Is there a relationship between phosphodiesterase type 5 inhibitors and biochemical recurrence after radical prostatectomy: a systematic review and meta-analysis
Conduct a systematic review and meta-analysis of studies to evaluate the association between the use of PDE5I and biochemical recurrence (BCR) after radical prostatectomy (RP).
We searched Embase (from 1996 to Feb 2018), PubMed (from 1996 to Feb 2018), and Cochrane library (from 1999 to Feb 2018), then manually searched the reference lists of key retrieved articles. Original studies that reported the risk of postoperative BCR for PDE5I users, as compared with non-PDE5I users, were included. Data including the characteristic of participants, the risk of BCR after RP and key criteria of study quality were collected. The pooled relative risks (RRs) were calculated with random-effects model.
A total of 5 cohort studies and 1 case–control study were conducted for data analysis (a total of 17752 participants). Only 1 cohort study reported adjusted RR greater than 1 (range for all derived RRs, 0.7–1.47). The meta-analysis revealed that the PDE5I users had no higher risk of BCR after RP (RR = 1.04, 95% confidence interval [CI], 0.79–1.36). Sensitivity analysis showed that the remaining pooled RR and 95% CI were not changed significantly by omitting each study. In addition, the 5-year BCR rate had no significant difference between PDE5I users and non-PDE5I users.
Our meta-analysis indicated that PDE5I treatment in men following RP did not increase the risk of BCR. The results preliminarily suggested that the use of PDE5I for erectile dysfunction after RP was oncologically safe. Nevertheless, more large sample cohort studies are needed to validate this conclusion.
KeywordsPhosphodiesterase type 5 inhibitors Biochemical recurrence Radical prostatectomy
This study was supported by Grant Nos. 81770703 and 81470927 from the National Natural Science Foundation of China and Grant No. 16PI294 from Project of the Health and Family Planning Committee of Sichuan Province.
Q He: Project development, Data analysis, Quality assessment, Manuscript writing. BH Liao: Data analysis, Quality assessment, Manuscript editing. KW Xiao: Data collection, Chart production. L Zhou: Protocol development. SJ Feng: Data collection. H Li: Manuscript editing. KJ Wang: Project development, Data management, Manuscript editing.
Compliance with ethical standards
Conflict of interest
The authors declare that no conflict of interest exists.
This meta-analysis was based on published studies. Therefore, ethical approval and informed consent are not required for this type of study.
- 1.Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L, Lin X, Greenfield TK, Litwin MS, Saigal CS, Mahadevan A, Klein E, Kibel A, Pisters LL, Kuban D, Kaplan I, Wood D, Ciezki J, Shah N, Wei JT (2008) Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med 358(12):1250–1261. https://doi.org/10.1056/NEJMoa074311 CrossRefPubMedGoogle Scholar
- 3.Michl U, Molfenter F, Graefen M, Tennstedt P, Ahyai S, Beyer B, Budaus L, Haese A, Heinzer H, Oh SJ, Salomon G, Schlomm T, Steuber T, Thederan I, Huland H, Tilki D (2015) Use of phosphodiesterase type 5 inhibitors may adversely impact biochemical recurrence after radical prostatectomy. J Urol 193(2):479–483CrossRefGoogle Scholar
- 4.Gallina A, Bianchi M, Gandaglia G, Cucchiara V, Suardi N, Montorsi F, Briganti A (2015) A detailed analysis of the association between postoperative phosphodiesterase type 5 inhibitor use and the risk of biochemical recurrence after radical prostatectomy. Euro Urol 68(5):750–753CrossRefGoogle Scholar
- 9.Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. Jama 283(15):2008–2012CrossRefGoogle Scholar
- 22.Zenzmaier C, Sampson N, Pernkopf D, Plas E, Untergasser G, Berger P (2010) Attenuated proliferation and trans-differentiation of prostatic stromal cells indicate suitability of phosphodiesterase type 5 inhibitors for prevention and treatment of benign prostatic hyperplasia. Endocrinology 151(8):3975–3984. https://doi.org/10.1210/en.2009-1411 CrossRefPubMedGoogle Scholar
- 27.Jerzak M, Kniotek M, Mrozek J, Gorski A, Baranowski W (2008) Sildenafil citrate decreased natural killer cell activity and enhanced chance of successful pregnancy in women with a history of recurrent miscarriage. Fertil Steril 90(5):1848–1853. https://doi.org/10.1016/j.fertnstert.2007.08.043 CrossRefPubMedGoogle Scholar
- 29.Li J, Shi Q, Pu C, Tang Y, Bai Y, Yuan H, Li X, Dong Q, Wei Q, Yuan J, Han P (2014) Phosphodiesterase type 5 inhibitors for the treatment of post-nerve sparing radical prostatectomy erectile dysfunction in men. Sci Rep 4:5801. https://doi.org/10.1038/srep05801 CrossRefPubMedPubMedCentralGoogle Scholar