Impact of Lymph Node Yield on Overall Survival in Patients Treated with Neoadjuvant Chemoradiotherapy Followed by Esophagectomy for Cancer: A Population-based Cohort Study in the Netherlands

Objective: To evaluate the impact of lymph node yield (LNY) on survival in patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy for cancer. Background: The value of an extended lymphadenectomy after nCRT for esophageal cancer is debated. Recent reports demonstrate no association between LNY and survival. This association has not yet been evaluated in larger cohorts. Methods: All patients who underwent nCRT followed by esophagectomy between 2005 and 2014 were identified from the Netherlands Cancer Registry. The association between LNY and overall survival was analyzed using multivariable Cox regression analyses, adjusting for diagnosis year, referral, hospital volume, age, sex, malignancy history, tumor location, histology, cTN-stage, surgical approach, radicality, and ypTN-stage. Analyses were performed with LNY as categorized predictor (<15 vs ≥15 nodes) and continuous predictor (per 10 additionally nodes). Results: A total of 2698 patients were included with a median overall survival of 34 months (range 4-143). A higher LNY was significantly associated with improved overall survival, both as categorized predictor (hazard ratio 0.77, 95% confidence interval 0.68-0.86) and as continuous predictor (hazard ratio 0.84, 95% confidence interval 0.78-0.90). Furthermore, a higher LNY was associated with favorable hazard ratios across subgroups, including both squamous cell carcinoma and adenocarcinoma, both cN0 and cN+, both transthoracic and transhiatal approaches, and both ypN0 and ypN+. Conclusions: This large population-based cohort study demonstrates an association between LNY and overall survival, indicating a therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, an extended lymphadenectomy should be the standard of care after nCRT.