Prognostic divergence of hematogenous and lymphatic metastases in patients with stage IV colorectal cancer

Background: In patients with stage IV colorectal cancer (CRC), the prognostic impact of lymph node metastasis (LNM) remains controversial. A qualifying cohort served to explore its importance. Methods: We selected 493 eligible patients with stage IV CRC for retrospective study. All were surgically treated between April 2007 and December 2020 at a high-volume cancer center in Japan. Subjects were stratified by presence/absence of LNM (N+M1 vs N0M1), and propensity score matching (PSM) was done at 1:1 ratio. We then compared cancer-specific (CSS) and overall (OS) survival rates before and after PSM, using Cox regression to identify pertinent independent risk factors. Results: Patients assigned to N+M1 and N0M1 groups totaled 384 (77.9%) and 109 (22.1%), respectively. Five-year OS proved superior for the N0M1 (vs N+M1) group, both before (41.7% vs 30.8%; p =0.020) and after (43.7% vs 26.5%; p =0.042) PSM. LNM also emerged as an independent prognosticator of OS in multivariate analyses conducted before (hazard ratio [HR]=1.5, 95% confidence interval [CI]: 1.09-2.08; p =0.014) and after (HR=1.72, 95% CI: 1.121-2.64; p =0.013) matching. The same was true of 5-year CSS, both before (N0M1, 46.1%; N+M1, 32.4%; p =0.009) and after (N0M1, 48.8%; N+M1, 28.0%; p =0.027) matching, again verifying LNM as an independent prognostic factor before (HR=1.6, 95% CI: 1.13-2.25; p =0.007) and after (HR=1.86, 95% CI: 1.185-2.90; p =0.007) PSM. Conclusions: In the setting of stage IV CRC, distant hematogenous metastasis (N0M1) confers a better prognosis than does regional LNM (N+M1). This apparent prognostic divergence must be reflected in refined tumor classification subsets.