The purpose of this study was to determine if a major pathologic response to therapy is defined entirely by pCR and if this definition is associated with increased survival. Although complete responses to trimodality therapy for EAC are uncommon, they are related to better outcomes. However, pCR is the primary endpoint in the vast majority of clinical trials and correlative studies. Patients diagnosed with locally progressed esophageal adeno-carcinoma between 1995 and 2017 were included in this prospectively maintained database, and researchers examined the results. 

Using Kaplan-Meier plots, they compared patients who had a pathologic nodal stage (ypN0) with those who had a higher percentage of tumor resection (TR) in the main tumor bed. Descriptive plots with restricted cubic spline functions were used to examine the optimal TR thresholds for differentiating patients in terms of OS, and associations were quantified using Cox multivariable analysis. Median overall survival (OS) was 48.3 months (95% CI, 42.2-58.8) after a median follow-up of 37.5 months (range, 0.4210.6) among 788 patients. Survival rates were significantly higher when no residual nodal illness was seen (P<0.001). 

The 90% to 99% TR and 100% TR survival curves were very comparable, and there was a statistically significant shift toward better OS at the 90% TR threshold. Multivariate research showed that a TR of 90% to 99% plus 100% was independently related to better OS than a TR of less than 50%. In addition to more than 90% TR in the primary tumor bed, ypN0 status is the strongest predictor of substantial pathologic response to trimodality therapy. Given these results, it’s possible that the criteria of substantial pathologic response can be widened from pCR to encompass TR of more than 90% and ypN0 as well. What this means for future clinical trials and correlational research is substantial.