More is not always better: higher lymph node yield is not associated with improved survival in stage I–III colorectal cancer

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Background: Colorectal cancer (CRC) is among the most prevalent malignancies worldwide and remains the second leading cause of cancer-related death. Curative treatment approaches rely on R0 resection with adequate regional lymphadenectomy. Current international guidelines recommend a lymph node yield (LNY) of at least 12 lymph nodes to ensure accurate pathological staging and to guide decisions regarding adjuvant therapy. However, it remains controversial whether this historically established threshold is sufficient to optimize oncological outcomes. The aim of this study was to evaluate the association between operative LNY and clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) in patients undergoing curative resection for CRC. Methods: This retrospective study included 333 patients who underwent colorectal cancer resection at a high-volume center in Germany between 2016 and 2023. Only patients with Union for International Cancer Control (UICC) stage I-III disease who underwent curative-intent R0 resection were included. Patients were stratified into two groups according to LNY: <20 versus ≥20 retrieved lymph nodes. Results: LNY of ≥20 was associated with distinct tumor- and treatment-related characteristics, including advanced local tumor stage, microsatellite instability (MSI), colon cancer, right hemicolectomy, and absence of neoadjuvant treatment. No significant differences were observed between the groups regarding nodal stage, number of positive lymph nodes, lymphatic invasion, surgical approach, urgency of surgery, intraoperative blood loss, major postoperative morbidity, anastomotic leakage, chyle leak, reoperation or length of hospital stay. Higher LNY was not independently associated with improved OS or DFS in the overall cohort. Subgroup analyses stratified by UICC stage showed no significant association between LNY ≥20 on OS or DFS in stage I, II, or III disease. In procedure-specific analyses, LNY ≥20 was associated with improved OS after anterior rectal resection. Conclusions: Overall, these findings suggest that higher LNY is not a general prognostic determinant of oncological outcomes, but may have procedure-specific prognostic relevance.

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