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Penile Shortening After RP, Erectile Dysfunction After RT, Social Support Networks & Recurrence After RP Volume 12 Number 10

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Reader Questions . . . . . . . . . . . . . . . . . . .1 Prostate Forum P.O. Box 6696 Charlottesville, VA 22906-6696 Phone: 434-220-3774 FAX: 434-974-6775 E--mail: [email protected] www.prostateforum.com

Editor-in-Chief: Charles E. Myers, Jr., MD Publisher:

Rose Sgarlat Myers, PT, PhD

Managing Editor: Jessica Myers-Schecter Staff Editor/Contributing Writer: Rod Schecter Assistant Editor: Gabrielle Myers Prostate Forum is published in Charlottesville, VA by Rivanna Health Publications, Inc.

Purpose: To provide useful, reliable, and current information about prostate cancer and its treatment in easy-tounderstand language. This information and the products and media advertised in this newsletter are advisory only; please consult your physician for specific medical or therapeutic advice.

I had a radical prostatectomy a year ago. The surgery appears to have been a success as my PSA has remained below 0.1 ng/ml. I am also able to have erections, but my penis seems shorter than it was before. Have you heard of this and what can be done about it?

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This is a common patient complaint after radical prostatectomy. Depending on the study, men can commonly lose 1/4 to 1/2 inch in penis length. Losses greater than this can be seen, but are not common. There are several ideas about why this loss occurs and thus what can be done about it.

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One idea is that when the prostate gland is removed, the urethra has to be pulled in to attach the bladder. Since the urethra then passes through and exists at the top of the penis, this may draw the penis into the body by a small margin.

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The other concept is that surgery interrupts the nerve and blood flow to the penis and that during the period of low blood and nerve supply to the penis, changes occur that shorten the penis and harm the tissues involved in erections. In animal models, you can show the development of severe changes that look as if they would be difficult to reverse. An erection occurs because the cavernous tissue in the penis fills with blood. When the penis is deprived of blood, as it would be during and after surgery, the elastic fibers in the cavernous tissue can be replaced by scar tissue. Scar tissue will typically shrink, making the penis smaller and harder to expand with blood. This tissue is surrounded by smooth muscle cells that also play a key role in the function of the penis. Damage to the nerves supplying any muscle will cause the muscle cells to start to die. These changes can easily account for not only a loss in length, but also girth and can result in a penis that does not expand adequately during an erection. Many urologists now prescribe PDE5 inhibitors like Viagra, Levitra, or Cialis daily or on a MondayWednesday-Friday schedule for a year after surgery to aid in penile rehabilitation. These drugs open the blood vessels, supplying the penis and seem to help many men. However, it appears that the PDE5 inhibitors are more effective at aiding the recovery of erections than they are in addressing the problem of penile shortening during surgery. Vacuum erection devices have become popular as a means of dealing with impotence after surgery. With these devices, the penis is placed in a cylinder from which air is pumped out. The resulting vacuum draws fresh blood into the penis, resulting in an erection. A ring is then placed around the base of the penis to keep the blood from leaving. The resulting erection is often more than adequate for sex. Of course, part of the problem after surgery is that the penile tissue is deprived of blood and thus oxygen. Since the vacuum erection devices excel in bringing fresh blood into the penis, it is possible that early use of this device might protect penile tissue from damage due to lack of normal blood flow. Indeed, over the past few years, a number of

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papers have reported marked reduction in post radical prostatectomy penile shrinkage following early use of the vacuum erection device starting simultaneously with removal of the catheter. Based on these publications, combined use of daily or thrice weekly PDE5 inhibitors with early use of the vacuum erection device would seem a reasonable and probably effective approach to preserving sexual function after surgery. We already have one clinical trial that shows the combination of PDE5 inhibitor and vacuum erection device are more effective than either alone in treating erectile dysfunction. My prostate cancer was treated with radiation therapy and adjuvant hormonal therapy. My testosterone has now returned to normal, but my sexual function is not what it was prior to treatment. I no longer produce semen when I ejaculate. Furthermore, my penis was about 6 inches prior to treatment, but is now 4.5 inches. It is also much thinner than it was before. My wife is post-menopausal and she has some discomfort with penetration during intercourse, so the smaller penis is not necessarily much of a problem for her. However, I am very upset by these changes. It makes me feel like less of a man. What can I do about these changes? You really packed quite a few issues into one question! Let us first start with the issues your wife faces. Post menopause, the vagina often lacks lubrication. It can also become less elastic, making it more difficult for the vagina to expand to accommodate a large penis. Girth may be more of a problem than length. Many post-menopausal women actually gain more pleasure from manual stimulation or oral sex than they do from penetration. So, your wife's situation would be a common one. Many men remain still focused on sex done the way they did it when they were in their prime. In other words, at this time of life, a large penis may be more impressive in the locker room than it is in your bedroom! Lack of semen production is common after radiation and the rule after radical prostatectomy. I know of no solution to this problem. Now, let us suppose that after talking with your wife, you decide you want to try to restore your penis to its former glory. We are now about to embark on a tour of the literature on penile

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enhancement. You can approach the problem of increasing the size of the penis by either stretching it to a greater length or pumping more blood into it and thus expanding it from within. Or you can call on the surgeons. I would guess because it must be quite profitable, I found a sizable literature on surgical enhancement of the penis. I was not impressed with that literature, nor the techniques used. Other than surgery, the technique that seems to have the most extensive support is the use of traction devices to stretch the penis. These are called penis extenders and they are designed to gently stretch the penis and can be used for hours a day. They have been extensively used to treat Peyronie's disease where the penis curves to one side because of scar tissue along the penile shaft. In these studies, the penile extenders, used for approximately 5 hours a day, did cause some straightening out of the penis. Additionally, over 612 months, the penis length increased by 0.5 to 1 inch. There are a number of competing products. Andropenis and X4 Labs are two brands that have been well reviewed and have been used successfully by a few of my patients. The websites of these two companies have helpful educational material, including videos (http://www.andropenis.com or http:/www.x4labs.com). These extenders place the penis under 6002,400 grams of traction. At 2,400 grams, that works out to be a maximum of just over 2.5 lb. On the internet, there are web forums devoted to penile enhancement-Pegym (www.pegym.com) and Thunder's Place (www.thundersplace.org) are two examples. There, you can read about traction taken to a much higher level via a technique called “hanging” where increasingly heavy weights are attached to the penis. I can find no clinical trials testing this more aggressive approach and both forums discuss the potential for injury using this approach. These same penis enlargement forums contain discussions about how to manually place the penis under stretch. The work with penis extenders already establishes the point that the penis will lengthen in response to gentle stretch over a matter of hours per day. It seems reasonable that manual stretch, which is likely to be intermediate between the extenders and hanging, would also cause some elongation. But I can find no pub-

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lished clinical trials documenting this. So, at the end of the day, I would regard the penile extenders as the best documented approach to penis extension. The vacuum erection device is the studied approach to expanding the penis by increasing the amount of blood drawn into the penis. As we outlined in the previous question, these devices have a clearly established role in temporarily expanding the penis to allow for intercourse. There is also a growing literature on the use of these devices to prevent shrinkage of the penis after radical prostatectomy. However, it is hard to find any evidence that the vacuum erection device results in permanent penis enlargement. The penis enhancement forums discuss a variety of manual techniques to increase pressure within the penis. Jelqing is the most common technique. This technique is applied to a partial, not a full erection. The man encircles the base of the penis using his thumb and forefinger to make an O that will act like a napkin ring that gently constricts the penis, increasing the pressure. This constriction is then moved steadily toward the glans penis over a 2-3 second period. The idea is that this movement increases pressure and forces the penis to remodel to a larger size. While this technique appears to be very popular in the forums, I cannot find any clinical trials documenting its effectiveness in penis enlargement. Keep in mind, this does not mean it doesn't work, it just means that the technique has not been studied. In fact, it is rather stunning to find such a popular approach to penis enlargement, recommended with great enthusiasm on the internet forums that is not supported by a single published clinical trial! My bottom line is that the most reasonable approach is to use the penile extender used at no more than 600-1,200 grams and see if it works for you. The published literature would suggest it is safe and it might work. The vacuum devices are probably best used as an erection aid when PDE5 inhibitors like Viagra, Cialis or Levitra are not effective enough or when the PDE5 inhibitors are medically contraindicated. I really do not know what to say about the various manual exercises advocated on the Internet forums because of a complete lack of clinical trial testing.

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I completed radiation therapy five years ago. My PSA remains stable below 0.2 ng/ml. In general, I did very well during treatment. I did get tired during radiation, but this disappeared within 6 months after treatment ended. I also had burning during urination. Also, I had to struggle to urinate and would often get up 3-5 times a night. After radiation was over, these urinary symptoms gradually subsided. However, I have noticed a gradual decrease in the quality of my erections. Starting two years ago, I was no longer able enter my wife without Levitra. Now, even with the help of Levitra, my erections are a bit soft. Is there anyway to improve the effectiveness of Levitra in this setting? I would say that various versions of this question rank as one of the most common issues I face at AIDP. This pattern of progressive erectile dysfunction years after radiation is quite common. As a result, I have a rather detailed approach to the problem. First, you need to know that your erectile dysfunction may have nothing to do with prostate cancer and its treatment. Diabetes and cardiovascular disease combine to account for more cases of erectile dysfunction than does prostate cancer treatment. These diseases damage the arteries supplying the penis and compromise erectile quality. Additionally, diabetes damages the nerves to your hands, legs, and penis. We always try to make sure our patients' blood pressure, blood sugar and cholesterol match national guidelines. Nevertheless, some of our patients do not do what they need to do to guard their health. Even in our clinic, these diseases serve often to limit sexual function. The first step to improving your sexual function should be to do a health inventory and fix any problems. All antihypertensive drugs are not equal when it comes to their impact on sexual function. During an erection, angiotensin plays a central role in terminating erections. Angiotensin also plays a role in high blood pressure and both angiotesin receptor blockers and ACE inhibitors treat hypertension by diminishing the impact of angiotensin on blood pressure. These two drug families have also been reported to improve erectile dysfunction. This is one reason why these two drug families form the foundation of our treatment of hypertension in men in our clinic.

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Erections happen because nitric oxide is released, which relaxes the arteries to the penis. The resulting influx of blood starts the erection process. The PDE5 inhibitors, Viagra, Cialis and Levitra, make the penis more responsive to nitric oxide. Radiation damage to arteries reduces the amount of nitric oxide produced, making the PDE5 inhibitors a reasonable first approach to erectile dysfunction after radiation therapy for prostate cancer. When the PDE5 inhibitors start to lose their effectiveness, one reasonable approach is to try to increase the amount of nitric oxide produced. Nitric oxide is produced from arginine and many patients experience improved erections if they add 2-3 grams of arginine twice a day. The normal diet contains aroung 5 grams of arginine and so this approach roughly doubles the amount of arginine available. There are a range of plant extracts that are reported to improve erections via enhancement of the nitric oxide pathway. These include ginkgo and pycnogenol, both of which have been reported to improve erectile function. The dose of ginkgo is 60-120 mg twice a day. Pycnogenol is usually used in a dose of 100 mg twice a day. Korean ginseng has also been reported to improve erections by enhancing the nitric oxide pathway. Magnesium supplementation has been reported to improve hypertension and also to improve erectile dysfunction. The recommended daily dose is around 200-300 mg. In practice, the dose of magnesium is limited by its tendency to cause diarrhea and thus its use as a treatment of constipation as milk of magnesia, magnesium citrate, and epsom salts. One small trial has reported that proprionyl carnitine has also been reported to improve erections, presumably because of its impact on arterial function. This is available as Optimized Carnitine from www.lef.org. Two randomized controlled trials and a larger number of single arm trials have reported on the ability of Trental to reverse radiation fibrosis. We commonly use this to prevent or treat radiation fibrosis and anecdotally this has coincided with improved erectile function. Once a man experiences erectile dysfunction, performance anxiety can add a psychogenic component to the problem. One very interesting trial

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reported that the addition of Dostinex (cabergoline) to PDE5 inhibition at a dose of 0.5-1.0 mg per week reversed psychogenic erectile dysfunction. I already use cabergoline in this dose range to reduce breast enlargement during hormonal therapy. In Chinese medicine, horny goat weed has traditionally been used to enhance male sexual function. I must admit that the very name has long stopped me from considering this product. However, Dr. Dattoli has several times mentioned to me that he has seen patients benefit. As a result, I recently looked into this herbal product. It turns out that this product contains icariin, a flavanol with fascinating properties. In laboratory models, it acts as a PDE5 inhibitor as well as enhancing nitric oxide production, both actions well chosen to aid erections. Unrelated to our current concern, it also improves bone density and appears to protect the brain from hypoxic injury. In the case of the brain, it induces the same SIRT1 linked to longevity as Resveratrol. Life Extension has recently marketed a product for erectile function called Prelox, that contains icariin, arginine, and pycnogenol. This is an interesting combination and initial reports from my patients have been positive. In any case, I expect we will hear a lot more about icariin biology at the laboratory level. I lost my wife last year to a stroke. This year, I was found to have a PSA of 132 ng/ml and the cancer had invaded my spine. I have no surviving family and my wife was my whole world, so I do not have a circle of friends. I am finding it very difficult to deal with the combination of grief over my wife's death and the cancer diagnosis. I feel so alone. I am close to the decision not to treat this cancer as I have no reason to go on living. Can you help me? My heart goes out to you. I remember when I was diagnosed with metastatic cancer, the support of my wife, family and friends helped sustain me through the difficulties of treatment. So I understand what you are going through. Multiple studies have documented the importance of having a social support system in place and have warned of the dangers of loneliness. At this point, you need to establish a social support network. Since there is some urgency

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here, I am going to suggest that your first step be to link up with the nearest prostate cancer support group. This is easy: just go to http://www.ustoo.org/chapter_nearyou.asp and look up the contact information. I favor this because it will immediately link you to other men dealing with prostate cancer. You will immediately plug into a support network designed to specifically address your most important problem. Depression and hopelessness are very serious problems in cancer patients. I have found that antidepressants, like Lexapro and Welbutrin, can often help patients through a tough spot such as the one you find yourself in. If you belong to a church, synagogue or other religious group, you should look into their support services. In my experience, these groups are often focused on providing succor to those who are suffering. For those of you who are currently doing well, this patient's problems should act as an alarm bell. Long before you are sick, you need to take care to see that you have a social support network. While marriage and family are common support networks, many do not have these advantages. I am a strong fan of living communities. By this, I mean not just a collection of people, but situations where people actually interact and get to know and care for each other. One of the trends in American life that I find most disturbing is the tendency for people to be come part of a faceless crowd. Even if you live in a large city, it is so easy to be isolated and alone. Please give thought to how you can establish rich links to those around you. As I mentioned, religion can provide this. A hobby or area of interest can do this as well. For example, you might join a garden group or hiking club. Charity can also work. You could volunteer for a local hospice program or other similar organization. I think these issues are so important that with every clinic visit, I give patients a very simple hopelessness scale to fill out. However, if you want to read more about this whole issue of hopelessness, the Beck Hopelessness Scale is very widely used. Wikipedia has a nice short essay on the topic (http://en.wikipedia.org/wiki/Beck_Hopelessness_ Scale). Your situation also combines several major life stresses and you need to know that these stresses

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Volume 12 Page 6 add up. I think one of the best ways of looking at this is the Holmes and Rahe stress test (http://en.wikipedia.org/wiki/Holmes_and_Rahe_str ess_scale). This scale provides patients and their physicians a way of calculating how much stress a patient has been exposed to and to anticipate the health impact of that stress. You should at least read the Wikipedia entry on the subject. You can actually calculate your own stress score. If you come out with a score over 300, you are at very high risk for additional health problems. Finally, you may want to see a psychologist or other professional. Many of my patients have found this approach to be of great help. During my hormonal therapy in 1999, I found the health crisis and its treatment had a major impact on my research productivity. For months I went to a local psychologist to help me work through various issues. I found this helpful despite having a rather extensive support network in place. I had a robotic prostatectomy 18 months ago. They found a Gleason 4+4=8 prostate cancer, but the cancer was contained within the gland and the surgical margins were clean. Six weeks after the surgery, my PSA was 0.1 ng/ml. The PSA moved to 0.2 by six months after surgery, but has stayed at this level ever since. My surgeon has referred me to a radiation therapist and both have recommended radiation therapy to my prostate bed. I have been reluctant to go ahead because they tell me that radiation may harm my sexual function and urine control. While my sexual function is not what it once was - I do not ejaculate - both my wife and I enjoy what we have. I also only leak urine when I am active in sports. Can you advise me? This is a great question. With prostate cancer recurrent after radical prostatectomy, the single most important factor is the PSA doubling time. This is exactly what it sounds like-the time it takes the PSA to double. While there are many articles on the PSA doubling time in this setting, the definitive publications come from Johns Hopkins and reflect the contribution of Dr. Walsh. If the PSA were doubling faster than 3 months, then we would be dealing with a very lethal disease that needs to be treated very aggressively. Radiation to the prostate bed alone would not usually be effective. More standard approaches

Number 10 Prostate Forum would be hormonal therapy alone or combined with radiation. While this is controversial, my standard approach has been to recommend hormonal therapy combined with radiation to the prostate bed and the lymph nodes along the common, external and internal iliac and obdurator arteries. Now, with the development of the Combidex and the USPIO ferreheme techniques for lymph node imaging, we are leaning toward careful staging prior to referral to the radiation oncologist. Between a 3-9 month doubling time indicates a cancer that is still dangerous, but management is less of a medical emergency. Our approach is otherwise the same as for the more aggressive and rapidly growing cancers. For PSA doubling times slower than 9 months, radiation to the prostate bed can be very effective. However, I think Dr. Walsh has done a major service by showing that these patients also do very well for ten years with just observation. Our initial approach to these patients is to try to arrest PSA progression by improving general health. We place these patients on a Mediterranean heart healthy diet. We recommend exercise and weight loss where indicated. We also recommend four supplements: vitamin D, pomegranate, resveratrol, and curcumin. Finally, we will often place these patients on Proscar or Avodart as both seem to have a major impact on PSA doubling time. Finally, I see patients who have an elevated PSA after surgery, but the PSA is not increasing at all. We also see patients whose PSA increased slowly for a period of time and then stopped without any treatment, diet or lifestyle change. I do believe that most of these patients have normal prostate tissue left at the time of surgery. The most dramatic case I have seen was a patient that had one half of the prostate gland left! This was done by a surgeon apparently learning how to do robotic prostatectomy. This is why I warn patients not to be on some surgeon's learning curve. In any case, these patients seem to do very well without any treatment at all. I suspect you may be one of those cases where normal prostate tissue was left at the time of surgery. After all, you had a Gleason 8 prostate cancer and it would be quite uncommon for such a cancer to arrest its growth at a PSA of 0.2 ng/ml. These cancers most often have a PSA doubling time faster than 6 months. In our clinic, we would

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place you on our growth arrest program and, at least initially, follow your PSA monthly. If the PSA continued to slow a lack of progression, we would then move to quarterly PSA measurements. We would also do an MRI of your pelvis to see if any evidence of prostate cancer could be detected in your prostate bed. You may remember several issues ago that I found a mass in the prostate bed of a patient who failed surgery. For this reason, we would do a digital rectal exam each time you visited our clinic. One might argue that it would be just safer to proceed with radiation to the prostate bed. The downside of that is that the radiation therapy would pose a serious risk to your sexual function. Also, you now have acceptable urine control and that could worsen considerably after radiation. So, were you my patient, I would make sure you understood the downside of radiation in this setting.

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Is it safe for PC patients to take Progesterone? I know some fellow Dattoli patients who are taking it based on Dr. John Lee’s work. Dr. Dattoli does not endorse taking it.

Well, progesterone and drugs related to progesterone have been extensively studied in prostate cancer patients. The results are hardly impressive and the potential toxicity serious. First, the response rates of prostate cancer to progesterone itself are not impressive. Also, some prostate cancers grow rapidly during progesterone treatment. Finally, this approach can trigger blood clots. Another way to look at progesterone would be to compare it to other treatment options. In that context, there are so many effective old and promising new treatments for prostate cancer, it is hard for me to understand why anyone would still consider this approach.

For An Appointment With Dr. Myers Contact

American Institute For Diseases Of The Prostate

434-964-0212 Voice (For appointments, press option #2 or #4) 434-964-0216 Fax Mailing Address P.O. Box 195, Earlysville, VA 22936-0195 Physical Address: 690 Bent Oaks Drive, Earlysville, VA 22936-0195 Office Hours: Tuesday - Friday 8 AM- 6 PM EST Maxine Hey, Medical Assistant, Option # 4; [email protected] Christine Rogers, Medical Clerk, Option # 2; [email protected]

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