Cornell University

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Cornell University
Weill Medical College

Cornell Institute for Reproductive Medicine

Center for Male Reproductive Medicine and Microsurgery

"State-of-the-Art Compassionate Care for the Infertile Couple"

RADIATION THERAPY ASSOCAITED ED

Introduction

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 to 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 form the erectile bodies (venous leak).

Following radiation therapy there are two primary determinants of ED, namely dose of 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 2 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 or maintaining erectile hardness. It is the tissue within the true erectile bodies (corpora cavernosa), which when damaged leads to ED. Dr. Mulhall, in his 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 does 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 is 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 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.

Managament 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.

Suggested Reading

1 Beard CJ et al: Complications after treatment with external-beam irradiation in early- stage prostate cancer patients: a prospective multiinstitutional outcomes study. Journal of Clinical Oncology. 15: 223-9., 1997.
2 Crook J: Effect of pelvic radiotherapy for prostate cancer on bowel, bladder, and sexual function: the patient's perspective. Urology. 47: 387-94., 1996.
3 Beard CJ et al: Radiation-associated morbidity in patients undergoing small-field external beam irradiation for prostate cancer. International Journal of Radiation Oncology Biology Physics. 41: 257-62., 1998.
4 Mantz CA et al: Potency probability following conformal megavoltage radiotherapy using conventional doses for localized prostate cancer. International Journal of Radiation Oncology Biology Physics. 37: 551-7., 1997.
5 Nehra A et al: Radiation Therapy For Prostate Cancer: Penile Hemodynamic And Structural Alterations. Journal of Urology 157: 180, 1997.
6 Hinman F, Jr.: Structure and function of the penis and male urethra, in Hinman F, Jr.: Atlas of urosurgical anatomy. Philadelphia, W.B. Saunders, 1993, pp 430-447.
7 Fisch H et al.: Dose of radiation received by the bulb of the penis correlates with the risk of impotence after 3-dimensional conformal radiotherapy fro prostate cancer. Urology. 57: 955-59, 2001.
8 Mulhall JP et al. Radiation Exposure To The Corporal Bodies During 3-Dimensional Conformal External Beam Radiation Therapy For Prostate Cancer. Journal of Urology, 167:539-542, 2002.25.
9 Zelefsky MJ et al: Comparison of the 5-year outcome and morbidity of three-dimensional conformal radiotherapy versus transperineal permanent iodine-125 implantation for early-stage prostatic cancer. Journal of Clinical Oncology. 17: 517-22., 1999.
10 Stock RG et al.: Penile erectile function after permanent radioactive seed implantation for the treatment of prostate cancer. Journal of Urology. 165: 436-439, 2001.



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