Impact of lymph node metastasis on prognosis in colorectal cancer patients with liver metastasis and staging systems Refinement: An international multicenter retrospective cohort study

Background

The current AJCC staging for colorectal cancer liver metastasis (CRLM) classifies stages IVA, IVB, and IVC based on organ metastasis, disregarding lymph node metastasis (LNM). We evaluated the prognostic impact of LNM in CRLM and proposed incorporating LNM into staging criteria.

Methods

Data were extracted from the SEER database (2010–2017) and a Chinese cohort (2009–2018), including 11,266 CRLM patients (9648 SEER; 1618 Chinese cohort). Kaplan-Meier and Cox regression analyses assessed cancer-specific survival (CSS) between LNM and non-LNM groups. Inverse probability treatment weighting (IPTW) was used for primary analysis, with subgroup analyses exploring LNM's prognostic impact.

Results

In both the SEER and Chinese cohorts, patients with LNM were significantly associated with worse CSS than patients without LNM before and after IPTW/sIPTW (all p < 0.001). Furthermore, LNM in the M1a subgroup still led to poorer prognosis (all log-rank p < 0.001). In contrast, in the M1b subgroup, the prognostic difference between those with and without LNM was not significant (log-rank p = 0.031 and 0.037, respectively, in the SEER and Chinese cohorts) because the P_FDR was set at 0.025. Additionally, in both cohorts, the 5-year CSS rates of M1a stage CRLM patients decreased with advancing N staging, regardless of the resectability of liver metastasis (all log-rank P < 0.001).

Conclusion

LNM has significant association with worse survival outcomes in CRLM patients, although this prognostic impact exhibits progressive attenuation with increasing liver metastatic burden. For patients with M1a stage CRLM, we suggest that incorporating N staging into their prognostic evaluation can further refine the AJCC TNM staging system.