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Diagnosis and Treatment of /Bladder Pain Syndrome: AUA Guideline Amendment

Philip M. Hanno, Deborah Erickson, Robert Moldwin* and Martha M. Faraday

From the American Urological Association Education and Research, Inc., Linthicum, Maryland

Purpose: The purpose of this amendment is to provide an updated clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain Abbreviations and Acronyms syndrome based upon data received since the publication of original guideline ¼ in 2011. AE adverse event Ò ¼ Materials and Methods: A systematic literature review using the MEDLINE BPS bladder pain syndrome database (search dates 1/1/83-7/22/09) was conducted to identify peer-reviewed BTX-A ¼ A publications relevant to the diagnosis and treatment of IC/BPS. This initial re- CP ¼ chronic view yielded an evidence base of 86 treatment articles after application of in- CPPS ¼ chronic clusion/exclusion criteria. The AUA update literature review process, in which syndrome an additional systematic review is conducted periodically to maintain guideline GTM ¼ global therapeutic currency with newly published relevant literature, was conducted in July 2013. massage This review identified an additional 31 articles, which were added to the evidence IC ¼ interstitial cystitis base of this Guideline. MPT ¼ myofascial physical Results: Newly incorporated literature describing the treatment of IC/BPS therapy was integrated into the Guideline with additional treatment information pro- Qol ¼ quality of life vided as Clinical Principles and Expert Opinions when insufficient evidence UTI ¼ existed. The diagnostic portion of the Guideline remains unchanged from the original publication and is still based on Expert Opinions and Clinical Principles. Accepted for publication January 16, 2015. Conclusions: The management of IC/BPS continues to evolve as can be seen by The complete guideline is available at http:// an expanding literature on the topic. This document constitutes a clinical www.auanet.org/education/guidelines/ic-bladder- pain-syndrome.cfm. strategy and is not intended to be interpreted rigidly. The most effective This document is being prined as submitted approach for a particular patient is best determined by the individual clinician independent of editorial or peer review by the and patient. As the science relevant to IC/BPS evolves and improves, the stra- Editors of The Journal of UrologyÒ. * Financial and/or other relationship with tegies presented will require amendment to remain consistent with the highest Taris Biomedical, Urigen Pharmaceuticals and standards of care. Afferent Pharmaceuticals.

For another article on a related Key Words: cystitis, interstitial; pelvic pain; urodynamics; topic see page 1676. lower urinary tract symptoms; diseases

INTRODUCTION while minimizing adverse events THIS guideline’s purpose is to provide and patient burden. The strategies direction to clinicians and patients and approaches recommended in regarding how to recognize intersti- this document were derived from tial cystitis/bladder pain syndrome, evidence-based and consensus-based conduct a valid diagnostic process, processes. IC/BPS nomenclature is a and, approach treatment with the controversial issue; for the purpose goals of maximizing symptom con- of clarity the Panel decided to refer trol and patient quality of life to the syndrome as IC/BPS and to

0022-5347/15/1935-1545/0 http://dx.doi.org/10.1016/j.juro.2015.01.086 THE JOURNAL OF ® Vol. 193, 1545-1553, May 2015 www.jurology.com j 1545 © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH,INC. Printed in U.S.A. 1546 AUA GUIDELINE AMENDMENT

consider these terms synonymous. This document construct the majority of the treatment portion of the provides an overview of the amendments made to algorithm. the 2011 Guideline and should, therefore, be viewed The initial and update reviews revealed insufficient in conjunction with the full Guideline available at publications to address IC/BPS diagnosis and overall http://www.auanet.org/education/guidelines/ic-bladder- management from an evidence basis and, therefore, the diagnosis and management portions of the algorithm pain-syndrome.cfm. The updated algorithm reflects (see figure) are provided as Clinical Principles or as these changes as well (see figure). Expert Opinion with consensus achieved using a modified Delphi technique if differences of opinion emerged.1 For a complete discussion of the methodology and evidence METHODOLOGY grading, please refer to the unabridged version of this An initial systematic review was conducted to identify Guideline. published articles relevant to the diagnosis and treatment of IC/BPS. Literature searches were performed on English language publications using the MEDLINE database from January 1, 1983 to July 22, 2009 using the BACKGROUND terms “interstitial cystitis,” “painful bladder syndrome,” Definition “bladder pain syndrome,” and “pelvic pain” as well as key The bladder disease complex includes a large group words capturing the various diagnostic procedures and of patients with bladder and/or urethral and/or treatments known to be used for these syndromes. With pelvic pain, lower urinary tract symptoms and regard to treatment, a total of 86 articles from the original literature searches met the inclusion criteria, and an sterile cultures, many with specific identifi- additional 31 relevant studies were retrieved as part of able causes. IC/BPS comprises a part of this com- the update literature review process. The Panel judged plex. The Panel used the IC/BPS definition agreed that these were a sufficient evidence base from which to upon by the Society of Urodynamics, Female Pelvic

Interstitial cystitis/bladder pain syndrome algorithm AUA GUIDELINE AMENDMENT 1547

Medicine & Urogenital Reconstruction: “An un- it may be greatly under diagnosed in the male pleasant sensation (pain, pressure, discomfort) population.” perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of Typical Course and Comorbidities more than six weeks duration, in the absence of IC/BPS is most commonly diagnosed in the fourth infection or other identifiable causes.”2 This defini- decade or after, although the diagnosis may be tion was selected because it allows treatment to delayed depending upon the index of suspicion for begin after a relatively short symptomatic period, the disease and the criteria used to diagnose it.7 A preventing treatment withholding that could occur history of a recent culture proven UTI can be iden- with definitions that require longer symptom du- tified on presentation in 18% to 36% of women, rations (i.e. six months). Definitions used in although subsequent cultures are negative.8,9 research or clinical trials should be avoided in Initially it is not uncommon for patients to report a clinical practice, as many patients may be mis- single symptom such as , frequency or pain, diagnosed or diagnosis and treatment may be with subsequent progression to multiple symp- delayed if these criteria are used.3 toms.10,11 Symptom flares, during which symptoms suddenly intensify for several hours, days or weeks, IC/BPS Symptoms are not uncommon. There is a high rate of prior pelvic Since the original publication of this Guideline, (especially hysterectomy) and levator ani three papers reported data from the RICE (RAND pain in women with IC/BPS, suggesting that trauma Interstitial Cystitis Epidemiology) study.4e6 One or other local factors may contribute to symptoms.12 of the RICE study objectives was to develop an It is important to note, however, that the high IC/BPS case definition for use in epidemiological incidence of other procedures, such as hysterectomy studies that had known sensitivity and specificity. or laparoscopy, may be the result of a missed diag- Berry et al reported findings from a literature re- nosis and does not necessarily indicate that the view, a structured expert panel process and a tele- surgical procedure itself is a contributing factor to phone interview validation study to derive an symptoms. It is also common for IC/BPS to coexist IC/BPS definition.4 They note that none of the with other unexplained medical conditions, such as existing epidemiological definitions had high sensi- fibromyalgia, , chronic fa- tivity or high specificity. As a result of this process, tigue syndrome, Sjogren’s syndrome, chronic head- two definitions emerged, one with high sensitivity aches and vulvodynia.13,14 These associations that correctly identified IC/BPS cases 81% of the suggest that there may be a systemic dysregulation time (with 54% specificity) and one with high spec- in some patients. Finally, patients with IC/BPS ificity that correctly excluded nonIC/BPS cases frequently exhibit mental health disorders, such as 83% of the time (with 48% sensitivity). The defini- and anxiety. While these symptoms may tions are captured in an 11-item questionnaire. be reactive in some IC/BPS patients, there is also See the Appendix for definitions, which the Panel some evidence that there may be a common biolog- notes that these are epidemiological case definitions ical mechanism involved. and are not appropriate for use as diagnostic criteria. Conceptualizing IC/BPS Berry et al used the questionnaire to determine It is not known whether IC/BPS is a primary prevalence of IC/BPS among adult females in the bladder disorder or whether the bladder symptoms U.S.5 This study yielded prevalence estimates from of IC/BPS are secondary phenomena resulting 2.7% to 6.53% (approximately 3.3 to 7.9 million U.S. from another cause. Converging data from several women age 18 or older). Only 9.7% of women who sources suggest, however, that IC/BPS can be met the definitions reported having been given an conceptualized as a bladder pain disorder that is IC/BPS diagnosis. Suskind et al modified the case often associated with voiding symptomatology and definition for use in men and used an additional other systemic disorders. Specifically, case definition derived from the NIH-Chronic Pros- IC/BPS may be a bladder disorder that is part of a tatitis Symptom Index to assess the prevalence and more generalized systemic disorder, at least in a overlap between IC/BPS and chronic prostatitis/ subset of patients. It has been suggested that chronic pelvic pain syndrome in men.6 This study IC/BPS is a member of a family of hypersensitivity yielded a prevalence estimate of 2.9% to 4.2% for IC/ disorders that affects the bladder and other soma- BPS and a prevalence of 1.8% for CP/CPPS. The tic/visceral organs and has many overlapping overlap between the two syndromes was approxi- symptoms and pathophysiology.15,16 An additional mately 17%. The authors note that these findings hypothesis is that IC/BPS might be just a part of suggest that the prevalence of IC/BPS in men ap- the continuum of painful vs nonpainful overactive proaches its prevalence in women and, therefore, bladder syndrome.17,18 1548 AUA GUIDELINE AMENDMENT

Impact on Psychosocial Functioning and Quality of foods or drinks and/or worsened with bladder filling Life and/or improved with contributed to a The effects of IC/BPS on psychosocial functioning sensitive case definition of IC/BPS.9 and QoL are pervasive and insidious, damaging The prototypical IC/BPS patient also may present work life, psychological well-being, personal re- with marked and frequency but lationships and general health.19 QoL is poorer in IC/ because these symptoms may indicate other disor- BPS patients than in controls.19,20 Rates of depres- ders, they do not exclusively indicate the presence sion are also higher.20,21 In addition, IC/BPS patients of IC/BPS. Voiding frequency is almost universal have significantly more pain, sleep dysfunction, ca- (92% of one population)26 but does not distinguish tastrophizing, depression, anxiety, , social the IC/ BPS patient from other lower urinary tract functioning difficulties and sexual dysfunction than disorders. Change in urinary frequency is valuable do nonIC/BPS age-matched women.22 Health-related to evaluate response to therapy but is of little help QoL in women with IC/BPS is worse than that of in diagnosis. Urinary urgency is also extremely women with , vulvodynia or overactive common (84% of the same population)26 but urgency bladder.23 Given that IC/BPS causes considerable is considered to be the characteristic symptom morbidity over the course of a patient’s life and loss of and, thus, it can actually of work during the most productive years of work confound the diagnosis. There may, however, be and family life, significant negative psychological qualitative differences in the urgency experienced and QoL impacts are not surprising.19 by IC/BPS patients compared to overactive bladder Sexual dysfunction has an especially important patients. IC/BPS patients may experience a more impact on the QoL of IC/BPS patients. In IC/BPS constant urge to void as opposed to the classic ICS patients sexual dysfunction is moderate to severe,24 definition of a “compelling need to urinate which is and occurs at high rates compared to controls.25,26 difficult to postpone.”30,31 Typically IC/BPS patients In women with treatment refractory IC/BPS poor void to avoid or to relieve pain, whereas overactive sexual function is a primary predictor of poor bladder patients void to avoid incontinence. Symp- mental QoL.27 Pain appears to mediate sexual toms of urinary urgency and frequency may precede dysfunction and its associated effects on QoL. symptoms of pain.11 Median time to the develop- Women with IC/BPS report rates of intercourse, ment of a full symptom complex of frequency, ur- desire and orgasm frequency in their adolescence gency and pain was reported to be two years in one that are similar to those reported by controls, but study.11 rates diverge in adulthood when IC/BPS patients report significantly more pain, fear of pain with Presentation of Male IC Patients intercourse and more sexual distress.25 The strong Historically, IC/BPS in men has been considered link between IC/BPS symptoms and psychosocial relatively unusual with a female-to-male ratio of functioning and QoL makes clear the critical 10:1.32,33 However, uncontrolled clinical series over importance of optimizing treatment of IC/BPS the past two decades have suggested that the inci- symptoms. Successful treatment of the medical dence of male IC/BPS may be higher than previously condition clearly brings improvement in functioning observed.34 Early clinical symptoms may begin with and QoL. In addition, response to therapy is asso- mild dysuria or urinary urgency. Mild symptoms ciated with improved sexual function and sleep, may progress to severe voiding frequency, with concomitant improvements in QoL.22,24 and suprapubic pain. The presence or absence of glomerulations on endoscopy is too nonspecific to Symptoms make the diagnosis of the disease in anyone who Pain (including sensations of pressure and discom- does not fit the symptom complex as defined. fort) is the hallmark symptom of IC/BPS. Typical Clinical findings mirror those of the female IC/BPS patients report not only suprapubic pain IC/BPS patient. On examination, suprapubic (or pressure, discomfort) related to bladder filling, tenderness is common along with external (peri- but pain throughout the , including in the neal) tenderness and internal (levator muscle) , , and rectum, and in extra tenderness/spasticity. with hydraulic genital locations such as the lower abdomen and distention of the bladder in men with IC/BPS back.9,26,28 Warren et al found that by using “pelvic commonly demonstrates diffuse glomerulations.34 pain” as the key descriptor 100% of his population Some data suggest that Hunner lesions are more fit the case definition.29 It is important that the common in male IC/BPS patients.35 term “pain” encompass a broad array of descriptors. Many patients use other words to describe symp- Male IC/BPS vs Chronic Prostatitis toms, especially “pressure” and may actually deny CP/CPPS, or NIH (National Institutes of Health) pain.28 Finally, pain that worsened with specific type III prostatitis,36 is characterized by pain in AUA GUIDELINE AMENDMENT 1549

the perineum, suprapubic region, testicles or tip of Treatment alternatives were then categorized as the penis.37 The pain is often exacerbated by uri- clinical principles, expert opinion or evidence-based nation or ejaculation. Voiding symptoms such as statements and divided into first-, second-, third-, sense of incomplete bladder emptying and urinary fourth-, fifth- and sixth- line groups. This hierarchy frequency are also commonly reported, but pain is was derived by balancing the potential benefits to the primary defining characteristic of CP/CPPS. It the patient with the invasiveness of the treatment, is clear that the clinical characteristics that define the duration and severity of potential AEs, and the CP/CPPS are very similar to those previously reversibility of potential AEs. Note that the hierar- described for IC/BPS. In general, the Panel believes chy was not established based on evidence strength. that the diagnosis of IC/BPS should be strongly Each set of treatments is presented below. One considered in men whose pain is perceived to be source of uncertainty was the Panel’s observation related to the bladder. However, it is also quite clear that most treatments may benefit a subset of pa- that certain men have symptoms that meet criteria tients that is not readily identifiable before treat- for both conditions (IC/BPS and CP/CPPS). In such ment and that no treatment reliably benefits most cases the treatment approach can include estab- or all patients. Therefore, on average and for a lished IC/BPS therapies as well as other therapies particular patient, uncertainty exists for most that are more specific to CP/ CPPS. treatments regarding the balance between benefits and risks/burdens. GUIDELINE AMENDMENTS First-line treatments. The Panel believes that all patients should be offered these treatments. Diagnosis The first-line treatment approaches presented in The diagnosis of IC/BPS can be challenging. Pa- the full-length Guideline are based on Clinical tients present with a wide spectrum of symptoms, Principles; insufficient literature was available to physical exam findings and clinical test responses. guide an evidence-based version. As such, these This complexity causes significant misdiagnosis, statements remain unchanged from the original under diagnosis and delayed diagnosis. Insufficient guideline. literature was identified to constitute an evidence Second-line treatments. Guideline Statement base for diagnosis of IC/BPS in clinical practice. The 13: lack of evidence is not surprising given the many “Appropriate manual tech- definitions of the disorder used and the focus of most niques (e.g. maneuvers that resolve pelvic, abdom- trials on NIDDK (National Institute of and inal and/or hip muscular trigger points, lengthen Digestive and Diseases) diagnostic criteria muscle contractures, and release painful scars and (note that the NIDDK diagnostic criteria are not other connective tissue restrictions), if appropri- appropriate for use outside of clinical trials).38,39 ately trained clinicians are available, should be For this reason, this section is based on Clinical offered to patients who present with pelvic floor Principles or Expert Opinions with consensus tenderness. Pelvic floor strengthening exercises achieved using a modified Delphi technique when (e.g. Kegel exercises) should be avoided.” (Stan- differences of opinion emerged. This section is dard; Evidence Strength: Grade A) intended to provide clinicians and patients with a Many patients with IC/BPS exhibit tenderness and/or banding of the pelvic floor musculature, framework for determining whether a diagnosis of 12,40 IC/BPS is appropriate. It is not intended to replace along with other soft tissue abnormalities. It is the judgment and experience of the individual not known whether those muscular abnormalities clinician faced with a particular patient. The update are usually primary pain generators (giving rise to literature review did not reveal any additional associated secondary bladder pain) or are them- publications to change any of the statements related selves secondary phenomena elicited by the primary to diagnosis. bladder pain of IC/BPS. Whatever their etiology, when such soft tissue abnormalities are present, Treatment clinical experience and a limited but high quality The Panel assessed the available data for each literature suggest that manual physical therapy can treatment to determine whether a specific inter- provide symptom relief. Specifically, Fitzgerald et al vention demonstrated sufficient efficacy to be reported findings from a randomized controlled trial included as a treatment alternative. The types of that tested ten 60-minute sessions over 12 weeks studies available (randomized trials, observational of myofascial physical therapy compared to global studies); quality of individual studies; consistency therapeutic massage in IC/BPS patients.41 At of outcome across studies; and generalizability of 3 months 59% of the MPT group reported moderate samples, settings and interventions were examined or marked improvement compared to 26% in the and overall evidence strength was determined. GTM group, a statistically significant difference. 1550 AUA GUIDELINE AMENDMENT

Improvements in pain, urgency, frequency and demonstrated significant improvements in pain scores on the IC symptom index, IC problem index VAS scores and maximum bladder capacity. and female sexual function index also were greater Importantly, the 200 U dose did not exert a greater in the MPT group than in the GTM group, although effect than the 100 U dose. Rates of AEs were much the differences were not statistically significant. higher and more serious in the 200 U group Very importantly, there is no evidence that physical with almost half of the group experiencing dysuria therapy aimed at pelvic floor strengthening (such and a third of the group exhibiting a large post-void as Kegel exercises) can improve symptoms and, in residual. These AEs were of sufficient concern fact, this type of pelvic floor therapy may worsen the that the remaining patients who had been ran- condition. domized to receive 200 U instead were treated with No well-designed studies have evaluated the 100 U, accounting for the imbalance in group size. possible therapeutic role of other forms of massage Re-treatment with BTX-A. Giannantoni et al or other forms of bodywork, although interventions treated patients with 200 U in the lateral bladder aimed at general relaxation have proven helpful walls and trigone with re-treatment when benefits in most other forms of chronic pain and can be began to decline (mean re-treatment interval recommended to IC/BPS patients. 5.25 months).43 Patients were followed for two years. Most measured outcomes exhibited signifi- Third-line treatments. While additional information cant improvement that was maintained over time was found through the update literature search with repeat injections. related to third-line treatments, these statements Pinto et al injected 100 U into the trigonal wall remain unchanged from the original guideline. with re-treatment upon symptom return and fol- Fourth-line treatments. Guideline Statement 19: lowed patients for up to three years.44,45 Duration of “Intradetrusor botulinum toxin A (BTX-A) may be improvements in pain VAS, frequency, voided vol- administered if other treatments have not provided ume and QoL were 9 to 10 months after adequate symptom control and quality of life or if each treatment. Nearly a third of patients had UTIs the clinician and patient agree that symptoms after treatment 2 (but not after the other treat- require this approach. The patient must be willing ments). No was reported and to accept the possibility that intermittent self- no clean intermittent self-catheterization was catheterization may be necessary post-treatment.” required.44 (Option; Evidence Strength: Grade C) Shie et al injected 100 U in the posterior and The update literature review retrieved ten new lateral bladder walls with re-treatment every six studies, including one randomized controlled trial months regardless of symptom status for a total of and nine prospective observational studies report- four treatments.46 After treatment one but not ing on a total of 378 patients. It should be noted that treatments two through four, hydrodistension was several studies appear to include overlapping pa- performed. Patients were followed for two years tient groups. As a group, these studies represent a with improvements in pain VAS, O’Leary-Sant major shift in how BTX-A is administered to treat scores and frequency restored with each treatment. IC/BPS in several ways, including the combination These authors did not address AEs. of BTX-A with hydrodistension, the use of primarily Re-treatment with BTX-A and hydrodistension. the 100 U dose, the use of repeat treatments with Kuo,47,48 and Lee and Kuo49 injected 100 U symptom return and following patients for years into the posterior and lateral bladder walls followed rather than months. Following evaluation of the by hydrodistension. The BTX-A plus hydro- new literature, the use of BTX-A was designated as distension treatment was repeated every six months a fourth-line treatment (as opposed to fifth-line in unless improvements were maintained. Patients the original guideline). were followed for two years. Generally, after each Combining BTX-A with hydrodistension. The treatment improvements were noted in pain VAS randomized control trial compared group 1) BTX-A scores, IC symptom index and IC problem index 200 U in the posterior and lateral bladder walls scores, frequency, nocturia and bladder capacity. with hydrodistension two weeks later, group 2) GRA based success rates were high, ranging BTX-A 100 U in the same sites with hydrodistension from 50% to 77% at various time points. Impor- and group 3) hydrodistension with a second hydro- tantly, two of the three reports note that patients distension two weeks later.42 Patients were followed with Hunner lesions did not improve with this for two years. Patients designated as successes regimen and were treated successfully with elec- based on a GRA were 80% at 3 months to 47% at trocautery or electrofulguration. AEs consisted 24 months in group 1, 72% at 3 months to 21% of UTIs in approximately 10% of patients (after at 24 months in group 2 and 48% at 3 months to 17% one of up to four treatments), dysuria in approxi- at 24 months in group 3. Only the BTX-A groups mately 42% with rates diminishing as number of AUA GUIDELINE AMENDMENT 1551

treatments increased, acute urinary retention in 1 often requires a trial and error algorithm based (after treatment 2), in 1 and necessity for approach. clean intermittent self-catheterization in 1 (after treatment 3). PANEL ACKNOWLEDGEMENT Based on the substantial new evidence retrieved The AUA would like to recognize the members of the in this update literature review, with consistent Diagnosis and Treatment of Interstitial Cystitis/ reports of substantially reduced morbidity with Bladder Pain Syndrome panel for their contribu- use of the 100 U dose, the Panel judged that use of tions to the development of the original Guideline BTX-A at the 100 U dose is appropriate as a fourth- that served as a basis for this amendment: Philip M. line treatment. The Panel notes that BTX-A should Hanno, David Allen Burks, J. Quentin Clemens, be administered by experienced practitioners Roger R. Dmochowski, Deborah Erickson, Mary Pat and that patients must be willing to accept the Fitzgerald, John B. Forrest, Barbara Gordon, Mikel possibility that intermittent self-catheterization Gray, Robert Dale Mayer, Diane K. Newman, Leroy may be necessary after treatment. This option is Nyberg Jr., Christopher K. Payne, Ursula Wessel- not appropriate for patients who cannot tolerate mann and Martha M. Faraday. catheterization, and is relatively contraindicated for patients with any evidence of impaired bladder Disclaimer emptying. The original version of this Interstitial Cystitis/ Fifth-line treatments. While additional information Bladder Pain Syndrome Guideline was created was found through the update literature search in 2011 by a multi-disciplinary Panel assembled by related to fifth-line treatments, these statements the Practice Guidelines Committee (PGC) of the remain unchanged from the original guideline. American Urological Association Education and Research, Inc. (AUA). This amended Interstitial Sixth-line treatments. While additional information Cystitis/Bladder Pain Syndrome Guideline was was found through the update literature search drafted in 2014 by a Guideline Amendment Panel. related to sixth-line treatments, these statements This amendment updates the original guideline remain unchanged from the original guideline document to reflect literature released following the with the exception of a statement related to the original publication. use of , which is not approved for The mission of the original and amendment use in the United States. Panels was to develop clinical guideline recom- mendations based on an in-depth evidence report of the peer-reviewed literature. The recommendations FUTURE RESEARCH are based on evidence strength, or where evidence is Patients with IC/BPS constitute a previously under not available, on Delphi-modification consensus recognized and underserved population in need of statements. The purpose of each guideline is to adequate medical management. Over the last provide physicians and non-physician providers 20 years there have been significant efforts directed (primary care and specialists) with a consensus of at understanding the etiology and the therapeutic principles and treatment plans for the management challenges of this disease. These efforts were of Interstitial Cystitis/Bladder Pain Syndrome spearheaded by U.S. patient support groups that Guideline. While these guidelines do not necessarily have urged the National Institutes of Health to establish the standard of care, AUA seeks to fund research studies to better understand IC/BPS recommend and to encourage compliance by prac- pathophysiology and to fund clinical studies to titioners with current best practices related to the identify valid treatment approaches. condition being treated. Treating IC/BPS patients presents a significant Funding of the original and amendment Panels challenge in clinical practice. Treatment ap- was provided by the AUA. Panel members receive proaches may be local (directed to the bladder) or no remuneration for their work. Panel members’ systemic, range from behavioral to pharmacolog- potential conflicts of interest are subject to rigorous ical, and may include many types of adjunctive and on-going review during the development of the therapy approaches intended to optimize quality of original Guideline and amendment Panel members life. Although there are evidenced-based data sup- are screened for conflicts throughout the amend- porting certain treatment approaches for patients ment process. in clinical studies, the unsolved question in clinical As medical knowledge expands and technology practice remains: Who is the ideal patient for a advances, AUA guidelines are subject to change. given treatment approach? Thus, until phenotyp- Evidence-based guidelines statements are not ab- ing improves and specific phenotype driven thera- solute mandates but thoroughly considered strate- pies can be recommended, treatment of IC/BPS gies for best practice under the specific conditions 1552 AUA GUIDELINE AMENDMENT

described in each document. For all these reasons, prescribing information about indications, contra- the guidelines do not pre-empt physician judgment indications, precautions and warnings. in individual cases. Treating physicians must take Although guidelines are intended to encourage into account variations in resources, and patient best practices and to reflect available technologies tolerances, needs, and preferences. Similarly, with sufficient data as of the date of close of the conformance with any clinical guideline cannot literature review, guidelines are necessarily time- assure a successful outcome. These guidelines and limited. Guidelines cannot include evaluation of all best practice statements are not intended to provide data on emerging technologies, pharmaceuticals or legal advice. management practices, including both those that The guideline text may include information or are FDA-approved, or those which may immediately recommendations about certain drug or device use come to represent accepted clinical practices. For this (‘off label’) that are not approved by the Food and reason, the AUA does not regard emerging technol- Drug Administration (FDA), or about ogies or management techniques not addressed by or substances not subject to the FDA approval pro- this guideline as manifestly experimental or inves- cess. AUA urges strict compliance with all govern- tigational. These emerging technologies or tech- ment regulations and protocols for prescription and niques may simply be too new to be included or fully use of these substances. The physician is encour- incorporated in the Panel’s evidence-based evalua- aged to understand and carefully follow all available tion at the time the guideline is developed.

APPENDIX RICE BPS/IC Case Definitions5

High Sensitivity Definition High Specificity Definition

Sensitivity 81%, specificity 54% for BPS/IC vs endometriosis, Sensitivity 48%, specificity 83% for BPS/IC vs endometriosis, vulvodynia vulvodynia and overactive bladder and overactive bladder Pain, pressure or discomfort in the pelvic area and daytime Pain, pressure or discomfort in the pelvic area and daytime urinary frequency 10þ or urinary frequency 10þ or urgency due to pain, pressure urgency due to pain, pressure or discomfort, no fear of wetting; and symptoms did not or discomfort, no fear of wetting resolve after treatment with ; and no treatment with hormone injection therapy for endometriosis

Exclusion criteria: , , , stroke, Parkinson disease, multiple sclerosis, , treatment, radiation treatment to pelvic area, tuberculosis affecting the bladder, , ovarian cancer, vaginal cancer, genital herpes,

REFERENCES 1. Hsu C and Sandford BA: The Delphi technique: cystitis/bladder pain syndrome and chronic 12. Peters KM, Carrico DJ, Kalinowski SE et al: making sense of consensus. Practical Assess- prostatitis/chronic pelvic pain syndrome in men: Prevalence of in patients ment, Research & Evaluation 2007; 12: 1. results of the RAND Interstitial Cystitis Epide- with interstitial cystitis. Urology 2007; 70: 16. miology Male Study. J Urol 2013; 189: 141. 2. Hanno P and Dmochowski R: Status of interna- 13. Buffington CA: Comorbidity of interstitial cystitis tional consensus on interstitial cystitis/bladder 7. Roberts RO, Bergstralh EJ, Bass SE et al: with other unexplained clinical conditions. J Urol pain syndrome/painful bladder syndrome: 2008 Incidence of physician-diagnosed interstitial 2004; 172: 1242. snapshot. Neurourol Urodyn 2009; 28: 274. cystitis in Olmsted County: a community-based 14. Warren JW, Howard FM, Cross RK et al: Ante- study. BJU Int 2003; 91: 181. 3. Hanno PM, Landis JR, Matthews-Cook Y et al: cedent nonbladder syndromes in case-control The diagnosis of interstitial cystitis revisited: 8. Porru D, Politano R, Gerardini M et al: Different study of interstitial cystitis/painful bladder syn- lessons learned from the National Institutes of clinical presentation of interstitial cystitis syn- drome. Urology 2009; 73: 52. Health Interstitial Cystitis Database study. J Urol drome. Int Urogynecol J Pelvic Floor Dysfunct 15. Bade J, Ishizuka O and Yoshida M: Future research 161: 15: 1999; 553. 2004; 198. needs for the definition/diagnosis of interstitial 10: 4. Berry SH, Bogart LM, Pham C et al: Develop- 9. Warren JW, Brown J, Tracy JK et al: Evidence- cystitis. Int J Urol, suppl., 2003; S31. ment, validation and testing of an epidemiolog- based criteria for pain of interstitial cystitis/ 16. Payne CK, Terai A and Komatsu K: Research ical case definition of interstitial cystitis/painful painful bladder syndrome in women. Urology criteria versus clinical criteria for interstitial bladder syndrome. J Urol 2010; 183: 1848. 2008; 71: 444. cystitis. Int J Urol, suppl., 2003; 10: S7. 5. Berry SH, Elliott MN, Suttorp M et al: 10. Warren JW, Diggs C, Brown V et al: Dysuria at 17. Homma Y, Ueda T, Tomoe H et al: Clinical Prevalence of symptoms of bladder pain syn- onset of interstitial cystitis/ painful bladder guidelines for interstitial cystitis and hypersen- drome/interstitial cystitis among adult females syndrome in women. Urology 2006; 68: 477. sitive bladder syndrome. Int J Urol 2009; 16: 597. in the United States. J Urol 2011; 186: 540. 11. Driscoll A and Teichman JM: How do patients 18. Philip J, Willmott S and Irwin P: Interstitial 6. Suskind AM, Betty SH, Ewing BA et al: with interstitial cystitis present? J Urol 2001; cystitis versus detrusor overactivity: a compara- The prevalence and overlap of interstitial 166: 2118. tive, randomized, controlled study of AUA GUIDELINE AMENDMENT 1553

using saline and 0.3 M chloride. 29. Warren JW, Meyer WA, Greenberg P et al: Using urgency-frequency syndrome. J Urol 2001; 166: J Urol 2006; 175: 566. the International Continence Society’s definition 2226. of painful bladder syndrome. Urology 2006; 67: 19. Clemens JQ, Link CL, Eggers PW et al: 1138. 41. Fitzgerald MP, Payne CK, Lukacz ES et al: Prevalence of painful bladder symptoms and Randomized multicenter clinical trial of myofas- effect on quality of life in black, Hispanic and 30. Diggs C, Meyer WA, Langenberg P et al: cial physical therapy in women with interstitial white men and women. J Urol 2007; 177: 1390. Assessing urgency in interstitial cystitis/painful cystitis/painful bladder syndrome (IC/PBS) and bladder syndrome. Urology 2007; 69: 210. pelvic floor tenderness. J Urol 2012; 187: 2113. 20. Rothrock NE, Lutgendorf SK and Kreder KJ: Coping strategies in patients with interstitial 31. Greenberg P, Tracy JK, Meyer WA et al: Short 42. Kuo HC and Chancellor MB: Comparison of cystitis: relationships with quality of life and interval between symptom onset and medical intravesical botulinum toxin type A injections depression. J Urol 2003; 169: 233. care as an indication of rapid onset of interstitial plus hydrodistention with hydrodistention alone cystitis/painful bladder syndrome. BJU Int 2007; for the treatment of refractory interstitial 21. Clemens JQ, Brown SO and Calhoun EA: Mental 100: 599. cystitis/painful bladder syndrome. BJU Int 2009; health diagnoses in patients with interstitial 104: 657. cystitis/painful bladder syndrome and chronic 32. Hand JR: Interstitial cystitis. J Urol 1949; 61: prostatitis/chronic pelvic pain syndrome: a case/ 291. 43. Giannantoni A, Mearini E, Del Zingaro M et al: control study. J Urol 2008; 180: 1378. Two-year efficacy and safety of botulinum A 33. Hanno P, Landis JR, Matthews-Cook Y et al: toxin intravesical injections in patients affected 22. Nickel JC, Christopher KP, John F et al: The diagnosis of interstitial cystitis revisited: by refractory painful bladder syndrome. Curr The relationship among symptoms, sleep distur- lessons learned from the National Institute of Drug Deliv 2010; 7: 1. bances and quality of life in patients with Health Interstitial Cystitis Database Study. J Urol 181: interstitial cystitis. J Urol 2009; 2555. 1992; 161: 552. 44. Pinto R, Lopes T, Frias B et al: Trigonal injection of botulinum toxin A in patients with refractory 23. Berry SH, Hayes RD, Suttorp M et al: Health- 34. Forrest JB and Vo Q: Observations on the bladder pain syndrome/interstitial cystitis. Eur related quality of life impact of interstitial presentation, diagnosis, and treatment of inter- Urol 2010; 58: 360. cystitis/painful bladder syndrome and other stitial cystitis in men. Urology 2001; 57: 26. 181: symptomatic disorders. J Urol 2009; 90. 45. Pinto R, Lopes T, Silva J et al: Persistent thera- 35. Forrest JB and Schmidt S: Interstitial cystitis, peutic effect of repeated injections of onabotu- 24. Nickel JC, Parsons CL, Forrest J et al: Improve- chronic nonbacterial prostatitis and chronic pel- linum toxin A in refractory bladder pain ment in sexual functioning in patients with vic pain syndrome in men: a common and syndrome/interstitial cystitis. J Urol 2012; 189: interstitial cystitis/painful bladder syndrome. frequently identical clinical entity. J Urol 2004; 548. J Sex Med 2008; 5: 394. 172: 2561. 46. Shie JH, Liu HT, Wang YS et al: Immunohisto- 25. Peters KM, Killinger KA, Carrico DJ et al: Sexual 36. Krieger JN, Nyberg L Jr and Nickel JC: NIH chemical evidence suggest repeated intravesical function and sexual distress in women with consensus definition and classification of pros- application of botulinum toxin A injections may interstitial cystitis: a case- control study. Urology tatitis. JAMA 1999; 282: 236. 2007; 70: 543. improve treatment efficacy of interstitial cystitis/ 37. Litwin MS, McNaughton-Collins M, Fowler FJ bladder pain syndrome. BJU Int 2013; 111: 638. 26. Tincello DG and Walker AC: Interstitial cystitis in et al: The National Institutes of Health Chronic 47. Kuo HC: Repeated onabotulinumtoxin-A the UK: results of a questionnaire survey of Prostatitis Symptom Index: development and injections provide better results than single in- members of the Interstitial Cystitis Support validation of a new outcome measure. J Urol jection in treatment of painful bladder syndrome. Group. Eur J Obstet Gynecol Reprod Biol 2005; 1999; 162: 369. 118: 91. Pain Physician 2013; 16: E15. 38. Striker GE: KUH notes. J Urol 1989; 142: 139. 27. Nickel JC, Tripp D, Teal V et al: Sexual function 48. Kuo HC: Repeated intravesical onabotuli- is a determinant of poor quality of life for 39. Wein AJ, Hanno PM and Gillenwater JY: Inter- numtoxinA injections are effective in treatment women with treatment refractory interstitial stitial cystitis: an introduction to the problem. In: of refractory interstitial cystitis/bladder pain cystitis. J Urol 2007; 177: 1832. Interstitial Cystitis. Edited by PM Hanno, DR syndrome. Int J Clin Pract 2013; 67: 427. Staskin, RJ Krane et al. London: Springer-Verlag, 28. Fitzgerald MP, Koch D and Senka J: Visceral and pp 3e15, 1990. 49. Lee CL and Kuo HC: Intravesical botulinum cutaneous sensory testing in patients with toxin A injections do not benefit patients with painful bladder syndrome. Neurourol Urodyn 40. Weiss JM: Pelvic floor myofascial trigger points: ulcer type interstitial cystitis. Pain Physician 2005; 24: 627. manual therapy for interstitial cystitis and the 2013; 16: 109.