Bacillus calmette-guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: a meta-analysis of the published results of randomized clinical trials

PURPOSE: We determined the short-term and long-term efficacy of bacillus Calmette-Guerin (BCG) and chemotherapy in the treatment of patients with carcinoma in situ (CIS). MATERIALS AND METHODS: A meta-analysis was performed on published results of randomized clinical trials comparing intravesical BCG to intravesical chemotherapy. RESULTS: Nine randomized trials including 700 patients with CIS compared BCG to either mitomycin C (MMC), epirubicin, adriamycin, or sequential MMC/adriamycin. Of 298 patients on BCG 203 (68.1%) had a complete response compared with 158 of 307 patients on chemotherapy (51.5%), a reduction of 47% in the odds of nonresponse on BCG (OR 0.53, p =0.0002). Based on a median followup of 3.6 years, 161 of 345 patients on BCG (46.7%) had no evidence of disease compared with 93 of 355 patients on chemotherapy (26.2%), a reduction of 59% in the odds of treatment failure on BCG (OR 0.41, p <0.0001). Although the long-term benefit of BCG was smaller in trials with MMC, BCG was superior to MMC in trials with maintenance BCG (OR 0.57, p =0.04). The reduction of 26% in the risk of progression on BCG (p =0.20) is consistent with the reduction of 27% (p =0.001) previously reported in a larger superficial bladder cancer meta-analysis. CONCLUSIONS: Intravesical BCG significantly reduces the risk of short and long-term treatment failure compared with intravesical chemotherapy. Therefore, it is considered to be the intravesical agent of choice in the treatment of CIS.     

The limits of bacillus Calmette-Guerin for carcinoma in situ of the bladder

PURPOSE: Historically carcinoma in situ of the bladder has been treated with radical cystectomy based on the aggressive and potentially invasive nature of this disease. The introduction in the late 1970s of intravesical bacillus Calmette-Guerin (BCG) has made this therapy the gold standard in the management of carcinoma in situ. Cases that are refractory or resistant to BCG therapy are a management dilemma with various available treatment options. MATERIALS AND METHODS: A comprehensive literature review of the current management of carcinoma in situ of the bladder was performed using MEDLINE, a review of current urology journals and abstracts from recent urology meetings. Data focused on BCG resistant carcinoma in situ of the bladder and current approaches in use for refractory disease. RESULTS: Complete and durable response rates have been reported in more than 70% of patients with carcinoma in situ who are treated with intravesical BCG. To our knowledge the optimal therapeutic regimen has not been established, although extended periods of treatment beyond the originally described 6-week course have not been shown to improve complete response rates. Prolonged administration of BCG is associated with adverse side effects. Various prognostic indicators of recurrence and progression exist that may identify a subset of cases unlikely to respond favorably to a conservative approach, including carcinoma in situ with associated stage T1 bladder lesions, diffuse and multifocal carcinoma in situ, multiple recurrences with intravesical therapy and extravesical involvement. Current molecular markers may also predict the response of carcinoma in situ to therapy. Treatment options available for BCG refractory carcinoma in situ of the bladder include intravesical chemotherapy, combined immuno-chemotherapy and radical cystectomy. Intravesical valrubicin and oral bropirimine have been shown to induce a complete response rate of 21% to 50%, although data on long-term followup are forthcoming. Radical cystectomy remains effective therapy for aggressive carcinoma in situ of the bladder. CONCLUSIONS: The current management of carcinoma in situ of the bladder is ill defined due to the variable natural history and unpredictable response of this disease to therapy. Controversy exists as to the optimal treatment of carcinoma in situ of the bladder since different forms of carcinoma in situ may exist that complicate therapeutic decisions for appropriate therapy. Some tumor characteristics are associated with more aggressive behavior and may be predictive of treatment outcome.     

Perioperative single dose instillation of epirubicin or interferon-alpha after transurethral resection for the prophylaxis of primary superficial bladder cancer recurrence: a prospective randomized multicenter study--FinnBladder III long-term results

PURPOSE: We evaluated the long-term efficacy of a single dose of interferon or epirubicin administered immediately after transurethral resection compared with transurethral resection alone for primary superficial bladder cancer recurrence. MATERIAL AND METHODS: A total of 200 patients with primary superficial stages Ta to T1, grades 1 to 3 bladder cancer were randomized into 3 treatment groups, including transurethral resection alone, transurethral resection plus 50 milliunits interferon-alpha2b and transurethral resection plus 100 mg. epirubicin. The primary end point was time to first recurrence. RESULTS: At a median followup of 72 months we observed a sustained effect of a single epirubicin instillation compared with other treatments. To date only 46% of the patients in group 3 have experienced recurrence in contrast to 73% and 68% in groups 1 and 2, respectively (p = 0.002). At 72 months the Kaplan-Meier disease-free estimates were 24%, 31% and 51% in groups 1 to 3, respectively (p = 0.002). The Cox multivariate model revealed a more than 2-fold relative risk of recurrence in group 1 versus group 3 (p <0.001). Other significant variables predicting recurrence were grade and the number of tumors. CONCLUSIONS: A single perioperative instillation of 100 mg. epirubicin causes a significant and sustained decrease in primary superficial bladder cancer recurrence, whereas a single dose of 50 milliunits interferon-alpha2b is ineffective for prophylaxis.     

Monitoring intravesical therapy for superficial bladder cancer using fluorescence in situ hybridization

PURPOSE: We evaluated fluorescence in situ hybridization (FISH) for assessing the response to therapy in patients with superficial bladder cancer receiving bacillus Calmette-Guerin or other intravesical therapies. MATERIALS AND METHODS: A total of 37 patients receiving intravesical therapy for superficial bladder cancer were enrolled in this study. Urine specimens were collected for FISH analysis just prior to the first intravesical therapy in 31 cases and just prior to or within 2 months following the last intravesical therapy in 37. FISH was done using the UroVysion probe set (Abbott Laboratories, Abbott Park, Illinois) with results considered positive if 5 or more cells demonstrated polysomy. Biopsy, cystoscopy and/or cytology results were then compared to FISH results to evaluate the usefulness of the test for monitoring intravesical therapy. RESULTS: Of the patients 25 had a negative and 12 had a positive post-therapy FISH result. All 12 patients with a positive post-therapy FISH result had tumor recurrence, while tumor recurrence was observed in 13 of the 25 with a negative post-therapy FISH result (HR 4.6, 95% CI 1.9 to 11.1, p <0.001). Of the patients with tumor recurrence 7 of 12 with a positive post-therapy FISH result had muscle invasive tumor and 2 of 25 with a negative post-therapy FISH result had muscle invasive tumor (HR 9.4, 95% CI 1.9 to 45.3, p = 0.001). CONCLUSIONS: FISH appears to be useful for monitoring patients with superficial bladder cancer for the response to intravesical therapy. Patients with a positive FISH result at the end of treatment are at high risk for progression to muscle invasive bladder cancer.     

Equivalent efficacy of mitomycin C plus doxorubicin instillation to bacillus Calmette-Guerin therapy for carcinoma in situ of the bladder

BACKGROUND: To elucidate the most efficient topical therapy for carcinoma in situ of the bladder, the efficacy of intravesical mitomycin C plus doxorubicin therapy was compared with bacillus Calmette-Guerin (BCG) therapy. The clinical behavior of the tumor was analysed according to the histological grade. METHODS: Forty-two patients with carcinoma in situ of the bladder were randomized to intravesical BCG (21 patients) or mitomycin C plus doxorubicin sequential therapy (21 patients) as first line treatment. The non-responders underwent the subsequent instillation of the other intravesical therapy alternately. Of the patients, 27 had grade 2 and 15 had grade 3 cancer. RESULTS: Both topical therapies were equally effective with initial response rates of 86% (18/21) for BCG and 81% (17/21) for mitomycin C plus doxorubicin, irrespective of the tumor grade. Of seven initial non-responders, five patients achieved a complete response by subsequent instillation, resulting in a total response rate of 95%. After a mean follow-up of 47 months, five patients (12%) developed disease progression. The progression rates were not different between the topical therapies, but were significantly higher in grade 3 than in grade 2 cases. CONCLUSION: It appears likely that mitomycin C plus doxorubicin instillation has an equivalent efficacy to BCG as the initial therapy of carcinoma in situ and the combination of them would be the most efficient treatment for the disease. Moreover, histological grading would be clinically useful in defining the tumor characteristics and behavior of carcinoma in situ of the bladder.     

Adjuvant intravesical treatment of superficial bladder cancer with a standardized mistletoe extract

PURPOSE: Adjuvant intravesical immunotherapy with bacillus Calmette-Guerin (BCG) for noninvasive superficial bladder cancer has been shown to decrease tumor recurrence significantly. However, serious local and systemic side effects of this treatment have promoted the use of other immunoactive substances, which to date have failed to show efficacy equal to that of BCG immunotherapy. MATERIALS AND METHODS: In the current phase I/II clinical trial an aqueous mistletoe extract standardized to mistletoe lectin was administered intravesically to 30 patients with superficial urothelial bladder carcinoma. About 4 weeks after transurethral resection each patient received 6 instillations at weekly intervals of 50 ml extract with mistletoe lectin concentrations between 10 and 5,000 ng/ml, which was retained in the bladder for 2 hours. Three patients per group received a dose, which was then doubled in the next group. Clinical followup consisted of examinations with cystoscopy, cytology and random biopsies. To detect cytokines and tumor necrosis factor-p75 receptor venous blood and urine samples were taken before instillation, and 2, 6 and 24 hours thereafter. RESULTS: The tolerability of intravesically administered mistletoe extract was good at all applied concentrations. None of the patients had local or systemic side effects according to WHO classification 1-4. Within the 12-month observation time study patients with pTa G2 and pT1 G2 tumors showed a recurrence rate of 33%, comparable to that in a local historical control group of patients with equal stage and grade who were treated with adjuvant BCG. Comparison of urine cytokine levels before instillation, and 2, 6 and 24 hours thereafter brought about no significant alterations in all measured cytokines. CONCLUSIONS: From these results it is concluded that standardized mistletoe extract could be a potential alternative adjuvant therapy for superficial bladder cancer. Nevertheless, the optimal intravesical treatment regimen has yet to be defined.     

Recurrence and progression of stage T1, grade 3 transitional cell carcinoma of the bladder following intravesical immunotherapy with bacillus Calmette-Guerin

PURPOSE: We prospectively examined the incidence of recurrence and progression in patients with stage pT1, grade 3 carcinoma of the bladder following complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: Between July 1987 and March 1999, 123 patients presenting to our clinic with superficial urothelial carcinoma (stage pT1, grades 1 to 3) received adjuvant intravesical immunotherapy with BCG after histologically confirmed complete transurethral tumor resection. Disease was stage pT1, grade 3 in 44 patients (36%). Median followup was 28 months (mean 43, range 5 to 141). RESULTS: Of the patients 36 (82%) with bladder preservation remained tumor-free during followup after 1 or 2 cycles of BCG. Superficial tumor recurred in 5 patients (11%) and muscle invasive progression was noted in 7 (16%). Radical cystectomy was performed in 4 cases (9%). Of the patients 5 (11%) died of cancer. Tumor-free survival for all patients was 89% (39 of 44). CONCLUSIONS: Adjuvant immunotherapy with BCG after complete transurethral resection of bladder tumor represents a highly effective primary treatment of stage pT1, grade 3 carcinoma of the bladder. Immediate radical cystectomy does not appear necessary.     

Radical cystectomy for primary neuroendocrine tumors of the bladder: the university of southern california experience

PURPOSE: Primary neuroendocrine tumors of the bladder are rare and they include small and large cell variants. We reviewed our experience with treating these tumors with radical cystectomy to evaluate their histopathological characteristics and clinical outcomes. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer at our institution, of whom 25 (1.2%) had neuroendocrine tumors of the bladder, including small cell carcinoma in 20 and large cell carcinoma in 5. Pure neuroendocrine-type histology was identified in 16 cases, including 1 with small and large cell features, while the remaining 9 had mixed histology, that is transitional cell carcinoma in 8 and adenocarcinoma in 1. Multi-agent chemotherapy was administered to 14 patients. RESULTS: Median patient age was 68 years (range 40 to 82) and 19 patients were male (76%). A total of 19 patients (76%) had lymph node involvement, of whom 2 had small liver metastases found intraoperatively, while only 4 (16%) had organ confined tumors and 2 (8%) had extravesical, node negative disease. These tumors tended to have a flat, ulcerative gross appearance with lymphovascular invasion, carcinoma in situ and necrosis present microscopically. Median followup was 11.8 years (range 18 days to 15.1 years). Five-year overall and recurrence-free survival was 10% and 13%, respectively. There was no significant survival difference between small and large cell carcinoma. Mixed histologies tended to do better than pure neuroendocrine tumors, although this did not attain statistical significance (p = 0.064). Patients receiving multimodality therapy had significantly better overall (p = 0.051) and recurrence-free (p = 0.003) survival than those treated with cystectomy alone. CONCLUSIONS: Neuroendocrine tumors of the bladder usually present with advanced pathological stage and portend a poor prognosis. Adjuvant chemotherapy protocols may provide improved survival compared with cystectomy alone.     

Percutaneous needle bladder neck suspension for the treatment of stress urinary incontinence in women: long-term results

PURPOSE: We evaluated the long-term results of percutaneous needle suspension using bone anchor devices for treating stress urinary incontinence in women. MATERIALS AND METHODS: We retrospectively evaluated the long-term results of percutaneous bladder neck needle suspension performed at our institution. None of the women had undergone any anti-incontinence surgery before percutaneous needle suspension. A telephone survey was done for all available patients. Subjective cure was defined as no evidence of incontinence, significant improvement as 0 to 1 protective pad soaked daily and patient satisfaction with incontinence level, and failure as more than 1 pad used daily, lack of patient satisfaction or a secondary procedure required to treat stress urinary incontinence. In cases considered failures a detailed video urodynamic study was performed when possible before any secondary procedure. RESULTS: In 1996 and 1997, 49 patients underwent percutaneous needle bladder neck suspension with bone anchors, of whom 42 (86%) were available for telephone interview. Mean patient age was 57 years (range 31 to 77) and mean followup was 29 months (range 16 to 52). As defined, subjective outcome in the 42 women was cure in 2 (5%), significant improvement in 5 (12%) and failure in 35 (83%). Of the 35 patients with treatment failure who did not undergo a secondary procedure 25 were asked to present for video urodynamics and 18 were evaluated. Urodynamics revealed demonstrable urinary incontinence, urethral hypermobility in 16 (88%), intrinsic sphincter deficiency in 1 (6%) and detrusor instability in 1 (6%). In 2 cases x-ray revealed that a bone anchor had dislodged and migrated into the pelvis. Serious osteomyelitis at the bone anchor site in 1 case required surgical débridement and 6 weeks of intravenous antibiotics. CONCLUSIONS: Percutaneous needle suspension is associated with poor long-term results in women with stress urinary incontinence. Other procedures should be considered.     

Use of the novel marker BLCA-1 for the detection of bladder cancer

PURPOSE: Bladder cancer specific nuclear structural alterations have been identified. We examined the expression pattern of one of these proteins, BLCA-1, in tissue and urine samples from individuals with bladder cancer as well as in samples from normal controls. MATERIALS AND METHODS: BLCA-1 sequence data were used to produce antibodies to this protein, which were used in immunoblot and enzyme-linked immunosorbent assays. RESULTS: BLCA-1 was detectable in tissue from patients with bladder cancer but not in normal adjacent areas of the bladder or in normal donor bladder tissue. This protein was also detectable in the urine of patients with bladder cancer by immunoblot and immunoassay. Using a cutoff of 0.025 optical density units (absorbance value) BLCA-1 was detected in 20 of 25 urine samples from patients with bladder cancer but in only 6 of 46 normal, high risk, prostate or renal cancer samples tested, resulting in a test with 80% sensitivity and 87% specificity. Expression of this protein did not appear to correlate with tumor grade. CONCLUSIONS: This research indicates that BLCA-1 is a urine based marker of bladder cancer which may be useful for the detection of this disease.     

A randomized controlled trial of short-term versus long-term prophylactic intravesical instillation chemotherapy for recurrence after transurethral resection of Ta/T1 transitional cell carcinoma of the bladder

PURPOSE: In a prospective randomized controlled study, we investigated the optimal schedule for intravesical instillation of epirubicin for maximizing its effect on prophylaxis and disease progression after transurethral resection of newly diagnosed Ta/T1 bladder cancer. MATERIALS AND METHODS: The patients were instilled with epirubicin (30 mg/30 ml in normal saline) within 24 hours after transurethral resection and then randomized into 2 groups after a definite histopathological diagnosis of Ta/T1 bladder cancer. One group of 77 patients received 19 intravesical instillations of epirubicin in the year after transurethral resection (group 1). The second group of 73 patients received 9 intravesical instillations of epirubicin during the 3 months after transurethral resection (group 2). Nonrecurrence rates and toxicity were compared. RESULTS: In the followup period, 10 group 1 patients (13.0%) and 23 group 2 patients (31.5%) had recurrent disease. The 3-year nonrecurrence rate was 85.2% in group 1, whereas it was 63.9% in group 2. The nonrecurrence rate of group 1 was significantly higher than that of group 2 throughout the observation period (p = 0.005). The incidence and severity of toxicity were not significantly different between the 2 groups. CONCLUSIONS: Our study indicates that long-term instillation of epirubicin is more effective than short-term instillation in preventing recurrence after transurethral resection of Ta/T1 bladder cancer.     

Intravesical bacillus Calmette-Guerin therapy for stage T1 grade 3 transitional cell carcinoma of the bladder: recurrence,progression and survival in a study of 57 patients

PURPOSE: Stage T1 grade 3 transitional cell carcinoma of the bladder is associated with a high risk of tumor recurrence and progression. We report our experience with stage T1 grade 3 bladder tumors treated with bacillus Calmette-Guerin (BCG) therapy in the last 10 years. MATERIALS AND METHODS: We analyzed the outcome in 57 consecutive patients treated with intravesical BCG for stage T1 grade 3 bladder cancer between 1991 and 2001. After initial transurethral resection all patients received a 6-week course of BCG therapy consisting of 1 instillation weekly. All patients underwent systematic biopsies at the end of the first BCG course. Patients with negative biopsies received maintenance BCG therapy, consisting of intravesical instillations each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months after the first course. Patients with residual tumor received a second course of 6 weekly instillations. Time to tumor recurrence and progression, and the rate of patient survival were retrospectively analyzed. RESULTS: Median followup was 53 months (range 9 to 110). Minimum followup was 2 years in 36 cases (63.2%) and 5 years in 28 (49.1%). After the first BCG course 50 patients (87.7%) had no residual disease, while 7 (12.3%) had residual tumor. The recurrence and progression rates were 42.1% and 22.8%, respectively. The rate of delayed cystectomy was 14%. The rate of disease specific survival was 87.7%. CONCLUSIONS: Our study confirms that BCG therapy is effective conservative treatment for patients with stage T1 grade 3 bladder tumors.     

Prognostic significance of lymphovascular invasion of bladder cancer treated with radical cystectomy

PURPOSE: We determined the prognostic significance of lymphovascular invasion (LVI) in patients treated for invasive transitional cell carcinoma of the bladder with radical cystectomy. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer with intent to cure. All patients with nontransitional cell carcinoma histology, palliative procedures, unknown lymphovascular status, less than pT1 pathological stage, or any neoadjuvant or adjuvant chemotherapy/radiation therapy were excluded, leaving 702 comprising the study cohort. Of the 702 patients 249 (36%) had LVI. RESULTS: Median followup was 11.0 years (range 8 days to 23.2 years). Overall 5 and 10-year survival was 51% and 34%, while 5 and 10-year recurrence-free survival was 66% and 64%, respectively. Ten-year recurrence-free survival in patients without LVI was 74% compared with 42% in those with LVI (p <0.0001). Similarly 10-year overall survival was 43% in patients without LVI compared with 18% in those with LVI (p <0.0001). In the organ confined/lymph node negative and lymph node positive pathological subgroups survival outcomes were significantly worse if LVI was present. Although a trend was observed, LVI status was not statistically significant in patients with extravesical node negative disease. Stepwise Cox regression analysis revealed that pathological subgroup (organ confined, extravesical and lymph node positive) (p <0.0001) and LVI status (p = 0.0004) were independent prognostic variables for recurrence-free and overall survival. CONCLUSIONS: Lymphovascular invasion appears to be an important and independent prognostic variable in patients with invasive bladder cancer treated with radical cystectomy. LVI status should be determined in cystectomy specimens, which may provide further risk stratification in patients following radical cystectomy.     

Impact of malpractice caps on use and outcomes of radical cystectomy for bladder cancer: data from the surveillance, epidemiology, and end results program

PURPOSE: The impact of malpractice awards on insurance premiums and health care delivery generates much concern. To our knowledge no data exist regarding the impact of caps, or upper limits, on awards for noneconomic damages (also termed pain and suffering) on health care delivery patterns or outcomes. We investigated the effect of caps on the use of and outcomes following aggressive surgical treatment (radical cystectomy) in patients with bladder cancer. MATERIALS AND METHODS: We performed a retrospective cohort study of patients with bladder cancer who underwent radical cystectomy, identified from the Surveillance, Epidemiology, and End Results (SEER) Program database. Cystectomy rates and post-cystectomy disease specific survival were compared between SEER regions with and without a cap, while controlling for other variables. RESULTS: A significantly greater proportion of patients with stages III and IV bladder cancer underwent cystectomy in SEER regions with a cap. Cap status was a significant predictor of survival from bladder cancer. CONCLUSIONS: Radical cystectomy for bladder cancer is performed more often even for advanced bladder cancer in geographic regions with a cap with a positive impact on survival. The institution of caps may have beneficial effects on patterns of health care beyond that of merely decreasing insurance premium costs.     

Sensitivity of human complement factor H related protein (BTA stat) test and voided urine cytology in the diagnosis of bladder cancer

PURPOSE: We compared the sensitivity of the BTA statdagger test, a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine, to that of voided urine cytology in patients with primary bladder cancer. We also assessed the effect of tumor size, number, histological grade and stage on test sensitivity. MATERIALS AND METHODS: We evaluated 151 patients with newly diagnosed bladder cancer in a prospective multicenter study. A voided urine sample obtained before transurethral bladder tumor resection was divided for culture, cytology and BTA stat testing. RESULTS: Overall sensitivity of the BTA stat test and urine cytology for detecting primary bladder cancer was 81.5% and 30.3%, respectively (p <0.0001). The sensitivity of each test increased as tumor size, number, histological grade and stage increased. CONCLUSIONS: Sensitivity of the BTA stat test was superior to that of voided urine cytology in all tumor categories. This noninvasive, easy to perform, point of care test may have the potential to replace cytology for diagnosing bladder cancer.     

Long-term results of amitriptyline treatment for interstitial cystitis

Purpose:

We performed a prospective, open label study to examine the safety and efficacy of the long-term administration of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC).

Materials and Methods:

A total of 94 patients were stratified into 2 groups, namely a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) group of those who fulfilled NIDDK criteria for IC and a nonNIDDK group of those who presented with characteristic IC symptoms but met at least 1 NIDDK exclusion criterion. Amitriptyline was received strictly at bedtime following an established self-titration protocol without a limitation of the maximum daily dose. Patients reporting improvement in a global response assessment questionnaire were considered treatment responders. Further efficacy measures were changes in pain and urgency, functional bladder capacity and frequency. Changes in the O′Leary-Sant IC index and rating of overall satisfaction with the therapeutic outcome were also reported.

Results:

Mean study followup ± SD was 19.0 ± 12.5 months. The response rate was 64% (60 patients). The overall mean dose was 55 mg (range 12.5 to 150). Side effects occurred in 79 patients (84%), including dry mouth in 79% and weight gain in 59%. Patient overall satisfaction with the therapeutic result was excellent or good in 43 (46%). The dropout rate was 31% (29 patients) after a mean treatment period of 6 weeks at a mean dose of 70 mg. Nonresponse to treatment was the primary reason for dropout in all cases, while side effects contributed to dropout in 25 (86%). Improvement in the various IC symptoms was statistically significant compared with baseline.

Conclusions:

Long-term administration of amitriptyline is a feasible, safe and effective treatment for IC, provided that the drug is used judiciously to minimize adverse effects. The therapeutic response to amitriptyline was uniformly observed in patients fulfilling NIDDK criteria and in those with the pure clinical diagnosis of IC.