5-YEAR URINARY AND SEXUAL OUTCOMES AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE PROSTATE CANCER OUTCOMES STUDY

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1 /05/ /0 Reprinted from Vol. 173, , May 2005 THE JOURNAL OF UROLOGY Printed in U.S.A. Copyright 2005 by AMERICAN UROLOGICAL ASSOCIATION DOI: /01.ju a 5-YEAR URINARY AND SEXUAL OUTCOMES AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE PROSTATE CANCER OUTCOMES STUDY DAVID F. PENSON,* DALE MCLERRAN, ZIDING FENG, LIN LI, PETER C. ALBERTSEN, FRANK D. GILLILAND, ANN HAMILTON, RICHARD M. HOFFMAN, ROBERT A. STEPHENSON, ARNOLD L. POTOSKY AND JANET L. STANFORD From the Departments of Urology and Preventive Medicine, Keck School of Medicine, University of Southern California (DFP, FDG, AH), Los Angeles, California, Department of Urology, University of Connecticut, Farmington, Connecticut (PCA), Division of Public Health Sciences, Fred Hutchinson Cancer Research Center (DM, ZF, LL, JLS), Seattle, Washington, Department of Medicine, New Mexico Veterans Affairs Health Care System and University of New Mexico (RMH), Albuquerque, New Mexico, Division of Urology, University of Utah School of Medicine (RAS), Salt Lake City, Utah, and Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute (ALP), Bethesda, Maryland ABSTRACT Purpose: Prior studies of postoperative outcomes following radical prostatectomy have been limited by selection bias and short-term followup. In this study we assessed temporal changes in urinary and sexual function up to 5years following radical prostatectomy in apopulation based cohort. Materials and Methods: Asample of 1,288 men with localized prostate cancer who underwent radical prostatectomy and completed abaseline survey within 6to 12 months of diagnosis were includedintheanalysis.twoand5-yearfunctionalandqualityoflifedatawerecollected,aswas information on the use of erectile aids. Temporal functional changes and potentially confounding or modifying factors were assessed using longitudinal regression models. Results: Of these men 14% reported frequent urinary leakage or no urinary control 60 months afterdiagnosis,whichwasslightlyhigherthanthe10%reportingincontinenceat24months(p 0.007). At 60 months 28% of the men had erections firm enough for intercourse compared with 22% at 24 months (p 0.003). Sildenafil was the most commonly used erectile aid (43% ever used) and 45% of users reported that it helped somewhat or a lot. Conclusions: Urinary and sexual dysfunction were common 5years following radical prostatectomy in this large, community based cohort of prostate cancer survivors. While a small minority of subjects experienced changes in urinary or sexual function between years 2and 5 after prostatectomy, functional outcomes remained relatively stable in the majority of participants. KEY WORDS: prostate, prostatic neoplasms, prostatectomy, urinary incontinence, impotence Prior reports concerning functional outcomes after radical retropubic prostatectomy have documented considerable though widely varying changes in 2-year urinary and sexual functionoutcomesfollowingradicalprostatectomydepending on the surgical expertise of the providers, study design and exact choice of outcomes. 1 7 While these studies are useful for counseling patients facing therapy decisions for localized prostate cancer, many are limited by selection bias, crosssectional study designs and relatively short followup (2 years or less). Additionally, most data were collected before 1998, when the Food and Drug Administration approved sildenafil for the treatment of erectile dysfunction. The limitations of these earlier reports underscore the need for further multicenter studies of long-term prostate cancer outcomes in the era of phosphodiesterase type-5 inhibitors. The Prostate Cancer Outcomes Study (PCOS) is such a Submitted for publication July 22, Study received approval from the institutional review board at each institution. Supported by Contracts N01-PC-67007, N01-PC-67009, N01-PC , N01-PC-67006, N01-PC and N01-PC from the National Cancer Institute, National Institutes of Health, Bethesda, Maryland to each of the participating institutions. *Correspondence: Department of Urology, 1441 Eastlake Ave., Suite 7416, Los Angeles, California (telephone: ; FAX: ; penson@usc.edu). S40 study. It is alarge, population based cohort study that has longitudinally evaluated health related quality of life (HRQOL) and functional outcomes in more than 3,500 men from 6Surveillance, Epidemiology and End Results (SEER) cancer registries with prostate cancer diagnosed in 1994 and In the current analysis we assessed temporal changes inurinaryandsexualfunctionupto5yearsfollowingradical prostatectomy in this cohort. METHODS PCOS. PCOS participants were ascertained using the National Cancer Institute SEER program. Acomplete description of the study design has been provided previously. 8 Briefly, black, white and Hispanic men diagnosed with prostate cancer from October 1, 1994 through October 31, 1995 who resided in an area covered by 1of 6SEER cancer registries (the states of Connecticut, New Mexico and Utah, and the metropolitan areas of Atlanta, Georgia, Los Angeles County, California and King County, Seattle, Washington) were eligible for inclusion. Subjects were identified within 6 months of diagnosis using arapid case ascertainment system. Because each SEER cancer registry is affiliated with a local academic institution, the institutional review board at each of these institutions approved the study. Please cite this article as J Urol 2008;179: S40 S44. DOI: /j.juro Copyright 2008 by AMERICAN UROLOGICAL ASSOCIATION.

2 5-YEAR URINARY AND SEXUAL OUTCOMES AFTER PROSTATECTOMY S41 Study cohort. Of the 5,672 eligible prostate cancer survivors initially contacted for inclusion in PCOS 3,533 (62.3%) provided informed consent and completed a 6 and/or 12- month HRQOL survey. For the current analysis of 5-year outcomes we included all 1,288 men who were 39 to 79 years old at diagnosis with clinically localized prostate cancer and who underwent radical prostatectomy as primary therapy within 6 months of the diagnosis date. Data collection and HRQOL questionnaires. Initially the physician of the subject was notified before patient contact. Eligible men were then contacted by mail (90%) or telephone/in person (10%) 6 months after the diagnosis date. They were asked to complete a self-administered survey and provide consent for access to medical records. This survey included information on demographics, prostate cancer treatment and medical history. In addition, information regarding urinary and sexual function just before diagnosis and in the last month was collected using modified versions of previously validated and reliable instruments In approximately 90% of cases baseline information was collected subsequent to diagnosis and treatment, and not actually measured immediately after diagnosis. In these cases subjects were asked to recall their baseline status prior to treatment. In no case was this recalled baseline information collected more than 6 months after diagnosis. Subjects were contacted again 12, 24 and 60 months after the diagnosis date. Each time they were asked to complete a survey that contained questions on functional status in the last month and erectile aid use. Outpatient and inpatient medical record abstraction completed at baseline (about 1 year after diagnosis) obtained details of the prostate cancer diagnosis, treatment and clinical characteristics of the disease. These records were used to abstract disease stage, tumor grade, primary treatment, use of a bilateral or unilateral nerve sparing surgical technique and therapy dates. Statistical analyses. Postoperative temporal changes in urinary and sexual function, and potentially confounding or modifying factors were assessed using longitudinal regression models 12 implemented in the Survey Data Analysis statistical package (SUDAAN, release 7.5, Research Triangle Institute, Research Triangle Park, North Carolina). The Horvitz-Thompson weight, which is the inverse of the sampling proportion for each sampling stratum (defined by study center, age and race), was used to obtain unbiased estimates of regression parameters for PCOS participants. 8 For subjects who were alive but had missing data functional outcomes were imputed using a hierarchical hot-deck imputation approach. 13 This approach was taken to minimize the bias that may be introduced by missing outcomes data, particularly in the latter years of followup. Imputed data were used in 123 cases (10.1%) at 6, in 139 (11.5%) at 12, in 234 (19.3%) at 24 and in 228 (18.8%) at 60 months. RESULTS Table 1lists baseline cohort clinical and sociodemographic characteristics. The majority of subjects were younger than 65 years (56%) and were nonhispanic white (74%). Most subjects were married, high school graduates and retired. The cohort was relatively healthy, although 39% of subjects reported hypertension, 14% had diabetes and 7% reported prior myocardial infarction. Although all subjects had clinically localized disease, pathological examination of surgical specimens revealed that 32% had regional (pt3 or higher) or distant (N or M ) disease. The majority of subjects had a Gleason score of 6 or 7 (56%). A total of 75 subjects (5.8%) died during the 5-year followup. Response rates in the 1,213 living subjects were 90% at 6 months, 88% at 12 months, and 81% at 2 and 5 years. Table 2lists patient reported urinary function and bother TABLE 1. Select demographic and clinical characteristics of 1,288 men with clinically localized prostate cancer undergoing radical prostatectomy in PCOS Group Adjusted % Age at diagnosis: or Older 3 Race/ethnicity: Black 14 Hispanic 12 White 74 Marital status: Married 82 Not married 16 Education level: Some high school 16 High school graduate or some college 45 College graduate 37 Unknown 2 Annual income ($): Less than 20, ,000 39, ,000 75, More than 75, Employment status: Full-time 31 Part-time 10 Retired 53 Other 5 Comorbid conditions: Hypertension 39 Arthritis 37 Diabetes 14 Depression 12 Chronic lung disease 7 Myocardial infarction 7 Heart failure 5 Stroke 3 Liver disease 2 Clinical stage: T1 32 T2 44 T1/T2 23 Pathological stage: Local (pt2) 67 Regional (pt3/4) 29 Distant (pn ) 3 Surgical pathological Gleason score: Unknown 5 Results adjusted for sampling weight based on the total number of eligible cases ascertained for the study. results. At baseline 3.4% of participants reported frequent urinary leakage or no control. This percent peaked 6 months after diagnosis with 25% of the men reporting frequent leakage or no control. By 24 months the proportion of men reporting this much leakage had decreased to 10.4%, although it increased to 13.9% 60 months after diagnosis (24 vs 60- month urinary control p 0.007). Although there was a slight worsening of certain urinary symptoms from years 2 to 5, the frequency of incontinence, number of urinary pads used and degree of urinary frequency remained relatively stable. Slightly more participants reported moderate to great bother from urinary incontinence at 60 months (at 24 months 13% vs 11%, p 0.4). Summary scores in the urinary function domain attained a nadir 6 months after diagnosis (59.0) but steadily increased through 24 months with little change at 60 months. Table 3lists patient reported sexual function and bother

3 S42 5-YEAR URINARY AND SEXUAL OUTCOMES AFTER PROSTATECTOMY TABLE 2. Urinary function and bother in 1,213 prostate cancer survivors who underwent radical prostatectomy in PCOS Measure (level) Baseline 6 Mos 12 Mos 24 Mos 60 Mos % Urinary control level: Total control Occasional leakage Frequent leakage No control % Incontinence frequency: None /Day or less Greater than 2/day % Pad use for incontinence: None /Day or Greater/day % Frequent need to urinate (less than 2 hrs): No/rarely Half time or less Greater than half time % How big a problem is incontinence: No problem Small Moderate to great Urinary function summary score (range 0 100) TABLE 3. Sexual function and bother in 1,213 prostate cancer survivors who underwent radical prostatectomy in PCOS Measure (level) Baseline 6 Mos 12 Mos 24 Mos 60 Mos % Sexual activity interest level: None Little/some Lot % Sexual activity frequency: None /Mo or greater /Wk or greater % Erections firm enough for intercourse: No Yes % Difficulty maintaining erection: None Little/some Lot No erections % How big a problem is sexual function: No problem Small Moderate to big Sexual function summary score (range 0 100) results. At baseline the majority of subjects (81%) reported erections firm enough for intercourse. However, 6 months after diagnosis only 9% of participants reported erections firm enough for intercourse. This number increased to 22% by 24 months after diagnosis. The 60-month survey was completed in 2000 and more subjects (28%) reported erections firm enough for intercourse (24 vs 60-month function p 0.003). A similar trend was noted in men reporting difficulties in maintaining erection with 26% stating that they had little or no difficulty maintaining erection at 24 months compared with 30% at 60 months. While erectile function slightly improved between 24 and 60 months after diagnosis, subjects reported minimal change in sexual activity. At 24 months 44% of the men reported no sexual activity and this proportion increased to 46% at 60 months (table 3). Finally, the proportion of men reporting that sexual function was a moderate or great problem decreased from 54% at 24 months to 46% at 60 months (p 0.001). Summary scores in the sexual function domain revealed a nadir 6 months after diagnosis (26), followed by a steady improvement through 60 months (39). The slight increase in sexual function scores from 24 to 60 months was not significant (p 0.47). In the multivariable model age was an important predictor of sexual function outcomes. Sexual function outcomes were stratified by nerve sparing status and age. Use of the nerve sparing technique was ascertained by reviewing operative reports in the medical record. Men in whom bilateral nerve sparing surgery was attempted were more likely to report erections firm enough for intercourse at 60 months than men whose records indicated they underwent unilateral or nonnerve sparing surgery (40% vs 23% and 23%, respectively, p 0.01). There was a significant trend effect of age on sexual function following bilateral nerve sparing surgery with 61% of 39 to 54-year-old men reporting erections firm enough for intercourse compared with 49% of those 55 to 59 years old, 44% of those 60 to 64 years old and 18% of those older than 65 years (p 0.001). The study cohort was queried regarding the use of various erectile aids during the 3 years prior to the 60-month survey (table 4). Atotal of 520 subjects (43%) had tried sildenafil, of whom 32% reported erections firm enough for intercourse and 13% reported that the medication helped a lot. Only 1 other aid, that is a penile prosthesis, was more effective than sildenafil in helping users achieve firm erections (sildenafil vs prosthesis 32% vs 47%). Of the men 46 (4%) had undergone surgical implantation of a penile prosthesis, of whom 47% reported erections firm enough for intercourse and 63%

4 5-YEAR URINARY AND SEXUAL OUTCOMES AFTER PROSTATECTOMY S43 TABLE 4. Erectile aid use and responses to item If you tried a particular erectile aid, how much did it help? in 1,213 prostate cancer survivors who underwent radical prostatectomy Erectile Aid No. Reporting That They Had Ever Used Particular Aid (%) % Reporting Erections Firm Enough for Intercourse % Response to How Much Did Particular Erectile Aid Help? A Lot Somewhat Not at All Unknown Vacuum erection device 302 (25) Intracavernous injection 204 (17) Sildenafil 520 (43) Other (alprostadil urethral suppository, 84 (7) yohimbine, etc) Psychotherapy 46 (4) Penile prosthesis 46 (4) stated that the prosthesis had helped a lot. Importantly the various treatment categories are not mutually exclusive. The patient reported response to sildenafil was then stratified by age, showing that men younger than 60 years were more likely to report that sildenafil use was helpful (table 5). Conversely sildenafil was much less helpful in men older than 60 years with the majority reporting no improvement in sexual function. When restricting analysis to the 128 men who underwent bilateral nerve sparing radical prostatectomy and used sildenafil, 63% of those 39 to 54 years old, 61% of those 55 to 59 years old, 46% of those 60 to 64 years old and 18% of those 65 years or older reported that sildenafil helped a lot or somewhat. DISCUSSION In PCOS a high proportion of men reported sexual dysfunction following radical prostatectomy. At 60 months of followup 55% of participants reported an inability to achieve any erections and only 28% had erections firm enough for intercourse. However, the proportion reporting adequate erections was significantly increased from the 22% noted at 24 months. The degree of sexual bother also decreased from 24 to 60 months. Furthermore, 14% of participants reported frequent urinary leakage or no urinary control 60 months after diagnosis. This represents a small but statistically significant increase from the 10% of men reporting this degree of incontinence at 24 months of followup. The observed improvement in erectile function at 60 months is somewhat surprising. Given that erectile dysfunction is associated with aging, 14 weexpected to see adecrease in sexual function in the 3-year interval between surveys. The unexpected improved function may be related to the introduction of sildenafil during this period and overall increased public awareness of erectile dysfunction resulting in more men seeking care for this problem. Alternately it may have been due to true late return of sexual function and/or related to recovery of the neurovascular bundles responsible for erection. 15 Finally, it is possible that the men lost to followup might have had significantly worse sexual outcomes than responders, leading to an overestimate of function at 5 years. The current study indicates that, while sildenafil can be effective in patients with prostate cancer treated with radical prostatectomy, they may not perceive it to be as helpful as previously reported. 16,17 InPCOS 45% of participants reported that sildenafil helped a lot or somewhat but only 31% of these subjects reported erections firm enough for intercourse. However, when we restricted our analysis to 192 men undergoing bilateral nerve sparing surgery, 49% of those who tried sildenafil (of whom many may also have used other erectile dysfunction aids) reported erections firm enough for intercourse. Furthermore, 62% of men younger than 60 years who underwent bilateral nerve sparing surgery and used sildenafil reported erections firm enough for intercourse. An updated report of Zippe et al described similar findings. 18 Briefly, PCOS observational data are suggestive that sildenafil improves erections in select patients after radical prostatectomy. Urinary incontinence is not unusual after radical prostatectomy, as previously reported. 1,19 However, the incidence of incontinence in PCOS is less than in these prior studies, likely related to our definition of continence as total control or occasional leakage. Others have studied various definitions of urinary continence and noted that the choice of definitioncansignificantlyaffectoutcomes. 20,21 Ifwedefined urinary continence as total control only, the proportion of men reporting urinary incontinence in the current study at 1 or 2 years after diagnosis would be similar to that in earlier reports. In the current study changes in the proportion of men experiencing moderate to great bother mirrored changes in the proportion of men reporting frequent leakage or no control, indicating that our choice of definition of urinary incontinence has validity. Briefly, PCOS data indicate that, while a small proportion of men who undergo radical prostatectomy experience some change in urinary continence more than 2 years after diagnosis, urinary function remains stable in the majority of surgical patients after year 2. The strengths of PCOS are its size, the population based and longitudinal design, and comprehensive outcomes assessments. However, there are some important potential limitations. A potential criticism of the current study is that baseline (pretreatment) assessments of urinary and sexual TABLE 5. Sildenafil use in 520 prostate cancer survivors who underwent radical prostatectomy and distribution of user responses to item How much did it help? stratified by age Age Group No. Survivors % A Lot % Somewhat % Not at All % Unknown %* %* Results adjusted for sampling weight based on the total number of eligible cases ascertained for the study and percents may not total 100% due to rounding (there was a significant trend of age on response to sildenafil at p 0.01). * Vs all others p 0.05.

5 S44 5-YEAR URINARY AND SEXUAL OUTCOMES AFTER PROSTATECTOMY function were done 6 months after diagnosis, which may have introduced recall bias. To assess the validity of retrospective recall in PCOS we compared the responses of 133 men who completed a questionnaire prior to treatment and again 6 months later. 22 Intraclass correlations varied between 0.7 and 0.82 for the disease specific domains of HRQOL, indicating that prostate cancer survivors accurately recall pretreatment function up to 6 months after treatment. The study is limited by the fact that medical record review cannot assess the quality of the individual nerve sparing procedure, or the surgical volume or expertise of the individual provider. Therefore, results regarding the influence of nerve sparing surgery should be interpreted with caution. Finally, the PCOS cohort is missing data at various time points in the data collection (10% to 18%). We tested for attrition bias by comparing trends in urinary and sexual function between subjects with complete data and those lost to followup. No significant differences were noted (data not shown) and, therefore, data were imputed for these subjects. The hot-deck imputation technique used in the current study has been applied in anumber of clinical settings in urology 23,24 and it has been shown to be valid. Interestingly when analysis was restricted to subjects with complete data, the results were quite similar to those using imputed data (data not shown). CONCLUSIONS To our knowledge the current study is the first population based, prospective, longitudinal study to document 5-year disease specific HRQOL and functional outcomes after radical prostatectomy in men with clinically localized prostate cancer. We found that 14% of subjects reported urinary incontinence and 71% were unable to achieve erections firm enough for intercourse. While a small minority of subjects experienced changes in urinary or sexual function between years 2 and 5 after prostatectomy, functional outcomes remained relatively stable in the majority of men. Because these findings are from a large, community based cohort of prostate cancer survivors, they may be more representative of the prostate cancer survivorship experience in the general population. These results should be helpful in counseling patients about therapy decisions for newly diagnosed, localized prostate cancer. REFERENCES 1. Steineck, G., Helgesen, F., Adolfsson, J., Dickman, P. W., Johansson, J. E., Norlen, B. J. et al: Quality of life after radical prostatectomy or watchful waiting. N Engl J Med, 347: 790, Catalona, W. J., Carvalhal, G. F., Mager, D. E. and Smith, D. S.: Potency, continence and complication rates in 1,870 consecutive radical retropubic prostatectomies. J Urol, 162: 433, Eastham, J. A., Kattan, M. W., Rogers, E., Goad, J. R., Ohori, M., Boone, T. B. et al: Risk factors for urinary incontinence after radical prostatectomy. J Urol, 156: 1707, Walsh, P. C., Marschke, P., Ricker, D. and Burnett, A. L.: Patient-reported urinary continence and sexual function after anatomic radical prostatectomy. Urology, 55: 58, Kao, T.-C., Cruess, D. F., Garner, D., Foley, J., Seay, T., Friedrichs, P. et al: Multicenter patient self-reporting questionnaire on impotence, incontinence and stricture after radical prostatectomy. J Urol, 163: 858, Litwin, M. S., Flanders, S. C., Pasta, D. J., Stoddard, M. L., Lubeck, D. P. and Henning, J. M.: Sexual function and bother after radical prostatectomy or radiation for prostate cancer: multivariate quality-of-life analysis from CaPSURE. Cancer of the Prostate Strategic Urologic Research Endeavor. Urology, 54: 503, Litwin, M. S., Pasta, D. J., Yu, J., Stoddard, M. L. and Flanders, S. C.: Urinary function and bother after radical prostatectomy or radiation for prostate cancer: a longitudinal, multivariate quality of life analysis from the Cancer of the Prostate Strategic Urologic Research Endeavor. J Urol, 164: 1973, Potosky, A. L., Harlan, L. C., Stanford, J. L., Gilliland, F. D., Hamilton, A. S., Albertsen, P. C. et al: Prostate cancer practice patterns and quality of life: the Prostate Cancer Outcomes Study. J Natl Cancer Inst, 91: 1719, Fowler, F. J., Jr., Barry, M. J., Lu-Yao, G., Roman, A., Wasson, J. and Wennberg, J. E.: Patient-reported complications and follow-up treatment after radical prostatectomy. The National Medicare Experience: (updated June 1993). Urology, 42: 622, Litwin, M. S., Hays, R. D., Fink, A., Ganz, P. A., Leake, B. and Brook, R. H.: The UCLA Prostate Cancer Index: development, reliability, and validity of a health-related quality of life measure. Med Care, 36: 1002, Talcott, J. A., Rieker, P., Clark, J. A., Propert, K. J., Weeks, J. C., Beard, C. J. et al: Patient-reported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study. J Clin Oncol, 16: 275, Liang, K. Y. and Zeger, S. L.: Longitudinal analysis using generalized linear models. Biometrika, 73: 13, Rubin, D. B.: Multiple Imputation for Nonresponse in Surveys. New York: John Wiley & Sons, Jonler, M., Moon, T., Brannan, W., Stone, N. N., Heisey, D. and Bruskewitz, R. C.: The effect of age, ethnicity and geographical location on impotence and quality of life. Br J Urol, 75: 651, Walsh, P. C. and Donker, P. J.: Impotence following radical prostatectomy: insight into etiology and prevention. J Urol, 128: 492, Zippe, C. D., Kedia, A. W., Kedia, K., Nelson, D. R. and Agarwal, A.: Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate (Viagra). Urology, 52: 963, Lowentritt, B. H., Scardino, P. T., Miles, B. J., Orejuela, F. J., Schatte, E. C., Slawin, K. M. et al: Sildenafil citrate after radical retropubic prostatectomy. J Urol, 162: 1614, Zippe, C. D., Jhaveri, F. M., Klein, E. A., Kedia, S., Pasqualotto, F. F., Kedia, A. et al: Role of Viagra after radical prostatectomy. Urology, 55: 241, Madalinska, J. B., Essink-Bot, M. L., de Koning, H. J., Kirkels, W. J., van der Maas, P. J. and Schroder, F. H.: Health-related quality-of-life effects of radical prostatectomy and primary radiotherapy for screen-detected or clinically diagnosed localized prostate cancer. J Clin Oncol, 19: 1619, Krupski, T. L., Saigal, C. S. and Litwin, M. S.: Variation in continence and potency by definition. J Urol, 170: 1291, Wei, J. T., Dunn, R. L., Marcovich, R., Montie, J. E. and Sanda, M. G.: Prospective assessment of patient reported urinary continence after radical prostatectomy. J Urol, 164: 744, Legler, J., Potosky, A. L., Gilliland, F. D., Eley, J. W. and Stanford, J. L.: Validation study of retrospective recall of disease-targeted function: results from the prostate cancer outcomes study. Med Care, 38: 847, Taylor, J. M., Cooper, K. L., Wei, J. T., Sarma, A. V., Raghunathan, T. E. and Heeringa, S. G.: Use of multiple imputation to correct for nonresponse bias in a survey of urologic symptoms among African-American men. Am J Epidemiol, 156: 774, Lubeck, D. P., Pasta, D. J., Flanders, S. C. and Henning, J. M.: Approaches to missing data inference results from CaPSURE: an observational study of patients with prostate cancer. Pharmacoeconomics, 15: 197, 1999