Neoadjuvant Therapy for Rectal Cancer Affects Lymph Node Yield and Status Without Clear Implications on Outcome: The Case for Eliminating a Metric and Using Preoperative Staging to Guide Therapy

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Background: Nodal status has long been considered pivotal to oncologic care, staging, and management. This has resulted in the establishment of rudimentary metrics regarding adequate lymph node yield in colon and rectal cancers for accurate cancer staging. In the era of neoadjuvant treatment, the implications of lymph node yield and status on patient outcomes remains unclear. Patient and Methods: This study included 1,680 patients with locally advanced rectal cancer from the NCCN prospective oncology database stratified into 3 groups based on preoperative therapy received: no neoadjuvant therapy, neoadjuvant chemoradiation, and neoadjuvant chemotherapy. Clinicopathologic characteristics and survival were compared between the groups, with univariate and multivariate analyses undertaken. Results: The clinicopathologic characteristics demonstrated statistically significant differences and heterogeneity among the 3 groups. The neoadjuvant chemoradiation group demonstrated the statistically lowest median lymph node yield (n=15) compared with 17 and 18 for no-neoadjuvant and neoadjuvant chemotherapy, respectively (P<.0001). Neoadjuvant treatment did impact survival, with chemoradiation demonstrating increased median overall survival of 42.7 compared with 37.3 and 26.6 months for neoadjuvant chemotherapy and no-neoadjuvant therapy, respectively (P<.0001). Patients with a yield of fewer than 12 lymph nodes had improved median overall survival of 43.3 months compared with 36.6 months in patients with 12 or more lymph nodes (P=.009). Multivariate analysis demonstrated that neither node yield nor status were predictors for overall survival. Discussion: This analysis reiterates that nodal yield in rectal cancer is multifactorial, with neoadjuvant therapy being a significant factor. Node yield and status were not significant predictors of overall survival. A nodal metric may not be clinically relevant in the era of neoadjuvant therapy, and guidelines for perioperative therapy may need reconsideration.

Author Contributions: Bekaii-Saab and Abdel-Misih formulated the scientific question (concept) and the associated data points of interest to be obtained from the NCCN cancer database. Schrag reviewed the initial concept with approval for use of the NCCN cancer database for this scientific inquiry. LW was involved in the statistical concepts and analysis of the acquired data. The qualitative data analysis, interpretation, and drafting of the manuscript were undertaken by Abdel-Misih and Bekaii-Saab. All authors (Weiser, Benson, Cohen, Lai, Skibber, Wilkinson, Weiser, Schrag, Bekaii-Saab, and Abdel-Misih) contributed to the review and editing of the manuscript. All authors had final approval of the version to be published and are in agreement to be accountable for all aspects of the work in ensuring questions related to the accuracy and integrity of the work are appropriately investigated and resolved. Correspondence: Sherif R. Z. Abdel-Misih, MD, 320 West 10th Avenue, M256 Starling-Loving Hall, Columbus, OH 43210. E-mail: sherif.abdel-misih@osumc.edu
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