Docs 'Astonished': ED Drugs Tied to Prostate Cancer Return

Nick Mulcahy

January 27, 2015

Sometimes a scientific hypothesis is all wrong but scientific understanding moves forward anyway. That might be the case in a study of men with prostate cancer.

In the study, researchers found an association between the use of erectile dysfunction (ED) drugs after radical prostatectomy and biochemical recurrence.

They were surprised by the findings; they had hypothesized that the drugs would be protective because multiple lab studies and an observational clinical study suggested an anticancer effect in the prostate.

"We were astonished. We expected opposite results," said lead researcher Uwe Michl, MD, from the Martini-Klinik Prostate Cancer Center in Hamburg, Germany, in an email to Medscape Medical News.

But, he added, the study should not change practice.

 
We still advise our patients to use PDE5 inhibitors on demand.
 

"We still advise our patients to use PDE5 [phosphodiesterase type 5] inhibitors on demand," he explained. "PDE5 inhibitors are effective in treating ED following nerve-sparing radical prostatectomy, assuming that there are still some spontaneous but insufficient erections."

"Our results need to be interpreted with caution," Dr Michl and his colleagues write in their study, which was published in the February issue of the Journal of Urology.

The findings about cancer risk are not entirely novel.

Sildenafil was associated with an increased risk for melanoma in 25,000 men in the Health Professionals' Follow-up Study (HPFS), as reported by Medscape Medical News.

Dr Michl reported that his team is hoping to work with the HPFS investigators to evaluate their data with respect to prostate cancer.

In their study, the German researchers reviewed data on 4752 consecutive men who had undergone radical prostatectomy from 2000 to 2010 at the Martini-Klinik, which is one of the world's largest centers for prostate cancer.

After surgery, about a quarter of the men (23.4%) were treated with a PDE5 inhibitor for ED, which is a common complication of the procedure and a known problem in aging men. The drugs used included sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis).

The other 76.6% of the men did not receive a PDE5 inhibitor.

The two patient groups were comparable on most clinical parameters.

Five-year biochemical recurrence-free survival estimates were lower in the treated than in the untreated group (84.7% vs 89.2%; P = .0006).

In other words, ED treatment with a PDE5 inhibitor was associated with a significant reduction in the rate of being free of recurrence.

The median follow-up in the study was 60.3 months.

The researchers speculate about possible mechanisms behind the adverse outcome.

"The effects of sildenafil and other selective PDE5 inhibitors on the immune system, on autonomic nerve development as well as on angiogenesis, are conceivable causes of our findings," they write.

The study is the first of its kind. No other research has looked at the use of these drugs after prostate cancer surgery and their impact on biochemical recurrence.

However, a previous observational study showed that the use of PDE5 inhibitors in men with ED (and no history of prostate cancer) was associated with a decreased incidence in the rate of prostate cancer (Asian J Androl. 2013;15:246-248). The investigators from Scott & White Healthcare in Temple, Texas, explain that men treated with PDE5 inhibitors might ejaculate more often than untreated men, which has been demonstrated to have a protective effect against prostate cancer (JAMA. 2004;291:1578-1586).

There have also been multiple reports from labs that these drugs might thwart cancer prostate cancer growth and postpone metastasis.

In fact, lab evidence on ED drugs in prostate and other cancers has prompted some investigators to call for the "repurposing" of PDE5 inhibitors for adjuvant chemotherapy (Front Pharmacol. 2013;4:82).

"Special Clinical Significance"

On multivariate regression analysis, the use of PDE5 inhibitors was an independent risk factor for biochemical recurrence (hazard ratio [HR], 1.38; P = .0035), Dr Michl and his colleagues report.

Notably, the team found no significant association between biochemical recurrence and age, body mass index (BMI), or smoking in that analysis. These three variables are known risk factors for ED and have been associated with biochemical recurrence after prostatectomy.

On propensity score matched analysis (parameters included prostate-specific antigen, Gleason score, and tumor stage), biochemical recurrence-free survival was significantly worse in the treated than in the untreated group (P = .005).

"Correction for several confounders did not change these results," Dr Michl said.

PDE5 inhibitors have "revolutionized" the treatment of ED, the researchers report. But right now, they say, it is not known whether that is a good or a bad thing for men who have undergone surgery for prostate cancer and use these drugs.

More study is needed, and men and their doctors await more data.

"Future results will be of special clinical significance as many patients use potency-enhancing drugs after radical prostatectomy," they write.

The authors have disclosed no relevant financial relationships.

J Urol. 2015;193:479-483. Abstract

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