Clinical fate of T0N1 esophageal cancer: results from the National Cancer Database

The long-term survival for patients with locally advanced esophageal cancer (EC) remains poor despite improvements in multi-modality care. Neoadjuvant chemoradiation (NCR) followed by surgical resection remains pivotal in the management of patients with EC. However, the outcome of patients whose primary tumor exhibits a complete response with residual regional nodal disease (T0N1) remains unclear as well as the role for adjuvant therapy. Utilizing the National Cancer Database we identified patients with EC who underwent NCR followed by esophagectomy who had subsequent pathology of T0N1. Baseline univariate comparisons of patient characteristics were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests as appropriate. Pearson's Chi-square test was used to compare categorical variables. Unadjusted survival analyses were performed using the Kaplan-Meier method comparing survival curves with the log-rank test. All statistical tests were two-sided and alpha (type I) error <0.05 was considered statistically significant. We identified 7,116 patients diagnosed with EC; 6,235 (87.6%) adenocarcinoma (AC), 881 (12.4%) squamous cell carcinoma (SCC) with a median age of 62 [21-88] years. There were 6,031 (84.8%) males and 1,085 (15.2%) females. R0 resections were achieved in 6,668 (93.7%) patients and this correlated to improved median survival 39.5 (R0) and 20.1 (R1) months respectively, P<0.001. The median nodes harvested were 13 [0-83] with a mean positive LN's of 1.4 +/- 2.9. Pathologic complete response (pCR) was achieved in 1,334 (18.7%), partial response (pPR) 2,812 (39.5%) and non-response (pNR) 2,970 (41.7%). There were 230 (3.2%) patients deemed as pathologic T0N1. The median survival of patients with pCR was 61.7 months compared to 32.1 months in the T0N1 patients P<0.001. T0N1 patients did not demonstrate an improved survival over T1/2 patients who had a median survival of 30.5 months, P=0.79. However, T0N1 did reveal an improved survival over T3/4 patients who had a median survival of 24.6 months, P=0.02. Adjuvant chemotherapy in T0N1 did not provide a benefit in survival, median survival adjuvant versus no adjuvant 30.8 vs. 32.1 months respectively, P=0.08. Multivariate analysis in T0N1 patients demonstrated only number of LN's positive, and histology SCC vs. ACC as predictive of survival, HR, 1.22, 95% CI: 1.10-1.36, P<0.001; HR, 0.43, 95% CI: 0.24-0.75, P=0.003, respectively. Patients with EC who exhibit a pathologic T0N1 after NCR have oncologic fates similar to node positive patients. Patients with pCR of the primary tumor and regional lymph nodes continue to demonstrate significant survival benefits over all remaining pathologic cohorts.