ED drugs tied to lower gastric cancer risk
Large retrospective study finds 30% reduction in gastric malignancy among men taking erectile dysfunction medications.
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11/11/2025
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by Kerri Miller
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.
Summary content
7 Key Takeaways
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The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.