Inverse effects of lymph node count on oncological outcomes in rectal cancer based on lymph node positivity status post-neoadjuvant CRT: a large-volume Chinese center experience.

Background: Neoadjuvant chemoradiation therapy (CRT) followed by total mesorectal excision (TME) is the standard of care for locally advanced rectal cancer (LARC). Current guidelines recommend dissecting at least 12 lymph nodes (LNs). However, the impact of LN count post-CRT on survival outcomes remains controversial. This study aimed to evaluate the relationship between LN count and oncologic outcomes in LARC patients treated with neoadjuvant CRT followed by surgery.

Methods: This retrospective analysis was conducted on 1483 patients with cT3-4N + LARC who underwent neoadjuvant CRT and curative resection. Univariate and multivariate analyses were performed to identify factors associated with achieving 12 or more LNs. Restricted cubic spline (RCS) and Cox proportional hazards models were used to assess the relationship between LN count and oncologic outcomes, including disease-free survival (DFS) and overall survival (OS). Exploratory subgroup analyses stratified patients by ypN positivity status.

Results: The mean number of LNs retrieved was 12.9 ± 6.8, with 55.7% of patients having 12 or more LNs examined. Laparoscopic surgery, tumor location (mid rectum), younger age, and lymph node status (pN2) were independent factors associated with achieving 12 or more LNs. RCS analysis revealed an inverse relationship between LN count and tumor response to CRT, but no association with OS and DFS in the overall cohort. ypN-negative patients tended to have a higher rate of liver metastases with an increased LN count (P = 0.010). However, in ypN-positive patients, a higher LN count was associated with improved DFS (P = 0.007) and a lower likelihood of lung metastases (P = 0.001). Using X-tile software, a cutoff value of 10 LNs was identified as optimal for DFS in stage 3 rectal cancer patients. Patients with 11 or more LNs examined had significantly better 5-year DFS (66.7% vs. 55.8%, P = 0.035) compared to those with fewer than 11 LNs.

Conclusion: Our study challenges the guideline of examining at least 12 LNs during rectal cancer surgery after CRT, as we observed an inverse relationship between LN count and tumor response to CRT. The inverse effects of LN count on oncological outcomes across various stages of LN positivity highlight the need for individualized treatment strategies based on lymph node positivity status. For ypN-negative patients, understanding that an increased LN count is associated with a higher risk of liver metastases can help identify high-risk stage 0-2 patients who may benefit from adjuvant therapy. For ypN-positive (stage 3) patients, achieving at least 11 LNs is necessary to ensure better oncological outcomes.