Penile rehabilitation after prostate cancer surgery
Think rehab, and you may conjure up the image of an athlete working his way back from a torn ligament or an older guy getting back on his feet after a total hip replacement. Penile rehabilitation is harder to picture. Indeed, it may sound more like a creative pick-up line than serious therapy, but it's a real, if unproven, program advanced by many urologists.
Before you decide that penile rehabilitation sounds like fun, remember that it's triggered by a diagnosis of prostate cancer. About 218,000 American men will receive that diagnosis this year, and all will face the difficult decision of what to do next. Some men will choose to defer treatment ("watchful waiting" and active surveillance programs). Others will decide to have radiation therapy (external beam radiation or brachytherapy with implanted seeds). And many men will opt to "get it all out" by undergoing the radical prostatectomy operation; it's a particularly good choice for younger men with life expectancies of over 10 years and aggressive-looking cancers still confined to the prostate itself.
Men who choose to have surgery face an additional decision since the procedure can be done using time-tested open surgery, less invasive laparoscopic surgery, or even newer robot-assisted techniques. It will take time to sort out the relative merits of these alternatives, but in each case, the experience and skill of the surgeon and his team is the major determinant of success.
By any method, the radical prostatectomy is generally safe, but like all treatments, it can have side effects. Bleeding and infection can complicate any operation, but they are relatively uncommon after prostatectomies. However, the surgery also has unique complications, including urinary incontinence (2% to 15%) and erectile dysfunction (ED), the most common side effect of all.
Erectile dysfunction is a problem because of the fine network of nerves and blood vessels that run along both sides of the prostate. These networks are essential for normal erections; if they are disrupted during surgery, ED is inevitable. That was the price a man paid for "getting it all out" until 1983, when Dr. Patrick Walsh introduced the anatomic radical prostatectomy, better known as the "nerve-sparing" operation, designed to preserve the neurovascular network, and with it, erectile function.
Nerve-sparing prostatectomies can be performed using open, laparoscopic, and robotic techniques, but nerve-sparing is not possible when the tumor extends right into the nerves. Even with nerve-sparing, virtually all men have ED early on, but some experience gradual improvement over a period of one to two years. Men under age 60 who had good sexual function before surgery and had the nerves on both sides of the prostate spared have the best chance of recovering erectile function, either spontaneously or with the help of sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis). Medical factors that reduce the likelihood of post-operative potency include smoking, diabetes, atherosclerosis, obesity, hypertension, and high cholesterol levels.
The nerve-sparing operation is an important advance; the reported success in achieving intercourse varies widely, but some 25% to 67% of men fail to recover erections satisfactory for intercourse after the surgery. Penile rehabilitation is designed to help these men.
Although it's a new idea, penile rehabilitation is a scientific offspring of a very old observation. Some 2,400 years ago, Hippocrates said, "That which is used develops; that which is not used wastes away." Or as the guys in the locker room put it, "Use it or lose it."
Like all organs, the penis depends on oxygen to keep its tissues healthy and functioning well. Oxygen is delivered by blood; because an erection involves a six-fold increase in penile blood flow, it increases tissue oxygenation. These observations have generated the belief that frequent sexual activity helps preserve erectile function as a man ages. There are only limited data to support this possibility, but tissue oxygenation may be the reason men have erections at night.
The average healthy man experiences three to five erections during sleep every night, each lasting up to 30 minutes. Most men who have normal nocturnal erections also develop brief erections when they nap during the day. Although testosterone levels are highest at night, hormones don't explain how nocturnal erections develop. Instead, the explanation lies in the nervous system, which signals the smooth muscle cells in the arteries of the penis to relax, allowing blood to rush into the spongy tissues of the corpora cavernosa, which swell, thus producing an erection.
The penile rehabilitation hypothesis says that even the best nerve-sparing operation is bound to inflict some damage on the network of nerves and blood vessels that surround the prostate. This damage reduces penile blood flow and oxygenation. Over time, this produces fibrosis (scarring) and the loss of elasticity and normal function in the corpora cavernosa, making erections progressively harder to come by.
If this explanation is correct, improving penile blood flow should protect sensitive tissues and promote recovery of erectile function. There are two major ways to increase penile blood flow, by local treatment with alprostadil or by oral treatment with one of the three ED pills.
Alprostadil (also known as prostaglandin E1) is a potent vasodilator; it widens arteries, allowing them to carry more blood. But its potency is a drawback as well as an asset. It is very effective in producing erections, but to be safe, it must be administered directly to the penis by using a tiny needle to inject the drug into the corpora cavernosa or by using MUSE (medicated urethral system for erection) to place a small alprostadil pellet into the urethra. Neither method sounds appealing, but both are effective and surprisingly well tolerated.
The ED pills (sildenafil, vardenafil, and tadalafil) are much easier to use, but their action is more complex. The crucial chemical for both spontaneous and medication-assisted erections is nitric oxide, which transmits the impulses of arousal between nerves and also relaxes muscle cells in the penile arteries, causing them to widen and admit more blood.
Nitric oxide is essential for a normal erection, but it does not act alone. It signals the arterial cells to produce cyclic guanosine monophosphate (cGMP), the chemical that increases the flow of blood to the penis. But the tissues of the penis also produce phosphodiesterase-5 (PDE5), an enzyme that breaks down cGMP.
In normal circumstances, the penis generates enough cGMP to produce a rigid erection and enough PDE5 to end the erection when ejaculation is complete. But in many men with ED, this intricate system is out of balance, and one of the ED pills may set things right. They all inhibit PDE5, increasing the supply of cGMP and improving erectile function.
Unlike alprostadil, the ED pills require both functioning nerves and sexual stimulation to produce an erection. Like alprostadil, they are usually used "on-demand" in preparation for sexual activity. When used this way, the ED pills restore erectile function in about 70% of nondiabetic men with ED. They are somewhat less effective in diabetics and even less likely to work after prostate cancer surgery. Still, on-demand ED pills have helped many men who have had successful nerve-sparing prostatectomies.
Although they are usually used on-demand, both alprostadil and the ED pills can be used on a daily basis. Indeed, daily sildenafil improves penile blood flow and arterial function in healthy men. Perhaps, then, daily treatment can help men regain erectile function after prostate cancer surgery.
It's an appealing theory — so appealing that a 2009 survey of over 600 urologists found that 86% already prescribe penile rehabilitation, with most recommending an ED pill. Penile rehabilitation has many supporters. But how well does it actually work?
Sex after surgery
There is no denying the importance of erections, both for sexual satisfaction and for reproduction. Still, it's a mistake to equate an erect penis with manliness, which is why the old term impotence (literally "loss of power") has been replaced by the medical diagnosis of erectile dysfunction. Even so, many people still don't understand that sexual fulfillment does not necessarily depend on a good erection. Many men with good erections fail to satisfy their partners or themselves, and the converse can be true for men with ED. And some men can even experience orgasms despite having ED following prostate surgery.
Mae West famously declared that "a hard man is good to find." It's fine to have a laugh about erections, but men facing treatment for prostate cancer should understand that there are other ways, ranging from cuddling, to manual or oral sex and sex "toys," to achieve mutual satisfaction. Most important of all is the intimacy and love that develop from honesty, sharing, understanding, and respect.
Since alprostadil was the first effective drug treatment for erectile dysfunction, it's fitting that it was the first medication used for penile rehabilitation. In 1997, Italian researchers studied 30 previously potent men who underwent nerve-sparing prostatectomies. Half the patients were randomly assigned to receive three alprostadil injections a week for 12 weeks, starting one month after surgery; the other men received no treatment. When the scientists evaluated the groups six months after the trial, men who had received alprostadil were more likely to have erections without medication than the untreated men in the comparison group. The alprostadil group also experienced more complications, and three men were unable to complete the 12-week treatment schedule. Limitations of the study include its small size and lack of a placebo control. A larger 2007 American report noted similar benefits from six months of thrice-weekly alprostadil urethral pellets, but the patients were not randomized, and there was no placebo group, two major drawbacks.
Although alprostadil got a head start, ED pills are the current favorites for penile rehabilitation. A 2008 study randomly assigned 76 men to receive nightly sildenafil or placebo for 36 weeks, starting four weeks after their nerve-sparing radical prostatectomies. When the men were evaluated eight weeks after the end of treatment, 27% of men in the sildenafil group reported satisfactory erectile function, but only 4% of the placebo group reported erections.
A second 2008 study found that another of the ED pills can also help men achieve erections after prostate cancer surgery, but it also put the role of prophylactic treatment and rehabilitation into perspective as well. A European trial randomly assigned 628 patients to receive either nightly vardenafil, on-demand vardenafil, or placebo for nine months following nerve-sparing surgery. During the treatment period, on-demand vardenafil outscored both nightly vardenafil and placebo. But when the men were re-evaluated after the study period, a similar percentage in each of the three groups (24%–29%) reported satisfactory erectile function without medication. In addition, after the rehab ended, on-demand vardenafil produced similar results in men who had been in each group, with 48% to 54% achieving satisfactory erections. All in all, although the ED pill helped men achieve erections after surgery, a rehab regimen started soon after surgery did not produce an advantage over ordinary on-demand treatment later on, and about half the men had erectile dysfunction despite using medication.
It is clear that alprostadil and the ED pills can increase penile blood flow and oxygenation, as can the vacuum pump device some men use for this purpose. All three treatments can help men achieve erections after prostate cancer surgery, but more study is needed to see if programs of prophylactic use for penile rehabilitation add to customary on-demand use. At this early stage, several preliminary studies suggest that alprostadil may be more effective than the ED pills. In contrast, a report found no difference between the two types of medications — but since there was no placebo group, it's not clear that either drug was actually effective for "rehabilitation." And since many men have erectile dysfunction despite any of the current treatments, scientists should investigate new approaches. For example, a Korean study of 50 men reported that a statin drug boosted the effectiveness of sildenafil following nerve-sparing surgery.
Where does this leave men with newly diagnosed prostate cancer? Since many prostate cancers grow slowly, the first decision is whether to begin treatment at once or to wait until there is clinical evidence that treatment is necessary. Next, men who opt for early treatment must decide between surgery, radiation, and less well-established methods. In making that decision, men should understand that ED is a common side effect of all treatments.
Penile rehabilitation offers hope, but with the information at hand, it would be a mistake for men to assume it will ensure erectile success after surgery. Instead, patients should keep the role of erections in perspective (see box above), and they should expect erectile problems, so they will be pleasantly surprised if erectile function recovers instead of being disappointed by operations that are successful in all other respects.