Prophylaxis of superficial bladder tumor with the intravesical instillation of bacillus Calmette-Guerin or anti-cancer agents. A retrospective study]

It was retrospectively analyzed whether intravesical instillation of bacillus Calmette-Guerin (BCG) or anti-cancer agents had prophylactic effect or not after removal of superficial bladder tumors. The results over a follow-up period ranging from 6 to 40 months showed 23.8 per cent recurrence in group 1 patients treated with BCG (21 patients), 46.7 per cent recurrence in group 2 treated with anti-cancer agents (45 patients) and 52.3 per cent recurrence in the group 3 (127 patients) which were not received any intravesical drugs. Long-term results among the 3 groups calculated with Kaplan-Meier method demonstrated that the instillation of BCG or of anti-cancer agents was more useful for prophylaxis, compared with the actuarial non-recurrence rates of group 3. The instillation of BCG showed good prophylactic effects especially in recurrent, grade 2 and pTa bladder tumors. The instillation of anti-cancer agents showed to provide prolonged protection from recurrence, but the instillation of BCG did not.     

Postoperative prophylactic intravesical instillation of cytosine arabinoside and mitomycin C in superficial bladder tumor: A follow-up study

A follow-up study was made on 225 Japanese patients with superficial bladder tumors who were treated postoperatively with intravesical instillation of cytosine arabinoside and mitomycin C nineteen times during one year. Cumulative recurrence rates of the tumor were 16.7 and 41.9 per cent during the first 1 and 3.5 years after surgery, respectively. These results are superior to the previous findings in cases in which instillation therapy was not given. Histologically, there was no definite difference in recurrence among the groups with low-grade and high-grade tumors. The recurrence rate of multiple tumors was higher than that of a solitary tumor. Earlier postoperative instillation appeared to be more effective during the initial one year after surgery.     

Topical chemoprophylaxis of superficial bladder cancer with mitomycin C and adjuvant hyaluronidase.

The effect of intravesical instillation of 200,000 IU hyaluronidase in addition to mitomycin C as chemoprophylaxis of superficial bladder cancer was evaluated. Based on our result of a previous study that this approach results in a significantly reduced recurrence rate (7.1 versus 32.1%), 43 patients undergoing transurethral resection of Ta-T1 tumors were retrospectively analyzed after a mean observation period of 48.5 months. During the 2 years of prophylactic therapy, tumor recurrence was seen in 6 patients (13.9%). Of the 37 patients who remained recurrence-free under treatment, 5 (13.5%) had recurrent tumors later during a mean observation period of 24.5 (18-42) months after treatment. These values are significantly lower than those obtained previously from a group of 63 patients treated with mitomycin alone, with recurrence rates of 33.3% during chemoprophylaxis and 26.2% thereafter (mean observation period 50.4 months). It appears that additive hyaluronidase enhances the local effect of mitomycin C in the intravesical chemoprophylaxis of bladder cancer, presumably by improving diffusion into the bladder mucosa and catalyzing the breakdown of a hyaluronic acid contained in a protective halo around malignant urothelial cells.     

The influence of lower urinary tract infection on the recurrence rate of superficial transitional cell carcinoma of the bladder

We studied retrospectively 78 patients with recurrent superficial bladder tumors in an effort to determine whether transitional tumor cells implant and grow preferentially in patients who have undergone endoscopic resection of stage T1 bladder tumors in the presence of an inflamed urothelium. Of the patients 32 (group 1) had an undetected lower urinary tract infection at the time transurethral resection was performed and 46 (group 2) were free of infection. All patients had intravesical chemotherapy by thiotepa (triethylenethiophosphoramide) and were treated with appropriate antibiotics as soon as the urinary tract infection was recognized from 24 to 48 hours postoperatively. Of the patients in group 1, 37.5 per cent had tumor recurrence in less than 6 months and 15.6 per cent in less than 3 months, compared to 30.4 and 6.5 per cent, respectively, in group 2. Although the tumor recurrence rates 3 and 6 months postoperatively were higher among the group 1 patients (with urinary tract infection) the difference between the 2 groups was not significant. Because the patients were treated by intravesical chemotherapy, and antibiotics in those with urinary tract infection, our study does not allow a definite conclusion regarding the contribution of urinary tract infection on the recurrence rate of superficial bladder tumors.     

A Randomized Prospective Study Comparing Long-Term Intravesical Instillations of Mitomycin C and Bacillus Calmette-Guerin in Patients with Superficial Bladder Carcinoma

Purpose

We compared the efficacy and toxicity of long-term mitomycin C versus bacillus Calmette-Guerin (BCG) instillation in patients at high risk for recurrence and progression of superficial bladder carcinoma.

Materials and Methods

Our randomized comparison study included 261 patients with primary dysplasia, or stage Tis, stage T1, grade 3 and multiple recurrent stage Ta/T1, grade 1 or 2 disease. Mitomycin C (40 mg.) or Pasteur strain BCG (120 mg.) was instilled weekly for 6 weeks, then monthly for up to 1 year and every 3 months during year 2.

Results

After a median followup of 39 months 49 percent of the patients given BCG and 34 percent given mitomycin C were disease-free (p less than 0.03), compared to 48 and 35 percent, respectively, of those with stage Ta or T1 disease, and 54 and 33 percent, respectively, of those with dysplasia or stage Tis tumor. Tumor progressed in 13 percent of patients, with no statistically significant difference observed regarding progression between the mitomycin C and BCG groups. Side effects were more common after BCG instillation, with 5 cases of severe side effects compared to 1 in the mitomycin C group. Treatment was stopped due to toxicity in 10 percent of the patients.

Conclusions

The majority of patients tolerated long-term intravesical therapy well. BCG instillation was hampered by more frequent side effects. BCG was superior regarding recurrence prophylaxis, since patients given BCG had fewer recurrences and a significantly longer time to treatment failure compared to those treated with mitomycin C. No statistically significant difference was observed regarding progression.     

Immunotherapy in bladder cancer with keyhole-limpet hemocyanin: a randomized study

A randomized, controlled study was begun in 1982 on the effect of keyhole-limpet hemocyanin and mitomycin C in the prevention of recurrent superficial bladder cancer (stages pTa to pT1, grades 0 to 3) in 44 patients. All tumors were resected and all patients were presumed to be free of tumor at initiation of the prophylactic instillations. Before the bladder instillation program was begun all patients in the keyhole-limpet hemocyanin group Ia were immunized with 1 mg. keyhole-limpet hemocyanin intracutaneously and then monthly bladder instillations of 10 mg. were given. The control group Ib received 20 mg. mitomycin C monthly. Of the 21 patients in the keyhole-limpet hemocyanin group Ia (mean followup 20.7 months) 3 (14.2 per cent) had recurrences, compared to 9 of 23 (39.1 per cent) in the mitomycin C group Ib (mean followup 18.3 months). The over-all preventive effect was significantly better (p less than 0.05, chi-square) in keyhole-limpet hemocyanin-treated patients than in those given mitomycin C. In 1984 a new single drug study (group II) was started with keyhole-limpet hemocyanin alone, administered as in group Ia. Of 81 patients in group II (nonrandomized, mean followup 22.8 months) 17 (20.9 per cent) had recurrences. Of the patients given keyhole-limpet hemocyanin 20 of 21 (95.2 per cent) in group Ia and 70 of 81 (86.4 per cent) in group II had complete and partial prevention (downgrading), compared to 16 of 23 (69.5 per cent) in group Ib. Our study was established to analyze the effect of a new method of immunotherapy; no adverse local or systemic side effects were noted.     

Intravesical instillation of mitomycin-C in 242 patients with superficial bladder cancer at high risk of recurrence: long-term results.

OBJECTIVE: The present study evaluated the long-term results of intravesical mitomycin C (MMC) instillation after transurethral resection (TUR) in 242 consecutive patients with superficial bladder cancer at high risk of recurrence (stage Ta, grade 1-3, or stage T1, grade 1 and 2, primary multiple or recurrent tumor). MATERIALS AND METHODS: 242 patients were treated with weekly instillations of 40 mg MMC for 8 weeks after TUR. Tumor-free patients then followed a maintenance course with monthly instillations for 3 months. RESULTS: Median follow-up of disease-free patients is 43.5 (range 23-112) months. The incidence of first recurrence is 59.5% (144/242 patients) with a median time to first recurrence of 29 months. 95 patients (39.3%) remained disease-free. Three had disease progression as the first event. The risk of recurrence was significantly higher for multifocal tumors (p = 0.0023, hazard ratio 1.79, 95% CI 1.23-2.59). Overall, patients have been followed for a median time of 57 (range 10-114) months. During this period the recurrence rate was 4.9. Eleven more patients had disease progression. The progression rate is 5.8% (14/242), with a mean time to progression of 34 months. At present 209 patients are alive, 6 have died of bladder cancer, 16 of causes unrelated to the disease and 11 (4.5%) have been lost to follow-up. Thus the crude survival rate is 86.4%, disease-specific mortality 2.5%, and non-disease-specific mortality 6.6%. CONCLUSIONS: Patients with multiple tumors seem to benefit the least from MMC instillation. Probably recurrent disease could be better prevented with intravesical bacillus Calmette-Guérin.     

Prophylactic intravesical instillation of mitomycin C and cytosine arabinoside for prevention of recurrent bladder tumors following surgery for upper urinary tract tumors: A prospective randomized study

BACKGROUND: A recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract is not rarely observed. A prospective randomized study was conducted to examine the significance of prophylactic intravesical instillation of mitomycin C (MMC) and cytosine arabinoside (Ara-C) to prevent recurrent bladder tumors after surgery for superficial transitional cell carcinoma of the upper urinary tract. METHODS: The patients were randomized into an instillation group, who received postoperative intravesical instillation of MMC (20 mg) and Ara-C (200 mg) 28 times over a period of 2 years, and a non-instillation group. The non-recurrence rate was then compared between the groups. RESULTS: Of the 27 patients registered, 25 patients (13 with instillation and 12 without instillation) were able to be evaluated, with a median follow-up period of 45 months. The non-recurrence rate of bladder tumors in the instillation group was higher than that in the non-instillation group. Although the difference was not statistically significant, the P-value (P = 0.079) demonstrated a strong trend. When any possible bias was allowed for a multivariate analysis, the difference was almost significant (P = 0.0567). No patients withdrew from this study due to any side-effects. CONCLUSION: The postoperative instillation of MMC and Ara-C may be a useful approach for reducing the recurrence of bladder tumors after surgery for upper urinary tract tumors.     

A trial of prophylactic thiotepa or mitomycin C intravesical therapy in patients with recurrent or multiple superficial bladder cancers

There were 40 consecutive patients with recurrent or multiple superficial stage Ta or T1 transitional cell cancer assigned randomly to receive prophylactic thiotepa or mitomycin C intravesical chemotherapy. Patients received 8 weekly instillations followed by 22 monthly treatments of either 60 mg. thiotepa or 40 mg. mitomycin C. Of 25 patients randomized to receive mitomycin C 4 had recurrence in a total of 337 patient-months (1.19 per 100 patient-months), while disease recurred in 1 of 15 patients randomized to receive thiotepa who were followed for a total of 220 patient-months (0.45 per 100 patient-months). No significant difference in recurrence rate was noted for either drug group (p equals 0.18). Toxicity requiring cessation of therapy was observed in 7 patients (28 per cent) on mitomycin C and none on thiotepa.     

表浅膀胱肿瘤电切术后膀胱内药物灌注预防肿瘤复发的临床观察

目的 观察表浅膀胱肿瘤电切术后膀胱内灌注丝裂霉素和吡柔比星预防肿瘤复发的疗效和安全性.方法 回顾性分析我科2007年2月至2009年10月间收治的130例表浅膀胱肿瘤患者的临床资料,所有患者均行经尿道膀胱肿瘤电切和术后膀胱内灌注丝裂霉素或吡柔比星,其中术后膀胱内灌注丝裂霉素70例,吡柔比星60例.观察术后1年肿瘤复发和灌注药物的副作用.结果 ①术后膀胱内灌注丝裂霉素和吡柔比星的1年复发率分别为11.4%（8/70）和16.7%（10/60）（P＞0.05）.在丝裂霉素组,病理分级G1、G2、G3级肿瘤1年复发率分别为12.2%、8%和25%,它们之间无显著差异（P＞0.05）;在吡柔比星组,病理分级G1、G2、G3级肿瘤1年复发率分别为4%、12.5%和54.5%,其中G3级肿瘤复发率明显高于G1和G2级肿瘤（P＜0.05）.②130例患者中,进行即刻膀胱内药物灌注（24h内）和非即刻灌注的1年复发率分别为4%（1/25）和16.2%（17/105）,两者之间有显著性差异（P＜0.05）.③灌注丝裂霉素和吡柔比星后全身副作用发生率分别为18.5% 和 1.5%（P＜0.05）,局部副作用发生率分别为4.3% 和 33.3%（P＜0.05）.结论 术后膀胱内灌注丝裂霉素和吡柔比星预防肿瘤复发的效果无显著性差异,但G3级肿瘤的复发率高于G1和G2级肿瘤,对其灌注方案有待进一步研究;术后即刻膀胱内药物灌注可有效降低肿瘤1年复发率,值得推广;术后膀胱内灌注丝裂霉素和吡柔比星的副作用在全身和局部发生率不同,但均可耐受;由于观察时间短和例数有限,观察结果有待进一步研究.     

Weekly mitomycin C followed by monthly bacillus Calmette-Guerin or alternating monthly interferon-alpha2B and bacillus Calmette-Guerin for prophylaxis of recurrent papillary superficial bladder carcinoma

PURPOSE: We evaluated alternatives to bacillus Calmette-Guerin (BCG) monotherapy using a new combination of chemotherapy and immunotherapy for recurrent superficial bladder carcinoma. MATERIALS AND METHODS: A total of 236 patients with frequently recurrent stage Ta or T1 bladder tumors were enrolled in our prospective, randomized, multicenter Finnbladder IV study. The initial mitomycin C instillation was instilled in all patients perioperatively after transurethral resection, followed by 4 weekly instillations of mitomycin C. Thereafter patients were randomized to receive monthly for up to 1 year BCG only or interferon-alpha2b and BCG alternating monthly. Primary end points were time to initial recurrence, recurrence rate (number of recurrences per patient-year) and recurrence index (number of recurrent tumors per patient-year). RESULTS: Of the 236 randomized patients 205 were eligible for study with a median overall followup of 30.7 months. Monthly BCG was superior to alternating monthly interferon-alpha and/or BCG with respect to time to initial recurrence (log rank test p <0.00001) as well as recurrence rate (0.4 versus 0.9, p <0.00001) and index (0.9 versus 3.0, p <0.00001). Side effects were limited. CONCLUSIONS: Monthly BCG given for up to 1 year preceded by perioperative and an additional 4 weekly mitomycin C instillations is a well tolerated mode of instillation therapy, providing excellent tumor control comparable to that of the best reported instillation regimens. No benefit was obtained by alternating interferon-alpha2b with BCG.     

Intravesical instillation of epirubicin in the prophylactic treatment of recurrent superficial bladder cancer

A retrospective study was performed to determine the efficacy of intravesical instillation of epirubicin in the prophylactic treatment for recurrent superficial bladder cancer when compared with no treatment controls. Seventeen patients with recurrent superficial bladder cancer received epirubicin (30 mg/40 ml in normal saline) seventeen times after transurethral resection (TUR). Historical controls consist of sixteen patients with recurrent superficial bladder cancer who received no adjuvant treatment after TUR. In the epirubicin group, 1-, 2- and 3-year recurrence free rates were 64.7%, 41.2% and 5.9%, respectively. In controls all of them recurred and 1- and 2-year recurrence free rates were 17.6% and 0%, respectively. The recurrence-free rate was significantly higher in the epirubicin group than in the controls (p < 0.05). We investigated whether intravesical instillation of epirubicin prolonged recurrence-free intervals when compared with recurrence-free intervals without adjuvant treatment after TUR in each patient. The 1- and 2-year recurrence free rates after initial TUR were 25% and 12.5%, respectively, and those with epirubicin treatment after TUR were 62.5% and 37.5%, respectively. Recurrence-free intervals were significantly prolonged by intravesical instillation of epirubicin as compared with those without adjuvant treatment in each patient. This study demonstrated the efficacy of intravesical instillation of epirubicin in the prophylactic treatment for superficial recurrent bladder cancer.     

Therapy of superficial bladder carcinomas

Treatment of superficial bladder carcinoma was derived by several large randomized trials. This group of cancers is stratified by differentiation grade and stage in three groups of different risk profiles (Ta G1-2 vs. T1 G1-2 vs. Tis/T1 G3). Standard therapy is fractionated transurethral resection (TUR). Adjuvant therapy after transurethral resection is not indicated in primary Ta G1-2 tumors because there is a low recurrence rate and no risk of tumor progression. The recurrence rate can be decreased up to 15% in recurrent Ta or T1 G1-2 tumors by intravesical therapy with mitomycin C (20 mg/instillation) or adriamycin (50 mg/instillation). Therapy should be limited to early (within 24 h post-TUR) and short-term treatment (4 x weekly, 5 x monthly). Alternatively, patients can be treated by intravesical BCG (strain Connaught or strain RIVM). Maintenance therapy is advantageous according to recurrence rate. Tumors with great malignant ability (Tis or T1 G3) will be treated initially with adjuvant BCG. Patients who fail are candidates for radical cystectomy within 3-6 months after initial diagnosis. There is no need - except in clinical trials - for the administration of unverified or not admitted drugs. Copyright Copyright 1999 S. Karger AG, Basel     

Superficial bladder tumors (stage pTa, grades 1 and 2): the importance of recurrence pattern following initial resection

We treated 414 new patients with stage pTa, grades 1 and 2 bladder tumors by transurethral resection between 1970 and 1982. All of the patients with grade 3 or previous upper tract tumors, or who had been treated at some stage with intravesical chemotherapy were excluded. Followup for 5 or more years was available in 188 of the patients. There was a low increase in T stage (6 per cent). Of the patients followed for 5 or more years 46 per cent remained free of tumor. Only 16 per cent of the patients had multiple tumors at presentation and 20 per cent had tumors of 10 gm. or more. These factors were associated with a worse prognosis. Patients free of tumor at 3 months had an 80 per cent chance of having no further recurrences and this rate remained the same up to 2 years from the start of the disease. Patients with a recurrence at 3 months were much less likely to remain free of tumor, and had a higher chance of recurrence at every future visit.     

Intravesical bacillus Calmette-Guerin instillation therapy in superficial bladder cancers--clinical study on prognostic factors

Intravesical instillation of Tokyo 172 strain bacillus Calmette-Guerin (BCG) was performed on 137 patients with superficial bladder cancer (Ta and T1) after transurethral tumor resection as a prophylaxis against tumor recurrence. The recurrence rate of tumors was compared with that of historical controls and was estimated by the person-years method. There were statistically significant decreases in recurrent tumors following BCG therapy. To clarify the efficacy of intravesical BCG therapy, prognostic significance of several factors were evaluated in 90 patients with initial bladder cancer treated with TUR and BCG instillation, and compared to those of controls. Prophylactic effects were statistically better for those with multiple tumors, grade 3 lesions or Ta lesions than for control patients. No correlation between purified protein derivative responsiveness and favorable results could detected. There were no marked side effects or fatal complications of BCG therapy during the observation periods. Our results suggest that BCG is able to change the biological behavior of superficial bladder cancers with multiple, high grade or low stage lesions. The intravesical BCG instillation seems to be effective and safe as a prophylaxis against the recurrence of superficial bladder tumors.     

Over expression of metallothionein predicts resistance of transitional cell carcinoma of bladder to intravesical mitomycin therapy

PURPOSE: Metallothionein, a low molecular weight intracellular protein, binds mitomycin with high affinity protecting the tumor DNA. We prospectively studied the relationship of metallothionein expression in bladder transitional cell carcinoma and resistance to intravesical mitomycin. MATERIALS AND METHODS: A series of 45 consecutive patients with superficial transitional cell carcinoma treated with intravesical mitomycin were studied. Resected tumor tissues were stained with metallothionein monoclonal antibody E9. Two pathologists scored staining intensity and distribution. All patients were followed with regular flexible cystoscopy. RESULTS: Median patient age was 73 years (range 44 to 89). Tumor grade was 1 to 3 in 6, 33 and 6 cases, respectively. In 20 patients (44.44%) tumor recurred after mitomycin therapy. Median cytoplasmic staining scores for recurrent and nonrecurrent tumors were 5 (range 0 to 61) and 0 (0 to 14), respectively. Median nuclear staining scores for recurrent and nonrecurrent tumors were 3 (range 0 to 56) and 0 (0 to 11), respectively. Median followup of patients without recurrence was 18 months (range 12 to 36). Nuclear and cytoplasmic staining scores were significantly higher in recurrent than in nonrecurrent tumors. There was no significant relationship of metallothionein expression with tumor grade. CONCLUSIONS: Over expression of metallothionein predicts the resistance of bladder transitional cell carcinoma to intravesical mitomycin therapy.     

Mitomycin C bladder instillation therapy for bladder tumors.

Patients with bladder tumors underwent a course of topical bladder instillation of 20 mg. mitomycin C in 20 ml. sterilized distilled water 3 times weekly for a total of 20 procedures. In 22 of the 50 patients (44 per cent) the tumors disappeared completely, while in 16 patients (32 per cent) there was partial disappearance and in 12 patients (24 per cent) there was no affect. Therefore, the total effective rate was 76 per cent. We concluded from our studies that mitomycin C topical therapy could be applied to low stage and low grade bladder tumors less than 1 cm. in diameter, without regard to the number of tumors. We now use mitomycin C topical therapy in all cases of bladder tumors. Local bladder reaction was noted in 3 cases but a complete course of therapy was accomplished in each case--in 2 cases without interruption of treatment and in 1 case by delaying treatment for 1 week. Abnormal values of hematocrit, white blood cells and platelets in blood were not observed during therapy.     

Monoclonal antibody 486 P 3/12: a valuable bladder carcinoma marker for immunocytology

Monoclonal antibodies directed against tumor-associated antigens of bladder carcinoma were used to identify tumor cells in bladder washout specimens of 40 patients with bladder carcinoma (group 1), 41 with no bladder disease or with urinary tract infections (group 2), 41 who received long-term mitomycin C instillation therapy after excision of the tumors (group 3) and 39 who received no prophylaxis after excision of the tumors (group 4). In all groups the same bladder washout specimen was used for standard urinary cytological and immunocytological tests. True positive results were obtained in 90 per cent of the patients in group 1 according to our immunocytological criteria and in 43 per cent according to standard cytology studies. No urine specimens in group 2 (controls) were immunocytologically positive, while 16 of 41 in group 3 and 17 of 39 in group 4 were positive immunocytologically but only 4 and 5, respectively, were positive according to standard cytology studies. Further followup of these patients will show whether cells positive for monoclonal antibody 486 P 3/12 will permit early detection of recurrent bladder cancer and whether one can identify patients who require prophylaxis after removal of the superficial bladder tumors.     

Treatment of superficial bladder cancer with intravesical mitomycin C: analysis of immediate and long-term response in 70 patients

A total of 70 patients received intravesical mitomycin C for treatment of superficial bladder cancer. The drug was instilled weekly for 8 weeks. Thirty-nine patients (56 per cent) had failed thiotepa therapy and 25 had high grade tumors. Of the patients 27 (39 per cent) had complete eradication of tumor at the initial 3-month evaluation and an additional 27 had a partial response. The response did not vary with initial tumor grade or stage. Followup averaged 28 months for the 70 patients. A muscle invasive tumor developed during followup in 7 per cent of the patients with an initial complete response, 15 per cent with a partial response and 25 per cent of the initial failures. To date 5 patients (7 per cent) have died of bladder cancer. Intravesical mitomycin C is an effective modality for treatment of superficial bladder cancer. Patients achieving a complete response are at little risk for progressive disease.     

Intravesical bacillus Calmette-Guerin instillation therapy of recurrent superficial bladder carcinomas resistant to intravesical anti-cancer chemotherapy

Tokyo strain bacillus Calmette-Guerin (BCG) was instilled in a dose of 80 mg in 40 ml normal saline to the bladder of 8 patients with recurrent superficial bladder carcinoma (Ta, Tl, Tis) resistant to mitomycin C and/or adriamycin intravesical instillation chemotherapy. Instillation was performed weekly for 6 weeks and 3 to 4 weeks after the last instillation, the response was assessed by cystoscopy and urine cytology. Patients who achieved complete response underwent monthly maintenance instillation for a year and inspection with cystoscopy and urine cytology every 3 months. Of the 7 patients who underwent therapeutic instillation, 3 (43%) achieved complete response, and 2 partial response. Two patients with no response had carcinoma in situ of grade 3 anaplasia. Two of the 3 complete responders were free of disease for 11 and 12 months, but another 1 developed intravesical recurrence 13 months later. One patient underwent prophylactic instillation and remained free of disease for 23 months. Side effects included frequency, urgency and pain on urination which were tolerable with anti-analgesics. Two patients underwent total cystectomy because of tumor progression and had typical lesions of prostatic tuberculosis.