Commentary - The Association between Phosphodiesterase Type 5 Inhibitors and Prostate Cancer: Results from the REDUCE Study

Erectile dysfunction (ED) is a condition that affects 20%-40% of men in the sixth decade of life, and 75% in the seventh decade1. The introduction of Phosphodiesterase type 5 inhibitors (PDE-5is) in 1998 to treat ED has shown positive results2-4. PDE-5i has also been suggested as having anticancer activity. However 3 recent studies examining the use of PDE-5i use, and BCR after prostatectomy and/or radiation have conflicting results5-7. Only 1 group has examined the relationship between PDE-5i and PC diagnosis. Although their study was limited to do methodological design, they showed that men using PDE-5i had lower chance of being diagnosed with PC8. The aims of this study is to improve on the previous study and further explore the association between PDE-5i use and PC diagnosis using the REDUCE data set. They hypothesis of the study was that PDE-5i would be associated with decrease in PC detection.

REDUCE was a 4-year multicenter, prospective, randomized, controlled double-blinded trial comparing the effect of dutasteride on PC diagnosis among men who had a negative prestudy biopsy9. In REDUCE, cancer ascertainment was uniform in all men by requiring mandated biopsies at 2 and 4 years regardless of PSA. Of the 8,122 men initially enrolled in the study, only 6,501 men were included in the analysis –no significant difference in baseline demographics. The association between baseline PDE-5i use with overall PC risk and disease grade (Gleason 2-6 and 7-10) was examined using adjusted logistic and multinomial regression analysis. Due to North American men having significantly higher use of PDE-5i, a secondary analysis was performed on North American men alone.

The results of this study showed that PDE-5i use was not associated with a decrease in PC cancer (OR 0.90, 95% CI 0.68 – 1.20, p = 0.476), low grade disease (OR 0.93, 95% CI 0.67-1.27, p=0.632) or high grade disease (OR 0.85, 95% CI 0.51 – 1 39, p=0.508). When looking at the secondary analysis of North American men, there was an inverse trend between PDE-5i use and PC diagnosis, however there was no statistically significant results (OR 0.67, 95% CI 0.42 – 1.07, p = 0.091). The limitations in the study were: PDE-5i use was not randomly assigned and the use rate was low, PDE-5i use was self-reported so some factors were unable to control, the study was only limited to white men, and the study period was limited to 4-years.

In conclusion, PDE-5I was not associated with decrease PC based on post-hoc analysis of REDUCE. There was an inverse relationship between PDE-5i and PC diagnosis in North American men, but it did not reach statistically significance. The study recommends future studies to further determine the association between PDE-5i and PC with longer follow-up and larger study populations.

Authors: Juzar Jamnagerwalla, Lauren E. Howard, Adriana C. Vidal, Daniel M. Moreira, Ramiro Castro-Santamaria, Gerald L. Andriole and Stephen J. Freedland

Affiliations: Division of Urology, Department of Surgery, Cedars-Sinai Medical Center (JJ, ACV, SJF), Los Angeles, California, Department of Biostatistics and Bioinformatics, Duke University (LEH) and Surgery Section, Durham Veterans Affairs Medical Center (SJF, LEH), Durham, North Carolina, Department of Urology, Mayo Clinic (DMM), Rochester, Minnesota, Research and Development, GlaxoSmithKline, Inc. (RC-S), King of Prussia, Pennsylvania, and Washington University School of Medicine in St. Louis (GLA), St. Louis, Missouri

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Reference:

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