Validity of the "Bother Score" in the Evaluation and Treatment of Symptomatic Benign Prostatic Hyperplasia

TREATMENT REVIEW Validity of the “Bother Score” in the Evaluation and Treatment of Symptomatic Benign Prostatic Hyperplasia Michael P. O’Leary, MD, MPH Department of Surgery, Harvard Medical School, Division of Urology, Brigham and Women’s Hospital, Boston, MA Benign prostatic hyperplasia (BPH) is a condition that is common among older men. It causes a variety of clinically significant lower urinary tract signs and symptoms. BPH is rarely life-threatening; the decision to seek treatment is frequently based on the degree to which patients find the symptoms bothersome and disruptive of daily activities. Recently developed reliable and valid outcome measures to evaluate treatments for BPH are clinical tools that urologists can use to determine the extent of bother and make treatment decisions. A single question used to determine the “bother score” provides a widely used and statistically valid measure of the need for treatment of BPH. Validation data support the argument that the bother score is a statistically reliable measure of treatment outcome in patients with BPH who view their symptoms as bothersome. [Rev Urol. 2005;7(1):1-10] © 2005 MedReviews, LLC Key words: Benign prostatic hyperplasia • Quality of life • Lower urinary tract symptoms • Bother score enign prostatic hyperplasia (BPH) is one of the most common conditions affecting older men, with a prevalence of 50% by age 60 years and 90% by the ninth decade of life.1,2 The development of BPH is associated with proliferation of the prostatic stroma and epithelium. This leads to an increase in prostatic weight and a spectrum of clinical manifestations known as lower urinary tract symptoms (LUTS). LUTS comprise voiding (obstructive) symptoms, such as B VOL. 7 NO. 1 2005 REVIEWS IN UROLOGY 1 “Bother Score” in BPH Treatment continued reduced stream, hesitancy, and straining, as well as storage (irritative) symptoms, including frequency, nocturia, and incontinence.2-4 The clinical signs associated with BPH are rarely life-threatening; the degree to which symptoms become bothersome or worrisome to the patient and disrupt his daily activities usually provides the basis for his decision to seek medical treatment. The recent Multinational Survey of cation of the bother score in treatment outcome studies. The goals of this report are to review the data validating the bother score as a tool for evaluating the clinical impact of LUTS in men with BPH, as well as to review its role in assessing treatment outcomes in these patients. Evaluation Enlargement and obstruction of the prostate gland secondary to BPH is the Patients with predominantly irritative symptoms of BPH are more likely to report that their quality of life is affected than are men with predominantly obstructive symptoms. the Aging Male (MSAM-7) determined that, although 90% of all men surveyed had LUTS, only 19% sought medical help for their urinary problems, and only 11% were medically treated.5 Before a physician can decide on a treatment for BPH, he or she should first evaluate the patient’s degree of bother and desire to receive treatment. In the past decade, reliable and valid outcome measures for the treatment of BPH have been developed to help urologists quantify the extent of bother, to help establish whether treatment for BPH and LUTS is appropriate to a patient. One particular question of the universally used International Prostate Symptom Score (IPSS), known as the “bother question,” is used to determine the bother score. This score is a valuable prognostic aid and is based on what the patient believes would be his ability to tolerate his current level of symptoms for the rest of his life.6 This article reviews the development of the IPSS bother question in the context of symptom score development from the original American Urological Association Symptom Index (AUASI). It also reviews appli- 2 VOL. 7 NO. 1 2005 REVIEWS IN UROLOGY underlying cause of LUTS in most men. The resulting complaint of urinary difficulties is the usual driving force leading to medical evaluation.3 The treatment of patients with LUTS typically begins with an evaluation for BPH, including a medical history that focuses on the nature of signs and symptoms, the patient’s general health (including sexual function), prior surgeries, and current medications. It is prostate cancer. The clinician should assess abnormalities in the size, consistency, and symmetry of the patient’s prostate in the course of this screening examination. Standard laboratory tests, such as urinalysis and measurement of serum creatinine, are also required. The presence of BPH signs and symptoms, coupled with DRE findings, laboratory results, and the ruling out of other potential diagnoses, provides the basis for a diagnosis of BPH.8 Men are generally hesitant to seek medical treatment for LUTS and typically do so only when symptoms become sufficiently bothersome to impact their quality of life (QOL).9 Most patients with mild symptoms are not sufficiently bothered to accept the risks of even noninvasive therapy.10 For some men the decision to pursue treatment might be driven by moderate or severe genitourinary symptoms, whereas in others, fear of prostate cancer, surgery, or impotence is the factor that drives the decision to seek medical attention.11 Patients with predominantly irritative symptoms of BPH are more likely to report The bother score is a valuable prognostic aid based on what the patient believes would be his ability to tolerate his current level of symptoms for the rest of his life. important to remember that BPHassociated LUTS generally result from irritative causes related to detrusor contractility, as well as from obstruction due to prostatic enlargement. Men whose age and demographic profiles place them in a group that is prone to BPH are generally also clinically appropriate candidates for screening for prostate cancer.7 A genitourinary examination, including a digital rectal examination (DRE), and prostate-specific antigen (PSA) assay should be included in screening for that their QOL is affected than are men with predominantly obstructive symptoms.12 Patients with BPH/LUTS frequently report interference with their daily routines. An international study of French and English men found that sleep, anxiety, outdoor mobility, leisure, usual daily activities, and well-being were the 6 aspects of QOL most acutely affected by prostatic symptoms.13 Lack of satisfaction with sexual relationships was rated as equally important by most of “Bother Score” in BPH Treatment the participants.13 Specific complaints included an inability to sleep through the night and being unable to drive for 2 hours without the need to stop and urinate. Psychological well-being, as well as anxiety and worry, which can impact sexual performance, were the aspects of psychological function that were most affected.13 Although patients seek treatment for relief of symptoms and improvement of QOL, physicians often base treatment choices on anticipated improvement of objective clinical signs, such as degree of bladder outlet obstruction and residual postvoid urine volume.9,14 Fortunately, urologists increasingly involve patients in making treatment decisions based not only on the specific signs but on the degree to which the symptoms bother the patient.10 Because of the central role of bothersomeness in the decision to seek treatment and in the development of treatment algorithms, urologists have developed a quantitative instrument to assess the degree of bother. Development of the IPSS and Bother Question The AUASI was developed and validated in 1992.15 The AUASI is a short, self-administered, and clinically sensible questionnaire designed to provide a BPH symptom score incorporating psychometric properties to capture the severity of symptoms. The AUASI comprised 7 questions: 6 of these, concerning nocturia, weak urinary stream, frequency, intermittence, incomplete emptying, and urgency, were chosen on the basis of their strong correlations with either of 2 global bother questions (Figure 1) about overall urinary difficulties; a seventh question assessed hesitancy, a classic symptom of BPH.15 Application of this measurement tool to clinical practice was carried out in 2 validation studies involving more than 300 patients. The results indicated that men with an AUASI score of 7 or less typically rated their urinary condition as not at all bothersome (the mild group), whereas those with scores of 8 to 19 had intermediate ratings (the moderate group), and those with AUASI scores of 20 or greater were bothered some or a lot by their symptoms (the severe group).15 The primary purpose of the AUASI was to provide an outcome measure for comparison of different treatment strategies for BPH, and it was found to provide a valid measure of symptom severity and to be sensitive to clinical changes. Implicit in the AUASI’s development was the need for a tool to discriminate between men more or less bothered by their symptoms.16 With accumulating evidence that a quantitative, standardized mechanism for capturing a patient’s self-perception of his condition was necessary for physicians to make appropriate choices for treatment, the IPSS was adopted in 1993 by the World Health Organization.11 The IPSS is based on the 7 original questions of the AUASI, with an additional question; this eighth question of the IPSS (AUASI global question number 2), the bother question, assesses the degree to which patients find their symptoms bothersome, now known as the bother score.15 Validation of the Bother Score The following section outlines support for the validity of the bother score from the published literature and newer, unpublished studies and demonstrates the considerable value of this important clinical assessment tool. Reliability Test–retest reliability. With the exception of questions on frequency and hesitancy, the test–retest reliability of the AUASI questions ranged Global Question 1 Overall, how bothersome has any trouble with urination been during the last month? 0 – Not at all bothersome 1 – Bothers me a little 2 – Bothers me some 3 – Bothers me a lot Global Question 2 If you were to spend the rest of your life with your prostate symptoms just as they are now, how would you feel about that? 0 – Delighted 1 – Pleased 2 – Mostly satisfied 3 – Mixed (about equally satisfied and dissatisfied) 4 – Mostly dissatisfied 5 – Unhappy 6 – Terrible Figure 1. Two global bother questions about overall urinary difficulty. Reprinted with permission from Barry MJ et al. J Urol. 1992;148:1549-1557.15 from 0.79 to 0.91 (Pearson correlation coefficients) for each of the individual symptom questions, and the test–retest correlations of the total scores were excellent (r = 0.92–0.93).15 A recent study designed to validate a new sexual function questionnaire has independently established the test– retest reliability of the bother score (Raymond Rosen, PhD, personal communication, March 2004). Internal reliability. Internal reliability of the bother score is demonstrated by the high correlation (coefficient, 0.82) of the answers to the two original global bother questions, indicating that the two items were measuring the same concept.9,15 Validity Construct validity. Six of the 7 AUASI questions demonstrated excellent correlations with both global bother questions (r > 0.5). The seventh question, regarding urinary hesitancy, was included because urologists consider hesitancy a classic symptom of VOL. 7 NO. 1 2005 REVIEWS IN UROLOGY 3 “Bother Score” in BPH Treatment continued Table 1 Correlations of AUA-7 With Global Bother Questions Question No.* 1 2 3 4 5 6 7 GB1 1 1.00 2 0.70 1.00 3 0.68 0.48 1.00 4 0.34 0.44 0.41 1.00 5 0.58 0.45 0.70 0.43 1.00 6 0.44 0.32 0.32 0.05 0.41 1.00 7 0.42 0.49 0.37 0.47 0.32 0.24 1.00 GB1 0.58 0.56 0.59 0.54 0.72 0.40 0.52 1.00 GB2 0.64 0.59 0.54 0.51 0.66 0.38 0.53 0.82 GB2 1.00 AUA-7, 7-item American Urological Association Symptom Index; GB1, GB2, global bother questions 1 and 2 (see Figure 1). Adapted with permission from Barry MJ et al. J Urol. 1992;148:1549-1557.15 *The first 7 numbers refer to the AUA-7 questions. BPH. Table 1 shows the correlations established for each of the final AUASI questions and the 2 global bother questions.15 In nearly all cases, the correlations were greater than 0.5 for both global bother questions. These findings confirm the validity of the bother questions as providing clinically relevant information. A new study offers independent confirmation that correlations of urinary symptoms with the IPSS bother questions are all significant. Administration of the IPSS along with a new sexuality and prostate health survey showed highly significant correlations between items for both the initial and follow-up values, as shown in Table 2.17 Further confirmation is found for the relationship between the bother question and 3 additional psychometric domains measured in the new sexuality and prostate health survey.5 Discriminant validity. The ability of the AUASI to distinguish BPH patients from controls was demonstrated in a study by Barry and colleagues.15 Using receiver operating characteristic (ROC) curves,9 the Barry study examined the distribution of 4 VOL. 7 NO. 1 2005 REVIEWS IN UROLOGY scores for 65 subjects with BPH and 53 controls. The area under the ROC curve for the total scores of the 7 questions was 0.87 ± 0.03, which suggests that a random control subject or BPH patient would be correctly classified 87% of the time. Extending this argument, the data in Table 1 are consistent with the prediction that even the single bother question would have good discriminant value in identifying BPH patients. These authors suggested that the AUASI should not be used alone to diagnose BPH but to augment other tools used by urologists and to assess symptom severity.15 Table 2 Correlations of IPSS Bother Question with 7 IPSS Questions*† IPSS Items Initial Test Follow-Up Test Total IPSS‡ 0.7746 0.7666 Are you emptying your bladder incompletely? (E) 0.5985 0.6185 Do you have to urinate again within 2 hours? (F) 0.6202 0.6708 Do you stop and start while urinating? (I) 0.5193 0.5555 Is it difficult to postpone urination? (U) 0.6124 0.6169 Have you had a weak urinary stream? (W) 0.6041 0.5786 Do you push or strain to begin urination? (H) 0.5073 0.4701 Do you get up to urinate at night? (N) 0.5449 0.4960 IPSS, International Prostate Scoring System17; legend for IPSS questions: E, emptying; F, frequency; I, intermittency; U, urgency; W, weak stream; H, hesitancy; N, nocturia. *Based on 249 cases. † All correlations (Spearman correlation coefficients) significant at P < .001. ‡ Score based on 7 IPSS items only, bother questions excluded. “Bother Score” in BPH Treatment Table 3 Relationship Between Global Bother Question Score Categories and AUA-7 Severity Score AUA-7 Severity Score GB1 Total Mild Moderate Severe Not at all 117 (45.3) 93 (84.5) 22 (20.4) 2 (5) A little 82 (31.8) 16 (14.5) 57 (52.8) 9 (22.5) Some 47 (18.2) 1 25 (23.1) 21 (52.5) A lot 12 (4.7) 0 4 8 (20) Total 258 (100) 110 (100) 108 (100) (0.9) (3.7) 40 (100) Data are presented as n (%). AUA-7, 7-item American Urological Association Symptom Index; GB1, global bother question 1 (see Figure 1). Data from Barry MJ et al. J Urol. 1992;148:1549-1557.15 the IPSS are derived from the MSAM7, the first large-scale multinational study of LUTS and sexual function in older men (aged 50–80 years).5 Analyses of the responses of more than 12,000 participants confirm that the IPSS bother question scores significantly correlate with IPSS symptom severity (P < .01) (Table 4, Figure 3). The vast majority (98.8%) of asymptomatic patients and 91.2% of mildly symptomatic patients had low (“good”; ≤2) bother scores, whereas Correlation of the Bother Score With Symptom Severity: Clinical Relevance The bother question is currently the most widely used QOL instrument for patients with BPH.18 One of the first questionnaires designed to measure QOL in patients with BPH was described in a 1988 study that examined 3 aspects of QOL: 1) patients’ ability to perform activities of daily living; 2) patients’ mental health during the previous month; and 3) patients’ frequency of being worried or bothered by illness.19 Patients with similar clinical signs reported considerable differences in the degree to which they were bothered by their symptoms. For example, some patients with severe signs reported little discomfort or worry about their health, whereas some with mild signs were very bothered by them.19 A clear Figure 2. Comparison of global bother question 1 scores and AUASI severity. AUASI, American Urological Association Symptom Index. Data from Barry MJ et al. J Urol. 1992;148:1549-1557.15 100 Global Bother Score, % Sensitivity The sensitivity of the AUASI was demonstrated by an evaluation of the relationship between increasing total scores and the first global bother question: “Overall, how bothersome has any trouble with urination been during the last month?” Table 3 shows clearly that a much larger percentage of patients who fell into the severe symptom category (≥20 points) rated the amount of bother from their symptoms as “some” or “a lot” (Figure 2).15 The index was also shown to detect clinically important changes in symptom relief after prostate surgery; among 27 patients to whom the index was administered, all but 1 had a decrease in total score for AUASI, and more than half had a decrease of at least 7 points.15 Although the question used was global bother question number 1, the strong correlation between question number 1 and question number 2—the currently used bother score— argues that the bother score magnitude is directly related to the severity of LUTS and that changes that occur in response to treatment can be measured. Independent data confirming the sensitivity of the bother question of 73.6% of patients with severe symptoms had high (“bad”; ≥4) bother scores. Among patients with moderately severe symptoms, 45.8% had low bother scores, 29.7% had average (mean) bother scores, and 24.5% had high bother scores. 80 Not at all A little Some A lot 60 40 20 0 Total Mild Moderate Severe Level of Severity VOL. 7 NO. 1 2005 REVIEWS IN UROLOGY 5 “Bother Score” in BPH Treatment continued Table 4 Correlation of IPSS Bother Question Score Categories With IPSS Severity (MSAM-7) IPSS Severity IPSS Bother Total Asymptomatic Mild Moderate Severe P (
2) Bad 1623 (12.6) 8 (0.6) 149 (2.1) 912 (24.5) 554 (73.6) .01 Mean Good 1736 (13.5) 7 (0.5) 477 (6.7) 1108 (29.7) 144 (19.1) 9500 (73.9) 1270 (98.8) 6466 (91.2) 1709 (45.8) 55 (7.3) Total 12,859 (100) 1285 (100) 7092 (100) 3729 (100) 753 (100) Data are presented as n (%). IPSS, International Prostate Symptom Score; MSAM-7, Multinational Survey of the Aging Male. Data from Rosen R et al. Eur Urol. 2003;44:637-649.5 majority of patients who were mildly or moderately symptomatic at the time of their surgery reported little or no discomfort from their prostate condition. The authors inferred that groups. These results showed that even though there were significant differences in the severity of urinary symptoms between the 2 groups, the AUASI provided a consistent meas- Symptoms related to storage (frequency, nocturia, incontinence) were embarrassing and disruptive of daily life and tended to be more bothersome. patients who were less bothered by their symptoms were less likely to feel the need for surgery to relieve those symptoms.19 These results highlight the significance of perceived bother in the evaluation and treatment of patients with moderate to severe LUTS. Data from a number of studies show a correlation between bother-associated scores and symptom parameters. A community-based international study compared the correlation between frequencies of symptoms, bother-associated scores, and interference with daily activities in several thousand men aged 40 to 79 years in the United States and Scotland.20 Results showed that although the Americans had higher overall scores for symptom frequency, symptom bother, and interference with daily activities than the Scottish men (P < .0002 for each comparison), the extent to which symptoms interfered with daily living within each symptom category was the same for the 2 community-based 6 VOL. 7 NO. 1 2005 REVIEWS IN UROLOGY ure of the perceived degree to which symptoms interfered with daily activities.20 The importance of the application of the bother score in the evaluation of LUTS is further illustrated in a study that examined the relationship between the prevalence of symptoms and the degree of bothersomeness caused by LUTS.21 Questionnaire data from 1271 men with LUTS from 12 countries were analyzed. Results of the study showed that the most commonly occurring symptoms were not necessarily the ones that bothered men the most. When symptoms were divided into domains of voiding and storage, symptoms related to voiding (hesitancy, reduced stream, terminal dribble) tended to be more prevalent, whereas symptoms related to storage (frequency, nocturia, incontinence) were embarrassing and disruptive of daily life and tended to be more bothersome.21 Figure 3. Correlation of IPSS bother question scores with IPSS severity in the MSAM-7 study. IPSS, International Prostate Symptom Score; MSAM-7, Multinational Survey of the Aging Male. Data from Rosen R et al. Eur Urol. 2003;44:637-649.5 100% 80% IPSS quality of life 60% Bad Mean Good 40% 20% 0% Asymptomatic Mild Moderate IPSS severity Severe “Bother Score” in BPH Treatment The association between symptom severity and bothersomeness of urinary symptoms was highlighted in a 5-year study conducted by the Department of Veterans Affairs.22 In this study, 556 patients with moderate symptoms of BPH were randomized to watchful waiting or transurethral resection of the prostate (TURP).22 Bothersomeness was assessed by an 11-item questionnaire that focused on discomfort, inconvenience, embarrassment, and anxiety about urinary tionnaire for BPH. The IPSS and AUA bothersome index were computed as well. Notably, this study found that overall QOL was affected mainly by irritative symptoms and that the bother score was the best determinant of how severely urinary symptoms interfered with activities of daily living and caused the patient to worry.23 A Japanese study that examined which factors were most bothersome to 423 newly diagnosed patients with symptomatic BPH Results showed that moderate to severe urinary symptoms substantially affect patients’ lives in terms of degree of bother, worry, interference with activities of daily living, and psychological well-being. symptoms. The global bother question, “Overall, how bothersome has your trouble with urination been?” appeared as the first item.22 The study found that the crossover rate from watchful waiting to TURP at the patients’ request was 36% at 5 years22; higher total bother scores at baseline were always associated with a higher crossover rate than less bother, and bother was more predictive of crossover than were symptoms.22 After crossover, the degree of bother from genitourinary symptoms was similar between the 2 groups and correlated with symptom improvement.22 This study reconfirmed the correlation between urinary signs and the clinical application of the bother score to assess bothersomeness of symptoms. Additional support for the correlation between urinary symptom severity and the bother score is provided by international studies.9,18,23-25 A study of a representative community sample of 2011 French men examined the impact of symptoms on level of bother and QOL. Bothersomeness level and QOL associated with 12 urinary symptoms were assessed by personal interviews using a validated ques- demonstrated a moderate to good correlation between symptom-specific QOL scores and IPSS (P < .0001; Spearman’s rank correlation coefficient r = 0.525–0.560).24 This study found that weak stream was a very bothersome symptom and concluded that the bother question (“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 it?”) was fundamental to the evaluation of symptom-specific QOL of patients with BPH.24 An American study of 2115 randomly selected community men with no previous prostate surgery or malignancy was conducted to evaluate the impact of urinary symptoms on health-related QOL, including degree of bother (based on AUA bother score).25 Results showed that moderate to severe urinary symptoms substantially affect patients’ lives in terms of degree of bother, worry, interference with activities of daily living, and psychological well-being. Specifically, patients with moderate to severe voiding symptoms reported 4 to 6 times the degree of bother and interference with activities of daily living and twice the level of worry compared with those with mild symptoms. The study concluded that urinary symptoms have significant impact on QOL and interference with daily activities, and the impact is more pronounced among men with more severe symptoms.25 A study to validate the Danish Prostatic Symptom Score system for use in BPH found that the total symptom score was correlated with the total bother score (Cronbach’s  r = 0.709; P < .001).9 These findings further establish the importance of valid clinical tools for assessing severity of symptoms, determining the degree to which the patient is bothered by symptoms, and evaluating the efficacy of interventions. A number of valid, reliable, and responsive scales reflecting improvement or deterioration in clinical status have been developed to assess the impact of LUTS on QOL in patients with BPH. These scales have shown that as symptom severity increases, QOL parameters, including bother, interference with daily activities, general health, and sexual satisfaction, are negatively affected.26 Collectively, the studies described above demonstrate the correlation between bother-associated scores and symptom parameters and further underscore the importance of the bother score in the evaluation and treatment of patients with moderate to severe LUTS. Correlation of the Bother Score with IPSS Symptoms in Clinical Trials The responsiveness (ie, ability to measure clinical change)27 of the bother score in the assessment of response to pharmacotherapy was demonstrated in the analysis of pooled data from 3 clinical trials with the once-daily, prolonged-release formulation of alfuzosin in patients with LUTS consistent with clinical VOL. 7 NO. 1 2005 REVIEWS IN UROLOGY 7 “Bother Score” in BPH Treatment continued Table 5 Improvement in Global Bother Score for Pivotal Alfuzosin Registration Trials ALFORTI29 Parameter Baseline Global Bother Score Difference P vs placebo Alfuzosin 10 mg once daily (n = 137) 3.3 (0.9) –1.1 (1.1) .0008 ALFUS30 Placebo (n = 152) 3.3 (1.0) –0.6 (1.2) Alfuzosin 10 mg once daily (n = 170) 3.8 (1.1) –0.7 (1.1) .002 Placebo (n = 167) 3.7 (1.1) –0.3 (1.1) Numbers in parentheses are standard deviations. BPH.28 The results of 2 of these randomized, placebo-controlled, doubleblind, parallel, 12-week trials (Alfuzosin once daily vs tid [ALFORTI], and Alfuzosin once daily, study conducted in United States [ALFUS]) have been reported previously.28-30 In the ALFUS study, a decrease of 2 or more points in the bother score occurred in a significantly greater percentage of patients who received alfuzosin (10 mg once daily and 15 mg once daily) than in controls (a decrease of approximately 21% for both groups vs 12% for placebo; P = .004 for the alfuzosin 10-mg group and P = .003 for the alfuzosin 15-mg group).30 Similarly, the ALFORTI study showed significant improvements in QOL scores in alfuzosin-treated patients compared with controls.29 These results demonstrate the test– retest reliability of the bother question (Table 5).29,30 A qualitative improvement in the bother score was detected in an analysis of pooled safety and efficacy data from these 3 similarly designed trials. The analysis showed a statistically significantly greater improvement in the bother score from baseline to endpoint with alfuzosin than with placebo (–1.0 ± 1.1 vs –0.7 ± 1.1; P < .001).28 Furthermore, this analysis showed that alfuzosin treatment produced a clinically significant thera- 8 VOL. 7 NO. 1 2005 REVIEWS IN UROLOGY peutic effect, including improvements in both obstructive and irritative subscores, which was reflected by improvements in the QOL index.28 Other pooled trial data (data on file, Sanofi-Synthelabo, New York, NY) showed strong correlations between bother score and IPSS total scores, with Spearman correlation coefficients equal to 0.42 and 0.48 at baseline in alfuzosin-treated and placebo-treated patients, respectively, and Spearman correlation coefficients equal to 0.53 and 0.54, respectively, for the corresponding changes from baseline in both parameters at endpoint. Spearman correlation coefficients between baseline bother scores and baseline subscores for irritative symptoms (alfuzosin, 0.42; placebo, 0.47), obstructive symptoms (alfuzosin, 0.29; placebo, 0.34), and nocturia (alfuzosin, 0.27; placebo, 0.33) were statistically significant for placebo and alfuzosin (P < .0001]). At endpoint, similarly strong statistically significant (P < .0001) correlations were seen, with Spearman correlation coefficients equal to 0.37 and 0.35 (irritative symptoms), 0.44 and 0.47 (obstructive symptoms), and 0.30 and 0.37 (nocturia), respectively, for alfuzosin and placebo. These data demonstrate that there is a positive correlation between the bother score and IPSS total scores and symptom subscores with or without treatment. Studies with other pharmacologic agents used for the management of BPH symptoms have also supported the importance of the bother score as a measure of QOL. For example, an integrated analysis of 2 randomized studies on the efficacy and tolerability of a controlled-release formulation of doxazosin compared with doxazosin standard (doxazosin-S) in patients with BPH demonstrated that both drugs produced similar improvements in the bother score from baseline, which were greater than changes seen in the placebo group, and both drugs were similarly efficacious in reducing clinical symptoms.31 Treatment with the doxazosin controlled-release formulation resulted in an improvement in the bother score from a mean of 3.7 ± 1.1 at baseline to 2.3 ± 1.3 at the final visit in patients receiving that drug, whereas the bother score for patients receiving doxazosin-S improved from 3.6 ± 1.1 at baseline to 2.3 ± 1.3 at the final visit.31 In another study of patients with BPH, doxazosin was added to another antihypertensive medication (angiotensin-converting enzyme inhibitor, calcium antagonist, diuretic, or ß-blocker). Patients in this study reported a reduction in prostatic symptoms, as well as an improvement in the bother score (baseline score, 4.3 ± 1.1; posttreatment score, 2.0 ± 1.1) in hypertensive patients with symptomatic BPH.32 Taken together, these data clearly demonstrate that the bother score meets the criterion for responsiveness (the ability to measure clinical change) established for scales used to evaluate therapeutic efficacy.27 Conclusion Numerous studies have evaluated bother in patients with BPH-associated LUTS. The answer to a single “Bother Score” in BPH Treatment clinical question, referred to as the bother question, provides a reproducibly valid tool for evaluating changes in the status of LUTS. The validity of a diagnostic tool depends on its relationship with clinical signs, reliability, sensitivity, and responsiveness to changes in symptoms. All of these parameters have been well established for the bother question of the IPSS. The bother score, therefore, is a valuable tool for the formulation of treatment strategies for patients with symptomatic BPH. The degree to which symptoms become bothersome or worrisome to a patient usually provides the basis for his decision to seek medical treatment. Patients who are less bothered by their symptoms are often less likely to seek treatment to relieve those symptoms, but those who are more bothered by their symptoms and seek treatment are more likely to respond to therapy. Although the conciseness and apparent simplicity of the bother score might lead some to question its utility for evaluating clinical trial outcomes, these very factors, together with its proven validity, demonstrate that it is both convenient and a reliably accurate tool for this purpose. Validation data reviewed in this article support the argument that the bother score is a valid and reliable measure of treatment outcome in patients troubled by LUTS associated with BPH. 10. 11. 12. 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Quality-of-life assessment in Main Points • The clinical signs associated with benign prostatic hyperplasia (BPH) are rarely life-threatening; the degree to which symptoms become bothersome or worrisome to the patient and disrupt his daily activities usually provides the basis for his decision to seek medical treatment. • Reliable and valid outcome measures for the treatment of BPH have been developed to help urologists quantify the extent of bother, to help establish whether treatment for BPH and lower urinary tract symptoms (LUTS) is appropriate to a patient. • One particular question of the universally used International Prostate Symptom Score (IPSS), known as the bother question, is used to determine the bother score, a valuable prognostic aid for which test–retest reliability and internal reliability have been demonstrated. • Analyses of the responses of more than 12,000 participants in a large-scale multinational study of LUTS and sexual function in older men confirm that scores on the IPSS bother question significantly correlate with IPSS symptom severity. • The responsiveness (ie, ability to measure clinical change) of the bother score in the assessment of response to pharmacotherapy has been demonstrated in the analysis of pooled data from 3 clinical trials. • Although the conciseness and apparent simplicity of the bother score might lead some to question its utility for evaluating clinical trial outcomes, these very factors, together with its proven validity, demonstrate that it is both convenient and a reliably accurate tool for this purpose. 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Safety and efficacy of alfuzosin 10 mg oncedaily in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies. BJU Int. 2003; 92:257-261. 29. 30. 31. 32. van Kerrebroeck P, Jardin A, Laval KU, van Cangh P. Efficacy and safety of a new prolonged release formulation of alfuzosin 10 mg once daily versus alfuzosin 2.5 mg thrice daily and placebo in patients with symptomatic benign prostatic hyperplasia. ALFORTI Study Group. Eur Urol. 2000;37:306-313. Roehrborn CG, for the ALFUS Study Group. Efficacy and safety of once-daily alfuzosin in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a randomized, placebo-controlled trial. Urology. 2001;58:953-959. Kirby RS, Andersen M, Gratzke P, et al. A combined analysis of double-blind trials of the efficacy and tolerability of doxazosin-gastrointestinal therapeutic system, doxazosin standard and placebo in patients with benign prostatic hyperplasia. BJU Int. 2001;87:192-200. Martell N, Luque M. Doxazosin added to singledrug therapy in hypertensive patients with benign prostatic hypertrophy. J Clin Hypertens (Greenwich). 2001;3:218-223.