Adult males aged 60 and older taking PDE-5 inhibitors demonstrated significantly reduced rates of gastric cancer compared with matched controls not receiving these medications, according to research presented at the American College of Gastroenterology 2025 Annual Scientific Meeting in Phoenix.
The retrospective cohort study analyzed 794,925 matched patients in each cohort after propensity score matching. Patients taking sildenafil, tadalafil, or vardenafil between January 1, 2015, and April 30, 2025, showed a statistically significant reduction in gastric cancer rates (OR 0.7). The protective association extended to colorectal malignancy, with the PDE-5 inhibitor group demonstrating reduced colon cancer rates (OR 0.68) compared with controls.
However, stratification by Helicobacter pylori status revealed a caveat. Among patients with H. pylori infection those taking PDE-5 inhibitors still faced substantially elevated gastric cancer risk (OR 2.33) compared with H. pylori-negative patients, suggesting the protective effect may be insufficient.
"We went further to do a subgroup analysis in patients with an active or past history of H. pylori infection, which is an established risk factor for gastric cancer," said lead author Chisom Nwaneki, MD, from Saint Peter's University Hospital in New Brunswick, New Jersey. "We found that the lower odds of gastric cancer were still present. However, after the subgroup analysis that lower odd was found to be insignificant."
The research team conducted an additional case-control analysis examining PDE-5 inhibitor use among H. pylori-infected patients with and without gastric cancer. "In patients with H. pylori without gastric cancer, there were higher odds of PDE-5 inhibitor use with an odds ratio of 0.57, and that was found to be significant," Dr. Nwaneki stated.
Before matching, the study identified 795,289 patients taking PDE-5 inhibitors and 9,513,128 not receiving these medications. After propensity score matching to control for confounders, each cohort comprised 794,925 patients with balanced baseline characteristics.
The findings build upon existing evidence suggesting anti-neoplastic properties of PDE-5 inhibitors in gastrointestinal malignancies. Prior animal and human studies have documented anti-tumor effects in colon cancer, prompting investigation into potential protective mechanisms against gastric adenocarcinoma.
"We recommend future prospective studies to further explore this anti-tumor effect on PDE-5 inhibitors against gastric cancer," said Dr. Nwaneki.
The research team reported no relevant financial relationships.
Source: ACG