Study Suggests PDE5 Inhibitors May Have Anti-Cancer Potential in Male Patients with CRC

A study published in Nature Communications suggested that potency enhancing phosphodiesterase-5 (PDE5) inhibitor drugs, such as sildenafil (Viagra), have an anti-cancer potential with the ability to improve a prognosis in patients with colorectal cancer (CRC).¹

“Available preclinical evidence suggests that PDE5 inhibitors could slow down the tumor growth and progression in mice, but it is still unknown whether PDE5 inhibitors can hinder the proliferation of cancer in humans. We tried to explore this using real-world medical data in Sweden,” Wuqing Huang, a PhD student at Lund University and one of the researchers behind the study, said in a press release.²

Using several nationwide registries, researchers identified all Swedish male patients (n = 1136) with colorectal cancer who had used PDE5 inhibitors following a cancer diagnosis. Notably, compared with those who did not use PDE5 inhibitors, those who did tended to be diagnosed at a younger age and at an earlier stage. Moreover, patients who used PDE5 inhibitors were more likely to get married and had a higher education and income level than patients who did not use PDE5 inhibitors. Additionally, these patients were less likely to be given aspirin and had a lower prevalence of comorbidity at baseline.

After a median follow-up of 4.25 years, 116 patients who used PDE5 inhibitors had died from CRC during the study period, generating the mortality rate of 20.20 each 1000 person-year. Contrastingly, the mortality rate was 37.87 each 1000 person-year among those who did not use PDE5 inhibitors.

Following adjustment for possible confounders, postdiagnostic use of PDE5 inhibitors was found to be associated with a decreased risk of death due to CRC (adjusted HR, 0.82; 95% CI, 0.67-0.99). Further, this observation was more pronounced in patients who underwent open surgery after diagnosis (adjusted HR, 0.72; 95% CI, 0.56-0.93), especially those with dispensation after surgery (adjusted HR, 0.69; 95% CI, 0.50-0.96).

In addition, compared with patients who did not use PDE5 inhibitors, post-diagnostic use of PDE5 inhibitors was significantly associated with a reduced risk of metastasis (adjusted HR, 0.85; 95% CI, 0.74-0.98). The decreased risk of metastasis was also more prominent among patients who underwent open surgery (adjusted HR, 0.74; 95% CI, 0.60-0.90) compared with those that did not undergo surgery (adjusted HR, 1.10; 95% CI, 0.90-1.35).

"The results of our study suggest that the anti-cancer ability of PDE5 inhibitors might be related to regulating immunosuppressive effects,” Huang explained. “However, randomized clinical trials are needed to confirm our research findings before PDE5 inhibitors can be used as an adjuvant drug for men with colorectal cancer, as well as experiments that explore the underlying biological mechanisms.”

Importantly, this study was limited male patients because only a few female patients were prescribed with PDE5 inhibitors in Sweden. However, the investigators suggested that it still may be worthwhile to explore whether the observed study findings can be replicated in female patients with CRC, given that female patients may have a better tolerance of PDE5 inhibitors.

"The observed findings should be interpreted with caution as this is an observational study and the biological mechanisms need to be explored further,” Jianguang Ji, a researcher at Lund University who was also involved in the study, said in the release. “We have already collaborated with other scientists to explore the underlying mechanisms by utilizing animal experiments and cancer organoid.”

References:

1. Huang W, Sundquist J, Sundquist K, Ji J. Phosphodiesterase-5 inhibitors use and risk for mortality and metastases among male patients with colorectal cancer. Nature Communications. doi: 10.1038/s41467-020-17028-4

2. Potency-enhancing drugs linked to decreased risks in men with colorectal cancer [news release]. Lund University. Published August 17, 2020. Accessed August 28, 2020. https://www.newswise.com/articles/potency-enhancing-drugs-linked-to-decreased-risks-in-men-with-colorectal-cancer?sc=sphr&xy=10021790