Differential Diagnosis of in Men

Jerry G. Blaivas,* Brian K. Marks, Jeffrey P. Weiss,†,‡ Georgia Panagopoulos and Chandra Somaroo

From the State University of New York Downstate Medical School (BKM, JPW, Brooklyn and Weill Medical College of Cornell University and Lenox Hill Hospital, New York, New York

Abbreviations Purpose: We determined the differential diagnosis of concomitant pathological and Acronyms conditions in men with overactive bladder symptoms. BOO ϭ bladder outlet obstruction Materials and Methods: We performed an observational, descriptive study to elucidate the differential diagnosis in men with overactive bladder symptoms BPE ϭ benign prostatic using a previously validated overactive bladder symptom questionnaire. All enlargement patients provided an extensive history, completed the self-administered question- ϭ OAB overactive bladder naire and a 24-hour voiding diary, and underwent physical examination, 24-hour pad test, uroflowmetry, post-void residual measurement, and Submitted for publication April 1, 2009. urodynamics. Selection criteria were developed to assign cases to a category, Supported by The Urocenter of New York. * Financial interest and/or other relationship including idiopathic overactive bladder, benign prostatic enlargement, benign with Bayer, Pfizer, Endegun and HDH. prostatic obstruction, neurogenic bladder, , cancer treat- † Correspondence: Veterans Affairs New York ment complications, , bladder stones and bladder diverticulum. Harbor Healthcare System, 800 Poly Pl., Mail Route Code 112A, Brooklyn, New York 11209 Results: Of 122 men who met selection criteria for overactive bladder detrusor (telephone: 718-836-6600, extension 6885; FAX: overactivity was identified in 99 (79%) on urodynamics. The differential diagnosis 212-838-3213; e-mail: [email protected]). was benign prostatic enlargement in 40 men (32%), benign prostatic obstruction ‡ Financial interest and/or other relationship with Ferring, Pfizer and Watson. in 27 (22%), complications of prostate cancer treatment in 25 (20%), neurogenic Supplementary material for this article can be bladder in 13 (11%), urethral stricture in 7 (6%), idiopathic overactive bladder in obtained at http://www.urologysite.com/. 6 (5%), in 2 (2%), bladder cancer in 1 (1%) and bladder diverticulum in 1 (1%). Conclusions: Overactive bladder is a complex diagnosis with many underlying, contributing urological pathologies. It should be considered a symptom complex and not a syndrome. Knowledge of the differential diagnosis in men with over- active bladder symptoms would hopefully provide clinicians with a diagnostic rubric to more specifically treat such patients with improved success.

Key Words: , overactive; diagnosis, differential; urinary bladder, neurogenic; prostatic hyperplasia; signs and symptoms

APPROXIMATELY 9% to 16% of the gen- prostatic obstruction, neurogenic blad- eral adult population has OAB symp- der, , bladder carcinoma, blad- toms.1,2 As defined by the International der stone, sphincteric incontinence and Continence Society, OAB is “urgency, postoperative causes.2,4–8 The etiology with or without urge incontinence, usu- and prevalence of these pathological ally with frequency and nocturia” and conditions in patients with OAB are “in the absence of infection or other less well-defined. proven etiology.” 3 However, often pa- Research has focused on the rela- tients with OAB symptoms have other tionship between the urodynamic find- proven etiologies. These concomitant ing of detrusor overactivity and associ- pathological conditions include BPE, ated urodynamic findings or urological

0022-5347/09/1826-2814/0 Vol. 182, 2814-2818, December 2009 ® 2814 www.jurology.com THE JOURNAL OF Printed in U.S.A. Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2009.08.039 DIFFERENTIAL DIAGNOSIS OF OVERACTIVE BLADDER IN MEN 2815

Table 1. OAB differential diagnoses therapy without other identified bladder or prostate pa- thology. Neurogenic bladder was defined as OAB symp- Differential Diagnosis No. Pts (%) toms in the presence of a known neurological disorder, BPE 40 (32) including cerebrovascular accident, myelopathy, Parkin- Benign prostatic obstruction 27 (22) son’s disease and multiple sclerosis. Idiopathic OAB was Prostate Ca treatment complications 25 (20) defined as urgency in the absence of the mentioned diag- Neurogenic bladder 13 (11) noses. Urethral stricture 7 (6) Idiopathic OAB 6 (5) Bladder stone 2 (2) RESULTS Bladder Ca 1 (1) Bladder diverticulum 1 (1) In 122 men who met OAB selection criteria mean age was 70 years (median 67, range 28 to 90). Uro- Total 122 (100) dynamics revealed detrusor overactivity in 99 men (79%). Table 1 lists differential diagnoses. Diagnosis in 13 patients with neurogenic bladder 9–11 disorders. Limited information is available on the was cerebrovascular accident in 6, myelopathy in 4, prevalence of associated urological diagnoses in pa- Parkinson’s disease in 1 and multiple sclerosis in 2. tients with OAB syndrome. We used a previously val- Cerebrovascular accident included traumatic hemi- 12 idated questionnaire to identify patients with OAB paresis, transient ischemic attack and stroke. My- and report the prevalence of concomitant urological elopathy was due to viral myelopathy, spinal steno- pathologies in this group. sis and surgical trauma. Based on modified Roehrborn criteria BPE was identified in 56 patients (table 2), of whom 15 had a MATERIALS AND METHODS diagnosis of BOO and 40 had symptomatic BPE We performed an institutional review board approved, without another diagnosis. OAB developed in 25 observational descriptive study to elucidate the differen- men after treatment for prostate cancer. Radical tial diagnosis in men with OAB symptoms. A previously was done in 21 men and all had validated OAB symptom questionnaire12 was adminis- tered in consecutive male patients who presented to 2 sphincteric incontinence and OAB. Four men had independent outpatient urology centers for evaluation of undergone radiation, including brachytherapy in 2, lower urinary tract symptoms during 1 year. Study inclu- and brachytherapy and external beam radiotherapy sion criteria were based on previously validated results.12 in 2. Two of the latter patients also had urethral The questionnaire consisted of 7 questions, each scored on obstruction. a 5-point scale of 0 to 4.12 Patients were included in the OAB cohort if their response was scored as 3 or 4 to the question, “How often do you get a sudden urge or desire to Table 2. Prostate size in all patients urinate that makes you want to stop what you are doing and rush to the bathroom?” Prostate Size No. Pts (%) All patients provided an extensive history, completed 0 15 (15) the self-administered questionnaire and a 24-hour voiding 1ϩ 25 (25) diary, and underwent physical examination, 24-hour pad 2ϩ 44 (44) test (in those with incontinence), uroflowmetry, post-void 3ϩ 8 (8) residual urine measurement, cystoscopy and urodynam- 4ϩ 4 (5) ics. Study selection criteria were developed to assign pa- Unknown 3 (3) tients to a category, including idiopathic OAB, BPE, be- Total 99* nign prostatic obstruction, neurogenic bladder, bladder Benign prostatic obstruction: cancer, complications of prostate cancer treatment, ure- 0 3 (13) thral stricture, bladder stones and bladder diverticulum. 1ϩ 4 (17) ϩ All questionnaires and completed assessments were 2 13 (57) 3ϩ 3 (13) reviewed by an independent research associate. Patients 4ϩ 0 were included in the study based on questionnaire results and placed in the appropriate category based on selection Total 23 criteria. BPE was characterized by prostate size and esti- No benign prostatic obstruction: 0 12 (16) mated by digital rectal examination, as modified from the ϩ 13 1 21 (28) study of Roehrborn et al. Prostate size was graded on a ϩ ϩ 2 31 (40) system of 0 to 4 with the modification 0 representing 3ϩ 5 (7) ϩ less than normal prostate size. Prostate size 2 or greater 4ϩ 4 (5) 13 was categorized as BPE. Prostatic obstruction was diag- Unknown 3 (4) nosed by a Schafer obstruction grade greater than 2. Com- Total 76 plications of prostate cancer treatment were defined as OAB symptoms after radical prostatectomy or radiation * Omitting men with prostate cancer. 2816 DIFFERENTIAL DIAGNOSIS OF OVERACTIVE BLADDER IN MEN

DISCUSSION struction were completely alleviated after transure- 18 As defined by the International Continence Society, thral prostate resection. In another small series OAB indicates a symptom complex comprising “ur- detrusor overactivity resolved on urodynamics in gency, with or without urge incontinence, usually 75% of patients after transurethral prostate resec- 19 with frequency and nocturia. . . in the absence of tion. Thus, treating BOO may provide more bene- infection or other proven etiology.”3 This definition fit since improvement on anticholinergics depends fails to address the well-known differential diagno- on patients continuing the medication indefinitely sis of OAB and the pathological conditions associ- but most discontinue it within a few months because of dissatisfaction with the level of improvement ated with these lower urinary tract symptoms. We 20 noted the prevalence of concomitant urological pa- and/or side effects. thologies in these men identified with OAB using a In our series 56 men had BPE, of whom 16 also validated questionnaire.12 Our study suggests that had BOO. The remaining 40 patients had symptom- most men with OAB have concomitant urological atic BPE without urodynamic evidence of obstruc- diagnoses. The data show that the most common tion. We do not claim that BPE causes OAB but do not exclude the possibility that a pathophysiological diagnoses were BPE (32% of cases), BOO (22%) and relationship exists. Thus, it is important to include complications of prostate cancer treatment (20%). BPE as part of the differential diagnosis. Further- Truly idiopathic OAB was found in only 5% of this more, patients with BPE are already being treated population. Considering this differential diagnosis empirically with 5␣-reductase inhibitors, implying intellectually engages the physician to consider new that at least some practitioners believe that BPE is diagnostic and treatment algorithms that may be a pathological condition that should be diagnosed more precise and effective. and treated. Current OAB treatment algorithms assume that In our series OAB developed in 25 men (20%) “OAB is an empiric diagnosis that can be used for after prostate cancer treatment. Sphincteric incon- the initial management after assessing symptoms”14 tinence often develops after radical prostatectomy and anticholinergic therapy remains the mainstay but it appears less well-known that these patients empirical regimen prescribed. Due to the paucity of may also have OAB requiring treatment. After pros- well controlled clinical studies there is insufficient tatectomy about 12% of men with sphincteric incon- evidence to determine whether any other medica- tinence also have detrusor overactivity on urodynam- tions are better or worse than anticholinergic ther- 21 15 ics. Also, after prostate cancer treatment patients apy. This rationale may result in suboptimal may have OAB and urethral obstruction. In our expe- treatment, as in men with unidentified prostatic rience successful treatment for urethral obstruction obstruction who present predominantly with ur- often relieves OAB symptoms. gency and are treated with anticholinergics. In OAB may be the presenting symptom of bladder this population 22% of patients with OAB symp- cancer even in the absence of . Although toms had BOO. These patients may derive more they were not included in this series, we treated 3 benefit from treatments directed at relieving patients without hematuria empirically with anti- BOO. cholinergics for up to 18 months for what proved to Approximately 50% to 75% of men with BOO on be invasive bladder cancer. Two such patients ulti- 16 urodynamics have OAB symptoms and it is esti- mately died of metastatic disease. mated that between 46% and 66% with prostatic This study is not the first to describe other uro- obstruction on urodynamics have detrusor overac- logical pathologies as coexisting or causing OAB. 9–11 tivity. It was recently suggested that patients on Concomitant pathological conditions with symp- combined tamsulosin and tolterodine therapy for toms dominated by OAB are documented in the lower urinary tract symptoms with urgency and literature. Lower urinary tract obstruction, in- frequency have significantly greater perception of cluding BPE and primary bladder neck dysfunc- treatment benefit compared to those on mono- tion, may coexist with or be a cause of OAB.4,7 In therapy or placebo.17 Since therapy with tolterod- 1 series the most commonly diagnosed causes of ine alone did not provide the same improvement, OAB were neurogenic bladder and prostatic obstruc- treating prostatic obstruction may provide benefit in tion.2 Other concomitant disorders were nonneurogenic patients with OAB symptoms and BOO. In men with causes, such as infection, bladder tumor, sphincteric in- OAB and prostatic obstruction surgical treatment continence, postoperative pathological conditions and for obstruction relieves detrusor overactivity and at bladder stones.2,5 Neurogenic etiologies include ce- least by implication OAB symptoms should also re- rebrovascular accident, Parkinson’s disease, multi- solve. This has been the case in our clinical experi- ple sclerosis, and myelodyspla- ence. Kageyama et al reported that certain detrusor sia.5–8 Many of these urological disorders related to overactivity patterns in patients with prostatic ob- OAB have been described in urodynamic studies. DIFFERENTIAL DIAGNOSIS OF OVERACTIVE BLADDER IN MEN 2817

Flisser et al characterized urodynamic data in a 90 years, median age was 67 years. Thus, results series of men and women with OAB symptoms and may not represent the general population. Women tabulated various associated diagnoses, including were not included in the study but they were studied BPE in 28% of cases, sphincteric incontinence in later. The differential diagnosis in a population of 17%, idiopathic urge incontinence in 29% and utero- women will be submitted for review. vaginal or bladder prolapse in 17%.22 Another 11% of patients had BOO, impaired detrusor contractility or neurogenic bladder conditions.” CONCLUSIONS The study has several limitations. Data collection OAB should be considered a symptom complex and was limited by the relatively small database and the not a syndrome. A syndrome is “the aggregate of retrospective nature of the analysis. Many patients symptoms and signs associated with any morbid were seen at a urological center specializing in lower process, together constituting the picture of the dis- urinary tract disorders, which may have increased ease.”23 OAB should not be considered a disease the likelihood that the cohort does represent the entity but a complex diagnosis with many underly- general male population. However, we previously ing contributing urological pathologies. Knowledge reported that the pathophysiology underlying symp- of the differential diagnosis in men with OAB symp- toms in men with lower urinary tract symptoms was toms would hopefully provide clinicians with a diag- similar in a primary urological setting and at a nostic rubric to more specifically treat such patients specialized center.9 Although patient age was 28 to with improved success.

REFERENCES 1. Abrams P: Describing bladder storage function: 9. Fusco F, Groutz A, Blaivas JG et al: Videourody- function in symptomatic elderly men. J Urol 1999; overactive bladder syndrome and detrusor over- namic studies in men with lower urinary tract 162: 142. activity. Urology 2003; 62: 28. symptoms: a comparison of community based versus referral urological practices. J Urol 2001; 17. Kaplan SA, Roehrborn CG, Rovner ES et al: 2. Wein AJ and Rackley RR: Overactive bladder: a 166: 910. Tolterodine and tamsulosin for treatment of men better understanding of pathophysiology, diagno- with lower urinary tract symptoms and overactive sis and management. J Urol 2006; 175: S5. 10. Hyman MJ, Groutz A and Blaivas JG: Detrusor bladder: a randomized controlled trial. JAMA instability in men: correlation of lower urinary 2006; 296: 2319. 3. Abrams P, Cardozo L, Fall M et al: The standar- tract symptoms with urodynamic findings. J Urol disation of terminology of lower urinary tract 2001; 166: 550. 18. Kageyama S, Watanabe T, Kurita Y et al: Can function: report from the Standardisation Sub- persisting detrusor hyperreflexia be predicted af- committee of the International Continence So- 11. Kaplan SA, Bowers DL, Te AE et al: Differential ter transurethral prostatectomy for benign pros- ciety. Neurourol Urodyn 2002; 21: 167. diagnosis of prostatism: a 12-year retrospective tatic hypertrophy? Neurourol Urodyn 2000; 19: analysis of symptoms, urodynamics and satisfac- 233. 4. Dmochowski RR and Staskin D: Overactive blad- tion with therapy. J Urol 1996; 155: 1305. 19. Sriplakich S and Promwatcharanon K: The reso- der in men: special considerations for evaluation 12. Blaivas JG, Panagopoulos G, Weiss JP et al: lution of detrusor over activity after medical and and management. Urology 2002; 60: 56. Validation of the overactive bladder symptom surgical treatment in patients with bladder outlet 5. Blaivas JG: The neurophysiology of micturition: a score. J Urol 2007; 178: 543. obstruction. J Med Assoc Thai 2007; 90: 2326. clinical study of 550 patients. J Urol 1982; 127: 13. Roehrborn CG, Sech S, Montoya J et al: Interex- 20. Basra RK, Wagg A, Chapple C et al: A review of 958. aminer reliability and validity of a three-dimen- adherence to drug therapy in patients with over- 6. Hebjorn S, Anderson JT, Walter S et al: Detrusor sional model to assess prostate volume by digital active bladder. BJU Int 2008; 102: 774. rectal examination. Urology 2001; 57: 1087. hyperreflexia: a survey of its etiology and treat- 21. Groutz A, Blaivas JG, Chaikin DC et al: The patho- ment. Scand J Urol Nephrol 1976; 10: 103. 14. Wein AJ: Diagnosis and treatment of the over- physiology of post-radical prostatectomy inconti- active bladder. Urology 2003; 62: 20. nence: a clinical and video urodynamic study. J Urol 7. Mostwin J: Pathophysiology: the varieties of 2000; 163: 1767. bladder overactivity. Urology 2002; 60: 22. 15. Roxburgh C, Cook J and Dublin N: Anticholinergic drugs versus other medications for overactive 22. Flisser AJ, Walmsley K and Blaivas JG: Urody- 8. Kolominsky-Rabas PL, Hilz MJ, Neundoerfer bladder syndrome in adults. Cochrane Database namic classification of patients with symptoms of B et al: Impact of after Syst Rev 2007; 4: CD003190. overactive bladder. J Urol 2003; 169: 529. stroke: results from a prospective population- based stroke register. Neurourol Urodyn 2003; 16. Ameda K, Sullivan MP, Bae RJ et al: Urodynamic 23. Stedman’s Medical Dictionary, 28th ed. Balti- 22: 322. characterization of non-obstructed voiding dys- more: Lippincott Williams & Wilkins 2006. 2818 DIFFERENTIAL DIAGNOSIS OF OVERACTIVE BLADDER IN MEN

EDITORIAL COMMENT

These authors make the important point that OAB, is undergoing scrutiny. If we can debate the inter- as a complex diagnosis with many underlying con- pretation of urgency, and OAB can be a singularity tributing urological pathologies and many causes, and, as I suggest, not a syndrome or symptom com- should be considered a symptom complex and not a plex, what is it? Until this is clarified we should be syndrome. I do not believe that OAB is a symptom careful how we use these terms. complex. By definition it is simply urgency. While it is not generally considered in this way, urgency alone is sufficient for the diagnosis. OAB is urgency Norman R. Zinner with or without urge incontinence, usually with fre- Department of Urology Geffen School of Medicine quency and nocturia. One can have incontinence, University of California-Los Angeles frequency and nocturia without OAB or urgency Los Angeles, California alone and have OAB. However, while urgency is Western Clinical Research, Inc. defined, it is an unclear, often debated concept that Torrance, California