The optimal number of lymph nodes examined for rectal cancer patients undergoing neoadjuvant long-course chemoradiotherapy.

Background: Numerous studies have documented a reduction in the number of lymph nodes (LNs) examined and the number of metastatic LNs in rectal cancer patients as a consequence of neoadjuvant chemoradiotherapy (NCRT). It is plausible that the current guidelines advocating a specific number of LNs to be examined in rectal cancer surgery may be inappropriate for patients undergoing neoadjuvant therapy. This study aimed to determine the optimal number of LNs to be examined in rectal cancer patients treated with NCRT. Methods: We conducted a retrospective analysis of clinicopathologic data from rectal cancer patients who underwent NCRT and radical resection at the Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer Center (NCC) from January 2004 to December 2015, as well as patients diagnosed with rectal cancer who received neoadjuvant therapy followed by surgery in the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. The optimal cutoff value for the number of examined LNs (ELNs) was determined using the X-tile software. Prognosis was assessed using the Kaplan-Meier method and log-rank test, while Cox regression analysis was employed to identify prognostic risk factors. Results: A total of 6,634 patients were included, comprising 391 patients in the NCC cohort and 6,243 patients in the SEER cohort. In the NCC cohort, there was no significant survival difference between patients with <12 ELNs and those with ≥12 ELNs, with the 5-year disease-free survival (DFS) rates of 72.0% and 76.5%, respectively (P=0.10). Furthermore, the X-tile software identified 7 as the optimal cutoff value for ELNs. In this cohort, patients with <7 ELNs had a 5-year DFS rate of 65.1%, compared to 76.3% for those with ≥7 ELNs (P=0.03). Multivariate Cox analysis revealed that the number of ELNs (cutoff value at 7) was the independent prognostic factor for DFS [hazard ratio (HR) =3.255, 95% confidence interval (CI): 1.796-5.897, P<0.001]. In the SEER cohort, the 5-year cancer-specific survival (CSS) rate was 81.2% for patients with <12 ELNs compared with 83.1% for those with ≥12 ELNs (P=0.10). Among these patients, those with <7 ELNs had a 5-year CSS rate of 79.1%, compared to 83.0% for those with ≥7 ELNs (P=0.04). Multivariate Cox analysis demonstrated that the number of ELNs (cutoff at 7) was an independent prognostic factor associated with CSS (HR =1.606, 95% CI: 1.308-1.970, P<0.001). Conclusions: The optimal minimum number of LNs to be examined in rectal cancer patients treated with NCRT appears to be 7. The current standard of examining ≥12 LNs may be inappropriate. This finding provides valuable insights for determining the appropriate number of ELNs during surgery for rectal cancer patients who have undergone neoadjuvant therapy.