Helicobacter pylori-naïve status is associated with poor prognosis and aggressive pathological features in undifferentiated-type gastric cancer: a multi-center retrospective cohort study

Background: Undifferentiated-type gastric cancer (UGC) is more pathologically aggressive and progresses faster than differentiated-type gastric cancer (DGC). However, the impact of Helicobacter pylori (Hp) status on survival outcomes and clinicopathological features of UGC remains unclear. Methods: This multi-center retrospective study analyzed 571 patients pathologically confirmed UGC from January 2011 to December 2021. Clinical and histopathological features and survival outcomes were compared between Hp-naïve undifferentiated-type gastric cancer (HpNUGC) and Hp-infected undifferentiated-type gastric cancer (HpIUGC). Results: 571 patients including 283 HpNUGC (49.6%) and 288 HpIUGC (50.4%) were enrolled in survival analysis. The 5-year event-free survival (EFS) and 5-year overall survival (OS) rates were significantly lower in the HpNUGC group compared to the HpIUGC group (EFS: 46.3% vs. 64.3%, P < 0.001; OS: 54.3% vs. 67.7%, P < 0.001). Hp-naïve status was associated with a 57% higher risk of disease progression, recurrence, or death, collectively termed “events” in this study (HR 1.57; 95% CI 1.20–2.04), and a 50% higher risk of all-cause mortality (HR 1.50, 95% CI 1.12–2.00). The HpNUGC lesions demonstrated larger tumor diameters (P < 0.001), deeper invasion depths (P < 0.001), more frequent lymphatic metastasis (P = 0.003), more advanced disease stages (P = 0.002), and higher rates of positive incision margins (P = 0.049). Conclusion: HpNUGC is associated with worse survival outcomes and exhibits more malignant pathological features compared to HpIUGC. Future prospective studies are needed to clarify the relationship between Hp status and the development and progression of UGC.