surgical intervention after neoadjuvant chemoradiation. They evaluated 6,292 patients over 9 years. The mean pCR rate was 15%, lower than in most reported phase II or phase III trials. Increasing the time to operation resulted in a higher pCR rate, which was associated with improved survival. The impact of delaying operative treatment with improved survival was not statistically significant on multivariate analysis. The retrospective nature of the study obviously makes definitive conclusions difficult to make. The quality and reliability of the data from the National Cancer Database, although a national resource, need to be considered. These deidentified data coming from hospital tumor registries are generally not verified for reliability by a physician. In this study, the interval from chemoradiation to operation was calculated by subtracting the days from diagnosis until the beginning and end of radiation and then this day from the day of operation. Although patients with squamous cell carcinoma did better, with more pCR, only 20% of this cohort had squamous cell carcinoma. Community Cancer Centers allegedly did worse, although recent data would suggest that volume is a key indicator for outcomes in esophageal surgical procedures. High-volume centers would be expected to have excellent outcomes regardless of whether they were academic institutions or not. The pCR was determined by the finding of the final TNM staging, that is, identification of posttreatment (and postresection), T0N0M0 as documented by the tumor registry. The median time to operation was 49 days. It is important for esophageal surgeons and their multidisciplinary cancer teams to recognize that the effect of radiation on tissue can be seen to occur within a 2- to 12-week window. With that in mind, the plan to wait after neoadjuvant therapy should be seen as an optimal window of opportunity. During this time, the patient can undergo careful restaging to rule out progression of disease, specifically to identify missed distant metastases such as small liver metastases. Likewise, during the interval from chemoradiation to surgical treatment, the patient’s physiologic condition should be optimized. This is a chance to improve nutrition with enteral or parenteral feeding and to get the patient’s nutritional status as close to the premorbid state as possible. Weight loss of more than 5% to 10% in itself can be a predictor of bad outcome and should be overcome. In addition, optimizing the patient’s cardiopulmonary status, including formal rehabilitation before the operation, should be considered. Lastly, by performing resection too soon, cancer cells that are “dying” but not yet “dead” are read as residual disease pathologically. Especially if there are micrometastases, this can appear subjectively as disease progression. Waiting for 8 weeks after chemoradiation seems the right time frame to optimize the “tumor kill” by documenting cell death while also allowing the patient to recover; there does not seem to be severe side effects, such as severe scarring, from “waiting too long” in this time frame, as was once thought. Whether waiting for this time frame to elapse will actually result in better survival cannot be determined at this time based on the current study. Further work on optimizing pathologic response rate and correlating it with survival should be undertaken prospectively. Is There a Benefit to Prolonging the Interval Between Neoadjuvant Chemoradiation and Esophagectomy in Esophageal Cancer?The Annals of Thoracic SurgeryVol. 102Issue 2PreviewEvidence 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. Full-Text PDF