Erectile function and quality of life after interstitial radiation
therapy for prostate cancer
RF SaÂnchez-Ortiz1, GA Broderick1,3*, ES Rovner1, AJ Wein1, R Whittington2and SB Malkowicz1
1Division of Urology, Department of Surgery, and the2Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA; and3Mayo Clinic, Jacksonville, FL, USA
Few studies have evaluated erectile function after interstitial radiation therapy for localized prostate cancer. Using a validated quality of life questionnaire, we assessed post-treatment erectile function and its relationship to treatment satisfaction and quality of life. We retrospectively reviewed the records of 171 consecutive patients who underwent Pd-103 or I-125 brachytherapy for prostate cancer between December 1992 and June 1998. Seventy percent of patients received neoadjuvant androgen deprivation therapy. All patients were mailed a validated questionnaire assessing sexual function and overall quality of life (UCLA Prostate Cancer Index and SF-36). Sixty-seven percent of all questionnaires were available for evaluation (114=171). The mean age was 69.1 y with a mean follow-up of 23 months (range 4 ± 72, median 24). Seventy-one percent of patients (81=114) had pre-treatment erections suf®cient for sustained vaginal penetration. Of these patients, potency was maintained in 49% of men (40=81). An additional 26% had erections ®rm enough for foreplay but not penetration (21=81). Erectile dysfunction rates were signi®cantly lower in younger patients (48%) vs older patients (55%). There was no difference in post-treatment potency between men who received neoadjuvant hormonal therapy and those who did not (P>0.05). In addition, there were no differences in physical function (86, scale 0 ± 100), general health perception (78), emotional well-being (83), energy=fatigue (74), and overall satisfaction (84) between men with erectile dysfunction and those without.
In summary, two years following brachytherapy 25% of patients complained of complete (20=81) or partial (26%, 21=81) erectile dysfunction, for an overall rate of 51% (41=81). Short-term neoadjuvant hormonal therapy (<3 ± 6 months) did not increase the likelihood of post-treatment erectile dysfunction. Interestingly, overall satisfaction rates among brachytherapy patients were high (84=100) and surprisingly did not correlate with post-treatment sexual function. Interna-tional Journal of Impotence Research(2000)12,Suppl 3, S18±S24.
Keywords:quality of life; prostate cancer; brachytherapy; erectile dysfunction
Introduction
Prostate cancer is the leading cause of cancer death in African-American men and the second leading cause of cancer death in Caucasian men.1Since the introduction of prostate-speci®c antigen as a screen-ing tool in asymptomatic men, the rate of detection and treatment of organ-con®ned prostate cancer has increased signi®cantly. Most urologists would agree that the nerve-sparing radical prostatectomy is the treatment of choice for disease-free survival in men with localized disease whose life expectancy ex-ceeds 10 y. For men with a shorter life expectancy, the most common forms of treatment include external beam and interstitial radiation therapy. With improved detection and declining age of the prostate cancer patient, there has been an increased
interest in the preservation of quality of life; that is erectile function and continence. It is logical to assume that erectile function forms an integral part of patient satisfaction and quality of life after prostate cancer treatment. However, while other studies have evaluated health-related quality of life after radical prostatectomy and external beam radiation, few studies have simultaneously evaluated the effect of interstitial radiation therapy on erectile function and health-related quality of life after prostate cancer treatment.2 ± 5Using the UCLA Prostate Cancer Index and RAND 36-item health survey, we evaluated the impact of interstitial radiation therapy on erectile function and its relationship to overall quality of life and patient satisfaction.
Materials and methods
We retrospectively reviewed the records of 171 consecutive patients who underwent interstitial *Correspondence: GA Broderick, Department of Urology,
Mayo Clinic, Jacksonville, FL 32224, USA. E-mail: [email protected]
radiation therapy for prostate cancer between Dec-ember 1992 and June 1998 at the Hospital of the University of Pennsylvania. All patients had organ-con®ned disease as determined by a staging evalua-tion consisting of physical examinaevalua-tion, serum PSA, transrectal prostate needle biopsy under ultrasound guidance, computerized tomography of the pelvis or endorectal coil MRI, and bone scan. Pre-operative erectile function was assessed at the time of the initial history and physical examination.
Transperineal palladium-103 (75% of patients) or iodine-125 (25%) seed implantation was performed using a template-guided peripheral-loading techni-que with a transrectal ultrasound probe as pre-viously described.6 Post-implant dosimetry was performed in all patients at 4 weeks to ensure a minimum dose of 115 Gy. Seventy-percent of pa-tients received neoadjuvant androgen deprivation therapy (80=114) to reduce prostate volumes to less than 50 g and for prophylaxis against post-procedure urinary retention. Sixty-®ve percent of patients received 3 months of hormones, 7% received 4 months, 9% received 5 months, and 17% received 6 months. Two patients were on active androgen blockade at the time of the study and were excluded. Pre-treatment erectile function was assessed by retrospective chart review. After undergoing treat-ment, all patients were mailed a validated self-administered questionnaire assessing overall quality of life. Questionnaires were pre-coded for identi®ca-tion and patients were asked to withhold their name from the returned questionnaire.
The UCLA Prostate Cancer Index is a 20-item questionnaire that quanti®es prostate cancer-speci-®c quality of life in the areas of incontinence, proctitis and sexual dysfunction. The UCLA Pros-tate Cancer Index has been shown to be reliable and valid in men with and without prostate cancer.3,7 Patients were also mailed the RAND 36-Item Health Survey 1.0 (SF-36) to quantify general health related quality of life on eight scales including physical function, role limitations due to physical problems, bodily pain, general health perceptions, emotional well-being, role limitations due to emotional pro-blems, social function and fatigue. The SF-36 has been shown to be reliable and valid in various populations.8,9 Sixty-eight percent of all question-naires were returned (116=171) and 114 (67%) could be evaluated. Data were extracted to assess erectile dysfunction and quality of life after treatment. Statistical comparisons were made using SigmaStat software (Jandel Corporation). APvalue of less than 0.05 was considered statistically signi®cant.
Results
The mean age was 69.1 y with a mean follow-up of 23 months. Demographic data are displayed in Table
1. Seventy-one percent of patients had pre-treatment erections suf®cient for sustained vaginal penetration (81=114). Of these patients, potency was maintained in 49% of patients (40=81). After treatment, 26% of patients had partial erections with foreplay but no erections ®rm enough to maintain penetration (21=81) and 25% (20=81) had complete erectile dysfunction (ED), for an overall ED rate of 51% (Figure 1).
Erectile dysfunction was slightly lower in men younger than 70 y old (48%) vs men of age 70 y or older (55%). This difference was statistically sig-ni®cant (P<0.05; Figure 2). Although this age difference in erectile function was identi®ed, there were no statistically signi®cant differences in health related or general quality of life between younger men and older men (Table 2).
We investigated whether the presence of pre-operative or postpre-operative erectile dysfunction correlated with quality of life by stratifying the data accordingly (Table 3). There were no differences in overall satisfaction, physical function, role lim-itations due to physical problems, bodily pain, general health perceptions, emotional well-being, role limitations due to emotional problems, social function or fatigue between men with erectile dysfunction and those without.
Post-treatment erectile function was assessed as a function of time since interstitial radiation. Table 1 Description of the sample
Age Mean: 69.1 (s.d.5.9)
Median: 70
Follow-up Mean: 23.1 months (13.0)
Median: 27 months Race
White 93% (mean age: 69.15.6)
African-American 7% (mean age: 66.47.8)
Hispanic 0
Other 0
Annual income (US$)
<20,000 8%
20,000 ± 30,000 5%
>30,000 87%
Education
Less than higher school 1%
High school, trade school,
some college 37%
College or higher 62%
Relationship status (%)
Living with spouse or partner 85%
In a signi®cant relationship
but not living together 3%
Not in a signi®cant relationship 12%
Working (part-time or full-time) (%) 37% Medical history (%) Diabetes 8% Cardiovascular disease 23% Respiratory disease 5% Gastrointestinal disease 7% Renal disease 3% Depression 3%
Alcohol or other drug problems 4%
Cigarette smoker 5%
Erectile function and quality of life after cancer therapy
RF SaÂnchez-Ortizet al
There was an interesting bimodal distribution of erectile dysfunction complaints following bra-chytherapy. Erectile dysfunction was lowest for
patients with an intermediate length of follow-up (between 19 and 28 months (30.7%)), and highest for patients at the extremes (follow-up <18 months (53.7%) or follow-up>29 months (62.8%), (Figure 3). These differences were statistically signi®cant and were unrelated to patient age (P<0.05).
Seventy percent of all patients treated received neoadjuvant hormonal therapy. After stratifying erectile function based on the use of hormonal therapy (with data only from men who received 6 months of hormones or less), we found that neoadjuvant hormonal therapy did not impact erectile function (P>0.05; Figure 4). Men who were receiving hormones at the time that they responded the questionnaire were excluded. In addition, there were no differences in quality of life parameters between men who received neoadjuvant hormones and those who did not (data not shown).
Discussion
Our data reveal that 51% of patients develop ED within 2 y of interstitial radiation therapy for prostate cancer, which is subjectively characterized as mild 26% or complete 25%. Speci®cally, follow-ing brachytherapy 26% of men had the ability to initiate penetration but could not maintain it; this designation correlates with question number 4 on the International Index of Erectile Function.11 Figure 1 Treatment-related erectile function after interstitial radiation therapy in patients with satisfactory preoperative erections.
Figure 2 Age-related erectile function after interstitial radiation therapy in patients with satisfactory preoperative erections. S20
In addition, there was a signi®cantly higher incidence of ED among patients 70 y and older vs
patients younger than 70. As anticipated, pre-treatment potency rates were age-speci®c, with 84% of men younger than 70 (n51) reporting no erectile dif®culties and 60% of men older than 70 (n63) reporting some erectile problems. Unfortu-nately, when the series was initiated contemporary sexual function questionnaires had not been intro-duced. We did not ®nd any differences in sexual function between men who received neoadjuvant hormonal therapy and those who did not. Interest-ingly, the rate of ED was highest in men at either extreme of follow-up: <18 months (53.7%) and>29 months (62.8%) (Figure 3). This bimodal
distribu-tion of erectile dysfuncdistribu-tion is probably related to separate treatment effects: lingering adverse effects of hormonal suppression and cumulative long-term effects of ionizing radiation on corporal in¯ow or tissues. Although we postulated that the group with the longest follow-up might have had higher rates of ED because it represented an older group of patients, we did not ®nd any correlation between length of follow-up, age and ED (Figure 3).
Several studies have evaluated the relationship between quality of life in men treated with radical prostatectomy, external beam radiation therapy or watchful waiting3 ± 5,10 However, there are very limited data on the effect of interstitial radiation therapy for localized prostate cancer and quality of Table 2 Age-related differences in urinary, bowel, and sexual quality of life domains
Younger men (<70 y old) Older men (70 y old) P value
No. subjects 51 (44.8%) 63 (55.2%)
Mean ages.d. 62.54.5 72.73.7 <0.0001
Percentage potent pre-operatively 84.3% 60.3% <0.05
Percentage potent post-operatively 48% 55% <0.05
Mean follow-up (months) 20.97.0 25.315.7 NS
Mean overall scores.d. 86.417.8 85.122.4 NS
Urinary function 94.012.1 92.813.9 NS Urinary bother 92.611.6 88.119.5 NS Bowel function 93.59.3 90.612.1 NS Bowel bother 91.517.9 88.222.2 NS Sexual function 52.425.1 38.328.8 P<0.04 Sexual bother 46.735.0 54.438.7 NS Physical function 91.819.3 85.126.3 NS Role, physical 88.729.1 83.234.2 NS Bodily pain 86.420.0 88.915.9 NS
General health perceptions 77.521.8 78.721.2 NS
Emotional well-being 82.917.9 83.213.3 NS
Role, emotional 85.332.2 88.326.9 NS
Social function 93.215.6 91.317.1 NS
Energy=fatigue 74.416.9 73.616.5 NS
Table 3 Quality of life data strati®ed by erectile function
Patients with good erectionsPatients with Patients with
All subjects pre-operative ED post-op post-op ED P value
No. subjects 114 33 (29%) 40 (49%) 41 (51%)
Mean ages.d. 69.15.9 69.89.6 68.54.1 72.01.2 P<0.05
Mean follow up (months) 23.113.1 24.315.8 21.010.2 22.911.5 NS
Mean overall scores.d. 84.422.1 83.320.1 88.325.4 83.917.8 NS
Urinary function 94.012.5 89.716.5 96.89.8 94.510.9 NS Urinary bother 89.717.2 87.919.2 89.118.9 90.415.2 NS Bowel function 91.611.3 87.614.8 92.77.9 93.010.7 NS Bowel bother 89.920.2 80.228.3 92.518.0 93.613.3 NS Sexual function 42.827.9 19.721.1 71.514.3 39.421.7 P<0.04 Sexual bother 51.737.6 37.939.2 80.324.8 38.933.5 NS Physical function 86.026.1 80.926.5 87.029.7 88.424.0 NS Role, physical 84.833.1 73.740.7 89.825.5 87.432.4 NS Bodily pain 87.817.0 82.219.5 91.214.7 89.516.7 NS General health 77.822.2 72.125.3 83.816.3 77.123.4 NS Emotional well-being 83.115.0 82.714.1 83.513.7 83.816.8 NS Role, emotional 86.829.4 87.030.5 80.935.0 89.226.1 NS Social function 91.816.4 88.418.7 94.112.2 93.812.7 NS Energy=fatigue 73.616.4 70.816.9 77.918.1 72.715.5 NS
Erectile function and quality of life after cancer therapy
RF SaÂnchez-Ortizet al
Figure 3 Treatment-related erectile dysfunction as a function of follow-up and age. Men with peroperative erectile dysfunction were excluded.
Figure 4 Effect of neoadjuvant hormonal therapy on erectile function after interstitial radiation therapy in patients with normal pre-treatment erections. Patients on active hormonal ablation were excluded.
life. Arterbery et al evaluated quality of life in 51 patients 6 months after interstitial radiation using the European Organization for Research and Treat-ment of Cancer (EORTC) genitourinary group ques-tionnaire.12 Seventy-nine percent of patients reported an excellent quality of life after treatment and all patients said that they would have the procedure again as their mode of treatment. Although sexual function was maintained in the majority of patients, no direct comparisons were made between erectile function and quality of life. Kleinberg et al at Memorial Sloan-Kettering Cancer Center followed 31 patients after transperineal iodine-125 implants to assess treatment-related urinary, gastrointestinal and sexual symptoms. With regards to sexual function, 28% of patients devel-oped dif®culty with erections or ejaculation at 6 months. While only 11% of patients had long-lasting sexual dysfunction, there was signi®cant recall bias since pre-operative erectile function was not available in most patients.14A recent study from Wake Forest University assessed quality of life and urinary function after interstitial brachytherapy using the Functional Assessment of Cancer Ther-apy-Prostate (FACT-P).14 This study evaluated pati-ents before brachytherapy, 1 month after treatment, and 3 months after therapy. While there was a decline in quality of life 1 month after therapy based on FACT-P scores, these returned to near baseline after 3 months. However, while this study also assessed urinary function using the International Prostate Symptom Score (I-PSS), it did not speci®-cally address changes in erectile function.
In our series, the UCLA Prostate Cancer Index and SF-36 scores were comparable or better than patients evaluated by others with the same instruments after radical prostatectomy, external beam radiation, or watchful waiting.3,4,7,10 While satisfaction in our patients was higher in all areas (physical function, role function, bodily pain, health perception, emo-tional well-being, social function and energy=
fatigue) when compared to these studies, across-study comparisons are not valid given the differ-ences in population characteristics.
Up to the date of publication, few studies have speci®cally addressed the impact of interstitial radiation therapy on erectile function.15,17,18 Stock et al followed 89 patients who underwent iodine-125 or palladium-103 implantation for a median of 15 months.15 While they reported a 39% decrease in sexual function after 2 y follow-up, only two patients were declared impotent following treat-ment. Their low rate of ED is clearly below what is to be expected from this population of patients, based on age alone. In our experience, erectile dysfunction occurred in 51% of brachytherapy patients. Our higher rates of ED may be a re¯ection of longer follow-up, and the fact that outcomes were patient-reported and assessed with a validated and reliable statistical instrument. Our current data con®rms
previous ®ndings of ED in a series of interstitial radiation therapy patients who had a shorter dura-tion of follow-up.16 In this study and the previous investigation approximately 70% of patients had pre-procedure erections suitable for penetration, which is consistent with age-speci®c data on ED in the Massachusetts Male Aging Study.18 Patient reported potency was 55% at mean follow-up of 18 months, very similar to the results of this study. What is most signi®cant about the current data is: the length of follow-up, the negligible impact of 6 months of testosterone suppression on long-term potency, and the fact that overall patient satisfaction and health-related quality of life remain high regardless of post-treatment erectile function.
Conclusions
Up to the date of publication, our series is the largest one with the longest follow-up speci®cally evaluat-ing the relationship between erectile function and quality of life after interstitial radiation therapy for prostate cancer. While the overall rate of ED was 51%, we found no correlation between sexual function and health-related quality of life or patient satisfaction. Erectile function may not play as important a role as we assume in overall satisfaction and quality of life for prostate cancer survivors. Larger, prospective trials utilizing validated sex questionnaires before and after therapy are needed to further evaluate the impact of ED in brachy-therapy patients.
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