November 9, 2008

Radical prostatectomy, or the surgical removal of the prostate, is still a gold standard therapy for localised prostate cancer in men who have a life expectancy of 10 years or more. Yet varying degrees of erectile dysfunction (ED) and urinary incontinence are quite common in men following this surgery. In fact, recent research indicates that it may take up to 4 years for men who have had a nerve-sparing radical prostatectomy to recover their erectile function. (This information is from Memorial Sloan-Kettering Cancer Center data presented to the American Urological Association Conference of 2004 by Manish Patel, Farhang Rabbani, Joseph Disa, James McKiernan, Paul Cozzi, and Peter Scardino.)

Of course, many factors affect a man's recovery of potency after a nerve-sparing radical prostatectomy: the position and extent of the cancer, the anatomy and health of the man, and the experience and artistry of his surgeon. "First and foremost, we are there to remove the cancer," reports Dr. Larry Goldenberg at the 2008 annual prostate cancer conference. So where the cancer is located in the prostate affects a man's risk of erectile dysfunction. You see, the nerves and blood vessels that are important for penile health run in "bundles" from behind the bladder, alongside the prostate, and into the penis. In a nerve-sparing radical prostatectomy, the surgeon takes the prostate out, leaves these nerve bundles in place, and reattaches the bladder to the urethra. "We're not going to leave cancer behind in order to spare a nerve," says Goldenberg.

A man's general health, age, and personal circumstances also have a lot to do with the risk of post-prostatectomy ED. Risk factors include being older than 60, having a vascular disease or diabetes, having high lipids (e.g., high cholesterol), being diagnosed with a high level of prostate cancer, smoking, being obese, having a non-motivated sexual partner, and using ED drugs pre-surgery. Goldenberg asks men to remember that assessment of their pre-operative erectile function is essential.

"It's the 'playing the piano' rule," he quips. "If you can play the piano before, you might be able to play the piano after, but I'm no piano teacher."

In order to understand how to rehabilitate the penis after a radical prostatectomy, we must understand the basic mechanisms of an erection. The nerves, arteries, veins, and psychological state of a man are all significant when it comes to penile health and achieving an erection. "A normal erection involves the nerves sending signals, the arteries opening up and pouring blood into the penis, and the veins shutting down so the blood stays in the penis until you're finished, and then the reverse happens: the arterial blood slows down, the veins open up, and the penis becomes flaccid again," Goldenberg explains. So surgery can affect this process in four main ways:

• Nerves can become traumatised or damaged. Traumatized nerves can recover, but neural trauma as well as nerve damage can lead to structural changes in erectile tissue. The most severe change is called denervation apoptosis. As Goldenberg explains it, "The nerves are important for the health of the tissue, so, if you remove the nerves going down to the penile tissue, the penis will atrophy: it will get smaller, it will get fibrotic, it may curve."
• Arteries (the accessory pudendal arteries) may become damaged, which will reduce blood flow to the penis.
• Veins may leak, which can cause fibrosis or scarring of the penis as well as affect erectile function.
• Psychological effects include the impact of a cancer diagnosis on relationships and anxiety centred on the resumption of intimacy after surgery.

What about penile rehabilitation?
After radical prostatectomy, then, there may be trauma or damage to nerves, arteries, veins, and a man's mental state. There will also be decreased levels of oxygen getting to the penis because of the loss of night-time erections, so men have less blood flow to the penis and can develop fibrosis. As Dr. Goldenberg explains, "Night-time erections---this is nature's way of keeping the penis healthy."

Oxygenation
The main premise behind treating erectile dysfunction, then, is to stimulate the circulation of blood into the penis. (Remember, blood carries oxygen to cells.) Doing this will protect the smooth muscles in the penis, the nerve tissue, and the blood vessel linings. "The integrity of these structures is critical while the nerves are repairing," Goldenberg says, so stimulating the blood flow to the penis, even if it doesn't give men an erection, is "keeping the tissues healthy while the nerves are recovering or the blood is finding its way back down there" more regularly.

Alprostadil injection therapy
Alprostadil is a vasodilator, a drug that helps increase blood flow. Some forms of the medicine are designed to be injected directly into the erectile tissue of the penis. Alprostadil injection therapy has been used to treat ED after radical prostatectomy. In 1997, Montorsi and others found that, of 30 patients randomized into two groups, 67 per cent of the patients who received alprostadil injections 3 time a week for 12 weeks recovered spontaneous erections sufficient for satisfactory sexual intercourse. Only 20 per cent of the men who did not receive this treatment recovered this degree of erectile functioning. (See a digest of this article.)

Sildenafil (Viagra)
This drug is classified as a PDE5 inhibitor (phosphodiesterase type 5 inhibitor). It works by blocking the action of the enzyme PDE5 and, consequently, increasing blood flow to the penis during sexual stimulation.

At the 2003 American Urological Association Conference, Dr. Padma-Nathan and others reported that men who took sildenafil nightly, beginning four weeks after they had undergone a nerve-sparing radical prostatectomy, were more likely to recover normal spontaneous erections at 48 weeks after surgery. (Read a report on this study.)

Just recently (September/October 2008), a randomized, double-blind, and placebo-controlled study of the effects of nightly sildenafil taken to prevent erectile dysfunction after prostate cancer surgery was halted because nightly administration of sildenafil for 36 weeks after surgery markedly increased the return of normal spontaneous erections. Only 4 percent of the placebo group versus 27 per cent of the group taking sildenafil reported that they were experiencing "erections good enough for satisfactory sexual activity." (Read an abstract of this study.)

Vardenafil (Levitra)
Vardenafil is another PDE5 inhibitor, one that has been used in a recent study entitled "Recovery of Erections: Intervention with Vardenafil Early Nightly Therapy" or REINVENT. According to Dr. Goldenberg, REINVENT is the best-designed study to date investigating PDE5 inhibitor therapy for recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. It randomly assigned men to three groups. One group took 10 mg of vardenafil nightly, which could be decreased to 5 mg if required. These men could also take a placebo on demand. The second group of men received a nightly placebo, but they could also take vardenafil on demand (when needed). The on-demand dose started at 10 mg but could be reduced to 5 mg or increased to 20 mg. The third group took a nightly placebo plus an on-demand placebo. "Every patient receives a pill every night," explains Goldenberg. "In the first arm of the study, it's a real pill that they are getting nightly, and the on-demand pill is fake. In the second arm, the nightly pill is a placebo, but the on-demand pill is real. And in the third group, those poor guys get a placebo all around." As you can see, the design of the study is rigorous: the men and researchers are "blind" to which group individuals are in, the men are assigned to groups randomly, and the research subjects (the men taking the pills) reflect the real-life population of patients undergoing bilateral nerve-sparing radical prostatectomy. Also, the study was large: it was conducted at 87 centres in Canada, the United States, Europe, and South Africa, and over 900 patients were enrolled, initially.

The findings were surprising. REINVENT researchers had expected that the men receiving nightly vardenafil would have the best results. However, "the highest recovery rate was for patients treated with on-demand and not nightly vardenafil," Goldenberg reports. "The results conclude that Levitra taken on demand shows a considerable and immediate benefit in patients with ED after a nerve-sparing prostatectomy," said Dr. Gerald Brock, Professor of Surgery, Division of Urology at the University of Western Ontario. "Seeing the outcome for successful intercourse around 46 per cent with Levitra is quite significant in this patient population, helping to pave the way for the most efficient approach in treating with PDE5 inhibitors after this type of surgery." (Click here for access to an article about this study that was published in the October 2008 issue of European Urology.)

"The way I am now managing my patients," Dr. Goldenberg says, "is that, when they have had the surgery I still start them on the nightly dose, but once a man reaches a point where he's continent, he's recovered from the surgery, his PSA is zero, and now what's left is 'let's get the sexual function going,' at that point I switch him from nightly to on-demand."

Do it your way and your partner's way
Throughout the journey back to sexual intercourse or sexual intimacy after prostate cancer surgery, men and their partners can seek sexual pleasure and fulfilment in many ways. Realistic expectations, patience, communication, a little risk taking or experimentation, and, above all, love are very important ingredients. Discuss your fears, feelings, frustrations, and fantasies with your partner. Practice (and help oxygenate the penis) through masturbation. Try sexual intimacy using outercourse before you try intercourse. But, most of all, do what works for you and your loved one.

Feel free to view Dr. Goldenberg’s 2008 conference presentation and those of other conference participants by clicking here.