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

Abstract

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 α (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.

Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study

“…However, the modalities used in the CREs also evaluate residual nodal disease. After nCRT, 4-9% of patients with SCC have a pathologically complete response at the primary tumor site with residual disease in the regional lymph nodes (ypT0N+), compared to 3-5% of patients with AC [23][24][25]. For these patients, higher ypN stage is correlated with worse overall survival [25].…”

“…However, these studies did not clearly specify the nCRT regimens that patients received. Moreover, the majority of patients probably did not receive nCRT according to the CROSS regimen since they were included before the results of the CROSS trial were published [23,24]. Accordingly, data of a large Dutch CROSS cohort comprising patients that were included in the CROSS-I and CROSS-II trials, post-CROSS cohort and the preSANO trial were analyzed.…”

Residual lymph node disease and mortality following neoadjuvant chemoradiation and curative esophagectomy for distal esophageal adenocarcinoma

“…Similar results were derived by another study, which also showed improved survival in node positive patients after adjuvant treatment. 18 Both of the aforementioned studies were based on the National Cancer Database (NCDB) and the rate of patients receiving adjuvant treatment was 15.3% and 10.7%, respectively, although only in the former study patients with positive LNs were included. In our study, the rate of administration of adjuvant treatment in patients with residual LN disease was 29.9%.…”

ypN0 in Patients With Definitive cN-positive Status After Preoperative Treatment Is a Prognostic Factor in Esophageal Cancer

“…ypT statuses can be classified into five grades following the criteria of the Japanese Classification of Esophageal Cancer (3) or the histological criteria presented by Mandard et al (13). Survival benefits were investigated among patients with primary tumors of grades I-III, but not grade IV, by the classification of pathological tumor regression grades I-IV, and only pCR was used as a biomarker (14)(15)(16). However, in recent reports, prognostic factors have been investigated by classification of pathological regression grades I-IV or grades 0-3 in metastatic lymph nodes as well as primary tumors in recent reports (6, 15-17).…”