Defining Sexual Outcomes after Treatment for Localized Prostate Carcinoma

Transcription

1 1773 Defining Sexual Outcomes after Treatment for Localized Prostate Carcinoma Leslie R. Schover, Ph.D. 1 Rachel T. Fouladi, Ph.D. 1 Carla L. Warneke, M.S. 1 Leah Neese, M.A. 1 Eric A. Klein, M.D. 2 Craig Zippe, M.D. 2 Patrick A. Kupelian, M.D. 3 1 Department of Behavioral Science, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. 2 Department of Urology, The Cleveland Clinic Foundation, Cleveland, Ohio. 3 Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio. Supported in full by a grant from the American Cancer Society, Help-Seeking for Sexual Problems after Prostate Cancer (no. TPRB PBP), Leslie R. Schover, Ph.D., principal investigator. Address for reprints: Leslie R. Schover, Ph.D., Department of Behavioral Science, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard-243, Houston, TX ; Fax: (713) ; lschover@mdanderson.org Received November 14, 2001; revision received April 15, 2002; accepted May 20, BACKGROUND. The objective of this survey was to identify factors associated with good sexual outcomes in a large group of survivors of localized prostate carcinoma. METHODS. A postal survey was sent to 2636 men in the Cleveland Clinic Foundation s Prostate Cancer Registry who either were treated with definitive radiotherapy or underwent prostatectomy for localized prostate carcinoma. The survey asked about demographic items, past and current sexual functioning, partner s sexual function and health, and a number of factors hypothesized to affect sexual satisfaction. Standardized questionnaires included the Sexual Self-Schema Scale- Male Version, the International Index of Erectile Function (IIEF), urinary and bowel symptom scales from the Los Angeles Prostate Cancer Index, and the Short Form Health Survey (SF-36). RESULTS. The return rate was 49%, yielding a sample of 1236 men at an average of 4.3 years post-treatment. Comparing responders with nonresponders suggested that the sample may have been somewhat biased toward men who were more interested in maintaining sexual function. At the time they were diagnosed with prostate carcinoma, 36% of men had erectile dysfunction (ED). Within the past 6 months, however, 85% of men reported having ED. Only 13% of men were having reliable, firm erections spontaneously, and another 8% of men were having erections with the aid of a medical treatment. Men were as distressed about loss of desire and trouble having satisfying orgasms as they were about ED. Of the 84% of men who reported having a current sexual partner, 66% indicated that she had a sexual problem. Younger age was associated strongly with better sexual outcome (global IIEF score). With demographic factors taken into account, better sexual outcome was related significantly to medical factors, including not having neoadjuvant or current antiandrogen therapy, undergoing bilateral nerve-sparing prostatectomy or brachytherapy, and having better mental and physical health composite scores on the SF-36. Sexual factors that were associated with a better outcome included having normal erections before treatment for prostate carcinoma, choosing a treatment based on the hope that it would preserve sexual function, having more sexual partners in the past year, and having a sexually functional partner. CONCLUSIONS. The great majority of men who survive prostate carcinoma do not achieve a return to functional sexual activity in the years after treatment. The priorities a man places on sexuality and on having a sexually functional partner are important factors in sexual satisfaction at follow-up, over and above the influence of age and medical factors. Cancer 2002;95: American Cancer Society. DOI /cncr KEYWORDS: prostate carcinoma, sexual function, sexual rehabilitation, erectile dysfunction. In recent years, both surgeons and radiation therapists have tried to modify treatments for patients with localized prostate carcinoma to minimize sexual morbidity. This has led to a competition, with each 2002 American Cancer Society

2 1774 CANCER October 15, 2002 / Volume 95 / Number 8 discipline promising high rates of preserved potency. Men who have been included in published case series typically have been younger compared with the average man who is diagnosed with prostate carcinoma and report normal pretreatment erectile function. The definition of a successful sexual outcome usually has been based on information from chart reviews or interviews suggesting that a man has achieved an erection firm enough for vaginal intercourse on at least one occasion. 1 With increasing use of medical treatments for erectile dysfunction (ED), the definition of success has broadened to include not only the ability to penetrate with spontaneous erections but also the ability to achieve intercourse with the aid of a noninvasive medical therapy. 2 We believe that men with newly diagnosed prostate carcinoma often have unrealistic expectations of sexual outcomes and that, in reality, most survivors experience severe and lasting sexual dysfunction and dissatisfaction. One recent case series reported that 86% of men who undergo bilateral nerve-sparing surgery can achieve erections functional for intercourse by 18 months postsurgery. 2 However, that sample was small (n 64 men, with complete data on sexual function for only 56 men), and the mean age was only 57 years. Men completed a standardized questionnaire on sexual function, but the researchers reported data on erections using only two items rather than using scale scores. One-third of those men were using sildenafil at the time of the survey. Follow-up studies using standardized questionnaires to assess sexual function and surveying larger, less highly selected, samples of men estimate that the percentage of men who recover erections firm enough to allow penilevaginal penetration on most occasions without aid from medical or surgical treatments for erection problems is closer to 20% than 70% after nerve-sparing radical prostatectomy. 3 9 Some of the superiority of nerve-sparing surgery over standard surgical techniques for preserving potency may be an artifact of selecting candidates with minimal or no comorbidities, good preoperative potency, young age, and small tumors (i.e., those most likely to recover reasonable sexual function). 10 With the development of computerized, accurately targeted techniques of radiation therapy, such as brachytherapy, 11 three-dimensional conformal therapy, and intensity-modulated therapy, a number of recent follow-up studies 3,5,7,9,16 18 as well as a metaanalysis of 40 previous surveys 1 have suggested that preservation of erections is superior after external beam irradiation than after radical prostatectomy, with rates of potency typically in the 30 60% range. However, as with surgery, issues of methodology may have inflated these reported success rates. Again, researchers report erectile function postradiotherapy only for men who report good pretreatment potency, even though men who have radiation therapy are often older, in poorer health, and more likely to have ED compared with surgical candidates. Furthermore, the duration of follow-up in almost all studies is inadequate. Whereas it may take up to 2 years for full recovery of erections after radical prostatectomy, at 24 months, the sexual function of patients who receive radiation therapy still is declining steadily. 12,13,17,19 Discussions of the sexual impact of surgery or radiation therapy tend to focus narrowly on erections. However, men who suffer erection problems also report decreased interest in having sex and a diminution of pleasure from sexual stimulation. 3,12,18 An even more profound, generalized loss of desire and arousability is the hallmark of the sexual problems men experience on antiandrogen therapy, which becomes a second-line treatment in about 25% of men who initially start out with localized disease. 5 Whether men are treated with orchiectomy, luteinizing hormone releasing hormone (LHRH) agonists, androgen blockers, or combination therapy, about 80% of men cease sexual activity altogether and report poor erectile function. 3,8,18,20,21 The literature suggests that significant sexual dysfunction, principally ED, is present in about 30 50% of men at the time they are diagnosed with prostate carcinoma. 3,12,18,22,23 After treatment for localized disease with surgery or definitive radiation therapy, rates of sexual dysfunction increase to the 50 80% range. When men need antiandrogen therapy for advanced prostate carcinoma, the rates of sexual dysfunction approach 80 90%. We undertook a detailed survey of the sexual function and satisfaction of men in the Prostate Cancer Registry at the Cleveland Clinic Foundation, which includes consecutive patients who were treated definitively for localized prostate carcinoma either with surgery or radiation therapy. Our specific objective was to develop a model of factors that influence positive sexual function and satisfaction in a large, unselected cohort of longer term survivors of prostate carcinoma. Figure 1 illustrates our hypothesized model. Because our ultimate goal was to develop an intervention to enhance sexual outcomes, factors that could not be modified (i.e., demographic variables) were added first to the model and were retained when they were identified as significant. We then proposed adding the influence of health-related variables. Finally, we tested the influence of sexual behavior and attitudes, because, among these factors, some may be the targets of psychosocial counseling.

3 Sex Rehabilitation and Prostate Carcinoma/Schover et al MATERIALS AND METHODS Patients At the time of our survey, the Prostate Cancer Registry of the Cleveland Clinic Foundation included 2636 men who were treated initially with definitive therapy for localized disease, including 1207 men postradical prostatectomy and 1429 men postdefinitive radiation therapy. The earliest year of treatment in the registry was 1986, although the majority of men (90%) were treated between 1992 and Thus, men in the registry were treated by more than 12 surgeons and radiotherapists with various levels of experience over a period of years during which treatment techniques were changing. The registry included 16% African- American men (n 427 men). Almost all of the remaining men were Caucasian. The men had been followed at 6-month intervals by chart review and checked for most recent laboratory values of prostate specific antigen (PSA). Patients whose follow-up care was outside of the institution were sent postal surveys to update their disease status. Phone updates with referring physicians also had been performed periodically. Information recorded in the registry included age, ethnicity, time since prostate carcinoma treatment, clinical tumor stage, pretreatment sexual potency (noted as yes or no by the physician), use of nerve-sparing surgery for radical prostatectomy (defined by chart review), radiation therapy technique, current status (either free of disease or in biochemical failure, as defined by PSA level), and initial use of neoadjuvant hormone therapy. Current use of antiandrogen therapy was ascertained by self-report on our survey. However, information on medical comorbidity was not available in the registry and was not obtained on the survey. FIGURE 1. Hypothesized and observed factors influencing global International Index of Erectile Function (IIEF) score. Underlined factors were significantly related to IIEF Global Score in bivariate analyses (P 0.01) but not in multivariate analyses. Factors marked with a dagger were significantly related to IIEF Global Score in multivariate analyses within each of the subsets of factors (P 0.01). Factors marked with an asterisk were significant in the final, linear regression model. Data Collection Men were mailed a questionnaire with a cover letter explaining the research and elements of informed consent. Returning the survey constituted proof of informed consent. The survey was not anonymous, because we wanted to link questionnaire responses with the registry information. The study was approved by the Institutional Review Boards of the Cleveland Clinic Foundation and the University of Texas M. D. Anderson Cancer Center. Men who did not return the initial questionnaire within 1 month received one reminder letter. Respondents received a booklet of United States Prostate Cancer Awareness postage stamps, worth $6.60, as a small compensation. Measures The questionnaires included items on demographic background and medical history. A series of multiplechoice items were created for this project based on our hypothesized model and were designed to supplement information from standardized questionnaires. Each of these items assessed a specific factor rather than forming subscales comprised of several items with measurable internal consistency. Items asked about erectile function in the year before respondents were diagnosed with prostate carcinoma; the degree to which a desire to maintain sexual function had influenced their choice of treatment for prostate carcinoma; changes in erectile function and sexual satisfaction as a result of treatment; and whether men perceived that they had a problem over the past 6 months with sexual desire, erections, or having satisfying orgasms (yes or no) and, for each problem marked yes, the degree of distress it caused (from none to extreme). Other items asked about numbers of sexual partners in a man s lifetime and within the past year, sexual orientation (defined in terms of both attraction and activity), and age of current sexual partner. One item asked men to check all problems experienced by their sexual partner, including loss of sexual desire, having health problems that interfered with sex, vaginal dryness or pain, and trouble reaching

4 1776 CANCER October 15, 2002 / Volume 95 / Number 8 orgasm. Men were asked separately if they ever sought help for a sexual problem before they were diagnosed with prostate carcinoma, during treatment, within the first year after treatment, or more recently. All current treatments for men with ED were listed. For each treatment, men were asked whether they would like to try it or whether thy had tried it and, if they had, to rate the impact of the treatment on their sex life and indicate whether they were still using it. The survey instrument also included several standardized questionnaires. The Sexual Self-Schema Scale-Male Version (SSSS-M) 24 measures individual differences in the sexual self-schema, a generalized positive versus negative view of oneself as a sexual person that influences both behavior and subjective experience. In women who were treated for gynecologic malignancies, a negative sexual self-schema score explained more of the variance in sexual responsiveness and sexual function compared with pretreatment sexual frequency, severity of medical treatment, or menopausal symptoms. 25 In our model, we predicted that men with a more positive sexual selfschema would report better sexual satisfaction and activity after they were treated for prostate carcinoma. 26 The International Index of Erectile Function (IIEF) 27 has five subscales: Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction, and Overall Sexual Satisfaction. The IIEF has a high degree of sensitivity to changes in sexual function with response to treatment. Thus, the global score includes both sexual function and satisfaction and served as our summary measure of sexual outcome. The IIEF asks about sexual function within the past 4 weeks, including one item on the frequency of sex. To have a measure of sexual function for men with ED who were not on treatment versus men with ED who currently were using a medical treatment, we asked men to indicate their use of ED treatments during the past 4 weeks. We included the urinary and bowel symptom scales from the University of California-Los Angeles Prostate Cancer Index (UCLA PCI). 28 These scales assess the most common urinary or bowel symptoms experienced by men who are treated for prostate carcinoma as well as the degree to which symptoms are bothersome. We predicted that persistent symptoms would impair sexual outcome. The Short Form Health Survey (SF-36) is probably the most widely used current measure of health-related quality of life. 29 The SF-36 has been used extensively in research on men with prostate carcinoma and quality of life as well as in research on men seeking help for ED, 30 allowing us to compare our survey sample with similar cohorts of men. We predicted that men with better perceived physical and mental health also would have better sexual outcomes. Statistical Analysis All statistical analyses were performed using SAS software (SAS, Inc. Cary, NC). Univariate statistical analyses were conducted to describe the demographic characteristics and medical treatment history of the sample of men contacted to participate in the survey. Descriptive statistics, including frequencies, means, and standard deviations (SDs), were calculated where appropriate. T tests and chi-square analyses were conducted to compare survey respondents with nonrespondents on demographic characteristics and medical treatment history. Among the survey respondents, psychometric analyses were conducted on scale scores where appropriate (e.g., SSSS-M, IIEF, PCI, SF-36 scales); Cronbach estimates for scoring of each measure exceeded 0.75, the level generally considered acceptable. Scale scores were estimated for individuals who provided responses to at least 90% of the items underlying a given measure, unless specified differently in the instrument s original scoring guidelines. Scoring was conducted under the assumption of a consistent response pattern to the items in each index. Among the survey respondents, bivariate analyses were conducted to examine the relation of measures of sexual outcome (the global score of the IIEF measuring a combination of function and satisfaction and the frequency of sex in the past month, measured by one item from the IIEF) with demographic, medical, and sexual factors. These analyses included independent sample t tests on group means, analyses of variance, chi-square contingency table analyses, and Pearson product moment correlation analyses, where appropriate. A hierarchical, generalized, linear modeling approach was used to develop models of the multivariate relation of measures of sexual outcome. Demographic variables were added first, then medical factors were added, followed by sexual factors, as illustrated in Figure 1. A sequential, backward selection approach to model development was adopted within each subset of factors. Variables within each subset were kept in the model if the significance of their relation to the outcome was P 0.01 in a multivariate analysis. Variables that achieved this level of significance within the demographic and medical subsets were not removed (i.e., they remained fixed in the model) when subsequent subsets were tested. Appropriate diagnostics (e.g., standardized change in values) were examined to explore the presence of consistently influential ob-

5 Sex Rehabilitation and Prostate Carcinoma/Schover et al TABLE 1 Comparison of Respondents and Nonrespondents Variable Respondents (n 1236) Nonrespondents (n 1311) P value Mean age SD (yrs) Mean SD time since treatment (yrs) Ethnicity (%) Caucasian: African American Other 1 1 Type of treatment (%) Surgery Radiation therapy Stage of prostate carcinoma T T T3 4 4 Neoadjuvant hormones (%) Biochemical failure (PSA) (%) Potent before diagnosis (%) SD: standard deviation; NS: not significant; PSA: prostate specific antigen. servations. The diagnostic analyses did not suggest the exclusion of any cases. Final models were constructed for sexual outcome and frequency using ordinary least-squares regression and including in the final analysis all factors from the analyses of demographic and medical subsets as well as the remaining sexual factors. Model parameter estimates were examined, and corresponding tests are reported for each data subset. RESULTS Sample Characteristics Our return rate was 49%, excluding 45 men who were deceased or had a cognitive disability that prevented them from completing the questionnaire and 44 men with invalid mailing addresses, yielding a sample of 1236 men. Based on the registry data, the mean age SD of our sample was years (range, years), and the mean time since treatment was years. Our sample was well educated: 8% of men had less than a high school education, and 23% of men had a postgraduate degree. Caucasian men comprised 90% of the sample, with 10% African-American men and 1% men of other ethnicities. Twenty-seven percent of men had undergone neoadjuvant hormonal therapy, and 8% of men reported current antiandrogen therapy for prostate carcinoma. The majority of men (86%) were married, and another 6% of men were in a committed relationship. Seventy-three percent of men had been in a relationship with their current sexual partner for 10 years. Survey Respondents versus Nonrespondents Table 1 compares men who did and did not return their questionnaires on a number of demographic and medical variables from the registry data. These comparisons suggest that African-American men were less willing to participate in the survey (30% response rate compared with 52% for Caucasian men). In addition, men who participated were slightly younger, were more likely to have undergone surgical treatment, and were more likely to have been potent before treatment. These latter three group differences suggest that men who responded may have been the most interested in staying active sexually. Reports of Pretreatment Sexual Function A chart review showed that 64% of men had been regarded as potent by their oncology physician at the time they were diagnosed with prostate carcinoma. According to the men s retrospective self-reports, 57% of men had normal erections and were sexually active before they were diagnosed with prostate carcinoma, 9% of men had normal erections but were not active with a partner at that time, 2% of men were using a medical treatment for ED to stay sexually active, 21% of men had ED but still were active sexually, and 12% of men had ED and were inactive sexually before their diagnosis. We compared the physician s rating of erectile function recorded before treatment with retrospective ratings by the men s self-reports (with men who reported normal erections with or without being sexually active categorized as sexually functional). The

6 1778 CANCER October 15, 2002 / Volume 95 / Number 8 two ratings were concordant for 72% of men (, 0.39, indicating fair to good agreement). Fourteen percent of men rated themselves as having been functional but were rated as dysfunctional by their physicians. Another 14% of men recalled having been dysfunctional pretreatment but had been rated functional in chart notes. Although this pattern did not reveal any consistent direction of bias, we used the physician rating in further analyses, because it was not subject to retrospective recall. 31,32 The desire to preserve erectile function did not influence 49% of men in their choice of treatment for prostate carcinoma, but it was a minor influence for 27% of men and a major influence for 24% of men. Six men in the sample defined themselves as primarily homosexual in orientation, and eight men defined themselves as bisexual. Thirty-one percent of men had only 1 sexual partner since age 18 years, 38% of men had 2 9 partners, and 31% of men had 10 partners. Prevalence of Sexual Dysfunction after Treatment for Prostate Carcinoma Only 14% of men reported that erections stayed the same or improved after treatment for prostate carcinoma. Erections became somewhat worse for 21% of men and became much worse for 65% of men. Fully 85% of respondents reported that ED was a problem within the last 6 months. In addition, 45% of the sample reported low sexual desire in the past 6 months, and 65% of the sample reported a problem with their orgasms (including, within this group, 31% who no longer tried to reach orgasm, 17% who tried but were unable to reach orgasm, 28% with orgasms that were disappointingly weak, 37% with dry orgasms, and 5% with premature ejaculation). The percentage of men with erection problems who rated themselves as moderately to extremely distressed about them was 61%, with 60% of men rating themselves distressed to a similar extent about desire problems and 64% of men rating themselves distressed about orgasm problems. In the past year, 44% of men had not been sexually active with a partner (although 86% of these men were married or in a relationship), 52% of men had one sexual partner, and 4% reported having more than one sexual partner. Men s ratings of sexual dysfunction in their partners also revealed a high prevalence of problems. Of the men who reported having a current partner, 42% indicated that their partner had low desire for sex, 10% reported that their partner had a health problem interfering with sex, 13% reported that their partner had vaginal dryness or pain with sex, and 14% reported that their partner had trouble reaching orgasm. More than one problem could be indicated, TABLE 2 Scores on the International Index of Erectile Function Domain score Cronbach No. Mean SD Mean SD for ED patient norms a Erectile function Orgasmic function b Sexual desire b Intercourse satisfaction b Overall satisfaction Global score SD: standard deviation; ED: erectile dysfunction. a Norms for 111 men with ED (mean age, 56 years) from validation of the International Index of Erectile Function (see Rosen et al. 27 ). Higher scores indicate better function. The SD for global score was not available. b T test indicated that this sample differed significantly from the normative sample (P 0.01): Unable to calculate for global score. and, overall, 66% of men with relationships indicated that their partner had at least one sexual dysfunction. Scores on the IIEF, a standardized measure of sexual dysfunction, are presented in Table 2. Mean values on the Orgasmic Function, Sexual Desire, and Intercourse Satisfaction subscales were significantly lower than those reported for the original normative sample of men with mixed types of ED, 27 indicating that our group of respondents were quite dysfunctional across all phases of the sexual response cycle. To identify men who had functional erections at the time of our survey, we used a score 22 on the Erectile Function subscale of the IIEF as a criterion. This score range has been validated and includes men with minimal/mild problems as well as totally normal erectile function. 33 Erectile Function scores were available for 1100 men in our sample. Within that group, 21% (n 231 men) scored 22, including 13% (n 142 men) of those who were achieving good erections spontaneously and 8% (n 89 men) of those who were using medical therapies for ED. To further assess the validity of this cut-off score, we compared the Erectile Function scores for the 15% of men who indicated on a separate yes-or-no question that they had no erection problem in the past 6 months (mean SD Erectile Function score, ) with the scores for the 85% of men who reported an erection problem in the past 6 months (mean SD Erectile Function score, ). A t test was significant at P (t[1090] 14.94). Erectile Function scores were correlated negatively with age in our sample (correlation coefficient [r] 0.28; P ). A Cochran Armitage trend test result was 6.66 (P ), showing a trend toward decreasing erectile function with age. Figure 2 illustrates this graphically, dividing our sample into quintiles by age.

7 Sex Rehabilitation and Prostate Carcinoma/Schover et al (odds ratio, 3.81; 95% confidence interval, ) compared with men who were classified as sexually dysfunctional before treatment. Of the men with good erections pretreatment, 18% achieved functional erections post-treatment without the use of medical therapy, and another 10% were functional with medical therapy. Only 5% of men who were classified with ED pretreatment achieved functional erections posttreatment without using medical therapies, and another 5% of men succeeded with the use of medical therapies. FIGURE 2. Percentage of men who achieved functional erections (erectile function score 22) by current age in quintiles (n 1100 patients). Correlation of ED with Treatment for Prostate Carcinoma Table 3 compares the percentage of men who achieved an Erectile Function score 22 across the six types of treatment for prostate carcinoma. Nervesparing radical prostatectomy was somewhat superior to other treatments in terms of both rates of full recovery of erections and better results with medical treatments for ED. Men who received brachytherapy had a similar rate of recovery of spontaneous erections, but they were not as successful in using medical treatments. Using the global IIEF score as the outcome variable, bilateral nerve-sparing prostatectomy and brachytherapy predicted better sexual outcome than all other treatments (F[5,1075] 16.36; P ), with Tukey Studentized range tests used to compare treatments in post-hoc analyses. When the men were divided simply into those who underwent surgery and those who received radiation therapy as their primary treatment, the groups did not differ significantly either on Erectile Function subscale scores or on their global IIEF scores. Correlation of ED with Pretreatment Erectile Function We compared the percentage of men who reported Erectile Function scores 22 according to whether they had been categorized by their physician as having normal erections or abnormal erections at the time they were diagnosed with prostate carcinoma. Pretreatment and post-treatment erectile function were associated significantly (n 1098 men with evaluable data; chi-square [1] 47.49; P ). Men who were classified by their physician as having good erections before treatment were almost 4 times more likely to have functional erections at the time of the survey Sexual Outcomes To examine factors that predict men s sexual function, frequency of sexual activity, and the success of medical treatments for ED, two outcome variables were created from our data. The global score of the IIEF was used as the outcome criterion summarizing both overall sexual function and satisfaction. One item of the IIEF that measures the frequency of attempts at sexual intercourse or activity in the past 4 weeks was used as the outcome variable for sexual frequency. In our sample, 55% of men were inactive in the past 4 weeks, 19% of men made 1 2 attempts, and 26% of men made 2 attempts at intercourse. Other Quality-of-Life Measures Table 4 compares mean SD scores on several standardized questionnaires for our sample with the same scores from normative, community samples. Our sample appears very similar to the normative group of mainly college-age men on the SSSS-M 24 and very similar to national norms for the SF-36 indices of physical and mental health, 34 which include the Physical Health Composite Score (PCS) and the Mental Health Composite Score (PCS). Each has a mean SD score of in community samples. 35 Our sample s scores also were similar to norms established in other large registries for patients with prostate carcinoma on the SF-36 and the UCLA PCI urinary and bowel function scales. 28,30 Variables Associated with Better Sexual Function and Satisfaction Although the results of bivariate analyses relating individual variables to global IIEF score are not presented in detail, underlining in Figure 1 indicates factors that were significant in bivariate analyses at a level of at least P 0.01 but that did not maintain a significant correlation to sexual outcome in multivariate analyses. Shading indicates factors that attained a significance of at least P 0.01 in multivariate analyses within each subset of factors entered into the model. Asterisks denote factors that remained signifi-

8 1780 CANCER October 15, 2002 / Volume 95 / Number 8 TABLE 3 Treatment Modality for Prostate Carcinoma and Ability to Achieve Functional Erections (Erectile Function score > 22), With or Without Medical Treatments for Erectile Dysfunction Treatment modality No. Functional, no medical treatment for ED (%) a Functional, using medical treatment for ED (%) b Prostatectomy with bilateral nerve sparing Prostatectomy with unilateral nerve sparing Prostatectomy without nerve sparing Brachytherapy Conformal or intensity-modulated radiation therapy Standard external beam radiation therapy Total sample 1081 c 13 8 ED: erectile dysfunction. a There were 142 men with an Erectile Function (EF) score 22 (mean age standard deviation [SD], years). b There were 89 men with an EF score 22 (mean age SD, years). c Information was missing for 155 patients on either treatment modality for prostate carcinoma (n 19 patients), EF score (n 135 patients), or both (n 1 patient). TABLE 4 Standardized Questionnaire Results for the Prostate Registry Respondents Compared with Normative Samples a Questoinnarie No. Cronbach for respondents Mean SD for respondents Mean SD for the normative sample Reference SSSS-M Andersen et al. 24 UCLA PCI (TUFB) Litwin et al. 28 UCLA PCI (TBFB) Litwin et al. 28 SF-36 MCS Ware 29 SF-36 PCS Ware 29 SD: standard deviation; SSSS-M: Sexual Self-Schema Scale-Male Version; UCLA PCI: University of California-Los Angeles Prostate Cancer Index; TUFB: Total Urinary Function and Bother; TBFB: Total Bowel Function and Bother; SF-36: Short-Form Health Survey; MCS: Mental Health Composite Scale; PCS Physical Health Composite Scale. a SSSS-M normative scores are for men who were unselected for health, with higher scores indicating a more positive sexual self-image. For UCLA PCI scales and the SF-36, higher scores indicate better function. Norms for the urinary and bowel scales are based on a large sample of patients with prostate carcinoma. Norms for the SF-36 scales are for community men who were unselected for health. cant in the final model, which retained significant factors from subsets 1, 2, and 3. Table 5 presents a statistical summary of the final model. The demographic factor that was associated most strongly with better sexual outcome (global IIEF score) was younger age. Having more education and being married also were significant when only demographic factors were included in the model, but not when the other subsets were added to the final model. With demographic factors taken into account, medical factors that were associated significantly with sexual outcome included not having had neoadjuvant or current antiandrogen therapy; undergoing bilateral, nerve-sparing prostatectomy or brachytherapy; and self-reported better mental (MCS) and physical health (PCS) on the SF-36. Years since treatment was a significant variable when only the demographic and health-related factor subsets were in the model, but not when sexual factors were added. Sexual factors explained additional variance in outcome. Significant factors included having normal erections before treatment (physician report), having been influenced more heavily by hopes of preserving sexual function in choosing a treatment, having more sexual partners in the past year, and having a sexually functional partner. The model explains 36% of the variance in IIEF global scores. Variables Associated with More Frequent Sexual Activity Table 6 demonstrates the same modeling procedure for the outcome variable of frequency of sexual activity. Again, younger age was the strongest demographic factor associated with more frequent sex, but marital status also was significant, with unmarried men with partners having more frequent sex than married men, who exceeded single men. These factors remained significant in the final model. Beyond these factors, medical factors that were associated significantly with

9 Sex Rehabilitation and Prostate Carcinoma/Schover et al TABLE 5 Model Developed with Hierarchical Linear Regression to Explain the Variance in International Index of Erectile Function Global Scores after Treatment for Prostate Carcinoma (n 972 patients) Source DF Mean square F statistic P value Demographic factors (fixed) Younger age Greater education Married partnered no partner Health-related factors (fixed) Yrs since treatment No neoadjuvant antiandrogen therapy No current antiandrogen therapy Erection-sparing treatment Perceived good physical health (PCS) Perceived good mental health (MCS) Sexual factors (not fixed) More sexual partners in past year Good sexual function before diagnosis Chose treatment to preserve sexual function Partner is sexually functional Model Error Corrected total 971 R Adjusted R DF: degrees of freedom; PCS: Physical Health Composite Scale; MCS: Mental Health Composite Scale; R 2 : correlation coefficient. TABLE 6 Model Developed with Hierarchical Linear Regression to Explain the Variance in Frequency of Sex after Treatment for Prostate Carcinoma (n 1049 patients) Source DF Mean square F statistic P value Demographic factors (fixed) Younger age Married partnered no partner Health-related factors (fixed) No current antiandrogen therapy Erection-sparing treatment More recent treatment Perceived good mental health (MCS) Sexual factors (not fixed) More sexual partners in past year Chose treatment to preserve sexual function Partner is sexually functional Model Error Corrected total 1048 R Adjusted R DF: degrees of freedom; MCS: Mental Health Composite Scale; R 2. correlation coefficient. more frequent sex initially and in the final model included no current antiandrogen treatment; undergoing bilateral, nerve-sparing prostatectomy; receiving treatment more recently; and reporting more positive mental health (SF-36 MCS). With demographic and medical factors taken into account, sexual factors that were associated significantly with having more frequent sex included having more sexual partners in the past year (with men without partners the having the least sex exceeded by men with one partner, who

10 1782 CANCER October 15, 2002 / Volume 95 / Number 8 had sex less frequently than the 4% of men with 2 partners), having a sexually functional partner, and having been influenced in the choice of treatment by the hope of preserving sexual function. The model explains 28% of the variance in sexual frequency. DISCUSSION The results of our survey confirm our impression that the literature has been overestimating the success of both surgery and radiation therapy in preserving sexual function. The great majority of men remained sexually dysfunctional and dissatisfied at an average of 4 years after localized treatment for prostate carcinoma. Only 13% of men reported recovering or retaining functional erections after treatment, and another 8% of men achieved a normal level of sexual function by using medical treatments for ED. The duration of follow-up in our sample allowed adequate time for men who underwent prostatectomy to recover firm erections and men who were treated with radiation therapy to experience gradual vascular damage to erectile function. Only 1.5% of men were less than 1 year post-treatment, and 87% of men were at least 2 years post-treatment, past the period of the most unstable sexual function. 12,13,17 Nerve-sparing radical prostatectomy and brachytherapy do show a significant advantage in sparing erectile function, even with variables such as age, clinical disease stage, and time since treatment taken into account. However, their superiority to other treatment techniques must be interpreted within the context of the generally dismal rates of sexual recovery. Contrary to the widely quoted findings of a meta-analysis of the literature published several years ago, 1 radiation therapy as a treatment category is not superior to radical prostatectomy in sexual outcome. Survey results also confirm the incremental, negative impact of hormone therapy on men s sexuality. Not only current antiandrogen treatment but also past use of neoadjuvant therapy impairs sexual activity, function, and satisfaction. Neoadjuvant therapy may have a permanent effect on the pituitary-gonadal axis. A recent prospective study of hormone levels at longterm follow-up after 3 6 months of neoadjuvant therapy with a luteinizing hormone-releasing hormone analogue showed that, although most men had serum testosterone levels within the normal range, levels remained significantly lower than at baseline. 36 Furthermore, levels of luteinizing hormone and folliclestimulating hormone at follow-up were elevated persistently. Several recent case series have demonstrated that neoadjuvant hormone therapy increases the rate of ED at follow-up after radiation therapy, although two other studies did not find a significant impact. 40,41 We believe that our results present a more accurate picture of men s sexual function after treatment for prostate carcinoma than past surveys. Not only was our sample far larger and better characterized than many, but we were able to ascertain probable bias in which men participated in the survey. Our return rate of 49% is very typical for lengthy surveys of patients with cancer focusing on sexuality. 42,43 The lesser return rate from African-American men was disappointing but not unexpected, given distrust about medical research 44 and more conservative values about sexuality 45 in the black community. At least within our sample, ethnicity was not related significantly to sexual outcome. Because men who chose to participate were younger, more likely to have undergone surgery, and more likely to have been rated potent by the physician before treatment, our results actually may overestimate positive sexual outcomes after treatment for prostate carcinoma. Another major methodological improvement is that our questionnaire was quite detailed and included a validated scale to measure sexual outcome. Our criterion for normal erections on the IIEF was a generous one, including some men with mild problems. 33 Men who score in this range would experience erection problems from much less than 50% of the time to almost never or never. The resulting 79% rate of ED, with or without using a medical treatment, corresponded closely to men s self-report on another yes-or-no item asking whether they had experienced an erection problem within the last 6 months (85%). Men who denied having an erection problem in the past 6 months on this item had a mean Erectile Function score of 20, close to the validated subscale criterion. The IIEF also has the advantage of measuring a broader range of aspects of sexual function. It was clear from our data that loss of desire for sex and difficulty enjoying orgasm were just as important in men s sexual dissatisfaction as ED. Other researchers are starting to use the IIEF to measure the efficacy of sildenafil in the treatment of men with prostate carcinoma. 46,47 The baseline mean global and subscale scores from these cohorts are quite comparable to ours, providing further evidence that the degree of sexual dysfunction in our sample was not discrepant with the findings of others. One recent follow-up of men who were treated with brachytherapy did use an Erectile Function subscale score of 11 as the criterion for potency. 19 Men who score in this range may be experiencing erection problems much more than 50% of the time, however.

11 Sex Rehabilitation and Prostate Carcinoma/Schover et al In fact, 11 is the mean Erectile Function score for men with ED in the normative sample for the IIEF, as summarized in Table Even with this loose cut-off value for potency, the 6-year actuarial rate for maintaining erectile function in the brachytherapy sample was only 39%, 19 far lower than the recovery rates reported by researchers assessing sexual function by interview at shorter follow-up intervals. Thus, our data are consistent with reports from other cohorts when similar methods were used. Men in our sample reported similar health-related quality of life on the SF-36 and similar or fewer problems with urinary or bowel symptoms as were reported in other large registries of patients with prostate carcinoma who were treated in academic medical centers. 16,28 The rate of ED at the time of diagnosis with prostate carcinoma in our sample also was well within the typical estimated range from the literature, whether based on physicians prospective reports (36%) or on men s retrospective self-reports of erections before their diagnosis (34%). 3,12,18,22,23 The 72% agreement between these two estimates of pretreatment erectile function is quite comparable to the 77% agreement reported in a sample from the Prostate Cancer Outcomes Study comparing baseline and retrospective estimates of erectile function after only 6 months of follow-up. 32 Our data did not reveal a bias for men to idealize their pretreatment erectile function. 31 Our sample was somewhat older (mean age at diagnosis, 64 years) compared with the men in many recent case series that examined the impact of treatment for prostate carcinoma on sexuality. We expected that at least 50% of the men in this age group, unselected for health, would have ED, 48 although it is clear that treatment for prostate carcinoma has an impact in addition to aging or other medical comorbidity. Although we did not directly measure comorbid medical problems, surveys of large samples of primary care patients suggest that the SF-36 PCS provides an accurate estimate of medical comorbidity. 49,50 Like our sample, a recent, large case-control study of men with localized prostate carcinoma and healthy controls found strong associations between sexual dysfunction and both the SF-36 PCS and the SF-36 MCS measures. 51 However, only a prospective, longitudinal study will clarify whether this relationship occurs because men with more impairment of physical and mental health are less likely to achieve successful sexual rehabilitation after treatment or because distress about sexual dysfunction has a negative influence on men s perceptions of their current mental and physical health. An inspection of Figure 1 demonstrates that most factors that were included in our hypothesized model do influence sexual outcomes of men who are treated for prostate carcinoma, although only a lesser number achieved significance in the final, multivariate model. What implications does the model have for developing an intervention to improve sexual outcomes? Our findings suggest that current efforts at sexual rehabilitation focus too narrowly on the mechanical rigidity of a man s erections. The factors beyond the effects of age, health, and treatment that are related strongly to sexual satisfaction at long-term follow-up are more cognitive and behavioral: having one or more current partners who are functional sexually, having had good sexual function before treatment, and putting a high priority on preserving sexual function in choosing a treatment. These are factors that may be targeted by sexual counseling interventions that would complement and enhance efforts at medical treatment for men with ED. We had expected that men s scores for SSSS-M would be a good summary measure of their motivation to stay active sexually. 24,25 The failure of the SSSS-M scores to retain significance in the multivariate model probably reflects their high correlations with the other sexual variables that did achieve significance. Andersen and colleagues did not include parallel factors in their work with women who had gynecologic carcinoma. The SSSS-M still may be a useful measure for use in clinical and research efforts with survivors of prostate carcinoma. Although the importance a man places on sex may be a personality trait, it also is possible to change men s negative beliefs about sex after they have been diagnosed with prostate carcinoma. For example, men often expect to lose sexual desire and function as they age, or they dismiss as unacceptable any treatment for ED that interferes with spontaneity of sex. Although the great majority of men in our survey had sexual partners available, 66% of partners also reportedly had sexual problems, including 42% who had lost desire for sex. Although we did not survey partners by mail to check the accuracy of the men s perceptions, we did interview a subset of 164 partners by phone. Fifteen percent reported low desire for sex, 17% cited their ill health or age as a barrier to sexual rehabilitation, and 15% had become resigned to the sexual problem. Thus, an important aspect of sexual counseling should including the partner in plans for sexual rehabilitation. The counselor can try to make sure that the couple has adequate sexual communication and stimulation skills to ensure a pleasurable experience for the partner. The program should try to ensure adequate treatment of health or menopause-related problems that may contribute to a woman s loss of interest

12 1784 CANCER October 15, 2002 / Volume 95 / Number 8 in sexual activity. Issues for same-sex couples should be quite similar, given that sexual orientation was not a factor influencing outcome in our survey. Men who have no current relationship may benefit from encouragement to date, despite their ED and fears of rejection. In this age group, single women far outnumber men, so that finding a partner is rarely a problem if a man is willing to look. Currently we are evaluating a pilot, four-session sexual counseling program along these lines for couples in which the man has had treatment for localized prostate carcinoma. We are varying whether the female partner attends all sessions or simply participates by completing questionnaires, reading handouts, and cooperating in behavioral change assignments. We hope that our efforts will be successful and can be disseminated on a wider basis to improve the long-term sexual satisfaction of men who are treated for prostate carcinoma. 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