ED Following Treatment for Prostate Cancer

Over the past two decades the number of cases of prostate cancer has soared. Approximately 50,000 new cases were diagnosed in 1981 and in 1997, more than 200,000 new cases were diagnosed. As the overall incidence of prostate cancer increases, the average age at the time of diagnosis has dropped dramatically from 72.2 years in 1983 to 69 years in 1994. These two factors combined have made sexual dysfunction following radical prostatectomy a far more important issue. Most urologists are aware that erectile dysfunction is frequent following radical prostatectomy (RP). Most fail to appreciate and/or fail to inform their patients regarding the other sexual dysfunctions, which include the absence of ejaculation (although orgasm is generally preserved), and also possible penile curvature or length loss. In a questionnaire-based study conducted by Dr. John Mulhall in 1998, 380 men who underwent RP were questioned regarding postoperative orgasm quality and the presence of pain with orgasm (dysorgasmia). In response to this questionnaire, one year postoperatively, 37% of men had not experienced orgasm, 30% of men who had orgasm said that they had significantly diminished quality overall, and 22% of men who experienced orgasm had some degree of orgasmic pain interfering with sexual relations.

In its original form, RP was a non-nerve sparing procedure, which was almost always associated with erectile dysfunction (ED) postoperatively. In 1982, Drs. Walsh and Donker, at Johns Hopkins University, reported on nerve sparing radical prostatectomy. At that time, it was hoped and believed that this approach would dramatically reduce the incidence of ED. At this point in time, this expected improvement has not been fully realized. What is appreciated is that preservation of the cavernous nerves does not necessarily mean the nerves’ function is intact. It is clearly understood that post-RP erectile function preservation is better in men of younger patient age, with cancer confined to the prostate, who have at least one nerve preserved, especially if the patient had normal erections prior to his operation. In 1996, Mulhall and Graydon published data on a group of patients who had pre- and post-RP erection function testing. Patients with post-RP ED underwent repeat testing at 6 and 24 months after surgery. All patients with postoperative erectile dysfunction had significant blood flow changes after surgery, partly explaining the ED rates after nerve-sparing surgery.

The causes of ED after this form of surgery include nerve injury, artery injury or deterioration in erection tissue structure and function after surgery. In 1997, Dr. Montorsi from Milan, Italy completed the first study looking at early postoperative preventive drug therapy for this problem. Immediate therapy after surgery, using penis injections, administered within the first two months of surgery resulted in a 67% incidence of return of a man’s own erections compared to 20% in men who had no treatment after surgery. The concept is that these erections induced after surgery can protect the erection tissue itself and promote the return of a man’s own erections. There is a strong body of opinion that suggests that men with poor erections after radical prostatectomy should be treated with medications to induce erections early after surgery. It is unknown at this time if the administration of sildenafil that fails to cause a rigid erection after radical prostatectomy can increase the chances of a man’s own erections returning.

When patients with prostate cancer present to the Sexual Medicine Program at The New York Presbyterian Hospital prior to undergoing radical prostatectomy surgery, they are counseled regarding all postoperative sexual dysfunctions including ejaculatory and orgasmic problems. During surgery, the urologic oncologists at this institution use techniques to minimize nerve trauma if possible. All patients are encouraged to seek postoperative evaluation and treatment for erection problems within the first 2 months of the procedure. When ED exists, the best approach is believed to be the commencement of early drug therapy in the form of oral agents (currently Viagra®), transurethral alprostadil (MUSE®) or penile injection therapy. When these treatments have failed or the patient is not a candidate for these three options then the use of vacuum erection device therapy or penile implant surgery may be of benefit to some patients. It is important that patients are followed up with on a regular basis to make sure that a successful drug therapy has been identified. The patients are encouraged to obtain 2-3 erections per week and this therapy is continued for 18 months postoperatively before a full idea is possible regarding return of the patient’s own erections.

Radiation Therapy and ED

Given the prevalence of prostate cancer and the reduction in the mean age at diagnosis, there has been an increase in the importance of discussing and treating sexual dysfunction following radiation therapy for prostate cancer. Radiation specialists have made great efforts over the last two decades to minimize the negative effects associated with radiation. While the advent of 3D conformal x-ray therapy and brachytherapy (seeds) have gone some way towards reducing radiation-induced ED, some men continue to suffer from this problem. At this point in time, it is unknown what the true incidence of sexual dysfunction is after brachytherapy and it remains to be seen whether newer techniques such as intensity modulated radiation therapy (IMRT) will improve upon impotence rates.

On review of the recent external beam radiation therapy literature, the incidence of post-treatment erectile dysfunction ranges from 38-62%; however, most of these analyses have used questionnaire or telephone interviews to collect information and these are notoriously inaccurate. Furthermore, the period of follow-up has generally been less than three years and it is accepted that the longer a patient lives after his radiation the more likely he is to develop ED. Radiation therapy can cause ED in three ways. Firstly, arterial blockage can occur due to the development of a condition called endarteritis obliterans, plus other more subtle changes can occur including direct damage to the lining of the blood vessels. Secondly, radiation-induced nerve damage may occur. It has been shown that there is a reduction in the number of erection-inducing nerves in the penis following exposure to low doses of radiation. Thirdly, direct erection tissue damage may occur and this can lead to leakage of blood from the erectile bodies (venous leak).

Following radiation therapy there are two primary determinants of ED, namely doseof radiation (how much) and field of radiation (how wide). Doses greater than 20 Gy (2000 rads) are frequently associated with large vessel injury. Typically, patients being treated with radiation for prostate cancer are receiving in excess of 70Gy. The wider the field of radiation, the less likely are blood vessels to recover. Given that the erection (cavernosal) artery is the only artery giving rise to erection, radiation exposure to this system may severely limit blood flow into the penis.

It is essential for all radiation practitioners and patients to understand penile anatomy and how it relates to the prostate gland. The prostate gland sits above a band of muscle (urogenital diaphragm) and it is separated from the back portion of the erectile body (crus) only by a distance of less than one centimeter. The urethra (urine channel) passes between the two erectile bodies into the bladder and as it does this it is known as the bulb of the penis. It is important to understand that the bulb plays little if any role in the development of or maintaining erectile hardness. It is the tissue within the true erectile bodies (corpora cavernosa), which when damaged leads to ED. Research has demonstrated that during 3D conformal x-ray therapy a significant dose of radiation is delivered to the back portion of the erectile bodies, approximating 30% of the entire dose of radiation received by the prostate. Further study has shown that IMRT may reduce this penile radiation exposure by more than 40%.

Brachytherapy and ED

While the long term effects of brachytherapy on erectile function are unknown, there is great interest in this form of treatment. Zelefsky et al at Memorial Sloan Kettering Cancer Center have conducted a study of their patients treated with both 3D CRT and brachytherapy. The five-year likelihood of post-treatment ED in patients who were initially fully potent was 43% for the conformal radiation group versus 53% for the brachytherapy group. Another study looked at men treated with permanent radioactive seed implantation for prostate cancer. Pre- and post-therapy erectile function was assessed and showed that the two factors found to have the most significant negative impact on post treatment potency were high radiation dose and pretreatment erectile function. The preservation of potency was 79% at three years and 59% at six years. Unfortunately, to date there has not been a study conducted with a design adequate to address the true incidence of post brachytherapy ED.

Management of Post-Radiation ED

Patients with radiation-induced erectile problems should be treated according to the process of care model (see section on Drug treatment of ED). This model indicates that the first line therapy includes management of associated medical conditions and psychological support combined with oral therapy. Second line includes vacuum erection device therapy, penile injection therapy, and transurethral prostaglandin suppository administration, and third line therapy is penile implant surgery.

The management algorithm used following radiation therapy at the Sexual Medicine Program at The New York Presbyterian Hospital includes comprehensive pre-therapy counseling of the patient with regard to sexual function, early post-treatment evaluation and early institution of a trial of drug treatment as soon as the patient experiences any deterioration in his erectile function. The patients are encouraged to develop regular erections with or without sexual relations and the patients are followed up on a regular basis to ensure appropriate early treatment.