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Natural history of voiding function after radical retropubic prostatectomy
ADULT UROLOGY
NATURAL HISTORY OF VOIDING FUNCTION AFTER RADICAL RETROPUBIC PROSTATECTOMY SHUNICHI NAMIKI, SHIGETO ISHIDOYA, SEIICHI SAITO, MAKOTO SATOH, TATSUO TOCHIGI, NAOMASA IORITANI, KOJI YOSHIMURA, AKITO TERAI, AND YOICHI ARAI
ABSTRACT Objectives. To report results from a 2-year longitudinal survey of lower urinary tract function and quality of life (QOL) in men after radical retropubic prostatectomy (RP) for localized prostate cancer. Methods. Between November 2001 and September 2003, self-report assessments were provided to 225 patients who underwent RP alone. The University of California Los Angeles Prostate Cancer Index (UCLA PCI), the International Prostate Symptom Score (IPSS), and the IPSS QOL score were administered before and 3, 6, 12, 18, and 24 months after RP. Results. The overall mean total IPSS and IPSS QOL score progressively improved with time. The mean scores of several components improved significantly postoperatively. No significant difference was observed in nocturia between the baseline assessment and any of the postoperative follow-up assessments. The IPSS of the younger patients continued to recover significantly more rapidly than that of the older patients after RP. According to the UCLA PCI scores, urinary function substantially declined just after RP and continued to recover but scored lower than the baseline. The mean total IPSS and IPSS QOL scores observed in men with a UCLA PCI urinary function score of 80 or more were significantly better than in men with scores less than 80 at 24 months postoperatively. Conclusions. Radical retropubic prostatectomy has a significant beneficial effect on lower urinary tract symptoms. The rate of improvement was lowest for nocturia among the seven symptoms of IPSS. Urinary continence after RP and age can affect the recovery of voiding function. UROLOGY 68: 142–147, 2006. © 2006 Elsevier Inc.
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adical retropubic prostatectomy (RP) has gained in popularity among Japanese urologists over the last decade and is a safe and effective treatment for localized prostate cancer.1 Stress urinary incontinence is a recognized complication of RP. The reported incontinence rates after RP range between 2.5% and 87%.2 The majority of men who underwent RP were between 50 and 70 years old. It has been shown that 44% of men with localized prostate cancer who present for RP have moderate to
Supported in part by a grant from the Ministry of Health and Welfare of Japan. From the Department of Urology, Tohoku University Graduate School of Medicine, Sendai; Department of Urology, Miyagi Cancer Center, Natori; Department of Urology, Sendai Shakaihoken Hospital, Sendai; and Department of Urology, Kurashiki Central Hospital, Kurashiki, Japan Reprint requests: Shunichi Namiki, M.D., Tohoku University Graduate School of Medicine, Department of Urology, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan. E-mail: namikin@ uro.med.tohoku.ac.jp Submitted: August 27, 2005, accepted (with revisions): January 10, 2006 © 2006 ELSEVIER INC. 142
ALL RIGHTS RESERVED
severe lower urinary tract symptoms (LUTS) that might be due to benign prostatic enlargement (BPE).3 In particular, nocturia is a major cause of sleep disturbance for men aged more than 50 years.4 Accordingly, evaluation of lower urinary tract function after RP is as important as that of urinary incontinence. Previously, we detailed the changes of urinary symptoms in men followed for 1 year after RP and found possible adverse effects of RP on nocturia and voiding frequency symptoms in selected patients.5 We expanded the study population and follow-up time to elucidate the intermediate-term natural history of voiding function after RP. MATERIAL AND METHODS Between November 2001 and September 2003, 255 men who underwent RP for localized prostate cancer were enrolled at Tohoku University Hospital and two affiliated hospitals and at Kurashiki Central Hospital. The RP was performed with essentially the same technique as originally described by Walsh.6 0090-4295/06/$32.00 doi:10.1016/j.urology.2006.01.030
To properly assess urinary function, LUTS and symptomspecific quality of life (QOL) were assessed with the International Prostate Symptom Score (IPSS) and IPSS QOL score.7 Urinary continence was estimated with the urinary function and bother domain of the University of California Los Angeles Prostate Cancer Index (UCLA PCI), which assesses prostatespecific health-related QOL.8 The questionnaire had already been translated into Japanese, and its validity and reliability had been previously tested.9 All patients were informed of their cancer diagnosis before being asked to fill out the questionnaires. Every patient who agreed to participate in this study received from their urologist a questionnaire, an informed consent form, and a prepaid envelope for returning the questionnaire. The baseline interview was conducted after the diagnosis. Follow-up interviews were conducted in person at scheduled study visits of 3, 6, 12, 18, and 24 months after RP. Statistical analyses were made with repeated-measure analyses of variance (ANOVA), MannWhitney U test, or chi-square test to compare the effects of RP. P ⬍0.05 was considered statistically significant.
RESULTS BACKGROUND CHARACTERISTICS OF THE STUDY GROUP Although 255 patients were asked to participate in the study, 30 patients who received hormonal ablation, postoperative radiotherapy, or both were excluded because the additional therapy could possibly affect urinary function. Thus, we analyzed 225 eligible patients who received RP alone. The mean (plus or minus standard deviation) patient age was 67.0 ⫾ 5.8 years (median 67 years; range, 48 to 78 years). At the time of the survey, 99% of the men were married or lived with a partner, and 49% were employed. The respondents showed a median preoperative prostate-specific antigen level of 8.4 ng/mL (range, 3.4 to 41 ng/mL). Histopathologically confirmed organ-confined disease was found in 81% (n ⫽ 183) of the surgical specimens. Most patients (81%) experienced comorbidities, but these comorbidities were well controlled. Of the 225 patients, 63 (28%) did not undergo nerve preservation, and 162 (72%) underwent either unilateral (112 patients) or bilateral (63 patients) nervesparing surgery. ASSESSMENT OF IPSS AND UCLA PCI The changes in voiding symptoms and urinary incontinence are shown in Table I. A total of 100%, 94%, 83%, 87%, 75%, and 84% of the patients filled out the questionnaire at baseline and 3, 6, 12, 18, and 24 months after RP, respectively. The mean total IPSS and IPSS QOL score showed statistically significant improvement after 6 months after RP. At 24 months after RP, 52% of the patients claimed to have “improved” (a 2-point or greater decrease), 21% remained “stable” (a change of ⫺1 to 1 point), and 26% claimed to have “worsened” (a 2-point or greater increase) compared with baseline. The patients who showed improved IPSS after RP reported better IPSS QOL scores. When the group UROLOGY 68 (1), 2006
was divided into those with initially mild (IPSS less than 8, 102 patients) or moderate/severe symptoms (IPSS 8 or greater, 113 patients), there was no change in the former (4.5 versus 4.2, P ⫽ 0.89) but a significant reduction in the latter (13.3 versus 8.2, P ⬍0.001) between before and after RP at 24 months. The mean scores of several components, such as emptying, intermittency, urgency, slow stream, and straining, improved significantly postoperatively. There were no differences in voiding frequency at 3, 6, and 12 months after RP compared with baseline. At 18 months or later, however, a significant improvement of voiding frequency appeared. The score of nocturia was substantially worse at 3 months than at baseline (P ⫽ 0.009). No significant difference was observed between baseline and 6 months or later. In detail, the rate of improvement in storage symptoms score, voiding symptom score, postvoid symptom score, and nocturia symptom score was 39%, 48%, 18%, and 6%, respectively. According to the UCLA PCI scores, the urinary function that reflects leakage substantially declined at 3 months and continued to recover at 6, 12, 18, and 24 months but scored lower than baseline (P ⬍0.001, respectively). Urinary bother had a significantly worse score at 3 months than that at baseline (P ⫽ 0.036). At 6 months after surgery, however, it returned to the baseline score (P ⬎0.05). With the definition of continence based on pad requirement, 96%, 51%, 84%, 88%, 89%, and 92% of men were continent at baseline and 3, 6, 12, 18, and 24 months postoperatively, respectively. The mean total IPSS observed in men with a UCLA PCI urinary function score of 80 or more was significantly better than in those with score less than 80 at 24 months postoperatively (5.1 versus 8.8, P ⬍0.001). Similarly, the patients with urinary function scores of 80 or more reported better IPSS QOL scores than those with scores less than 80 (2.1 versus 4.0, P ⬍0.001). Figure 1A–F shows the mean IPSS, IPSS QOL, storage, voiding, postvoid symptoms, and nocturia scores, stratified by age. At baseline, there were no significant differences in IPSS and IPSS QOL scores between the younger patients (65 years old or younger, n ⫽ 74) and the older patients (older than 65 years, n ⫽ 151) (P ⫽ 0.412, 9.3 versus 10.0 and P ⫽ 0.422, 3.7 versus 3.9, respectively). At 24 months, RP had a favorable impact on LUTS for both age groups (both P ⬍0.01) (Fig. 1A). Furthermore, there was a tendency for the IPSS of the younger patients to continue to recover more rapidly than that of the older patients at 2 years after RP (P ⫽ 0.006, repeated-measure ANOVA). With regard to the IPSS QOL score, RP was associated with significant improvements in the score for both younger and older patients compared with baseline (both P ⬍0.01). However, the patterns of 143
TABLE I. IPSS QOL score, and UCLA PCI urinary domain of patients who underwent radical prostatectomy P Value vs Baseline
Parameter Total IPSS Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Emptying Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Voiding frequency Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Intermittency Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Urgency Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Slow stream Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Straining Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Nocturia Baseline 3 mo 6 mo 12 mo 18 mo 24 mo
144
9.07 ⫾ 6.08 7.76 ⫾ 5.05 6.94 ⫾ 4.86 6.60 ⫾ 5.58 6.35 ⫾ 5.20 6.55 ⫾ 5.69
— 0.113 0.002 ⬍0.001 ⬍0.001 ⬍0.001
1.08 ⫾ 1.21 0.92 ⫾ 1.06 0.78 ⫾ 1.17 0.58 ⫾ 1.24 0.59 ⫾ 0.99 0.66 ⫾ 1.03
— 0.402 0.007 ⬍0.001 ⬍0.001 0.002
1.58 ⫾ 1.36 1.85 ⫾ 1.37 1.54 ⫾ 1.29 1.50 ⫾ 1.38 1.25 ⫾ 1.35 1.13 ⫾ 1.33
— 0.087 0.844 0.340 0.015 0.003
0.85 ⫾ 1.21 0.62 ⫾ 1.10 0.39 ⫾ 0.82 0.52 ⫾ 1.01 0.39 ⫾ 0.76 0.58 ⫾ 1.13
— 0.054 ⬍0.001 0.001 ⬍0.001 0.019
1.03 ⫾ 1.18 0.92 ⫾ 1.21 0.85 ⫾ 1.04 0.78 ⫾ 1.15 0.81 ⫾ 1.25 0.58 ⫾ 1.02
— 0.324 0.248 0.011 0.036 ⬍0.001
1.91 ⫾ 1.64 0.90 ⫾ 1.22 0.95 ⫾ 1.38 0.98 ⫾ 1.36 0.92 ⫾ 1.37 0.93 ⫾ 1.23
— ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
0.90 ⫾ 1.31 0.57 ⫾ 0.97 0.69 ⫾ 1.10 0.56 ⫾ 1.08 0.60 ⫾ 0.99 0.64 ⫾ 1.25
— 0.059 0.048 0.003 0.018 0.036
1.73 ⫾ 0.97 1.97 ⫾ 1.01 1.75 ⫾ 0.82 1.68 ⫾ 0.95 1.79 ⫾ 1.05 1.89 ⫾ 1.13
— 0.091 0.685 0.579 0.802 0.360
TABLE I. Continued P Value vs Baseline
Parameter Quality of life score Baseline 3 mo 6 mo 12 mo 18 mo 24 mo UCLA PCI Urinary function Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Urinary bother Baseline 3 mo 6 mo 12 mo 18 mo 24 mo
3.73 ⫾ 1.60 3.62 ⫾ 1.46 3.11 ⫾ 1.43 2.93 ⫾ 1.42 2.89 ⫾ 1.58 2.84 ⫾ 1.48
— 0.483 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
94.8 ⫾ 14.0 68.5 ⫾ 24.3 83.0 ⫾ 21.2 84.3 ⫾ 18.4 84.6 ⫾ 18.8 85.0 ⫾ 18.8
— ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
85.7 ⫾ 23.8 78.6 ⫾ 27.3 88.5 ⫾ 22.8 90.4 ⫾ 15.6 89.7 ⫾ 19.5 87.7 ⫾ 19.8
— 0.036 0.336 0.059 0.315 0.836
KEY: UCLA PCI ⫽ University of California, Los Angeles Prostate Cancer Index; IPSS ⫽ International Prostate Symptom Score; QOL ⫽ quality of life. Data are presented as mean ⫾ standard deviation.
alteration in the IPSS QOL score were different for the two age groups (P ⬍0.001, repeated-measure ANOVA) (Fig. 1B). The younger patients showed significantly better storage symptoms than the older patients throughout the postoperative period (P ⬍0.05) (Fig. 1C). Although each group showed improved symptoms of voiding frequency after RP, the younger patients showed fewer episodes of voiding symptoms (P ⬍0.001, repeated-measure ANOVA) (Fig. 1D). Although the postvoid symptoms at baseline seemed to be equivalent in the two age groups, the younger patients showed significantly greater improvement throughout the postoperative period (P ⬍0.05) (Fig. 1E). The older men claimed more frequent nocturnal voiding than the younger men before RP (P ⫽ 0.009, 1.3 versus 1.8). On the other hand, neither group had significant changes in nocturia throughout the postoperative period. Moreover, the younger men claimed significantly more episodes of nocturia at 3 months than at baseline (1.3 versus 1.9, P ⫽ 0.032). There were no differences between the younger and older men in terms of postoperative nocturia (Fig. 1F). Because among the categories only nocturia showed no improvement throughout the study period, the impact of RP on nocturia was further analyzed. The 225 consecutive men were divided into two groups according to baseline nocturia symptom score: group N1 with nocturia scores of 0 or 1 (n ⫽ 98), and group N2 with a score of 2 or more UROLOGY 68 (1), 2006
FIGURE 1. (A–F) Longitudinal changes of lower urinary tract symptoms over time, according to patient age. (A) Total International Prostate Symptom Score; (B) quality of life score; (C) storage symptoms score; (D) voiding symptoms score; (E) postvoid symptoms score; (F) nocturia symptom score; (G) longitudinal change of nocturia symptom score over time, stratified by baseline symptom score: N1 with nocturia score of 0 or 1, and N2 with nocturia score of 2 or more.
(n ⫽ 127) (Fig. 1G). The N1 group experienced a significant deterioration of nocturia at 3 months (versus baseline, P ⬍0.001). Then, their nocturia gradually decreased with time, but it never returned to the baseline level (baseline versus any time point, P ⬍0.01). In group N2, however, the nocturia symptom score was equivalent between baseline and the postoperative periods of 3 and 6 UROLOGY 68 (1), 2006
months. After 12 months, the nocturia score improved progressively and thereafter remained stable (P ⬍0.01). COMMENT Our study represents a 2-year, prospective, consecutive series in which we examined the impact of 145
RP on LUTS. The mean total IPSS and IPSS QOL score showed significant improvement after RP. Especially in men with moderate or severe urinary symptoms, RP improved the total IPSS more significantly, as reported in previous studies.5,10 The positive effects of RP on LUTS had a greater beneficial impact than the negative effects of stress urinary incontinence. This improvement in the IPSS, however, was not noted in men with no or mild symptoms but rather in those with moderate to severe symptoms. Therefore, LUTS in men selected for RP might be attributable to underlying BPE rather than prostate cancer. At baseline, the older patients reported more increased frequency of nocturnal voiding than the younger patients, which was similar to the results reported by other groups.11 It is noteworthy that nocturia did not improve, whereas a substantial improvement of other urinary symptoms was observed after RP. Furthermore, patients experienced a significant deterioration of the nocturia score just after RP. It has been reported that nocturia is the least specific symptom associated with BPE and the least sensitive to treatment for BPE.12 The current study revealed that postprostatectomy nocturia showed similar tendencies. Previous communitybased studies reported two or more episodes of nocturia in 24% to 45% of elderly men.13 The present study found that more than 50% of the patients arose to void two or more times at night 24 months after RP. These findings and ours suggest that nocturia is influenced markedly not only by obstruction of the prostatic urethra but also by bladder capacity, detrusor- and sphincter-related factors, or increased production of urine at night. We compared these results with those from our previous study, which included the initial 152 patients with 1-year follow-up after RP.5 In our current study, the “voiding frequency” composite score tended to increase in the early postoperative period, but significant improvement was observed in the second year after RP. Recently, several investigators reported that, after RP, a number of patients are affected by impaired detrusor contractility, which might coexist with sphincter weakness, bladder overactivity, and/or decreased compliance.14,15 Wide anatomic dissection around the prostate during RP might disrupt the afferent and efferent innervation of the trigone and neobladder neck and cause partial denervation of the detrusor muscle. Our finding suggests that RP can induce voiding frequency complications immediately after surgery but that these decrease with time. According to our survey based on the UCLA PCI, it seems to be difficult for patients treated with RP to return completely to baseline urinary continence. However, approximately 90% wore no pads. Consequently, the recovery from urinary bother was ob146
served early at 6 months and in the remaining postoperative periods, showing that postoperative incontinence, if any, was minimal in the majority of the patients. In line with our results, Lepor et al.16 stated that 97% of men treated with RP regained continence by 24 months after RP. In addition, stress urinary incontinence after RP had an adverse effect on LUTS. Jung et al.17 found that a significant decrease in bladder compliance and detrusor overactivity might be sustained by bladder denervation during RP or by a deficient sphincter with urine leakage into the urethra, stimulating urethral afferents. These results imply that stress incontinence can induce and/or increase detrusor instability. The present study extended observations on the impact of RP on IPSS, IPSS QOL score, storage, voiding, postvoid symptoms, and nocturia by examining the influence of the age of the patients. Our study confirmed that younger men seemed to recover in terms of the IPSS and IPSS QOL score more rapidly than the older patients after 2 years. To our knowledge, no study to date has evaluated the impact of age on LUTS after RP. Several studies have stated that urinary symptoms depended on age and the presence of BPE.18,19 In addition, detrusor overactivity is one of the most common causes of LUTS and is often associated with bladder outlet obstruction and BPE. This observation might be explained by sphincter weakness, bladder overactivity, and/or decreased compliance, as well as other conditions, such as comorbidities. The lack of objective data, such as prostate volume, uroflow variables, voiding volume, and postvoid residual is a limitation of the present study design. Furthermore, Blanker et al.20 stressed that the IPSS underestimated the prevalence of nocturia, that a lack of agreement existed between the subjective and objective data on nocturnal frequency, and that frequency–volume charts were the most valid instrument for diagnosing nocturia. The UCLA PCI and IPSS were selected because they seem to be the most widely used instruments for capturing these outcomes in clinical research. Despite these limitations, these results will assist physicians in providing clinically relevant information to patients who elect surgery. We emphasize that it is important to assess LUTS, as well as urinary incontinence, after RP. REFERENCES 1. Arai Y, Egawa S, Tobisu K, et al: Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan. BJU Int 85: 287–294, 2000. 2. Foote J, Yun S, and Leach GE: Postprostatectomy incontinence. Pathology, evaluation, and management. Urol Clin North Am 18: 229 –241, 1991. 3. Schwartz EJ, and Lepor H: Radical retropubic prostatectomy reduces symptom scores and improves quality of life UROLOGY 68 (1), 2006
in men with moderate and severe lower urinary tract symptoms. J Urol 161: 1185–1188, 1999. 4. Weiss JP, and Blaivas JG: Nocturia. J Urol 163: 5–12, 2000. 5. Namiki S, Saito S, Ishidoya S, et al: Adverse effect of radical prostatectomy on nocturia and voiding frequency symptoms. Urology 66: 147–151, 2005. 6. Walsh PC: Anatomical radical retropubic prostatectomy, in Walsh PC, Retik AB, Vaughan ED Jr, et al (Eds): Campbell’s Urology, 7th ed. Philadelphia, WB Saunders, 1998, pp 2565–2588. 7. Barry MJ, Fowler FJ, O’Leary MP, et al: The American Urological Association symptom index for benign prostatic hyperplasia. J Urol 148: 1549 –1577, 1992. 8. Litwin MS, Hays RD, Fink A, et al: The UCLA Prostate Cancer Index: development, reliability, and validity of a healthrelated quality of life measure. Med Care 36: 1002–1012, 1998. 9. Kakehi Y, Kamoto T, Ogawa O, et al: Development of Japanese version of the UCLA Prostate Cancer Index: a pilot validation study. Int J Clin Oncol 7: 306 –311, 2002. 10. Lepor H, and Kaci L: The impact of open radical retropubic prostatectomy on continence and lower urinary tract symptoms: a prospective assessment using validated self-administered outcome instruments. J Urol 171: 1216 –1219, 2004. 11. Yoshimura K, Terada N, Matsui Y, et al: Prevalence of and risk factors for nocturia: analysis of a health screening program. Int J Urol 11: 282–287, 2004. 12. Homma Y, Yamaguchi T, Kondo Y, et al: Significance of nocturia in the International Prostate Symptom Score for benign prostatic hyperplasia. J Urol 167: 172–176, 2002.
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13. Fultz NH, and Herzog AR: Epidemiology of urinary symptoms in the geriatric population. Urol Clin North Am 23: 1–10, 1996. 14. Gohma MA, and Boone TB: Voiding patterns in patients with post-prostatectomy incontinence: urodynamic and demographic analysis. J Urol 169: 1766 –1769, 2003. 15. Hellstrom P, Lukkarinen O, and Kontturi M: Urodynamics in radical retropubic prostatectomy. Scand J Urol Nephrol 23: 21–24, 1989. 16. Lepor H, Kaci L, and Xue X: Continence following radical retropubic prostatectomy using self-reporting instruments. J Urol 171: 1212–1215, 2004. 17. Jung SY, Fraser MO, Ozawa H, et al: Urethral afferent nerve activity affects the micturition reflex; implication for the relationship between stress incontinence and detrusor instability. J Urol 162: 204 –212, 1999. 18. Andersson SO, Rashidkhani B, Karlberg L, et al: Prevalence of lower urinary tract symptoms in men aged 45-79 years: a population-based study of 40 000 Swedish men. BJU Int 94: 323–331, 2004. 19. Tubaro A, La Vecchia C, for the Uroscreening Study Group: The relation of lower urinary tract symptoms with lifestyle factors and objective measures of benign prostatic enlargement and obstruction: an Italian study. Eur Urol 45: 767–772, 2004. 20. Blanker MH, Bohnen AM, Groenveld FPMJ, et al: Normal voiding patterns and determinants of increased diurnal and nocturnal voiding frequency in elderly men. J Urol 164: 1201–1205, 2000.
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NATURAL HISTORY OF VOIDING FUNCTION AFTER RADICAL RETROPUBIC PROSTATECTOMY SHUNICHI NAMIKI, SHIGETO ISHIDOYA, SEIICHI SAITO, MAKOTO SATOH, TATSUO TOCHIGI, NAOMASA IORITANI, KOJI YOSHIMURA, AKITO TERAI, AND YOICHI ARAI
ABSTRACT Objectives. To report results from a 2-year longitudinal survey of lower urinary tract function and quality of life (QOL) in men after radical retropubic prostatectomy (RP) for localized prostate cancer. Methods. Between November 2001 and September 2003, self-report assessments were provided to 225 patients who underwent RP alone. The University of California Los Angeles Prostate Cancer Index (UCLA PCI), the International Prostate Symptom Score (IPSS), and the IPSS QOL score were administered before and 3, 6, 12, 18, and 24 months after RP. Results. The overall mean total IPSS and IPSS QOL score progressively improved with time. The mean scores of several components improved significantly postoperatively. No significant difference was observed in nocturia between the baseline assessment and any of the postoperative follow-up assessments. The IPSS of the younger patients continued to recover significantly more rapidly than that of the older patients after RP. According to the UCLA PCI scores, urinary function substantially declined just after RP and continued to recover but scored lower than the baseline. The mean total IPSS and IPSS QOL scores observed in men with a UCLA PCI urinary function score of 80 or more were significantly better than in men with scores less than 80 at 24 months postoperatively. Conclusions. Radical retropubic prostatectomy has a significant beneficial effect on lower urinary tract symptoms. The rate of improvement was lowest for nocturia among the seven symptoms of IPSS. Urinary continence after RP and age can affect the recovery of voiding function. UROLOGY 68: 142–147, 2006. © 2006 Elsevier Inc.
R
adical retropubic prostatectomy (RP) has gained in popularity among Japanese urologists over the last decade and is a safe and effective treatment for localized prostate cancer.1 Stress urinary incontinence is a recognized complication of RP. The reported incontinence rates after RP range between 2.5% and 87%.2 The majority of men who underwent RP were between 50 and 70 years old. It has been shown that 44% of men with localized prostate cancer who present for RP have moderate to
Supported in part by a grant from the Ministry of Health and Welfare of Japan. From the Department of Urology, Tohoku University Graduate School of Medicine, Sendai; Department of Urology, Miyagi Cancer Center, Natori; Department of Urology, Sendai Shakaihoken Hospital, Sendai; and Department of Urology, Kurashiki Central Hospital, Kurashiki, Japan Reprint requests: Shunichi Namiki, M.D., Tohoku University Graduate School of Medicine, Department of Urology, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan. E-mail: namikin@ uro.med.tohoku.ac.jp Submitted: August 27, 2005, accepted (with revisions): January 10, 2006 © 2006 ELSEVIER INC. 142
ALL RIGHTS RESERVED
severe lower urinary tract symptoms (LUTS) that might be due to benign prostatic enlargement (BPE).3 In particular, nocturia is a major cause of sleep disturbance for men aged more than 50 years.4 Accordingly, evaluation of lower urinary tract function after RP is as important as that of urinary incontinence. Previously, we detailed the changes of urinary symptoms in men followed for 1 year after RP and found possible adverse effects of RP on nocturia and voiding frequency symptoms in selected patients.5 We expanded the study population and follow-up time to elucidate the intermediate-term natural history of voiding function after RP. MATERIAL AND METHODS Between November 2001 and September 2003, 255 men who underwent RP for localized prostate cancer were enrolled at Tohoku University Hospital and two affiliated hospitals and at Kurashiki Central Hospital. The RP was performed with essentially the same technique as originally described by Walsh.6 0090-4295/06/$32.00 doi:10.1016/j.urology.2006.01.030
To properly assess urinary function, LUTS and symptomspecific quality of life (QOL) were assessed with the International Prostate Symptom Score (IPSS) and IPSS QOL score.7 Urinary continence was estimated with the urinary function and bother domain of the University of California Los Angeles Prostate Cancer Index (UCLA PCI), which assesses prostatespecific health-related QOL.8 The questionnaire had already been translated into Japanese, and its validity and reliability had been previously tested.9 All patients were informed of their cancer diagnosis before being asked to fill out the questionnaires. Every patient who agreed to participate in this study received from their urologist a questionnaire, an informed consent form, and a prepaid envelope for returning the questionnaire. The baseline interview was conducted after the diagnosis. Follow-up interviews were conducted in person at scheduled study visits of 3, 6, 12, 18, and 24 months after RP. Statistical analyses were made with repeated-measure analyses of variance (ANOVA), MannWhitney U test, or chi-square test to compare the effects of RP. P ⬍0.05 was considered statistically significant.
RESULTS BACKGROUND CHARACTERISTICS OF THE STUDY GROUP Although 255 patients were asked to participate in the study, 30 patients who received hormonal ablation, postoperative radiotherapy, or both were excluded because the additional therapy could possibly affect urinary function. Thus, we analyzed 225 eligible patients who received RP alone. The mean (plus or minus standard deviation) patient age was 67.0 ⫾ 5.8 years (median 67 years; range, 48 to 78 years). At the time of the survey, 99% of the men were married or lived with a partner, and 49% were employed. The respondents showed a median preoperative prostate-specific antigen level of 8.4 ng/mL (range, 3.4 to 41 ng/mL). Histopathologically confirmed organ-confined disease was found in 81% (n ⫽ 183) of the surgical specimens. Most patients (81%) experienced comorbidities, but these comorbidities were well controlled. Of the 225 patients, 63 (28%) did not undergo nerve preservation, and 162 (72%) underwent either unilateral (112 patients) or bilateral (63 patients) nervesparing surgery. ASSESSMENT OF IPSS AND UCLA PCI The changes in voiding symptoms and urinary incontinence are shown in Table I. A total of 100%, 94%, 83%, 87%, 75%, and 84% of the patients filled out the questionnaire at baseline and 3, 6, 12, 18, and 24 months after RP, respectively. The mean total IPSS and IPSS QOL score showed statistically significant improvement after 6 months after RP. At 24 months after RP, 52% of the patients claimed to have “improved” (a 2-point or greater decrease), 21% remained “stable” (a change of ⫺1 to 1 point), and 26% claimed to have “worsened” (a 2-point or greater increase) compared with baseline. The patients who showed improved IPSS after RP reported better IPSS QOL scores. When the group UROLOGY 68 (1), 2006
was divided into those with initially mild (IPSS less than 8, 102 patients) or moderate/severe symptoms (IPSS 8 or greater, 113 patients), there was no change in the former (4.5 versus 4.2, P ⫽ 0.89) but a significant reduction in the latter (13.3 versus 8.2, P ⬍0.001) between before and after RP at 24 months. The mean scores of several components, such as emptying, intermittency, urgency, slow stream, and straining, improved significantly postoperatively. There were no differences in voiding frequency at 3, 6, and 12 months after RP compared with baseline. At 18 months or later, however, a significant improvement of voiding frequency appeared. The score of nocturia was substantially worse at 3 months than at baseline (P ⫽ 0.009). No significant difference was observed between baseline and 6 months or later. In detail, the rate of improvement in storage symptoms score, voiding symptom score, postvoid symptom score, and nocturia symptom score was 39%, 48%, 18%, and 6%, respectively. According to the UCLA PCI scores, the urinary function that reflects leakage substantially declined at 3 months and continued to recover at 6, 12, 18, and 24 months but scored lower than baseline (P ⬍0.001, respectively). Urinary bother had a significantly worse score at 3 months than that at baseline (P ⫽ 0.036). At 6 months after surgery, however, it returned to the baseline score (P ⬎0.05). With the definition of continence based on pad requirement, 96%, 51%, 84%, 88%, 89%, and 92% of men were continent at baseline and 3, 6, 12, 18, and 24 months postoperatively, respectively. The mean total IPSS observed in men with a UCLA PCI urinary function score of 80 or more was significantly better than in those with score less than 80 at 24 months postoperatively (5.1 versus 8.8, P ⬍0.001). Similarly, the patients with urinary function scores of 80 or more reported better IPSS QOL scores than those with scores less than 80 (2.1 versus 4.0, P ⬍0.001). Figure 1A–F shows the mean IPSS, IPSS QOL, storage, voiding, postvoid symptoms, and nocturia scores, stratified by age. At baseline, there were no significant differences in IPSS and IPSS QOL scores between the younger patients (65 years old or younger, n ⫽ 74) and the older patients (older than 65 years, n ⫽ 151) (P ⫽ 0.412, 9.3 versus 10.0 and P ⫽ 0.422, 3.7 versus 3.9, respectively). At 24 months, RP had a favorable impact on LUTS for both age groups (both P ⬍0.01) (Fig. 1A). Furthermore, there was a tendency for the IPSS of the younger patients to continue to recover more rapidly than that of the older patients at 2 years after RP (P ⫽ 0.006, repeated-measure ANOVA). With regard to the IPSS QOL score, RP was associated with significant improvements in the score for both younger and older patients compared with baseline (both P ⬍0.01). However, the patterns of 143
TABLE I. IPSS QOL score, and UCLA PCI urinary domain of patients who underwent radical prostatectomy P Value vs Baseline
Parameter Total IPSS Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Emptying Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Voiding frequency Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Intermittency Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Urgency Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Slow stream Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Straining Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Nocturia Baseline 3 mo 6 mo 12 mo 18 mo 24 mo
144
9.07 ⫾ 6.08 7.76 ⫾ 5.05 6.94 ⫾ 4.86 6.60 ⫾ 5.58 6.35 ⫾ 5.20 6.55 ⫾ 5.69
— 0.113 0.002 ⬍0.001 ⬍0.001 ⬍0.001
1.08 ⫾ 1.21 0.92 ⫾ 1.06 0.78 ⫾ 1.17 0.58 ⫾ 1.24 0.59 ⫾ 0.99 0.66 ⫾ 1.03
— 0.402 0.007 ⬍0.001 ⬍0.001 0.002
1.58 ⫾ 1.36 1.85 ⫾ 1.37 1.54 ⫾ 1.29 1.50 ⫾ 1.38 1.25 ⫾ 1.35 1.13 ⫾ 1.33
— 0.087 0.844 0.340 0.015 0.003
0.85 ⫾ 1.21 0.62 ⫾ 1.10 0.39 ⫾ 0.82 0.52 ⫾ 1.01 0.39 ⫾ 0.76 0.58 ⫾ 1.13
— 0.054 ⬍0.001 0.001 ⬍0.001 0.019
1.03 ⫾ 1.18 0.92 ⫾ 1.21 0.85 ⫾ 1.04 0.78 ⫾ 1.15 0.81 ⫾ 1.25 0.58 ⫾ 1.02
— 0.324 0.248 0.011 0.036 ⬍0.001
1.91 ⫾ 1.64 0.90 ⫾ 1.22 0.95 ⫾ 1.38 0.98 ⫾ 1.36 0.92 ⫾ 1.37 0.93 ⫾ 1.23
— ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
0.90 ⫾ 1.31 0.57 ⫾ 0.97 0.69 ⫾ 1.10 0.56 ⫾ 1.08 0.60 ⫾ 0.99 0.64 ⫾ 1.25
— 0.059 0.048 0.003 0.018 0.036
1.73 ⫾ 0.97 1.97 ⫾ 1.01 1.75 ⫾ 0.82 1.68 ⫾ 0.95 1.79 ⫾ 1.05 1.89 ⫾ 1.13
— 0.091 0.685 0.579 0.802 0.360
TABLE I. Continued P Value vs Baseline
Parameter Quality of life score Baseline 3 mo 6 mo 12 mo 18 mo 24 mo UCLA PCI Urinary function Baseline 3 mo 6 mo 12 mo 18 mo 24 mo Urinary bother Baseline 3 mo 6 mo 12 mo 18 mo 24 mo
3.73 ⫾ 1.60 3.62 ⫾ 1.46 3.11 ⫾ 1.43 2.93 ⫾ 1.42 2.89 ⫾ 1.58 2.84 ⫾ 1.48
— 0.483 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
94.8 ⫾ 14.0 68.5 ⫾ 24.3 83.0 ⫾ 21.2 84.3 ⫾ 18.4 84.6 ⫾ 18.8 85.0 ⫾ 18.8
— ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
85.7 ⫾ 23.8 78.6 ⫾ 27.3 88.5 ⫾ 22.8 90.4 ⫾ 15.6 89.7 ⫾ 19.5 87.7 ⫾ 19.8
— 0.036 0.336 0.059 0.315 0.836
KEY: UCLA PCI ⫽ University of California, Los Angeles Prostate Cancer Index; IPSS ⫽ International Prostate Symptom Score; QOL ⫽ quality of life. Data are presented as mean ⫾ standard deviation.
alteration in the IPSS QOL score were different for the two age groups (P ⬍0.001, repeated-measure ANOVA) (Fig. 1B). The younger patients showed significantly better storage symptoms than the older patients throughout the postoperative period (P ⬍0.05) (Fig. 1C). Although each group showed improved symptoms of voiding frequency after RP, the younger patients showed fewer episodes of voiding symptoms (P ⬍0.001, repeated-measure ANOVA) (Fig. 1D). Although the postvoid symptoms at baseline seemed to be equivalent in the two age groups, the younger patients showed significantly greater improvement throughout the postoperative period (P ⬍0.05) (Fig. 1E). The older men claimed more frequent nocturnal voiding than the younger men before RP (P ⫽ 0.009, 1.3 versus 1.8). On the other hand, neither group had significant changes in nocturia throughout the postoperative period. Moreover, the younger men claimed significantly more episodes of nocturia at 3 months than at baseline (1.3 versus 1.9, P ⫽ 0.032). There were no differences between the younger and older men in terms of postoperative nocturia (Fig. 1F). Because among the categories only nocturia showed no improvement throughout the study period, the impact of RP on nocturia was further analyzed. The 225 consecutive men were divided into two groups according to baseline nocturia symptom score: group N1 with nocturia scores of 0 or 1 (n ⫽ 98), and group N2 with a score of 2 or more UROLOGY 68 (1), 2006
FIGURE 1. (A–F) Longitudinal changes of lower urinary tract symptoms over time, according to patient age. (A) Total International Prostate Symptom Score; (B) quality of life score; (C) storage symptoms score; (D) voiding symptoms score; (E) postvoid symptoms score; (F) nocturia symptom score; (G) longitudinal change of nocturia symptom score over time, stratified by baseline symptom score: N1 with nocturia score of 0 or 1, and N2 with nocturia score of 2 or more.
(n ⫽ 127) (Fig. 1G). The N1 group experienced a significant deterioration of nocturia at 3 months (versus baseline, P ⬍0.001). Then, their nocturia gradually decreased with time, but it never returned to the baseline level (baseline versus any time point, P ⬍0.01). In group N2, however, the nocturia symptom score was equivalent between baseline and the postoperative periods of 3 and 6 UROLOGY 68 (1), 2006
months. After 12 months, the nocturia score improved progressively and thereafter remained stable (P ⬍0.01). COMMENT Our study represents a 2-year, prospective, consecutive series in which we examined the impact of 145
RP on LUTS. The mean total IPSS and IPSS QOL score showed significant improvement after RP. Especially in men with moderate or severe urinary symptoms, RP improved the total IPSS more significantly, as reported in previous studies.5,10 The positive effects of RP on LUTS had a greater beneficial impact than the negative effects of stress urinary incontinence. This improvement in the IPSS, however, was not noted in men with no or mild symptoms but rather in those with moderate to severe symptoms. Therefore, LUTS in men selected for RP might be attributable to underlying BPE rather than prostate cancer. At baseline, the older patients reported more increased frequency of nocturnal voiding than the younger patients, which was similar to the results reported by other groups.11 It is noteworthy that nocturia did not improve, whereas a substantial improvement of other urinary symptoms was observed after RP. Furthermore, patients experienced a significant deterioration of the nocturia score just after RP. It has been reported that nocturia is the least specific symptom associated with BPE and the least sensitive to treatment for BPE.12 The current study revealed that postprostatectomy nocturia showed similar tendencies. Previous communitybased studies reported two or more episodes of nocturia in 24% to 45% of elderly men.13 The present study found that more than 50% of the patients arose to void two or more times at night 24 months after RP. These findings and ours suggest that nocturia is influenced markedly not only by obstruction of the prostatic urethra but also by bladder capacity, detrusor- and sphincter-related factors, or increased production of urine at night. We compared these results with those from our previous study, which included the initial 152 patients with 1-year follow-up after RP.5 In our current study, the “voiding frequency” composite score tended to increase in the early postoperative period, but significant improvement was observed in the second year after RP. Recently, several investigators reported that, after RP, a number of patients are affected by impaired detrusor contractility, which might coexist with sphincter weakness, bladder overactivity, and/or decreased compliance.14,15 Wide anatomic dissection around the prostate during RP might disrupt the afferent and efferent innervation of the trigone and neobladder neck and cause partial denervation of the detrusor muscle. Our finding suggests that RP can induce voiding frequency complications immediately after surgery but that these decrease with time. According to our survey based on the UCLA PCI, it seems to be difficult for patients treated with RP to return completely to baseline urinary continence. However, approximately 90% wore no pads. Consequently, the recovery from urinary bother was ob146
served early at 6 months and in the remaining postoperative periods, showing that postoperative incontinence, if any, was minimal in the majority of the patients. In line with our results, Lepor et al.16 stated that 97% of men treated with RP regained continence by 24 months after RP. In addition, stress urinary incontinence after RP had an adverse effect on LUTS. Jung et al.17 found that a significant decrease in bladder compliance and detrusor overactivity might be sustained by bladder denervation during RP or by a deficient sphincter with urine leakage into the urethra, stimulating urethral afferents. These results imply that stress incontinence can induce and/or increase detrusor instability. The present study extended observations on the impact of RP on IPSS, IPSS QOL score, storage, voiding, postvoid symptoms, and nocturia by examining the influence of the age of the patients. Our study confirmed that younger men seemed to recover in terms of the IPSS and IPSS QOL score more rapidly than the older patients after 2 years. To our knowledge, no study to date has evaluated the impact of age on LUTS after RP. Several studies have stated that urinary symptoms depended on age and the presence of BPE.18,19 In addition, detrusor overactivity is one of the most common causes of LUTS and is often associated with bladder outlet obstruction and BPE. This observation might be explained by sphincter weakness, bladder overactivity, and/or decreased compliance, as well as other conditions, such as comorbidities. The lack of objective data, such as prostate volume, uroflow variables, voiding volume, and postvoid residual is a limitation of the present study design. Furthermore, Blanker et al.20 stressed that the IPSS underestimated the prevalence of nocturia, that a lack of agreement existed between the subjective and objective data on nocturnal frequency, and that frequency–volume charts were the most valid instrument for diagnosing nocturia. The UCLA PCI and IPSS were selected because they seem to be the most widely used instruments for capturing these outcomes in clinical research. Despite these limitations, these results will assist physicians in providing clinically relevant information to patients who elect surgery. We emphasize that it is important to assess LUTS, as well as urinary incontinence, after RP. REFERENCES 1. Arai Y, Egawa S, Tobisu K, et al: Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan. BJU Int 85: 287–294, 2000. 2. Foote J, Yun S, and Leach GE: Postprostatectomy incontinence. Pathology, evaluation, and management. Urol Clin North Am 18: 229 –241, 1991. 3. Schwartz EJ, and Lepor H: Radical retropubic prostatectomy reduces symptom scores and improves quality of life UROLOGY 68 (1), 2006
in men with moderate and severe lower urinary tract symptoms. J Urol 161: 1185–1188, 1999. 4. Weiss JP, and Blaivas JG: Nocturia. J Urol 163: 5–12, 2000. 5. Namiki S, Saito S, Ishidoya S, et al: Adverse effect of radical prostatectomy on nocturia and voiding frequency symptoms. Urology 66: 147–151, 2005. 6. Walsh PC: Anatomical radical retropubic prostatectomy, in Walsh PC, Retik AB, Vaughan ED Jr, et al (Eds): Campbell’s Urology, 7th ed. Philadelphia, WB Saunders, 1998, pp 2565–2588. 7. Barry MJ, Fowler FJ, O’Leary MP, et al: The American Urological Association symptom index for benign prostatic hyperplasia. J Urol 148: 1549 –1577, 1992. 8. Litwin MS, Hays RD, Fink A, et al: The UCLA Prostate Cancer Index: development, reliability, and validity of a healthrelated quality of life measure. Med Care 36: 1002–1012, 1998. 9. Kakehi Y, Kamoto T, Ogawa O, et al: Development of Japanese version of the UCLA Prostate Cancer Index: a pilot validation study. Int J Clin Oncol 7: 306 –311, 2002. 10. Lepor H, and Kaci L: The impact of open radical retropubic prostatectomy on continence and lower urinary tract symptoms: a prospective assessment using validated self-administered outcome instruments. J Urol 171: 1216 –1219, 2004. 11. Yoshimura K, Terada N, Matsui Y, et al: Prevalence of and risk factors for nocturia: analysis of a health screening program. Int J Urol 11: 282–287, 2004. 12. Homma Y, Yamaguchi T, Kondo Y, et al: Significance of nocturia in the International Prostate Symptom Score for benign prostatic hyperplasia. J Urol 167: 172–176, 2002.
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13. Fultz NH, and Herzog AR: Epidemiology of urinary symptoms in the geriatric population. Urol Clin North Am 23: 1–10, 1996. 14. Gohma MA, and Boone TB: Voiding patterns in patients with post-prostatectomy incontinence: urodynamic and demographic analysis. J Urol 169: 1766 –1769, 2003. 15. Hellstrom P, Lukkarinen O, and Kontturi M: Urodynamics in radical retropubic prostatectomy. Scand J Urol Nephrol 23: 21–24, 1989. 16. Lepor H, Kaci L, and Xue X: Continence following radical retropubic prostatectomy using self-reporting instruments. J Urol 171: 1212–1215, 2004. 17. Jung SY, Fraser MO, Ozawa H, et al: Urethral afferent nerve activity affects the micturition reflex; implication for the relationship between stress incontinence and detrusor instability. J Urol 162: 204 –212, 1999. 18. Andersson SO, Rashidkhani B, Karlberg L, et al: Prevalence of lower urinary tract symptoms in men aged 45-79 years: a population-based study of 40 000 Swedish men. BJU Int 94: 323–331, 2004. 19. Tubaro A, La Vecchia C, for the Uroscreening Study Group: The relation of lower urinary tract symptoms with lifestyle factors and objective measures of benign prostatic enlargement and obstruction: an Italian study. Eur Urol 45: 767–772, 2004. 20. Blanker MH, Bohnen AM, Groenveld FPMJ, et al: Normal voiding patterns and determinants of increased diurnal and nocturnal voiding frequency in elderly men. J Urol 164: 1201–1205, 2000.
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