PDE5 inhibitors eg Taladalfal etc. 2 papers, one a cohort study showing positive survival association. The second about invitro studies

[Graham49]

The association of phosphodiesterase-5 inhibitors with the biochemical recurrence-free and overall survival of patients with prostate cancer following radical prostatectomy

Author links open overlay panelKelsey T.DanleyM.D.aAlanTanM.D.bWilliam J.CatalonaM.D.cRobinLeikinPh.D.dIreneHelenowskiPh.D.eBorkoJovanovicPh.D.eMichaelGurleyB.A.dTimothy M.KuzelM.D.b

doi.org/10.1016/j.urolonc.2...

Highlights

•We analyzed documented PDE5 inhibitor use in prostate cancer post radical prostatectomy

•Documented PDE5 inhibitor use has a positive association with overall survival

•Documented PDE5 inhibitor use has a positive association with biochemical relapse-free survival

•Further studies investigating this association are needed for validation

Abstract

Purpose

To determine whether phosphodiesterase-5 inhibitor documentation is associated with biochemical relapse-free and overall survival of patients with prostate cancer treated with radical prostatectomy.

Materials and methods

We undertook a retrospective cohort analysis of 3,100 patients with prostate cancer treated with radical prostatectomy between 2003 and 2015. The patients were categorized as a phosphodiesterase- 5- inhibitor user or non-user. The biochemical relapse-free and overall survival at 5-years and 10-years were determined.

Results

Of the patients, 1,372 reported phosphodiesterase-5 inhibitor documentation, and 1,728 did not. The biochemical recurrence-free survival for non-users at 5- and 10-years follow-up was 87.6% and 85.3%, respectively, and the overall survival at these time intervals was 97.9% and 94.5%. The biochemical recurrence-free survival for phosphodiesterase-5 inhibitor users was 94.3% and 93.2% at 5- and 10-years follow-up, respectively, and overall survival was 99.2% and 95.8% at these intervals. The hazard ratio for biochemical recurrence-free survival was 0.44 (CI 0.34–0.56) and for overall survival was 0.65 (CI 0.45–0.94). On the multivariate analysis, phosphodiesterase-5 inhibitor documentation was associated with a lower risk of biochemical recurrence and death when corrected for the other variables. Age at surgery and Gleason scores >8 was associated with a higher risk of death. Higher pathological stage, higher Gleason score, presence of lymph node metastases, and nonwhite race were associated with a higher risk of recurrence.

Conclusion

This retrospective analysis revealed a significant association of postoperative phosphodiesterase-5 inhibitor documentation with biochemical recurrence-free- and overall survival in patients with localized prostate cancer treated with radical prostatectomy. Larger scale studies are warranted to investigate the clinical significance of this association.

Open AccessReview

Tadalafil and Steroid Hormones Interactions in Adipose, Bone and Prostate Tissues: Focus on Translational Perspectives

by Emanuela Alessandra Greco 1,2, Cristina Antinozzi 2ORCID, Luigi Di Luigi 2ORCID, Antonio Aversa 3,*ORCID and Paolo Sgrò 2ORCID

1 Department Unicusano, University “Niccolò Cusano”, 00166 Rome, Italy

2 Department of Movement, Human and Health Sciences, “Foro Italico” University, 00135 Rome, Italy

3 Department of Experimental and Clinical Medicine, Magna Græcia University, 88100 Catanzaro, Italy

*Author to whom correspondence should be addressed.

Academic Editors: Natasha Kyprianou and Fabrice Lucien-Matteoni

Int. J. Mol. Sci. 2022, 23(8), 4191; doi.org/10.3390/ijms23084191

Received: 3 March 2022 / Revised: 6 April 2022 / Accepted: 8 April 2022 / Published: 11 April 2022

(This article belongs to the Special Issue Emerging Concepts and Novel Therapeutics to Overcome Treatment Resistance in Prostate Cancer)

Abstract

Tadalafil is a selective phosphodiesterase type-5 (PDE5) inhibitor that is approved for the treatment of men with erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH) -associated symptoms. Besides its classical actions on PDE5 within the genitourinary tract, where the specific enzyme expression is maximal, it may exert different systemic effects. This is mainly due to the pleiotropic distribution of PDE5 enzyme throughout the human (and animal) body, where it can exert protective effects in different clinical conditions. Recently, it has been demonstrated that tadalafil may display novel actions on androgen receptor (AR) expression and activity and cytochrome P19a1 (Cyp19a1) and estrogen receptor β (ERβ) expression in different in vitro systems, such as adipose, bone and prostate cancer cells, where it can act as a selective modulator of steroid hormone production. This may determine novel potential mechanism(s) of control in pathophysiologic pathways. In this review, we summarize basic research and translational results applicable to the use of tadalafil in the treatment of obesity, bone loss and prostate cancer. View Full-Text

Keywords: tadalafil; prostate cancer; aromatase; adipocytes; bone; androgen receptors; obesity; osteoporosis

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Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

[Scout4answers]

Use it or lose it.

[kapakahi]

Would this indicate its benefits for those who haven't had RP? The thing is, I was taking this for a few years before I was dx with PC, and I've never stopped.

[Graham49 in reply to kapakahi]

Here are the results from the retrospective cohort study. A good positive association was shown for overall survival and biochemical recurrence for those who had RP. You might have to wait a long time for studies to answer your question definitively. I suggest you ask your oncologist for his opinion.

"Results

Of the patients, 1,372 reported phosphodiesterase-5 inhibitor documentation, and 1,728 did not. The biochemical recurrence-free survival for non-users at 5- and 10-years follow-up was 87.6% and 85.3%, respectively, and the overall survival at these time intervals was 97.9% and 94.5%. The biochemical recurrence-free survival for phosphodiesterase-5 inhibitor users was 94.3% and 93.2% at 5- and 10-years follow-up, respectively, and overall survival was 99.2% and 95.8% at these intervals. The hazard ratio for biochemical recurrence-free survival was 0.44 (CI 0.34–0.56) and for overall survival was 0.65 (CI 0.45–0.94). On the multivariate analysis, phosphodiesterase-5 inhibitor documentation was associated with a lower risk of biochemical recurrence and death when corrected for the other variables. Age at surgery and Gleason scores >8 was associated with a higher risk of death. Higher pathological stage, higher Gleason score, presence of lymph node metastases, and nonwhite race were associated with a higher risk of recurrence."