By: Dan Sperling, MD

Background: The use of erectile dysfunction (ED) medications such as Viagra, Cialis and Levitra (a class of drugs called PDE5 inhibitors, or PDE5i) is known to be safe when used as directed. These drugs have benefited millions of men by improving erectile function, and they are often prescribed after nerve-sparing prostatectomy as they often enable men to perform sexually while waiting for the return of spontaneous function. Laboratory studies with animals, and clinical studies with men who suffer from ED (with no prior history of prostate cancer), have produced evidence that the drugs may offer a beneficial immune-response to existing cancers, or even a preventive function against developing prostate cancer through ejaculating more frequently. However, no systematic studies have been done on whether PDE5i use for ED after prostatectomy had any bearing on the cancer returning. Therefore, a research team from the famed Martini-Clinic Prostate Cancer Center in Hamburg, Germany designed a clinical study to examine the impact of such drugs on the rates of biochemical recurrence (rising PSA).[i]

This was a retrospective study; the authors reviewed the records of 4752 consecutive cases of nerve-sparing RP between Jan. 2000 and Dec. 2010. Following surgery, 1110 patients (23.4%) were prescribed PDE5 inhibitors, whereas 3624 (76.6%) were not. The average follow-up for all cases was 5 years. The estimated rates of 5-year biochemical recurrence-free survival (BRFS) are shown in the following table:

The difference in reported recurrence-free rates is statistically significant (not attributed to chance).

The lead author, Uwe Michi, described his team as “astonished” at the results and encouraged caution before arriving at conclusions.[ii] While their single-center results suggest that PDE5i may adversely impact biochemical recurrence, the authors write that more studies, both retrospective and prospective, “are necessary to confirm this effect and to elucidate its mechanism.” In the meantime, clinic physicians still advise their RP patients to use these drugs on demand if they are dealing with post-treatment ED.

There is more than one hypothesis as to why this large, single center’s data seems to contradict earlier, more optimistic findings about the correlation between PDE5i and prostate cancer, including an unknown biological mechanism that affects some men while not others. An important factor could be an inherent selection bias. The following points should be taken into account:[iii]

The study showed no difference in rates of biochemical recurrence between smokers and non-smokers after treatment for prostate cancer, but such a difference has been clearly established in several other studies.

• Age and body mass index (BMI) are also known risk factors for erectile dysfunction, and may facilitate biochemical recurrence after a radical prostatectomy; however, in this study, neither age nor BMI were independently associated with biochemical recurrence-free survival.
• Only a minority of the patients in the current study cohort were actually smokers (but they were distributed equally between the PDE5 and non-PDE5 groups).

Time and future publications will shed light on the surprising findings of Michi and his team. Perhaps the opening observation of a Medscape article on this subject sums up the situation for now: “Sometimes a scientific hypothesis is all wrong but scientific understanding moves forward anyway.”[iv]

[i] Michi U, Molfenter F, Graefen M et al. Use of phosphodiesterase type 5 inhibitors may adversely impact biochemical recurrence after radical prostatectomy. U Urol. 2015 Feb;193:479-483. Full article available at http://www.jurology.com/article/S0022-5347(14)04366-3/pdf

[ii] http://www.medscape.com/viewarticle/838783

[iii] http://prostatecancerinfolink.net/2015/01/29/does-use-of-pde5-inhibitors-post-treatment-affect-risk-for-biochemical-recurrence/

[iv] http://www.medscape.com/viewarticle/838783