BERKELEY, CA (UroToday.com) - The American Urological Association (AUA) this month announced its first guideline for the condition the AUA now refers to as “interstitial cystitis/bladder pain syndrome” or “IC/BPS.” This 4-year effort originally began in 1998 and was aborted a year later when it was determined that the extensive literature search 13 years ago did not demonstrate enough data with which to generate a guideline. The committee was reformulated a decade later around representatives of the urologic community with experience in both clinical IC/BPS research and patient care. To this group were added a gynecologist, neurologist, NIDDK representative, patient advocacy representative, and experienced clinical nurses. The AUA appointed a PhD methodologist to guide the process and assure proper evaluation of source manuscripts and use of appropriate guideline methodology. Suzanne Pope organized production of the many phases of guideline formation.
Committee members included this correspondent, David Brooks, Quentin Clemens, Roger R. Dmochowski, Deborah Erickson, Mary Pat FitzGerald, John Forrest, Barbara Gordon, Mikel Gray, Robert Mayer, Diane K. Newman, Leroy Nyberg, Christopher Payne, Ursala Wesselmann, and Martha Faraday. The full guideline report is available at www.auanet.org/guidelines.
The guideline was based on publications from 1983 to 2009. Eighty-six articles met the stringent inclusion criteria and formed an evidence base sufficient to support treatment recommendations. Diagnosis and management recommendations were deemed to be clinical principles or expert opinion as there was insufficient data in the literature to construct this portion of the guideline on evidence alone. Highlights of the guideline follow.
Interstitial cystitis/bladder pain syndrome is defined as “an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than 6 weeks duration, in the absence of infection or other identifiable causes.”
The committee addressed the thorny question of distinguishing IC/BPS in the male from chronic nonbacterial prostatitis NIH type III prostatitis. The latter is characterized by pain in the perineum, suprapubic region, testicles or tip of the penis. The pain is often exacerbated by urination or ejaculation. Voiding symptoms such as sense of incomplete emptying and urinary frequency are commonly reported, but pain is the primary defining characteristic of CP/CPPS. The panel states that the diagnosis of IC/BPS should be strongly considered in men with pain, pressure, or discomfort perceived to be related to the bladder with at least one associated urinary symptom. Some men may meet criteria for both conditions. In those situations, therapy directed at one or both conditions may be appropriate.
The diagnostic approach of the guideline is based on clinical principles or expert opinion. As opposed to the section on treatment, the lack of evidence in the literature did not support an evidence-based approach to diagnosis. The following guideline statements are quoted verbatim.
- The basic assessment include a careful history, physical examination, and laboratory examination to document symptoms and signs that characterize IC/BPS and exclude other disorders commonly associated with IC/BPS in the differential diagnosis.
- Baseline voiding symptoms and pain levels should be obtained in order to measure subsequent treatment effects.
- Cystoscopy and/or urodynamics should be considered when the diagnosis is in doubt; these tests are not necessary for making the diagnosis in uncomplicated presentations. Complicated presentations include the presence of gross or microscopic hematuria. This requires the standard hematuria evaluation including imaging, urine cytology, and endoscopy. Also a part of the complicated designation would be urinary incontinence, gastrointestinal signs or symptoms, gynecologic signs or symptoms, sterile pyuria, and urgency suggestive of overactive bladder.
The guideline then prescribes statements based on clinical principals underlying overall management.
- Treatment strategies should proceed using more conservative therapies first with less conservative therapies employed if symptom control is inadequate for acceptable quality of life. Surgical treatments, other than fulgeration of Hunner's lesions, are appropriate only after other treatment alternatives have been exhausted, or at any time in the rare instance when an end-stage small, fibrotic bladder has been confirmed and the patient’s quality of life suggests a positive risk-benefit ratio for major surgery.
- Initial treatment type and level should depend on symptom severity, clinical judgement, and patient preferences.
- Multiple simultaneous treatments may be considered if it is in the best interests of the patient.
- Ineffective treatments should be stopped once a clinically meaningful interval has elapsed.
- Pain management should be continually assessed for effectiveness. If inadequate, consideration should be given to a multidisciplinary approach and the patient referred appropriately.
- The IC/BPS diagnosis should be reconsidered in the patient showing no improvement after multiple interventions.
The guideline notes that “first line treatments” suitable for all patients include education about normal bladder function, education about IC/BPS, the risks and burdens of available treatment alternatives, and the fact that no single treatment has been found effective for the majority of patients. They should understand that multiple therapeutic options may be required and combination can improve symptoms such as managing fluid intake, avoiding foods that trigger symptoms, and avoiding types of exercise that the patient finds triggers pain. Over the counter preparations that include quercitin, calcium glycerophosphates, and urinary analgesics may be worth trying. Stress management is also recommended.
Manual physical therapy by an appropriately trained physical therapist along with pain management is included in second line therapy. Also included are oral medications (amitriptyline, cimetidine, hydroxyzine, pentosanpolysulfate) and intravesical therapies (Dimethylsulfoxide, heparin, lidocaine). Physical therapy is designated a clinical principle, while oral and intravesical therapies are designated as options. The latter term implies that the balance between benefits and risk/burdens is uncertain or relatively equal and the decision to use any of these therapies is best made by the clinician in conjunction with the patient.
Cystoscopy under anesthesia with short-duration, low-pressure hydrodistention is a third-line treatment in the guideline. If presenting symptoms justify, it can be done earlier in the treatment algorithm. If Hunner’s lesions are present, the guideline recommends fulguration or injection with triamcinolone.
Fourth line treatment is a trial of neurostimulation, and if successful, implantation of a permanent neurostimulation device. Fifth line in the algorithm is the use of either cyclosporine A or Intradetrusor botulinum toxin A (BTX-A). The former carries the risks of an immune modulator including potential development of lymphoma, and the latter carries a risk of urinary retention requiring clean intermittent catheterization for management. The guideline makes an important statement regarding 4th and 5th line treatments, and even puts this statement into the published algorithm. It is worth repeating here. “The evidence supporting the use of neuromodulation, cyclosporine A, and BTX for IC/BPS is limited by many factors including study quality, small sample sizes, and lack of durable follow up. None of these therapies have been approved by the US Food and Drug Administration for IC/BPS. The panel believes that none of these interventions can be recommended for generalized use for this disorder, but rather should be limited to practitioners with experience managing this syndrome and willingness to provide long term care of these patients post intervention.”
Surgical reconstructive therapies including substitution cystoplasty, urinary diversion, cystectomy) form the 6th line therapies and are recommended in carefully selected patients for whom all other therapies have failed to control symptoms and improve quality of life. For patients with “end-stage” structurally small bladders, diversion is indicated at any time clinician and patient believe appropriate.
The guideline concludes with a list of therapies that should not be employed. This includes long-term oral antibiotic administration, intravesical bacillus Calmette-Guerin, intravesical resiniferatoxin, high-pressure (>80-100cm), long duration (> 10 minutes) hydrodistention, and long-term systemic glucocorticoid administration.
An abbreviated version of the guideline will appear in the Journal of Urology this spring. The detailed web version has been posted on the American Urological Association web site. www.auanet.org/guidelines. As with all guidelines, it is a work in progress and will be modified as new information is developed.