Level of evidence for claims of sildenafil inhibiting cancer metastasis

Causal inference becomes stronger from bottom to top

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Large-scale randomized controlled trials (RCTs)

As of the time of publication, no large-scale RCTs have been completed to verify the cancer metastasis prevention/treatment effects of sildenafil.

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Small-scale prospective clinical trials

Prospective studies directly measuring dosage, safety, and metastasis indicators in humans are still lacking.

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Large-scale retrospective observational studies

Analysis of 20-year records of 5 million people in Clalit, including over 40,000 male cancer patients. Includes papaverine negative control. However, cancer stage is not adjusted.

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Animal models

Reduced lung metastasis in breast, lung, and colon cancer mouse models. Vardenafil replication, cross-validated via PDE5a gene knockout.

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Cell/mechanism experiments

Inhibition of migration and survival in human breast, prostate, colon, and lung cancer cell lines. Confirmed cGMP-NPC1 binding and lysosomal cholesterol accumulation.

Precedent to consider. The cancer prevention effect of statins was repeatedly reported as a 20-30% reduction in observational studies, but in a meta-analysis of 26 RCTs with 86,936 participants (JAMA 2006), the difference disappeared with an odds ratio of 1.02 for cancer incidence and 1.01 for cancer mortality. The results of a 2023 meta-analysis of 35 RCTs were the same.