Active Helicobacter pylori Infection and Survival Outcomes in De Novo Metastatic Colorectal Cancer: A Retrospective Cohort Study.

BACKGROUND

The prognostic significance of Helicobacter pylori (H. pylori) infection in metastatic colorectal cancer (mCRC) remains uncertain. Most prior studies have focused on colorectal neoplasia risk and have relied on serological markers rather than assessment of active infection. We evaluated the association between histologically confirmed H. pylori status and clinicopathological features, systemic inflammatory markers, and survival outcomes in patients with de novo mCRC.

METHODS

In this retrospective single-center cohort study, consecutive patients diagnosed with de novo mCRC between September 2011 and December 2025 who underwent synchronous upper gastrointestinal endoscopy at diagnosis were included. H. pylori status was determined histopathologically. Overall survival (OS) was estimated using the Kaplan-Meier method and compared with the log-rank test. Prognostic factors were analyzed using univariable and multivariable Cox proportional hazards models with prespecified sensitivity and exploratory interaction analyses.

RESULTS

Among 168 patients, 77 (46%) were H. pylori positive. Right-sided tumors were more frequent in H. pylori-positive patients (43% vs. 17%, p < 0.001), as was BRAF mutation (12% vs. 3%, p = 0.044). Baseline neutrophil-to-lymphocyte ratio was higher in the H. pylori-positive group (median 4.34 vs. 2.74, p = 0.002). Median OS was longer in H. pylori-positive patients (33 vs. 19 months; log-rank p < 0.001). In multivariable analysis, right-sided tumor localization (HR 2.11, 95% CI: 1.648-2.716; p < 0.001), RAS mutation (HR 1.94, 95% CI: 1.612-2.794; p < 0.001), and H. pylori negativity (HR 1.94, 95% CI: 1.569-2.812; p < 0.001) remained statistically significant. These findings were consistent across sensitivity analyses. Significant interactions were observed for tumor sidedness (p < 0.001) and NLR category (p = 0.002).

CONCLUSIONS

Histologically confirmed H. pylori positivity was associated with a distinct clinicopathological profile and longer overall survival in patients with de novo mCRC. Given the observational design, these findings should be interpreted as hypothesis-generating and require validation in prospective and multi-center studies.