ABSTRACT: Erectile dysfunction is a common sequela following potentially curative local treatment for early-stage carcinoma of the prostate gland. With larger studies and longer follow-up, it is clear that erectile dysfunction following prostate brachytherapy is more common than previously reported, with a myriad of previously unrecognized sexual symptoms. Approximately 50% of patients develop erectile dysfunction within 5 years of implantation. Several factors including preimplant potency, patient age, the use of supplemental external-beam irradiation, radiation dose to the prostate gland, radiation dose to the bulb of the penis, and diabetes mellitus appear to exacerbate brachytherapyrelated erectile dysfunction. The majority of patients with brachytherapy- induced erectile dysfunction respond favorably to sildenafil citrate (Viagra). Despite reports questioning the potency-sparing advantage associated with brachytherapy, recent elucidations of brachytherapyrelated erectile dysfunction may result in refinement of treatment techniques, an increased likelihood of potency preservation, and ultimately, improved quality of life.

Over the past decade, prostate brachytherapy has been used increasingly as definitive treatment for early-stage carcinoma of the prostate gland, with the majority of the literature on brachytherapy reporting biochemical results as favorable as those in the most positive radical prostatectomy and externalbeam radiation therapy series.[1-4] Because of a lack of definitive evidence supporting the efficacy of one local treatment approach over another, quality-of-life (QOL) parameters have assumed greater importance. It has been widely asserted that preservation of potency is more likely following brachytherapy, but longer follow-up has raised substantial doubts about brachytherapy's potency- sparing advantage.[5,6] In addition, brachytherapy results in a myriad of previously unrecognized effects on sexual function.[7,8]

Erectile dysfunction has been estimated to affect up to 30 million American men and is a common sequela of potentially curative local treatment for early-stage carcinoma of the prostate gland.[9] The National Institutes of Health (NIH) Consensus Conference defined erectile dysfunction as "the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance" and recommended the development of reliable methods for assessing the symptoms of erectile dysfunction and evaluating treatment outcomes.[9] Erectile dysfunction has a deleterious effect on quality of life, including diminished physical and emotional well-being, marital discord, and loss of self-esteem.[9-12]

Following brachytherapy, the use of either palladium-103 or iodine-125 with or without supplemental external- beam irradiation resulted in erectile dysfunction in 6% to 61% of cases.[5-7,13-22] With additional follow- up, continued deterioration in erectile function is expected due to the normal aging process.[23] The documentation of sexual function following prostate brachytherapy may help to elucidate the etiology of erectile dysfunction, refine treatment techniques, and lead to an increase in the likelihood of potency preservation.

QOL Instruments

Investigators are increasingly evaluating postimplant QOL with survey instruments far more detailed than previously published scales such as those of the Radiation Therapy Oncology Group (RTOG).[24] These more detailed instruments were created in an attempt to enable more uniform reporting of lifestyle effects and facilitate comparisons between different modalities. Although admirable in their intent, such efforts culminate in scores of, for example, urinary bother, functional well-being, and expanded prostate cancer index composite (EPIC) scores that are so nebulous, they are almost meaningless to patients or investigators other than QOL aficionados.[ 25-28] To make matters worse, none of the current QOL instruments adequately capture brachytherapyrelated sexual dysfunction. In fact, a variety of sexual symptoms other than erectile dysfunction occur following prostate brachytherapy.

FIGURE 1

Survey of Sexual Function

Although QOL experts have been working to homogenize QOL parameters for comparison between treatment modalities, Merrick and colleagues have detailed specific sexual changes related to brachytherapy by means of an in-depth survey of sexual function that combines the specific erectile questions of the International Index of Erectile Function (IIEF) with a number of more detailed topics. Hematospermia, orgasmalgia (pain at the time of orgasm), and alteration in the intensity of orgasm were reported in the first year postimplant by 26%, 15%, and 38% of patients, respectively (Figure 1).[7]

Orgasmalgia normally occurs within the first 6 to 12 months following implantation and is probably related to inflammation of the terminal portion of the ejaculatory ducts and the urethra.[8] Hematospermia  occurs as both an early and late phenomenon, is probably due to radiation- induced capillary fragility, and appears to be of no clinical significance.[8] These side effects are of limited duration in most patients.

Prostate brachytherapy does affect sexual function and, unfortunately, standard survey tools do not address these changes. In order for QOL instruments to accurately reflect sexual function following brachytherapy, new validated instruments that address brachytherapy-specific symptomatology will have to be developed.

Assessment of Sexual Potency After Prostate Brachytherapy

TABLE 1

Specific Erectile Function Questions of the International Index of Erectile Function

The wide range of erectile dysfunction after prostate brachytherapy may result from differences in follow-up and may be distorted by the method of data collection. Litwin et al reported that physician ratings of patient symptoms do not correlate well with patient self-assessment of QOL.[29] To date, only one brachytherapy potency study has exclusively used a patient-administered validated instrument.[6] The IIEF comprises 15 questions in five domains (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction) and has been validated as a sensitive and specific tool for the evaluation of male sexual function.[30,31] Merrick et al used the specific erectile questions of the IIEF (Table 1), with potency defined as an IIEF score ≥ 11.[6,7]

TABLE 2

Mount Sinai Four-Tiered System for Grading Erectile Function

In contrast, Stock and colleagues at Mount Sinai School of Medicine formulated a four-tiered system in which erectile function was graded on a scale of 0 to 3, with the score primarily assigned by the physician during an interview with the patient (Table 2).[5,14] The Mount Sinai scoring system is currently being used in two prospective randomized prostate brachytherapy trials.[32] The remainder of the literature on potency following brachytherapy has either used an unvalidated patient questionnaire administered via telephone interview[ 17] or has defined potency by either a subjective physician interpretation of erections sufficient for vaginal penetration[18-20,22] or without any defining criteria.[13,21]

Potency Preservation

TABLE 3

Potency Preservation After Permanent Prostate Brachytherapy

After brachytherapy, wide ranges of erectile dysfunction have been re-   ported, possibly the result of differences in patient follow-up, definitions of erectile dysfunction, and mode of data collection (Table 3).[5-7,13,14,16-22] In studies of QOL outcomes, information should ideally be obtained by direct patient surveys.[29] Early investigators uniformly reported high potency rates with 1 to 3 years of follow- up.[13,16,19]

Using a validated patient-administered QOL instrument, Merrick and colleagues reported a 39% 6-year rate of potency preservation for patients undergoing brachytherapy with or without supplemental external-beam irradiation and/or hormonal manipulation; among patients who did not receive radiation, the potency preservation rate was 52%.[6] This finding is comparable to prior 5- and 6- year potency results from Mount Sinai and Memorial Sloan-Kettering for patients undergoing brachytherapy as a monotherapeutic approach.[5,16]

Recently, Potters et al reported a 76% rate of potency preservation at 5 years for patients undergoing monotherapeutic brachytherapy.[22] In addition, these investigators found that 80% of brachytherapy-induced erectile dysfunction was apparent by 24 months,[22] whereas two other studies reported median times to the development of brachytherapy-induced erectile dysfunction of 17 and 6 months, respectively.[6,16]

Timing of Impotence

Using more reliable tools and longer follow-up, two factors regarding postimplant erectile dysfunction have become apparent. First, there is a significant incidence of immediate postimplant impotence that is presumably related to needle trauma.  Merrick and colleagues reported that 6 of 34 patients developed severe erectile dysfunction (IIEF < 6) in the immediate postimplant period.[7] Long-term potency among patients experiencing immediate postimplant erectile dysfunction has not been detailed, but our impression is that many will improve spontaneously over time.

FIGURE 2

Overall Potency Following Brachytherapy-Based Treatment of Prostate Cancer

The second important factor that has become clear is that erectile dysfunction increases with time after treatment. Series with longer followup have uniformly reported lower rates of potency preservation (see Figure 2).[5,6,22]

Potency preservation rates following all treatment approaches are significantly lower when patientadministered questionnaires rather than physician interview are used to collect data. Moreover, the use of patient-administered questionnaires following radical prostatectomy has resulted in dramatically differing results.[ 33-36] Three studies that used patient-administered questionnaires reported a 7% to 44% rate of poten-  cy preservation following radical prostatectomy.[34-36]

In contrast, a study in 64 patients that used a validated patient-admin  istered questionnaire and a definition of potency as "the ability to engage in unassisted intercourse with or without sildenafil citrate [Viagra]" reported that 86% were potent 18 months following radical prostatectomy.[ 33] Only two patients were exclusively dependent on sildenafil. However, a possible selection bias may have been present, because only 38% of the 59 patients who agreed to participate in the study returned all four questionnaires.