0022-5347/01/1652-0430/0 THE JOURNAL OF UROLOGY® Copyright © 2001 by AMERICAN UROLOGICAL ASSOCIATION, INC.®

Vol. 165, 430 – 435, February 2001 Printed in U.S.A.

THE DEVELOPMENT OF ERECTILE DYSFUNCTION IN MEN TREATED FOR PROSTATE CANCER TIMOTHY SIEGEL, JUDD W. MOUL,*,† MARIANNE SPEVAK, W. GREGORY ALVORD RAYMOND A. COSTABILE‡

AND

From the Urology Service, Department of Surgery, Walter Reed Army Medical Center, Washington, D.C., Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda and Contemporary BioStatistics, Silver Spring, Maryland, and Urology Service, Department of Surgery, Madigan Army Medical Center, Tacoma, Washington

ABSTRACT

Purpose: Erectile dysfunction is a common side effect in men treated for prostate cancer. Previously published studies document the incidence of erectile dysfunction in men treated for prostate cancer to be between 20% and 88%. To our knowledge a prospective evaluation focused on the development of erectile dysfunction in men treated for prostate cancer has not elucidated components of its chronology or risk factors. Materials and Methods: A centralized prospective database of 2,956 patients diagnosed with prostate cancer at a single institution was studied in regard to pretreatment and posttreatment erectile dysfunction. Of these 2,956 patients 802 had sufficient information regarding erectile function and comprise our study population. Factors analyzed in regard to treatment and erectile dysfunction include treatment modality, that is radical prostatectomy, external beam radiation therapy and watchful waiting, and ethnicity, patient age, clinical stage and tumor histological grade. Results: No significant difference was noted in the posttreatment erectile function between patients treated with radical prostatectomy or external beam radiation (10% versus 15%). Patients selecting watchful waiting had the lowest risk of erectile dysfunction. Clinical stage and race were significant predictors for the development of erectile dysfunction in the watchful waiting and external beam radiation treatment groups. Conclusions: Erectile dysfunction develops in greater than 80% of patients treated for prostate cancer. External beam radiation has the same risk for erectile dysfunction as radical prostatectomy. KEY WORDS: impotence, prostatic neoplasms, therapeutics

Prostate cancer will have a significant impact on men’s health in 2001, with an estimated 180,000 new cases diagnosed and almost 32,000 deaths attributed to this disease.1 There has been a modest decrease in the incidence of prostate cancer since 1997.1–3 The lifetime probability of developing prostate cancer is 1 in 6.1 The majority of men diagnosed with prostate cancer in the United States will elect treatment, and with it comes the potential risk of morbidity. Complications of prostate cancer therapy include erectile dysfunction, which can be significant, incontinence and bowel dysfunction. These complications may significantly diminish quality of life.4 – 8 Of patients receiving therapy 45% list the maintenance of quality of life as a principal concern when selecting prostate cancer therapy.9 Treatment selection

is often made after consideration of related side effects and subsequent quality of life. Erectile dysfunction will affect 16% to 82% of men following radical prostatectomy and 2% to 34% of those receiving external beam radiation therapy.10 –18 The anatomical nerve sparing radical prostatectomy technique is no guarantee that erectile function will be preserved.10 Previous studies have suggested a lower incidence in erectile dysfunction in patients treated with external beam radiation16 but they involved small numbers of patients with followup of less than 24 months. We prospectively examined the development of erectile dysfunction in 3 groups of men who had undergone therapy for prostate cancer. Patients were stratified based on selected therapy, including radical prostatectomy, external beam radiation and watchful waiting. Patients began therapy after discussions with their physicians regarding risks and benefits. The majority of patients were evaluated by radiation oncologists and urologists before receiving therapy in an equal access military health care system.

Accepted for publication August 25, 2000. The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the U. S. Army or the Department of Defense. Supported by Grant WU 2857-98 from the Center for Prostate Disease Research, a program of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland, funded by the U. S. Army Research and Material Command. MATERIALS AND METHODS * Requests for reprints: Center for Prostate Disease Research, 1530 E. Jefferson St., Rockville, Maryland 20852. As of September 1998, 2,956 patients were registered at † Financial interest and/or other relationship with Dade-Behring, Inc., Astra-Zeneca, Genotherapeutics, Metastatin Pharmaceuticals, the Center for Prostate Disease Research with the diagnosis of prostate cancer. The database was queried for patients Schering and TAP Pharmaceuticals. ‡ Financial interest and/or other relationship with Alza Pharma- diagnosed with prostate cancer before April 1998, allowing ceuticals, Pfizer, TAP Pharmaceuticals, Vivus Inc., Mentor, AMS for at least 6 months of followup. Since our goal was to and Novartis. compare rates of erectile dysfunction after treatment of clinEditor’s Note: This article is the second of 5 published in this ically localized prostate cancer, we eliminated from study all issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions patients with newly diagnosed clinical stages C and D prostate cancer, which was secondary to almost universal treaton pages 596 and 597. 430

THE DEVELOPMENT OF ERECTILE DYSFUNCTION IN MEN TREATED FOR PROSTATE CANCER

ment with hormones, and 1,692 patients with insufficient data on pretreatment and posttreatment erectile function, clinical stage, pathological grade or followup of less than 2 visits. We also eliminated from study 445 patients receiving primary hormonal therapy secondary to variability in protocols for this therapy at our institution. Patients treated with brachytherapy (9) and cryotherapy (8) were also eliminated from study due to short followup and small numbers. Thus, the final study cohort included 802 patients. As part of the Department of Defense Center for Prostate Disease Research program, Walter Reed Army Medical Center is 1 of 10 military medical centers designated to collect prospective and retrospective comprehensive clinical data on prostate cancer cases. As of 1 January 1994 data collection became prospective on new prostate cancer cases at Walter Reed Army Medical Center. Retrospective data were collected on patients with prostate cancer treated since 1970 through inpatient and outpatient record review and patient interviews. Standardized data collection forms for transrectal ultrasound biopsy, registration, staging, surgery, radiation therapy, hormonal therapy, cryotherapy, brachytherapy, followup and autopsy were developed. At each followup patients are questioned about erectile function and notation regarding erectile ability is made. Due to the referral patterns at our institution, patients choosing radiation therapy are initially seen at the urology clinic and then referred to the radiation therapy department. In addition, these patients are also followed after therapy at the urology and radiation therapy clinics using the same standardized collection forms. These data are entered into a custom designed relational database. This project and the Center for Prostate Disease Research database have been approved by the Walter Reed Department of Clinical Investigation Human Use Institutional Review and the Research Administration Department at the Uniformed Services University. To correlate grade and stage with the entire database interval we adhered to certain definitions. Grading of pathological specimens conformed to the Gleason system and was categorized as well (Gleason 2 to 4), moderately (5 to 7) and poorly (8 to 10) differentiated.19 Clinical staging using the Whitmore-Jewett staging system corresponded to the 1992 American Joint Committee on Cancer TNM classification.20 The T1c cancers were designated as clinical stage B0. Patients were divided into 3 treatment groups, including radical prostatectomy, external beam radiation therapy and watchful wait. A total of 419 patients underwent radical prostatectomy and had sufficient information regarding erectile function before and after therapy. Of these patients 42 underwent unilateral and 213 underwent bilateral nerve sparing radical prostatectomy, while in the remainder nerve sparing was either unknown or not attempted. Megavoltage external beam radiation was given to 319 men using 6 to 15 MV. photon energy. Treatment was delivered using either a 4-field box technique or bilateral 120 degree arcs with a median dose of 6,840 cGy. in 180 to 200 cGy. fractions. All patients were evaluable for erectile function before and after therapy. There were 64 patients in the watchful wait group and all had adequate data for evaluation of erectile function. They were followed every 3 to 4 months during year 1 after prostate cancer diagnosis and every 6 months thereafter. Patients were typically offered alternative prostate cancer therapy if they had 3 consecutive increases in serum prostate specific antigen or clinical progression. Erectile dysfunction was defined as erections consistently inadequate for vaginal penetration. Physicians were instructed to ask patients about the quality of erection at each followup visit. Based on physician questioning the followup form was marked as potency—yes, no, partial or unknown. Patients unable to describe the quality of erections or those for whom the physician did not record erectile dysfunction

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data were excluded from study. Patients with partial or unknown erectile function before treatment or watchful waiting were excluded from the start of study. Erectile function was recorded before and after therapy. Time of development of erectile dysfunction was noted and compared among groups. Patients were further stratified according to age, race, and pathological grade and clinical stage of disease. Data in our study were evaluated using data descriptive techniques, standard methods for rates and proportions, contingency table analyses, nonparametric methods and survival analysis. Pearson and likelihood ratio chi-square statistics were computed for tests concerning contingency tables and chi-square decompositions. As all interpretations of outcomes were in agreement, probability values from Pearson chi-square statistics are reported. Post hoc pair wise tests were performed following significant global results. We adopted a modified Bonferroni type strategy to control compounding type I error rates, and for some post hoc analyses we report probability values 0.01 and 0.05 as marginal. Kaplan-Meier plots were constructed for disease-free, defined as time to recurrence of disease, survival and other time to event analyses. Differences in survival distributions were assessed with the log-rank test, and commercial software was used to perform statistical calculations. RESULTS

Demographic and disease data of the 802 men are shown in table 1. Mean patient age was 66 years (range 44 to 88). Of the patients 500 (65%) were 70 years old or younger and 268 (34%) were older than 70. Mean followup for this cohort was 53 months (median 51) (see figure). Of the patients 190 (24%) were black, 563 (70%) were white and only 49 (6%) were Hispanic, Asian or of unknown ethnicity. The majority (89%) of patients in all treatment groups had clinical stage B disease, and most of the tumors were well (42%) and moderately (44%) differentiated. Before receiving therapy for prostate cancer 530 (69%) patients had erections sufficient for intercourse (table 2). Patients who selected radical prostatectomy had a significantly higher incidence (77%) of normal erectile function before therapy than the external beam radiation (61%) or watchful waiting (55%) group (p ⬍0.0001). Only 10% of patients who underwent radical prostatectomy regained spontaneous erections adequate for penetration after surgery. In the external beam radiation group 46 patients (15%) had sufficient erections after therapy, and in the watchful waiting group had 24 (38%) with adequate erections at last followup. Comparing erectile function among treatment groups after therapy there was a significant differ-

TABLE 1. Patient demographics No. (%) Pt. age: 70 Yrs. or younger Older than 70 yrs. Unknown Race: White Black Other/unknown Clinical stage: A B Unknown Pathological stage: Well Moderate Poor Unknown Treatment groups: Radical prostatectomy External beam radiation Watchful waiting

500 (62) 268 (33) 34 (5) 563 (70) 190 (24) 49 (6) 58 (7) 713 (89) 31 (4) 340 (42) 349 (44) 41 (5) 72 (9) 419 (52) 319 (40) 64 (8)

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Followup with primary treatment (Tx)

TABLE 2. Comparison of erectile function before therapy and of decrease in potency among cancer treatment groups No. Watchful Waiting (%)

No. Radical Prostatectomy (%)

No. External Beam Radiation (%)

Pretreatment potency: Yes 35 (54.7) 303 (77.3) No 29 (45.3) 89 (22.7) Posttreatment potency: Yes 24 (37.5) 39 (10.0) No 40 (62.5) (17% decrease) 353 (90.1) (67% decrease) 392 Totals 64 Radical prostatectomy versus watchful waiting p ⬍0.0001, external beam radiation versus watchful waiting p ⬍0.0001 and external beam radiation p ⫽ 0.2673 Pearson chi-square test.

192 (61.1) 123 (38.9) 46 (14.6) 269 (85.4) (46% decrease) 315 radical prostatectomy versus

TABLE 3. Comparison of decrease in potency across clinical stages

ence between radical prostatectomy versus watchful waiting (p ⬍0.0001) and external beam radiation versus watchful waiting (p ⬍0.0001). No significant difference in the percentage with erectile function after therapy (10% versus 15%) was noted between patients who underwent radical prostatectomy versus external beam radiation (p ⫽ 0.2673, table 2). Taking into account the higher pretreatment potency rate for those patients who underwent radical prostatectomy, there was a significant difference in decrease in potency between radical prostatectomy (67%) versus external beam radiation (46%, p ⬍0.0001). A total of 771 patients had adequate data for clinical stage and potency comparison. The majority of patients who received active treatment (92%) had clinical stage B disease. The development of erectile dysfunction after therapy based on clinical stage is shown in table 3. Using log-linear analysis pretreatment potency was independent of clinical stage (p ⫽ 0.6783). We then used a Pearson chi-square test and confirmatory contingency table analysis to compare clinical stage versus treatment received. Men undergoing radical prostatectomy had no significant difference in the erectile dysfunction rate when comparing stage A versus stage B disease (p ⫽ 0.334). Men who underwent external beam radiation also had no significant difference in erectile dysfunction based on clinical stage (p ⬍0.1297). In the watchful waiting group clinical stage had no relationship between potency at diagnosis and at followup. All treatment groups had a significant decrease in potency regardless of stage (table 3). When comparing the relationship of race with external beam radiation and the development of erectile dysfunction there was a significant difference among ethnic groups. Potency decreased in 38% of black (p ⬍0.0001) and in 51% of white (p ⬍0.0001) men. The lower decrease in potency for black compared to white men was statistically significant

No./Total (%) Stage A

Stage B

Radical prostatectomy: Pretreatment potency 15/18 (83.3) 288/374 (77.0) Posttreatment potency 1/18 (5.6) 38/374 (10.2) % Decrease 77 66.8 p Value 0.0002 ⬍0.0001 External beam radiation: Pretreatment potency 13/20 (65) 179/295 (60.7) Posttreatment potency 7/20 (35) 39/295 (13.2) % Decrease 30.0 47.5 p Value 0.0143 ⬍0.0001 Watchful waiting: Pretreatment potency 10/20 (50.0) 25/44 (56.8) Posttreatment potency 6/20 (30.0) 18/44 (40.9) % Decrease 20.0 15.9 p Value 0.0455 0.0348 There were 771 patients who had clinical stage and erectile function data available for analysis.

(p ⫽ 0.035, table 4). In black men who chose watchful waiting the pretreatment potency rate was 60%, and the followup potency rate was 40%, representing a nonsignificant loss of potency of 20% (p ⫽ 0.1573). White men had a significant change in erectile function during followup (17% decrease in potency, p ⬍0.01). However, when comparing black to white men these decreases in potency were not significantly different. The development of erectile dysfunction in each treatment group based on pathological grade is shown in table 5. Erectile dysfunction in the radical prostatectomy (p ⬍0.0001) and external beam radiation (p ⬍0.0001) groups was significant across all pathological grades. In those patients who chose watchful waiting the decrease in potency was not significant for either well or moderate pathological grades. Erectile dys-

THE DEVELOPMENT OF ERECTILE DYSFUNCTION IN MEN TREATED FOR PROSTATE CANCER TABLE 4. Comparison of decrease in potency versus ethnicity No./Total (%) Black Men Radical prostatectomy: Pretreatment potency 68/92 (73.9) Posttreatment potency 9/92 (8.7) % Decrease 65.2 p Value* ⬍0.0001 External beam radiation: Pretreatment potency 49/88 (55.7) Posttreatment potency 16/88 (18.1) % Decrease 37.5 p Value† ⬍0.0001 Watchful waiting: Pretreatment potency 6/10 (60.0) Posttreatment potency 4/10 (40.0) % Decrease 20.0 p Value 0.1573 * Percent decrease 65% versus 67% p ⫽ 0.743. † Percent decrease 38% versus 51% p ⫽ 0.035.

White Men 228/293 (77.8) 31/293 (10.6) 67.2 ⬍0.0001 138/217 (63.6) 27/217 (12.4) 51.2 ⬍0.0001 29/53 (54.7) 18/53 (34.0) 20.7 0.0126

function rates were compared among patient age groupings of younger than 60 years, 60 to 70 and older than 70. For this analysis 768 men had data adequate for erectile function and age. Patients in all age groups had a significant loss of erectile dysfunction after therapy (table 6). When stratified for age there was no difference in the development of erectile dysfunction. There was no decrease in potency in men younger than 60 years who chose watchful waiting. However, when comparing decrease in potency among age groups there was no significant difference (table 6). Although the majority of patients older than 70 years were in the external beam TABLE 5. Comparison of decrease in potency across pathological grades No./Total (%) Well

Moderate

Poor

Radical prostatectomy: Pretreatment potency 136/176 (77.3) 143/186 (77.9) 21/26 (80.8) Posttreatment potency 17/176 (9.7) 19/186 (10.3) 2/26 (7.7) % Decrease 67.6 66.7 73.1 p Value ⬍0.0001 ⬍0.0001 ⬍0.0001 External beam radiation: Pretreatment potency 83/125 (66.4) 78/143 (54.6) 11/14 (78.6) Posttreatment potency 22/125 (17.6) 18/143 (12.6) 1/14 (17.1) % Decrease 48.0 42.0 71.5 p Value ⬍0.0001 ⬍0.0001 ⬍0.0001 Watchful waiting: Pretreatment potency 21/39 (53.9) 12/20 (68.0) Not performed Posttreatment potency 14/39 (35.9) 8/20 (40.0) Not performed % Decrease 17.9 20.0 Not performed p Value 0.0348 0.0455 Not performed A total of 730 patients had pathological grade and erectile function data available for analysis.

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radiation and watchful waiting treatment groups, age had no significant effect on the decrease in potency seen across all treatment groups. DISCUSSION

The ability to preserve potency after prostate cancer therapy is controversial. Conflicting clinical evidence suggests that erectile dysfunction develops after radical prostatectomy in 10% to 90% of patients.10 –13 This disparity to preserve potency can be attributed to differences among the methods used to document and evaluate erectile dysfunction, surgical technique of prostatectomy, academic or community based surgical practice, and prospective or retrospective data collection.21 A similar disparity is noted in studies on preservation of potency after external beam radiotherapy.14, 17, 18 Potency rates have been documented after external beam radiation in 20% to 80% of patients. Explanations for the discrepancy in preserving potency after external beam radiation include lack of prospective data, variability in radiation dosing and delivery, and short-term followup (less than 24 months). A significant factor confounding the development of erectile dysfunction in patients with prostate cancer is its incidence in the aging male population. The risk of erectile dysfunction is estimated at 26/1,000 men annually, increasing with age, lower educational status, diabetes, heart disease and hypertension.22 Ascribing causality to a symptom, that is erectile dysfunction, with multiple risk factors may be difficult. Selection of treatment for prostate cancer is frequently based on the delineation of a risk-to-benefit ratio by the patient and physician.23 A most frequent and important risk of prostate cancer therapy is the development of erectile dysfunction. Long-term comparative studies are essential to compare the relative risk of developing erectile dysfunction with different prostate cancer therapies. The incidence of erectile dysfunction in our study population was highly dependent on whether a patient selected therapy for prostate cancer or was observed. No significant difference was noted in the high rate of developing erectile dysfunction in patients selecting prostatectomy or external beam radiation therapy. Other studies have reported a lower impact on sexual function in patients receiving external beam radiation but mean followup was only 12 to 24 months.24 Unlike radical prostatectomy in which erectile dysfunction is immediately apparent postoperatively, patients who receive external beam radiation experience a gradual decline in sexual function during a longer followup.25 Ionizing radiation is thought to initiate erectile dysfunction by accelerating microvascular angiopathy causing cavernosal fibrosis and dysfunction. This process may take years to

TABLE 6. Comparison of decrease in potency versus patient age Pt. Age (yrs.) No./Total 59 or Younger (%)

No./Total 60–70 (%)

No./Total 71 or Older (%)

Radical prostatectomy: Pretreatment potency 102/125 (81.6) 174/226 (77.0) 26/40 (65.0) Posttreatment potency 13/125 (10.4) 23/226 (10.2) 3/40 (7.5) % Decrease 71.2 66.8 57.5 p Value* ⬍0.0001 ⬍0.0001 ⬍0.0001 External beam radiation: Pretreatment potency 12/21 (57.1) 73/109 (67.0) 1,105/183 (57.4) Posttreatment potency 2/21 (9.5) 25/109 (9.3) 18/183 (9.8) % Decrease 47.6 44.0 47.5 p Value† 0.0001 ⬍0.0001 ⬍0.0001 Watchful waiting: Pretreatment potency 3/4 (75.0) 11/15 (73.0) 21/45 (46.7) Posttreatment potency 3/4 (75.0) 7/15 (46.7) 14/45 (31.1) % Decrease 0 26.7 15.6 p Value – 0.046 0.035 * Younger than 60 versus 60 to 70 (p ⫽ 0.398), younger than 60 versus older than 70 (p ⫽ 0.106) and 60 to 70 versus older than 70 (p ⫽ 0.254). † Younger than 60 versus 60 to 70 (p ⫽ 0.762), younger than 60 versus older than 70 (p ⫽ 0.995) and 60 to 70 versus older than 70 (p ⫽ 0.561).

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THE DEVELOPMENT OF ERECTILE DYSFUNCTION IN MEN TREATED FOR PROSTATE CANCER

cause clinically significant erectile dysfunction. Prostatectomy causes erectile dysfunction due to intraoperative damage to the neurovascular mechanism initiating erections. Erectile dysfunction develops immediately after prostatectomy with return of function in a variable fashion. Due to the differing times of onset of erectile dysfunction after external beam radiation or radical retropubic prostatectomy, it may be easier to document it after prostatectomy. We were concerned that patients referred for external beam radiation may have represented a different population than those electing radical prostatectomy. Pretreatment potency in patients choosing external beam radiation was lower than that in those undergoing radical prostatectomy. Patient age, clinical stage and pathological grade were similar for patients receiving external beam radiation or radical prostatectomy but those who chose watchful waiting were older. Information on co-morbid conditions that would represent risk factors for erectile dysfunction, including diabetes, hypertension, smoking and vascular disease, were not compared. Previous studies on potency after radical prostatectomy have shown greater ability to preserve potency in younger patients with low stage and low grade prostate cancer.12 Our study did not reveal a significant difference in the development of erectile dysfunction in patients receiving external beam radiation or radical prostatectomy based on age, clinical stage or pathological grade. The majority of patients in both treatment groups (80.8%) had well or moderately differentiated stage B prostate cancer. This stage and/or grade bias may have prevented us from discerning a difference in the development of erectile dysfunction in patients with stage A or C or poorly differentiated prostate cancer. A significant difference was noted in the development of erectile dysfunction after external beam radiation in black men. If cultural reporting bias was to blame for this difference, a similar bias should have been made in the radical prostatectomy group. Higher androgen levels and differences in androgen receptor density in the corpora cavernosa may protect the erectile mechanism from the damaging effects of external beam radiation. Further research is needed to determine if this difference by ethnicity is real. The low postoperative potency rates in our study population reflect an honest assessment of sexual morbidity in a large, tertiary, university backed, residency training program with multiple staff and resident surgeons. Of the patients 61% underwent a unilateral or bilateral nerve sparing procedure according to the prospective data sheet completed by the surgeons immediately postoperatively. Patients selecting watchful waiting had the greatest chance of preserving potency at our institution (see figure). The incidence of erectile dysfunction after watchful waiting followup (17% decrease in potency) is similar to that in an age matched population without known prostate cancer.22 Patients who elect nonnerve sparing radical prostatectomy or external beam radiation therapy should expect a high incidence (greater than 85%) of erectile dysfunction after therapy. CONCLUSIONS

In our study erectile dysfunction occurred in greater than 80% of patients treated for prostate cancer at 1 large hospital with multiple providers. Although we noted some significant differences when comparing black and white men, there were still consistently significant decreases in potency across all clinical stages, regardless of age, ethnicity and pathological grade. In our experience erectile dysfunction did not develop based on the type of therapy received, but whether a patient received active therapy for prostate cancer. REFERENCES

1. Landis, S. H., Murray, T., Bolden, S. et al: Cancer Statistics, 1999. CA Cancer J Clin, 49: 8, 1999

2. Denmeade, S. R. and Isaacs, J. T.: Prostate cancer: where are we and where are we going? Br J Urol, suppl., 79: 2, 1997 3. Kosary, C. L., Gloeckler Ries, L. A., Miller, B. A. et al: SEER Cancer Statistics Review, 1973–1992. Bethesda, Maryland: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute. Bethesda, Maryland, 1996 4. Lubeck, D. P., Litwin, M. S., Henning, J. M. et al: Changes in health-related quality of life in the first year after treatment for prostate cancer: results from CaPSURE. Urology, 53: 180, 1999 5. Lubeck, D. P., Litwin, M. S., Henning, J. M. et al: Measurement of health-related quality of life in men with prostate cancer: the CaPSure database. Qual Life Res, 6: 385, 1997 6. Testa, M. A. and Simonson, D. C.: Assessment of quality-of-life outcomes. N Engl J Med, 334: 835, 1996 7. Litwin, M. S., Hays, R. D., Fink, A. et al: Quality-of-life outcomes in men treated for localized prostate cancer. JAMA, 273: 129, 1995 8. Wasson, J. H., Cushman, C. C., Bruskewitz, R. C. et al: A structured literature review of treatment for localized prostate cancer. Prostate Disease Patient Outcome Research Team. Arch Fam Med, 2: 1487, 1993 9. Crawford, E. D., Bennett, C. L., Stone, N. N. et al: Comparison of perspectives on prostate cancer: analyses of survey data. Urology, 50: 366, 1997 10. Geary, E. S., Dendinger, T. E., Freiha, F. S. et al: Nerve sparing radical prostatectomy: a different view. J Urol, 154: 145, 1995 11. Walsh, P. C. and Donker, P. J.: Impotence following radical prostatectomy: insight into etiology and prevention. J Urol, 128: 492, 1982 12. Walsh, P. C., Partin, A. W. and Epstein, J. I.: Cancer control and quality of life following anatomical radical retropubic prostatectomy: results at 10 years. J Urol, 152: 1831, 1994 13. Walsh, P. C.: Anatomic radical prostatectomy: evolution of the surgical technique. J Urol, part 2, 160: 2418, 1998 14. Mantz, C., Song, P., Farhangi, E. et al: Potency probability following conformal megavoltage radiotherapy using conventional doses for localized prostate cancer. Int J Radiat Oncol Biol Phys, 37: 551, 1997 15. Fowler, F. J., Jr., Barry, M. J., Lu-Yao, G. et al: Patent-reported complications and follow-up treatment after radical prostatectomy. The national Medicare experience: 1988 –1990 (updated June 1993). Urology, 42: 622, 1993 16. Robinson, J. W., Dufour, M. S. and Fung, T. S.: Erectile functioning of men treated for prostate carcinoma. Cancer, 79: 538, 1997 17. Nguyen, L. N., Pollack, A. and Zagars, G. K.: Late effects after radiotherapy for prostate cancer in a randomized doseresponse study: results of a self-assessment questionnaire. Urology, 51: 991, 1998 18. Lilleby, W., Fossa, S., Waehre, H. R. et al: Long-term morbidity and quality of life in patients with localized prostate cancer undergoing definitive radiotherapy or radical prostatectomy. Int J Radiat Oncol Biol Phys, 43: 735, 1999 19. Gleason, D. F.: Histologic grading and clinical staging of prostatic carcinoma. In: Urologic Pathology: The Prostate. Edited by M. Tannenbaum. Philadelphia: Lea and Febiger, chapt. 9, pp. 171–197, 1977 20. Ohori, M., Wheeler, T. M. and Scardino, P. T.: The New American Joint Committee on Cancer and International Union Against Cancer TNM classification of prostate cancer. Clinicopathologic correlations. Cancer, 73: 104, 1994 21. Litwin, M. S., Lubeck, D. P., Henning, J. M. et al: Differences in urologist and patient assessments of health related quality of life in men with prostate cancer: results of the CaPSURE database. J Urol, 159: 1988, 1998 22. Johannes, C. B., Araujo, A. B., Feldman, H. A. et al: Incidence or erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts Male Aging Study. J Urol, 163: 460, 2000 23. Thompson, I. M.: Counseling patients with newly diagnosed prostate cancer. Oncology (Huntingt), 14: 119, 2000 24. McCammon, K. A., Kolm, P., Main, B. et al: Comparative quality-of-life analysis after radical prostatectomy or external beam radiation for localized prostate cancer. Urology, 54: 509, 1999 25. Litwin, M. S., Flanders, S. C., Pasta, D. J. et al: Sexual

THE DEVELOPMENT OF ERECTILE DYSFUNCTION IN MEN TREATED FOR PROSTATE CANCER 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, 1999 EDITORIAL COMMENT The authors report on erectile dysfunction after watchful waiting, radiation and surgery for prostate cancer using the Center for Prostate Disease Research database, which is an important national resource. The take home messages are the increase in erectile dysfunction was substantial and similar among patients undergoing radiation and radical prostatectomy, and those treated by surveillance had a significant albeit lesser increase in erectile dysfunction. These sobering results disagree with the common perception that erectile dysfunction is nonexistent with surveillance, and is infrequent after radiation and slightly greater with surgery. A number of study limitations may affect the results encountered. A validated erectile dysfunction instrument, that is one that has been proved to portray accurately erectile function, was not used, and the degree of erectile dysfunction was assessed by the physician, which is a method known to be associated with biased results. The wide variety of individuals performing nerve sparing prostatectomy may have also influenced the results. Additionally, the frequency of determination of erectile dysfunction was not reported nor was it reported exactly when it was assessed. The figure shows that, depending on when sexual function is assessed following initial prostate specific antigen management, differing results will be found. A constant decrease in sexual function is expected in older men, and the recov-

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ery pattern after treatment depends on the type of treatment. As such, a 3-month assessment would show many men impotent after radical prostatectomy while a later assessment would capture the gradual return of function. However, a later assessment would find a worsening quality of erections in men after radiation and would be confounded by the gradual background loss of sexual function. We have also found that if one is not careful in asking the question, men who are treated for erectile dysfunction, for example sildenafil, vacuum devices and so forth because of complete impotence, will respond that they are potent but it is with treatment. Despite the methodological weaknesses of this study, several other carefully conducted observational series have reached similar conclusions. Litwin et al found a significant increase in erectile dysfunction after radiation and surgery with gradual recovery after surgery but a recovery and then increase after radiation (reference 25 in article, see figure). Data were only available for 24 months. A study by McCammon et al, with a previously used instrument to assess sexual function, also revealed similar rates of erectile dysfunction after radiation and surgery (reference 24 in article). Similar to the present study, Stanford et al found in a sample of 1,291 men from 6 United States regions that radical prostatectomy was associated with a 60% risk of impotence at 18 months or greater postoperatively.1 Nerve sparing surgery had a minimal impact on potency. In the case of radiation Turner et al found only a 60% reduction in potency at 24-month followup.2 Finally, Jonler et al found that of men followed with surveillance who were potent at diagnosis 77% had a reduction in erectile function with only 29% of them able to attain an erection at the time of the questionnaire.3 What do we learn from this growing body of literature? Erectile dysfunction is common in all men after diagnosis of prostate cancer whether treated with surgery or radiation, or even if they choose surveillance alone. Variations in rates among series are more likely to be due to methods of assessment and patient selection than to actual differences in outcomes. The only absolute method to determine the actual difference in erectile dysfunction with various treatments will be randomized clinical trials using validated instruments with repetitive measures, which is a goal that is unlikely to be reached. Future observational studies should focus on better characterization of patients before treatment as co-morbidities dramatically affect the risk of erectile dysfunction. Ian M. Thompson, Jr. Division of Urology University of Texas Health Science Center San Antonio, Texas

Values are not precise, but reflect general trends in erectile function. Note differences from baseline erectile function and function following treatment depend on when assessment is conducted. Posttreatment function values are from Litwin et al (reference 25 in article). ED, erectile dysfunction. Rad Prost, radical prostatectomy. Post-op, postoperative. XRT, external beam radiation.

1. Stanford, J. L., Feng, Z., Hamilton, A. S. et al: Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study. JAMA, 283: 354, 2000 2. Turner, S. L., Adams, K., Bull, C. A. et al: Sexual dysfunction after radical radiation therapy for prostate cancer: a prospective evaluation. Urology, 54: 124, 1999 3. Jonler, M., Nielsen, O. S. and Wolf, H.: Urinary symptoms, potency, and quality of life in patients with localized prostate cancer followed up with deferred treatment. Urology, 52: 1055, 1998