Phosphodiesterase-5 inhibitors use and risk for mortality and metastases among male patients with colorectal cancer

Wuqing Huang,Kristina Sundquist,Jan Sundquist,Jianguang Ji

doi:10.1038/s41467-020-17028-4

Abstract

Phosphodiesterase-5 (PDE5) inhibitors are suggested to have anti-tumor effects and to inhibit surgery-induced immunosuppression. We aimed to explore whether post-diagnostic use of PDE5 inhibitors was associated with a better prognosis among male patients with colorectal cancer (CRC) and the role of open surgery in the association. Here we show that post-diagnostic use of PDE5 inhibitors is associated with a decreased risk of CRC-specific mortality (adjusted HR = 0.82, 95% CI 0.67-0.99) as well as a decreased risk of metastasis (adjusted HR = 0.85, 95% CI 0.74-0.98). Specifically, post-operative use of PDE5 inhibitors has a strong anti-cancer effect. The reduced risk of metastasis is mainly due to distant metastasis but not regional lymphatic metastasis. PDE5 inhibitors have the potential to be an adjuvant drug for patients with CRC to improve prognosis, especially those who have undergone open surgery.

Highlights

Phosphodiesterase-5 (PDE5) inhibitors are suggested to have anti-tumor effects and to inhibit surgery-induced immunosuppression
By combining several national databases in Sweden, we aim to explore the antitumor effects of PDE5 inhibitors in a population-based cohort and demonstrate that: (1) post-diagnostic use of PDE5 inhibitors is associated with a lower colorectal cancer (CRC)-specific mortality; (2) postdiagnostic use of PDE5 inhibitors could reduce the incidence of metastasis among male patients who were diagnosed with CRC; and (3) the anticancer effect of PDE5 inhibitors is stronger among patients who received open surgery
By linking to the Swedish Cancer Registry and the Swedish Prescribed Drug Register, we identified a total of 12,465 male patients diagnosed with CRC at Stage I, II, or III during the study period

Summary

Introduction

Phosphodiesterase-5 (PDE5) inhibitors are suggested to have anti-tumor effects and to inhibit surgery-induced immunosuppression. Based on the evidence mentioned above, we hypothesized that inhibition of PDE5 might be associated with a reduced risk of tumor progression and mortality among patients with CRC, and the effect might be stronger among patients who have received open surgery. By combining several national databases in Sweden, we aim to explore the antitumor effects of PDE5 inhibitors in a population-based cohort and demonstrate that: (1) post-diagnostic use of PDE5 inhibitors is associated with a lower CRC-specific mortality; (2) postdiagnostic use of PDE5 inhibitors could reduce the incidence of metastasis among male patients who were diagnosed with CRC; and (3) the anticancer effect of PDE5 inhibitors is stronger among patients who received open surgery

Objectives

Methods

Results

Conclusion