Factors Associated with the Timing of Liver Metastasis After Colorectal Cancer Surgery: A Retrospective Multicenter Study.

Purpose: This study aimed to determine the optimal temporal threshold for distinguishing "early" from "late" liver metastasis in patients who developed liver metastasis after colorectal cancer (CRC) surgery, and to evaluate whether KRAS and BRAFV600E mutations, along with other clinicopathological factors, are associated with the timing of liver metastasis. Methods: This retrospective study utilized clinical and pathological data from patients who developed liver metastasis after radical CRC surgery at two centers from 2019 to 2023. X-tile software was used to identify the optimal temporal threshold. Logistic regression analysis was applied to determine if KRAS/BRAFV600E mutations and other potential factors are independently associated with the time to onset of liver metastasis. Results: X-tile analysis identified 11 months post-surgery as the optimal cutoff for distinguishing early metachronous liver metastasis (EMLM) from late metachronous liver metastasis (LMLM), classifying 114 cases into the EMLM group and 72 into the LMLM group. Comparative analysis indicated statistically significant differences between the two groups in lymphovascular tumor emboli, perineural invasion, and postoperative adjuvant therapy (p < 0.05). Logistic regression analysis revealed that neither KRAS mutation (OR, 1.185; 95% CI: 0.641-2.190; p = 0.587) nor BRAFV600E mutation (OR, 2.836; 95% CI: 0.302-26.642; p = 0.363) was independently associated with the timing of liver metastasis. In contrast, postoperative adjuvant therapy showed a statistical association with a likelihood of LMLM (OR, 0.253; 95% CI: 0.105-0.611; p = 0.002). Conclusions: This study identified 11 months post-CRC surgery as the optimal cutoff for differentiating EMLM versus LMLM. In this cohort, no statistically significant association was observed between KRAS/BRAFV600E mutations and the timing of liver metastasis, whereas postoperative adjuvant therapy was statistically correlated with the likelihood of LMLM. This stratification may guide personalized surveillance strategies and provide valuable insights for future mechanistic investigations into the temporal heterogeneity of post-surgical liver metastasis. However, the interpretation and generalization of the findings require external validation in prospective cohorts.