Urinary and Sexual Function After Radical Prostatectomy for Clinically Localized Prostate Cancer:  The Prostate Cancer Outcomes Study FREE

Prostate cancer is the most frequently diagnosed solid tumor in US men. An estimated 179,300 men will be diagnosed as having the disease in 1999,¹ and in more than 70% of these patients, the disease will be clinically localized.² Treatment options for men with tumors confined to the prostate who have at least a 10-year life expectancy include radical prostatectomy, external beam radiation, brachytherapy, or expectant management. Each of these approaches is associated with a different spectrum of morbidity and effects on quality of life, which may be short-term or long-term.

To make informed choices about treatment alternatives, patients with prostate cancer and their physicians need accurate information to assess the potential and pattern of complications associated with each option. Numerous investigators have assessed urinary and sexual function 1 or more years after radical prostatectomy, with rates of incontinence ranging from 4% to 40% and impotence from 29% to 75%.^3- 12 These findings reflect the experiences of patients from selected clinical practices,^{3- 5,7- 9,12} a health maintenance organization,¹⁰ and Medicare recipients.^6,11 Differences in patient mix, study size, and data collection methods may explain the wide range of results.

Limited data are available to describe the outcome experiences of unselected population-based patients. We report results from the multicenter Prostate Cancer Outcomes Study (PCOS), which has completed longitudinal assessments of functional status in a large community-based cohort of patients with prostate cancer treated with radical prostatectomy for clinically localized disease.

The methods used in the PCOS have been described elsewhere.¹³ Briefly, African American, white, and Hispanic men diagnosed as having primary prostate cancer between October 1, 1994, and October 31, 1995, who were residents of areas covered by 6 population-based Surveillance, Epidemiology, and End Results cancer registries were eligible. At the time of diagnosis, patients resided in Connecticut, New Mexico, Utah, the Atlanta, Ga, metropolitan area, Los Angeles County, California, or King County, Washington, which includes Seattle. All men aged 39 to 89 years were eligible in 5 registries and those aged 60 to 89 years were eligible in King County. The study was approved by the institutional review board of each participating institution.

A total of 11,137 eligible cases were identified, and 5672 were randomly sampled for PCOS according to defined age and race/ethnicity strata. Of the sampled cases, 4736 (83.5%) were contacted and invited to participate, and 3533 (62.3%) completed a 6- and/or 12-month survey. The reasons for nonresponse were inability to locate the patient (n = 413), physician refusal (n = 380), patient refusal (n = 1087), illness or mental incompetence of the patient (n = 143), and other reasons (n = 116). Medical record abstracts were completed for 3486 (98.7%) of the sampled, participating cases.

For this analysis of surgery, we selected all PCOS patients aged 39 to 79 years with histologically confirmed, clinically localized prostate cancer who underwent radical prostatectomy as primary treatment within 6 months of diagnosis date and who had both survey and medical records data (n = 1301). We excluded 10 patients with missing data on key variables, leaving 1291 patients for analysis.

Following physician notification, eligible sampled patients were contacted by mail (90.2%) or telephone/in-person (8.8%) 6 months after diagnosis date and asked to complete a self-administered questionnaire and provide consent for access to medical records. Men who completed the 6-month survey and those who were sampled but who did not complete a 6-month survey were mailed a 12-month survey. At approximately 24 months following diagnosis, patients who had completed an earlier survey were mailed another follow-up questionnaire. Of the 1291 patients in this analysis, 1042 (80.7%) completed a 6- and/or 12-month survey and a 24-month survey.

The 6-month survey obtained information on demographics; treatment of prostate cancer; medical history; urinary, bowel, and sexual function at baseline (just before diagnosis) and during the past month; satisfaction with treatment; and quality of life. Survey questions related to function were adapted from previously used reliable and validated instruments.^6,12,14 The 12-month and 24-month surveys contained similar questions that focused on functional status during the past month. The interval from diagnosis to survey closely approximated the interval from surgery to survey. At the 12- and 24-month surveys, the median time since surgery was 10.5 and 22.5 months, respectively. Patients had undergone prostatectomy at least 18 months previously when the 24-month survey was completed.

Medical record abstracts ascertained details of the prostate cancer diagnosis and treatment and clinical characteristics of the disease. Office and hospital records were used to define stage of disease, tumor grade, primary treatment, and dates of therapy.

To assess temporal changes in urinary and sexual function and potentially confounding or modifying factors that affect these functions after radical prostatectomy, longitudinal regression models¹⁵ implemented in SUDAAN¹⁶ were used. The Horvitz-Thompson weight, that is, the inverse of the sampling proportion for each sampling stratum (defined by age, race, and study center), was used to obtain unbiased estimates of the regression parameters for the target population of patients with prostate cancer undergoing radical prostatectomy who were eligible for this analysis.

Dependent variables were urinary (level of urinary control, frequency of incontinence, use of pads, frequency of urination, and extent of any problem with incontinence) and sexual (interest in sex, frequency of sex, firmness of erections, difficulty maintaining erections, and extent of any problem with sexual function) function measured at 6, 12, and 24 months. In addition, the first 4 items in each category were combined to yield a composite score,¹⁰ ranging from 0 to 100. A score of 100 on the sexual scale would represent a man who reported interest in sex, sexual activity several times a week, erections firm enough for sexual intercourse, and no difficulty maintaining erections. A score of 40 may represent a man who was interested in sex and was engaging in some form of sexual activity but whose erections were not firm enough for intercourse. Independent variables used in the analysis were survey time, baseline values of the dependent variables, age, race, marital status, income, education, employment status, clinical stage, and pathologic grade.

For continuous, binary, and multinomial responses, linear regression, logistic regression, and multinomial logistic regression models, respectively, were used. The statistical significance level for each covariate effect on each dependent variable was examined. The interaction effects of period by baseline measures and period by important model-identified covariates were examined by adding these interaction terms to the model. A change in the mean function score from baseline was tested by a paired t test. All P values were 2-sided.

The distributions of patients with prostate cancer according to selected demographic and clinical characteristics are provided in Table 1. A total of 56.4% of patients were younger than 65 years at diagnosis (mean age at diagnosis, 62.9 years). Most patients were white, married, high school or college educated, of middle income, and retired. Based on surgical pathologic findings, most of the tumors were Gleason score 7 (31.1%) and were of local stage (66.8%). Arthritis and hypertension were the most prevalent medical conditions reported.

Urinary function was assessed by 5 questions about each of the 4 different periods. The proportion of men reporting total urinary control increased after surgery from 20.5% at 6 months to 31.9% by 24 months (Table 2). Overall, 40.2% of the patients reported occasional urinary leaking, 6.8% frequent urinary leaking, and 1.6% no urinary control 24 months after diagnosis (≥18 months after surgery). At the time of the 24-month survey, 11.9% experienced incontinence more than 2 times daily, and 3.3% required 3 or more pads per day. Overall urinary function based on the composite score decreased from 91.2 at baseline to 75.1 at 24 months (P<.001). The level of bother improved over time, with 8.7% of the patients reporting that incontinence was a moderate-to-big problem at 24 months.

Regression models were used to examine the effects of selected covariates on measures of urinary function. As expected, the period after surgery was the strongest predictor of urinary function. Income was related to the mean incontinence function score, with men who had higher incomes reporting better function at all time points compared with lower-income groups (P = .04). Marital status was also associated with urinary function, with 33.2% of married men reporting no incontinence at 24 months compared with 26% of unmarried men (P = .006). Race, education, employment status, and tumor stage and grade were not associated with urinary function.

Age was related to the level of urinary control, frequency of incontinence, and bother. We evaluated measures of urinary function according to age and period in more detail (Table 3). Compared with younger men, those aged 75 to 79 years experienced the highest level of incontinence at 24 months (13.8% vs 0.7%-3.6%, P = .03). The oldest age group also had more frequent incontinence (40.8% vs 10.0%-15.9% of younger men experienced incontinence more than twice a day, P<.001). Men younger than 60 years were less likely to be incontinent at 24 months than older men, as measured by total incontinence (0.7%) or frequent (>2 times per day) incontinence (10.0%). The effects of age on urinary control (P = .03) and frequency of incontinence (P = .008) were statistically significant. In addition, there were statistically significant age-by-period interactions for these 2 measures of urinary function, with younger men regaining function sooner than older men.

The surveys also asked about treatment for strictures and incontinence. Overall, 16.1% of the cohort reported surgery for treatment of strictures, and 15.8% used medication to treat incontinence during the 24-month follow-up period.

Sexual function was assessed by several questions (Table 4). Analyses were completed for all men in the cohort and for only those men who reported a sexual partner at the time of the baseline or 6-month survey (80.9% of the cohort). Since the findings were similar, only the results for the entire cohort are provided. At 24 months (≥18 months after surgery), 59.9% of men reported that erections were not firm enough for sexual intercourse, and 44.2% were unable to have any erections (Table 4). Of the 15.8% of men who reported at baseline that erections were not firm enough for intercourse, 95.3% reported that they remained impotent. For comparison, of the 72.7% of men who were potent at baseline, 72.4% reported that their erections were not firm enough for intercourse at 18 or more months after surgery. Among men who were potent at baseline, the proportion who were impotent 18 or more months after surgery varied according to whether a nerve-sparing procedure was attempted: 65.6% of non–nerve–sparing, 58.6% of unilateral nerve–sparing, and 56.0% of bilateral nerve–sparing procedures produced impotence (P = .001 comparing non–nerve-sparing to bilateral nerve–sparing patients). The mean sexual function score significantly decreased from 71.5 at baseline to 38.6 at 24 months (P<.001). Before the diagnosis of prostate cancer, 17.9% of patients felt that sexual function was a moderate-to-big problem. On the 24-month survey, 41.9% reported that sexual functioning was a moderate-to-big problem.

Regression models were used to examine the effects of selected covariates on sexual function and bother. Tumor stage and grade were unrelated to sexual outcomes. The period when the survey was completed and the level of baseline sexual function were the strongest predictors of subsequent sexual function. Men with better sexual function at baseline reported better sexual function at each follow-up survey (P<.001). Age, race, education, and having a sexual partner were also related to outcomes. The frequency of sexual activity was strongly associated with age (P<.001), with men in the youngest (<60 years) age group reporting more frequent sexual activity at each period compared with older men. At 24 months, a higher proportion of men younger than 65 years reported that sexual function was a moderate-to-big problem compared with men 65 years or older (57.1% of younger vs 48.0% of older men, P<.001). Education also was related to sexual function (P = .008). Men with a college or postgraduate education reported the highest frequency of sexual activity and the lowest level of bother about sexual performance at all periods compared with men with less education.

We performed a more detailed analysis of potency according to age, race, and period. As shown in Table 5, the proportion of men potent at 24 months was higher in those younger than 60 years (39.0%) compared with the older age groups (15.3%-21.7%; P<.001). The effect of age on erectile function (P = .02) and the age-by-period interaction (P<.001) was statistically significant, indicating that the youngest men (<60 years) had better outcomes and regained sexual function sooner than older men.

Function also varied by race, with African American men experiencing a better outcome (Table 5). A total of 38.4% of blacks reported firm erections at 24 months compared with only 21.3% of whites and 25.9% of Hispanics (P = .001).

We also examined the proportions of men who reported using aids for erectile dysfunction. During the 24-month follow-up, these treatments were used: vacuum suction device, 26.8%; penile injections, 21.4%; medication, 9.0%; counseling by a sex therapist or psychologist, 7.6%; and penile implant or prosthesis, 3.7%.

Patients were asked about general effects of prostate cancer and its treatment on other aspects of life. Small proportions of men reported experiencing a lot of physical discomfort (3.1%), were worried about their health (5.0%), were limited in their daily activities (3.1%), or were bothered a lot by the prostate cancer or its treatment (5.6%) at 24 months. About half of the patients were delighted or pleased with their surgery, and only 4% were dissatisfied. At 18 or more months after surgery, 71.5% of the patients said that they would make the same treatment choice, although this varied by race (blacks, 56.4%; whites, 76.1%; and Hispanics, 61.4%). Only 7.3% reported that they would not choose radical prostatectomy again.

These results provide the first description, to our knowledge, of outcomes experienced by a cohort of unselected, population-based patients who have undergone radical prostatectomy. Our findings are likely to be more representative of the occurrence of urinary and sexual dysfunction following surgery for localized prostate cancer in men in the community compared with earlier studies, which were limited to single or multiple institutional-based patient series. Overall, we found that at 18 or more months after surgery, 8.4% of patients were incontinent and 59.9% were impotent. The proportion of men bothered by the lack of urinary control was 8.7% at 24 months; however, 41.9% reported that sexual function was a moderate-to-big problem. Urinary function varied by age and sexual function by age and race. Despite significant declines in both urinary and sexual performance levels, most men were satisfied with their treatment choice.

In addition to its population-based design, another strength of the study is the large number of patients available, particularly those younger than 65 years. These attributes provide the opportunity to adequately evaluate outcomes in community-based patients who choose prostatectomy as primary treatment. For this study, we collected self-reported outcomes data directly from patients rather than relying on medical records, which may not adequately record functional status following treatment.^17- 18 Further, we obtained information to assess potential confounding and modifying factors and baseline information on functional status, which allowed us to compare outcomes before and after diagnosis and treatment.

Our study also has several limitations. Overall, 62.3% of eligible, sampled men participated in the survey. It is possible that nonparticipants experienced different levels of urinary and sexual dysfunction than were reported by participants. In comparing those who did with those who did not complete a study survey, however, there were no major differences in the distributions of age, race, or stage of disease. In addition, a 24-month survey was not completed by 19.2% of those who had completed an earlier survey. To assess possible bias, we examined the distributions of demographic factors and urinary and sexual function at baseline and 12 months for men who did compared with those who did not complete a 24-month survey. Men who did not complete a 24-month survey were more likely to be older and black or Hispanic and to have less education and a lower income. At 12 months, the nonrespondents had more incontinence (4.5% compared with 2.4% of respondents) and less impotence (56.0% compared with 75.5% of respondents). These differences, however, are associated with minimal bias due to the overall high level of response on the 24-month survey.

Another potential limitation is recall bias, since baseline (prediagnosis) function was assessed on the 6-month survey. We conducted a reliability study on 133 patients who completed a baseline survey immediately after diagnosis and a 6-month survey. Recall of baseline function at 6 months was identical to baseline function reported immediately after diagnosis for 69% or more of the men on each item. However, men overestimated baseline function at 6 months for 2 items: frequency of incontinence and erections firm enough for intercourse. To the extent that recall bias exists in our data, the mean change scores for incontinence and sexual function may be overestimated. Such a bias would not affect results for other individual survey items or responses about current function on the follow-up surveys.

Frequent urinary leakage or total incontinence was reported by 8.4% of our cohort at 24 months (≥18 months after surgery), with 11.9% of men experiencing incontinence more than twice a day and 3.3% using 3 or more pads each day. These results are similar to those reported from several clinic- and hospital-based patient series that found that 4% to 12% of patients who had undergone prostatectomy were incontinent a year or more after treatment.^3- 5,7,9,12 However, our estimates of urinary dysfunction are lower than the 31%¹¹ and 40%¹⁰ levels of incontinence reported among older men. We found that age was a significant predictor of urinary function, with elderly men experiencing the most incontinence.

The 3.3% of men using pads for incontinence at 24 months in our cohort is similar to the 4% using 2 or more pads per day reported by Murphy et al,⁷ based on a large series of patients from multiple institutions. In contrast, Talcott et al¹² found that 35% of men were using pads 12 months after prostatectomy, and Fowler et al¹¹ noted that 31% of Medicare patients surveyed 2 to 4 years after surgery reported use of pads and/or clamps. Talcott et al¹² suggested that 35% is likely to be an overestimate, since some men wear pads as a precaution. In the study by Talcott et al,¹² incontinence 12 months after surgery was reported by 9% of men younger than 65 years and 15% of those 65 years or older at diagnosis. Our estimate of incontinence also varied by age. At the time of the 24-month survey, 6.6% of younger men (<65 years) were incontinent compared with 10.7% of older (≥65 years) men.

Although the mean incontinence function score was significantly lower at 24 months compared with baseline, only 8.7% of our cohort reported that incontinence was a moderate-to-big problem 24 months after diagnosis. This estimate is similar to the 6% of patients bothered by incontinence at 12 months after treatment in the patient series reported by Braslis et al⁹ but lower than the 34% reported by Jonler et al.⁸

The frequency of impotence in our cohort (59.9%), as measured by the inability to have erections firm enough for sexual intercourse at 18 or more months after prostatectomy, is higher than the estimated 32% to 53% and 39% of men experiencing impotence reported by Catalona et al⁵ and Steiner et al,³ respectively. However, both of these studies were based on patient series from single institutions. Our cohort also reported a higher level of erectile dysfunction than the 52% noted in health maintenance organization members¹⁰ and the 46% reported for Medicare patients.¹¹ Among men who were potent at baseline, the proportion who were impotent at 18 or more months after radical prostatectomy differed somewhat according to whether the surgery was nerve sparing (65.6% non–nerve-sparing, 58.6% unilateral, and 56.0% bilateral nerve-sparing patients were impotent). These results are similar to some previous studies that showed that potency differs by type of procedure.^5,19 Sexual dysfunction also varied by age and race. In men younger than 65 years, 55.1% reported impotence compared with 66.1% of men 65 years and older. In addition, as of the 24-month survey, 37.6% of younger men (<65 years) compared with 52.6% of older men (≥65 years) reported that they were unable to have any erections. The frequency of firm erections at 24 months was higher in African American men (38.4%) compared with whites (21.3%) or Hispanics (25.9%). Our study is, to our knowledge, the first to examine functional status in minority populations.

The mean sexual function score in our cohort declined from 71.5 at baseline to 38.6 by 18 or more months after surgery (P<.001). These results did not differ notably when examining all men in the cohort compared with those who reported a sexual partner at baseline or 6 months. An assessment of bother showed that at 24 months, 41.9% of men felt that their sexual function was a moderate-to-big problem. Younger men (<65 years) were more likely to report that sexual function was a moderate-to-big problem compared with men 65 years and older (45.4% vs 37.3%), although younger men reported better sexual function at all time points compared with their older counterparts.

Despite the level of urinary incontinence and sexual dysfunction reported on the 24-month survey, most men (75.5%) were satisfied or pleased with their treatment, and most (71.5%) would choose radical prostatectomy again. These results on satisfaction are similar to other reports.^8,11 In earlier studies, 88% to 92% of men undergoing prostatectomy reported that they would select surgery again.^8- 9,11,20 Our lower estimate may reflect differences in study design, size, and patient population.

In summary, our results provide new information on urinary and sexual function at multiple points after radical prostatectomy in a large population-based cohort of patients with clinically localized disease. These estimates of incontinence and sexual dysfunction measured at 18 or more months after surgery should be particularly helpful to community-based patients faced with difficult treatment options. Since follow-up of this population-based cohort is ongoing, we hope to provide more information on functional status in the future. The ability to obtain long-term follow-up information on this large cohort should provide new insights into the temporal changes in function that can be used to predict outcomes in similar patients undergoing radical prostatectomy.