RELATIONSHIPS BETWEEN AMERICAN UROLOGICAL ASSOCIATION SYMPTOM INDEX, PROSTATE VOLUME, PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA

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American Urological Association symptom index for BPH RELATIONSHIPS BETWEEN AMERICAN UROLOGICAL ASSOCIATION SYMPTOM INDEX, PROSTATE VOLUME, AND DISEASE-SPECIFIC QUALITY OF LIFE QUESTION IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA Chia-Chu Liu, Chii-Jye Wang, Shu-Pin Huang, Yii-Her Chou, Wen-Jeng Wu, and Chun-Hsiung Huang Department of Urology, Kaohsiung Medical University, Kaohsiung, Taiwan. The American Urological Association (AUA) symptom index is both valid and reliable in identifying the need to treat patients with benign prostatic hyperplasia (BPH) and in monitoring their response to therapy. We evaluated the relationships between AUA symptom index, disease-specific quality of life question, and prostate volume in patients with BPH. A total of 100 patients who came to Kaohsiung Medical University Hospital, Taiwan, for help due to lower urinary tract symptoms (LUTS) and who were diagnosed with BPH between October 2002 and June 2003 were included in the study. All patients were evaluated using transrectal ultrasonography, AUA symptom index, and disease-specific quality of life question. The diseasespecific quality of life question showed good correlation with AUA symptom score (r = 0.815, p < 0.01), but weak correlation with prostate volume (r = 0.225, p < 0.05) and age (r = 0.274, p < 0.05). Prostate volume had weak correlation with AUA symptom score (r = 0.251, p < 0.05) and age (r = 0.472, p < 0.01), but good correlation with prostate specific antigen (r = 0.638, p < 0.01). In addition to AUA symptom index, we suggest using the disease-specific quality of life question to evaluate the influence on quality of life and response to treatment in clinical practice. Moreover, we should assess the impact of BPH symptoms rather than the increase in prostate volume during the management of BPH. Key Words: benign prostatic hyperplasia, ultrasonography, symptoms, aging (Kaohsiung J Med Sci 2004;20:273 8) Benign prostatic hyperplasia (BPH) has a high prevalence in the male population that increases with age [1,2]. It often produces chronic and progressive lower urinary tract symptoms (LUTS) or chronic complications, leading many men to seek treatment [2,3]. The American Urological Association (AUA) symptom index is now widely used to assess patients with suspected BPH. It consists of a series of seven questions that address obstructive and irritative voiding symptoms [4]. The index has been shown to be clinically sensible, reliable, valid, and reproducible [4,5]. The AUA symptom index has been adopted by the World Health Organization (WHO) as the International Prostate Symptom Score (IPSS) after the addition of one diseasespecific quality of life question as a means of assessing the global impact of BPH on quality of life [6]. The aim of this study was to evaluate the relationships between AUA symptom index, the disease-specific quality of life question, and prostate volume in patients who came to our hospital for LUTS suggestive of BPH. Received: January 14, 2004 Accepted: March 16, 2004 Address correspondence and reprint requests to: Dr. Chii-Jye Wang, Department of Urology, Kaohsiung Medical University, 100 Shih- Chuan 1 st Road, Kaohsiung 807, Taiwan. E-mail: urology@kmu.edu.tw 2004 Elsevier. All rights reserved. PATIENTS AND METHODS Patients who came to Kaohsiung Medical University Hospital, Taiwan, between October 2002 and June 2003 complaining of LUTS suggestive of BPH were included in 273

C.C. Liu, C.J. Wang, S.P. Huang, et al this study. No patients had received medication for BPH in the previous month. Patients who had a history of neurogenic disease, urethral stricture, or bladder tumor that would interfere with micturition, or who came for help with an indwelling catheter due to urine retention, were excluded from the study. Patients who had concomitant urinary tract infection (UTI) or distal ureter stone were also excluded. During evaluations, any patient with an abnormal digital rectal examination or elevated serum prostate specific antigen (PSA) level (> 4 ng/ml) was asked to undergo prostate biopsy to exclude prostate cancer. If prostate cancer was found, the patient was excluded. The evaluations included AUA symptom index, the disease-specific quality of life question (bother score), digital rectal examination, transrectal ultrasonography (7-MHz 8551 Probe, 2001 Medical Ultrasound Scanner; B-K Medical A/S, Herlev, Denmark), serum PSA (Immulite 2000 PSA assay; Diagnostic Products Corp, Los Angeles, CA, USA), and urinalysis. Prostate volume was calculated using the prostate ellipsoid formula: (π/6) (anterior posterior diameter) (transverse diameter) (sagittal diameter). The AUA symptom index includes seven items to evaluate LUTS (incomplete emptying, frequency, intermittency, urgency, weak stream, hesitancy, and nocturia), with the score of each item ranging from 0 to 5 points. The total symptom score was obtained by adding the seven scores (range, 0 to 35 points), and was categorized as mild ( 7), moderate (8 19), or severe ( 20). For symptomatic classification, we divided the symptom score into an obstructive subscore (sum of scores for questions 1, 3, 5, and 6) and an irritative subscore (sum of scores for questions 2, 4, and 7). The disease-specific quality of life question was phrased as follows: If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?, and the answering scale ranged from 0 (delighted) to 6 (terrible). The AUA symptom index questions and the disease-specific quality of life question were administered to all patients with instruction from doctors. Results are expressed as mean ± standard deviation, unless otherwise indicated. Pearson s correlation coefficient is used to express the strength of the correlations between age, prostate volume, PSA level, AUA symptom score, obstructive subscore, irritative subscore, and bother score. Data were considered significant if p was less than 0.05. Statistical differences between mild, moderate, and severe symptom groups were compared using the ANOVA procedure. A p value of less than 0.05 was considered statistically significant. 274 RESULTS From October 2002 to June 2003, 107 patients came to our hospital for help due to LUTS suggestive of BPH. Seven patients were excluded from this study, five for concomitant UTI, one for concomitant bladder tumor, and one for prostate cancer that was confirmed by prostate biopsy initiated for an elevated PSA level. A total of 100 patients were included in the study. The mean age was 59.6 ± 10.66 years (median, 59 years; range, 40 90 years). The mean prostate volume was 34.89 ± 16.40 ml (median, 29.6 ml; range, 20.0 120 ml). The mean total AUA symptom score was 11.54 ± 6.84 (median, 11; range, 1 33), the mean obstructive subscore was 6.38 ± 4.67 (median, 6; range, 0 20), and the mean irritative subscore was 5.16 ± 2.99 (median, 5; range, 0 13). The mean bother score was 3.37 ± 1.36 (median, 4; range, 0 6). The mean PSA level was 2.71 ± 4.79 ng/ml (median, 0.995 ng/ml; range, 0.12 11.90 ng/ml). The correlations between age, prostate volume, PSA level, AUA symptom score, obstructive subscore, irritative subscore, and bother score are shown in Table 1. All patients were divided into groups according to total AUA symptom score: mild (n = 31), moderate (n = 58), and severe (n = 11). There was a statistically significant difference in age among the three groups (p = 0.02), with a greater mean age in the severe symptom group. However, there was no statistically significant difference in prostate volume and PSA level among the three groups (Table 2). DISCUSSION BPH is a common condition among older men, resulting in chronic LUTS that are bothersome, impair physiologic and functional well-being, and interfere with activities of daily living [7,8]. The main reasons for patients to seek treatment for BPH are subjective symptoms, feeling bothered, and negative impact on quality of life [2,3]. The AUA symptom index is a seven-item scale developed by a multidisciplinary measurement committee of the AUA, and is primarily intended for use as an evaluative measure for BPH [4]. The validity (the extent to which a tool measures what it is supposed to measure), reproducibility (the extent to which a tool gives consistent results in stable individuals over time), and responsiveness (the ability to detect clinical change) of the AUA symptom index have been well documented by several studies [4,9 13]. The AUA symptom index is both valid and reliable in

American Urological Association symptom index for BPH Table 1. Relationship among different variables by Pearson s correlation coefficient Age r p Prostate volume r 0.472* p < 0.001 PSA r 0.420* 0.638* p < 0.001 < 0.001 Age Prostate volume PSA Total score Obstructive subscore Irritative subscore Total score r 0.252 0.251 0.095 p 0.011 0.012 0.346 Obstructive subscore r 0.218 0.221 0.052 0.933* p 0.029 0.027 0.605 < 0.001 Irritative subscore r 0.236 0.230 0.136 0.828* 0.571* p 0.018 0.022 0.177 < 0.001 < 0.001 Bother score r 0.274* 0.229 0.077 0.815* 0.763* 0.672* p 0.006 0.022 0.446 < 0.001 < 0.001 < 0.001 *p < 0.01; p < 0.05. PSA = serum prostate specific antigen; Bother score = disease-specific quality of life question. Table 2. Characteristics of the three symptom groups Mild (0 7), n = 31 Moderate (8 19), n = 58 Severe (20 35), n = 11 p Age, yr 57.80 ± 10.60 59.03 ± 10.5 67.63 ± 8.54 0.02 Prostate volume, cm 3 30.71 ± 12.25 36.04 ± 18.4 40.56 ± 13.81 0.16 PSA, ng/ml 2.70 ± 6.08 2.28 ± 3.25 4.99 ± 6.98 0.23 Total AUA score 3.90 ± 1.94 13.29 ± 3.57 23.81 ± 3.79 Obstructive subscore 1.52 ± 1.87 7.47 ± 2.90 14.36 ± 3.20 < 0.01 Irritative subscore 2.39 ± 1.52 5.83 ± 2.26 9.45 ± 2.46 < 0.01 Bother score 1.97 ± 0.91 3.79 ± 0.91 5.09 ± 0.83 < 0.01 PSA = serum prostate specific antigen; AUA = American Urological Association. identifying the need to treat patients and in monitoring their response to therapy [4]. The AUA practice guidelines committee recommends that the AUA symptom index should be used as the symptom-scoring instrument in the initial assessment of each patient presenting with BPH. The extent of further evaluation and treatment is suggested according to whether symptoms are mild (0 7), moderate (8 19), or severe (20 35) [14]. However, the AUA symptom index has also received considerable criticism because it is unable to discriminate BPH from other types of voiding dysfunction in either male or female patients [6,15,16], to differentiate obstructed from non-obstructed BPH [17 19], or to differentiate either form of BPH from detrusor hyperreflexia [19,20]. It is critical to assess symptoms and quality of life from a patient s perspective when deciding BPH treatment. The condition-specific impact score is much more sensitive to differences in symptoms than general measures of quality of life. The WHO International Consultation on BPH has recommended the use of the AUA symptom index and a single disease-specific quality of life question that asks patients to assess their feelings about their symptoms for studies of BPH treatment. The disease-specific quality of life question is a good single item for assessing the quality of life and treatment outcome, and is more readily interpretable on an individual clinical basis than a numeric index [11]. The symptoms of BPH can be divided into obstructive 275

C.C. Liu, C.J. Wang, S.P. Huang, et al and irritative complaints. Obstructive symptoms result from mechanical and dynamic obstruction, but irritative symptoms result from the secondary response of the bladder to the increased outlet resistance. As prostatic enlargement occurs, mechanical obstruction may result from intrusion into the urethral lumen or bladder neck, leading to a higher bladder outlet resistance. The prostate stroma is rich in adrenergic nerve supply, so the tone of the prostatic urethra may increase, creating dynamic obstruction when the prostate grows. In our study, we tried to divide the AUA symptom score into obstructive and irritative subscores, to observe which symptoms have better correlation with the bother score. The obstructive subscore (r = 0.763, p < 0.001) had better correlation than the irritative subscore (r = 0.673, p < 0.001). It seems that patients may care more about obstructive symptoms than irritative symptoms. Further studies may be needed to confirm this. We also found that the bother score had good correlation with the AUA symptom score (r = 0.815, p < 0.01), but weak correlation with prostate volume (r = 0.225, p < 0.05) and age (r = 0.274, p < 0.05). Prostate volume was weakly correlated with the AUA symptom score (r = 0.251, p < 0.05) and age (r = 0.472, p < 0.01), but had good correlation with PSA level (r = 0.638, p < 0.01). The results were similar to those obtained by Bosch et al in 1995 [6], who found good correlation between AUA symptom score and bother score (r = 0.74, p = 0.001), but weak correlation between AUA symptom score and total prostate volume (r = 0.19, p < 0.001) and age (r = 0.09, p = 0.04). The lack of relationship between prostate volume and symptoms may be due to variable patterns of prostatic enlargement. Excess growth in the transitional zone can produce enlargement without significant obstructive symptoms. Such growth was reported in an autopsy study [21]. On the other hand, periurethral enlargement or nodular growth can produce obstructive symptoms with no great enlargement of the gland as a whole [22]. We also divided patients into three groups according to their AUA symptom scores. No statistically significant differences in prostate volume and PSA level were found among the three groups. However, there was a statistically significant difference in age (p = 0.02); patients in the severe symptom group were older. Chute et al found that incomplete emptying, intermittency, urgency, weak stream, and nocturia were strongly age-related [1]. Kojima et al found similar results [23]. Therefore, aging may also play an important role in the development of LUTS. Although Garraway et al adopted prostate weight ( 20 g) as the criterion for BPH [24], some studies preferred 276 the presumed circle area ratio [23,25]. Presumed circle area ratio is the ratio of the area of maximum prostatic section to the area of a presumed circle having the same circumference as that of the section. It is based on the idea that the degree of obstruction in BPH can be evaluated by estimating how closely a horizontal section of the entire prostate approaches a circle on transrectal sonography [23]. Kojima et al found a stronger correlation between presumed circle area ratio and symptom score (r = 0.150, p < 0.0001) than between prostate volume and symptom score (r = 0.072, p < 0.0001) using simple regression analysis, so they suggested that presumed circle area ratio was preferable to prostate volume in representing the degree of BPH in terms of the severity of urinary symptoms [23]. Further studies are needed to evaluate whether the appearance or size of the prostate plays an important role in the development of urinary symptoms. In conclusion, it is critical to assess symptoms and quality of life from a patient s perspective in assessing BPH treatment. In addition to the AUA symptom index, we suggest using the disease-specific quality of life question to evaluate the influence of symptoms on quality of life and response to treatment in clinical practice, as recommended by the WHO International Consultation on BPH. We found that the disease-specific quality of life question showed good correlation with the AUA symptom score, but neither AUA symptom score nor the disease-specific quality of life question had good correlation with prostate volume. Therefore, we should focus on the impact of BPH symptoms, rather than the increase in prostate volume, during the management of BPH. REFERENCES 1. Chute CG, Panser LA, Girman CJ, et al. The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol 1993;150:85 9. 2. Borth CS, Beiko DT, Nickel JC. Impact of medical therapy on transurethral resection of the prostate: a decade of change. Urology 2001;57:1082 6. 3. Nickel JC. Long-term implications of medical therapy on benign prostatic hyperplasia end points. Urology 1998;51(Suppl 4A):50 7. 4. Barry MJ, Fowler FJ Jr, O Leary MP, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol 1992;148:1549 57. 5. O Leary MP, Barry MJ, Fowler FJ Jr. Hard measures of subjective outcomes: validating symptom indexes in urology. J Urol 1992;148:1546 8.

American Urological Association symptom index for BPH 6. Bosch JL, Hop WC, Kirkels WJ, Schroder FH. The International Prostate Symptom Score in a community-based sample of men between 55 and 74 years of age: prevalence and correlation of symptoms with age, prostate volume, flow rate and residual urine volume. Br J Urol 1995;75:622 30. 7. Hartung H. Do alpha-blockers prevent the occurrence of acute urinary retention? Eur Urol 2001;39:13 8. 8. Roberts RO, Jacobsen SJ, Rhodes T, et al. Natural history of prostatism: impaired health states in men with lower urinary tract symptoms. J Urol 1997;157:1711 7. 9. Barry MJ, Cockett AT, Holtgrewe HL, et al. Relationship of symptoms of prostatism to commonly used physiological and anatomical measures of the severity of benign prostatic hyperplasia. J Urol 1993;150:351 8. 10. Barry MJ, Girman CJ, O Leary MP, et al. Using repeated measures of symptom score, uroflowmetry and prostate specific antigen in the clinical measurement of prostate disease. J Urol 1995;153:99 103. 11. Fowler FJ Jr, Barry MJ. Quality of life assessment for evaluating benign prostatic hyperplasia treatment. Eur Urol 1993;24(Suppl 1):24 7. 12. Barry MJ, Fowler FJ Jr, O Leary MP, et al. Correlation of the American Urological Association symptom index with selfadministered versions of the Madsen-Iversen, Boyarsky and Maine Medical Assessment Program symptom indexes. J Urol 1992;148:1558 63. 13. Lawerence K. Measurement properties of the AUA symptom score: a methodological clarification. Br J Urol 1996;77:175 80. 14. AUA Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: diagnosis and treatment recommendations. J Urol 2003;170: 530 47. 15. Nitti VW, Kim Y, Combs AJ. Correlation of the AUA symptom index with urodynamics in patients with suspected benign prostatic hyperplasia. Neurourol Urodyn 1994;13:521 9. 16. Lepor H, Machi G. Comparison of AUA symptom index in unselected males and females between fifty-five and seventynine years of age. Urology 1993;42:36 41. 17. Yalla SV, Sullivan MP, Lecamwasam HS, et al. Correlation of American Urological Association symptom index with obstructive and nonobstructive prostatism. J Urol 1995;153:674 80. 18. Sirls LT, Jay J, Kirkemo A. Does the American Urological Association symptom score correlate with urodynamic obstruction? J Urol 1995;153:275A. [Abstract 187] 19. Chapple C, Woo HH, Rosario DJ, Fleet C. Correlation of IPSS symptom score with findings on video pressure-flow studies. J Urol 1995;153:275A. [Abstract 188] 20. Chancellor MB, Rivas DA, Keeley MA, et al. Similarity of the American Urological Association Symptom Index among men with benign prostatic hyperplasia (BPH), urethral obstruction not due to BPH and detrusor hyperreflexia without outlet obstruction. Br J Urol 1994;74:200 3. 21. McNeill JE. Origin and evolution of benign prostatic enlargement. Invest Urol 1978;15:340 5. 22. Simpson RJ, Fisher W, Lee AJ, et al. Benign prostatic hyperplasia in an unselected community-based population: a survey of urinary symptoms, bothersomeness and prostatic enlargement. Br J Urol 1996;77:186 91. 23. Kojima M, Nava Y, Inoue W, et al. The American Urological Association symptom index for benign prostatic hyperplasia as a function of age, volume and ultrasonic appearance of the prostate. J Urol 1997;157:2160 5. 24. Garraway WM, Collins GN, Lee RJ. High prevalence of benign prostatic hypertrophy in the community. Lancet 1991; 338:469 71. 25. Ukimura O, Kojima M, Inui E, et al. A statistical study of the American Urological Association symptom index for benign prostatic hyperplasia in participants of mass screening program for prostatic disease using transrectal sonography. J Urol 1996; 156:1673 8. 277

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