Future of ED treatment may lie in cell-based therapies

Ottawa-The future of erectile dysfunction (ED) management following prostate cancer surgery will likely include novel options, among them cell-based therapies, North American experts in the field predict.  

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"After any cancer surgery, the goal is cancer control and getting the patient back to as normal a life as possible," said Anthony Bella, MD, in an interview at the 2015 Canadian Urological Association annual meeting in Ottawa. 

Phosphodiesterase-type-5 (PDE-5) inhibitors have demonstrated success in treating ED that results after radical prostatectomy (RP), but there remains an unmet need to treat ED in a proportion of patients who are treated surgically for prostate cancer, said Dr. Bella, assistant professor of urology at the University of Ottawa and associate scientist in neuroscience at the Ottawa Health Research Institute in Ottawa.

He discussed the topic in an educational forum on controversial issues in men’s health. Other topics included optimal approaches to preserving erectile function after RP and whether testosterone replacement therapy raises cardiovascular disease risk.

"If nerves are fibrosed, the oral agents won't work," he said, adding that intracavernosal injection therapy is underutilized in the post-RP setting for men.

Cell-based therapies may address ED that is refractory to PDE-5 inhibitors and may even have better efficacy than PDE-5 inhibitors, he noted.

"Future therapies to prevent ED need to target the downstream effects of nerve injury or compromised blood flow,” Dr. Bella added.

Next - 'Holy grail': Stem cells that repair smooth muscle

‘Holy grail’: Stem cells that repair smooth muscle

The "holy grail" of tissue repair would be to use stem cells in the body that can help repair smooth muscle, Dr. Bella explained. One of the growth factors that has proven effective in promoting erectile function subsequent to cavernous injury is glial growth factor-2 (GGF2), which was demonstrated in a rat model (J Sex Med 2015; 12:897-905).

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"We can do it in such a way that we recruit the cells to come to the area and do what they are designed to do. We know that tissue and cellular repair are facilitated by using your own stem cells,” Dr. Bella said.

It may be GGF2, energy, or a novel molecule that facilitates cellular repair.

"We would redefine the paradigm of ED management," he said.

Sources of stem cells could be bone marrow or adipose tissue, said Dr. Bella, but he cautioned that the oncogenic potential of any stem cells would have to be heavily considered in any intervention.

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"We are very early when it comes to cell-based therapies. The early studies are designed for safety,” Dr. Bella said.

Next: Stem cell therapy could permit reversal of venous leak

Dr. MulhallDiscussion participant John Mulhall, MD, MSc, said protection of smooth muscle and the endothelium is a key goal of preserving erectile function after RP and put forth that stem cell therapy may permit the reversal of a complication like venous leak.

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Animal data point to the value of pre-treatment of the cavernous nerve injury model, noted Dr. Mulhall (J Sex Med 2015; 12:1713-21). Moreover, recently published research highlights that once-daily tadalafil (Cialis) initiated early on after nerve-sparing RP protects penile length and could play a role in the protection of the cavernosum that occurs subsequent to nerve-sparing RP (Urology 2015; 85:1090-6).

"Daily Cialis [was shown] to prevent smooth muscle degeneration," said Dr. Mulhall, director of the male sexual and reproductive medicine program at Memorial Sloan Kettering Cancer Center and professor of urology at Weill Cornell Medical Center, New York.

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ED management should ideally be striving to get men back to their baseline erectile function prior to RP and not just producing some degree of erectile function, he said. Ultimately, ED management post RP will likely involve multimodal therapy, he added.

Next: Overlap between urologic, CV health

Overlap between urologic, CV health

Dr. BrockThe overlap between urologic health and cardiovascular health is increasingly faced by urologists treating men for ED, said discussion moderator and participant Gerald Brock MD, professor of surgery and urology program director at Western University, London, Ontario.

This recognition has raised concerns about testosterone replacement therapy for hypogonadal men, Dr. Brock explained. A review of recent studies, however, did not find evidence for the assertion that testosterone therapy is linked to increased cardiovascular risk in men (Postgrad Med 2015; 127:159-65).  Still another issue is the definition of what constitutes hypogonadal. Dr. Brock put forth that patients who have less than 12 nmol/L of total testosterone and the presence of symptoms should receive treatment.

Clinicians should not routinely dissuade patients with prostate cancer from considering testosterone therapy, but there should be a reasonable lag time before initiating testosterone therapy after prostate cancer treatment, with patients with stable PSA values being better candidates for testosterone therapy.

"Many of us believe that testosterone probably has an anti-inflammatory component effect like PDE-5 inhibitors do," Dr. Brock said.

More on Men's Health:

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Is there hope for UF, EF recovery at >12 months post-RP?

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