Results of 6 weekly intravesical bacillus Calmette-Guerin instillations on the treatment of superficial bladder tumors

We evaluated 104 patients with superficial bladder tumors for response to intravesical bacillus Calmett-Guerin therapy. Patients received 6 weekly intravesical bacillus Calmette-Guerin instillations and they were followed for response every 3 months with urinary cytology, cystoscopy and bladder biopsy. Patients were considered treatment failures if either the cytology studies or biopsies were positive for tumor. Of 65 patients who failed the initial treatment course 57 were given an additional 6-week course of therapy. One 6-week course of bacillus Calmette-Guerin was successful in 20 of 55 patients (36 per cent) treated for prophylaxis, 12 of 32 (37 per cent) treated for carcinoma in situ and 7 of 17 (41 per cent) treated for residual tumor. The response rate for the total patient population treated with 1, 6-week course was 37.5 per cent (39 of 104). A second 6-week course was successful in 19 of 29 patients (65 per cent) treated for prophylaxis, 11 of 18 (71 per cent) treated for carcinoma in situ and 4 of 10 (40 per cent) treated for residual tumor. The response rate for all patients receiving a second course of bacillus Calmette-Guerin was 59.6 per cent (34 of 57). Of 6 patients who refused another 6-week course of bacillus Calmette-Guerin 4 had additional recurrences and 3 of these 4 suffered invasive disease. The over-all therapeutic response rate for patients treated with either 6 or 12 weeks of therapy was 70 per cent. These results suggest that 6 weeks of intravesical bacillus Calmette-Guerin do not provide optimal therapy for superficial bladder tumors. The data further suggest that more intensive regimens may increase therapeutic efficacy.     

Two courses of intravesical bacillus Calmette-Guerin for transitional cell carcinoma of the bladder

Bacillus Calmette-Guerin intravesical immunotherapy is becoming the adjunctive treatment of choice for patients with recurrent superficial transitional cell carcinoma of the bladder. The recurrence rates following bacillus Calmette-Guerin therapy reported to date vary widely but generally they fall within the 20 per cent range. The results of retreatment of bacillus Calmette-Guerin failures with a second 6-week course of intravesical bacillus Calmette-Guerin have not been reported previously. We report the response rates of 61 patients treated with a single 6-week course of intravesical bacillus Calmette-Guerin, and 25 patients who failed to respond to the initial course and were treated with a second 6-week course. Intravesical bacillus Calmette-Guerin therapy (120 mg. Pasteur strain) was administered weekly for 6 weeks. No intradermal injections of bacillus Calmette-Guerin were given. Patients were followed with urinary cytology and bladder biopsy every 3 months. Patients with tumor at followup were treated with a second 6-week course of intravesical bacillus Calmette-Guerin. Of 19 patients with carcinoma in situ 8 (42 per cent) responded to the initial course of bacillus Calmette-Guerin, while 5 of 9 (56 per cent) became free of tumor after the second course, for a cumulative response rate of 68 per cent (mean followup 13.5 +/- 2.1 months). Of 13 patients treated for residual papillary tumors 6 (46 per cent) responded to the initial course of bacillus Calmette-Guerin and 3 of 7 (43 per cent) to the subsequent course, providing a cumulative response rate of 69 per cent (mean followup 14.8 +/- 2.8 months). Of 29 patients treated for prophylaxis against tumor recurrence 20 (69 per cent) remained free of tumor after a single 6-week course, while 6 of 9 (67 per cent) were free of tumor after the second treatment course. A 90 per cent cumulative response rate was observed in the prophylaxis category (mean followup 12.8 +/- 1.3 months). Over-all 48 of 61 patients (79 per cent) were observed to respond when all 3 categories and both treatment courses were considered. Individually, the response rate for each 6-week treatment course was 56 per cent (34 of 61 and 14 of 25, respectively). Toxicity for each treatment course was well tolerated and consisted of dysuria/frequency, hematuria and a flu-like syndrome. Toxicity was progressively more severe with prolonged treatment. Retreatment with a second course of bacillus Calmette-Guerin is warranted for patients failing the initial treatment course.(ABSTRACT TRUNCATED AT 400 WORDS)     

Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer

An actuarial analysis of the risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer was performed for 100 consecutive patients treated for carcinoma in situ (29), prophylaxis against recurrent tumor (51) or residual superficial papillary tumor (21). The risk-to-benefit ratio at entry into bacillus Calmette-Guerin therapy (7 per cent risk of invasive cancer developing, 5 per cent risk of metastases and 77 per cent prospect for status free of tumor) and in patients who had failed only 1 course of bacillus Calmette-Guerin therapy (11 per cent invasive cancer, 14 per cent metastases and 58 per cent free of tumor) were highly favorable. However, among patients who had failed 2 or more courses of bacillus Calmette-Guerin therapy the risks of invasive (30 per cent) or metastatic (50 per cent) cancer developing exceeded the prospects for eradicating the superficial tumor present (20 per cent) with further therapy. The results suggest that patients who have failed 2 courses of bacillus Calmette-Guerin therapy (as given in our treatment protocol) should be considered for alternative treatment.     

Long-term effect of intravesical bacillus Calmette-Guerin on flat carcinoma in situ of the bladder

Intravesical bacillus Calmette-Guerin is effective therapy for multifocal carcinoma in situ of the bladder. The duration of this favorable response and its effect on disease progression are the subject of this report. Between March 1978 and July 1981, 47 patients with diffuse, often symptomatic, carcinoma in situ were treated with intravesical bacillus Calmette-Guerin and followed every 3 to 4 months with cystoendoscopy, biopsy and urine cytology for 3 to 6 years. All patients had had prior or concurrent superficial papillary tumors controlled initially by transurethral resection and fulguration 2 to 3 weeks before bacillus Calmette-Guerin treatment. Of the 47 patients 23 were entered into a randomized study, and received intravesical and percutaneous bacillus Calmette-Guerin. Another 24 patients with carcinoma in situ were treated with intravesical bacillus Calmette-Guerin alone. Bacillus Calmette-Guerin (Pasteur strain) was given intravesically (120 mg. in 50 ml. saline) weekly for 6 weeks. Of the 47 patients 32 (68 per cent) are free of disease (negative urine cytology, cystoendoscopy and biopsy): 15 (65 per cent) after combined bacillus Calmette-Guerin for a median duration of 51 months (range 37 to 75 months) and 17 (71 per cent) after intravesical bacillus Calmette-Guerin alone for a median of 45 months (range 36 to 53 months). Of the 23 patients in the randomized study 4 (17 per cent) have required cystectomy for local progression of disease compared to 17 of 26 controls (65 per cent) who were randomized to transurethral resection and fulguration alone. Cystectomy was performed 3 to 27 months after bacillus Calmette-Guerin treatment and in 3 patients tumor was localized to the prostate gland (no tumor found within the bladder). These data indicate that intravesical bacillus Calmette-Guerin is capable of producing long-term remissions of carcinoma in situ in high risk patients and may prevent or delay progression of disease necessitating cystectomy.     

Long-term results of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer

Between January 1978 and February 1984, 120 patients with superficial bladder tumors and/or carcinoma in situ were enrolled in previously reported therapeutic trials of bacillus Calmette-Guerin. Of all treated patients 78 per cent responded to initial therapy, with a followup of 13 to 120 months (median 67 months). Of the 18 patients who failed 10 were treated with repeat, intensified courses. Nine patients who had recurrent tumors within 3 to 30 months after initiation of bacillus Calmette-Guerin therapy (median 6 months) eventually ceased having recurrence. Status free of disease in the 9 patients ranged from 25 to 90 months since the last recurrence (median 64 months). With retreatment of some of the early failures, the initial success rate of 78 per cent was increased to 89 per cent. These data support the concept that intravesical immunotherapy with bacillus Calmette-Guerin should be repeated in patients who initially appear not to respond. The data also suggest that bacillus Calmette-Guerin induces a durable beneficial response rather than simply delays eventual tumor recurrence.     

The management of superficial bladder tumors and carcinoma in situ with intravesical bacillus Calmette-Guerin

A phase II study was performed to assess the role of bacillus Calmette-Guerin as a prophylaxis against recurrent stages O and A bladder tumors, and in the treatment of existing superficial bladder tumors and carcinoma in situ. Tice strain bacillus Calmette-Guerin (1 vial, 2 to 8 times 10(8) organisms in 60 cc saline) was instilled intravesically without cutaneous inoculation. Instillations were given weekly for 6 weeks and then monthly or until recurrence in 22 patients with a history of recurrent tumors, while 22 with existing stages O and A transitional cell carcinoma, and 19 with carcinoma in situ were treated weekly for 8 weeks and then monthly for 12 months or until failure. Complications included cystitis in 88 per cent of the patients (severe in 20 per cent), fever in 15 per cent, a flu-like syndrome in 13 per cent, edema and pruritus in 1.5 per cent, and ureteral stenosis in 1.5 per cent. Twelve patients (19 per cent) did not complete the study owing to toxicity. Of the patients in the prophylaxis group 67 per cent have had no tumor recurrence 10 to 26 months (mean 15 months) after therapy. Of the patients with existing tumors 36 per cent had complete regression following bacillus Calmette-Guerin therapy and 23 per cent had a partial response. Among the patients with carcinoma in situ 13 (68 per cent) had reversal to normal urothelium and 3 (16 per cent) had marked improvement. None of the patients had recurrence at 11 to 20 months. Intravesical Tice strain bacillus Calmette-Guerin is effective as a prophylaxis against recurrent superficial bladder tumors and in the treatment of carcinoma in situ.     

Monitoring intravesical bacillus Calmette-Guerin treatment of bladder carcinoma with flow cytometry

Flow cytometry of bladder irrigation specimens was studied in 22 patients with low stage bladder carcinoma who were treated by transurethral resection of visible tumor followed in 3 to 5 weeks by a course of intravesical bacillus Calmette-Guerin. The most informative examinations were just before the first bacillus Calmette-Guerin treatment, 6 weeks after completing a 6-week course of treatment (3 months) and at 9 months. Of the patients 10 had recurrent tumors after therapy; recurrence was anticipated correctly by flow cytometry at the 12-week followup examination in 6 of the 10 patients and suspected in another. Of 12 patients who remained clinically free of disease for a minimum of 15 months after bacillus Calmette-Guerin therapy flow cytometry identified correctly 7 at 12 weeks, while 1 had a partial response and the remaining 4 reverted to a negative status at 9 months. Of interest, only 4 of the 22 patients were free of disease by flow cytometry at the start of bacillus Calmette-Guerin treatment despite attempted ablation of the tumor by transurethral resection, suggesting that intravesical administration of bacillus Calmette-Guerin destroys existing carcinoma in situ in some cases.     

Long-term followup of patients treated with 1 or 2, 6-week courses of intravesical bacillus Calmette-Guerin: analysis of possible predictors of response free of tumor

We report our long-term experience with 104 patients treated for recurrent superficial bladder tumors followed for a mean of 48 +/- 2 months (range 6 to 83 months). Patients received 6 weekly intravesical bacillus Calmette-Guerin instillations, and were followed for response with urinary cytology, cystoscopy and bladder biopsy. Patients were considered treatment failures if either urinary cytology or biopsy results were positive for tumor. Of 69 patients who failed the initial treatment course 60 were given an additional 6-week course of therapy. A 6-week course of bacillus Calmette-Guerin was successful in 19 of 55 patients (35%) treated for prophylaxis, 10 of 32 (31%) treated for carcinoma in situ and 6 of 17 (35%) treated for residual tumor. The response rate for the total patient population treated with 1, 6-week course was 34% (35 of 104). Another 6-week course was successful in 32 of 60 patients (53%). The over-all response rate free of tumor for patients treated with either 6 or 12 weeks of therapy was 64%. The mean interval free of tumor was 48 months. We evaluated tumor type, stage and grade in conjunction with muscle invasion to assess potential indicators of response to a second course of bacillus Calmette-Guerin. Of 13 patients with carcinoma in situ and 45 with papillary disease 5 (38%) and 26 (58%), respectively, responded to a second course of bacillus Calmette-Guerin (not significantly different). In contrast, 5 of 8 carcinoma in situ failures (63%) had muscle invasive disease, compared to only 3 of 19 papillary nonresponders (16%) (p less than 0.02). These results suggest that intravesical bacillus Calmette-Guerin for the treatment of superficial bladder tumors is an effective long-term therapy. One 6-week course may be ineffective for some patients and another 6-week course provides long-term survival free of tumor for many course 1 failures. Patients who present with carcinoma in situ after a single 6-week course of intravesical bacillus Calmette-Guerin have a significantly higher risk for muscle invasive disease than those with recurrent papillary tumors.     

Intravesical bacillus Calmette-Guerin therapy for in situ transitional cell carcinoma involving the prostatic urethra

A total of 23 patients presenting with multifocal superficial bladder cancer and concomitant in situ transitional cell carcinoma of the prostatic urethra (mucosal in 19 and ductal in 4) underwent transurethral resection and intravesical bacillus Calmette-Guerin therapy. Median followup was 51.6 months (range 6 to 105 months). Of the 23 patients 13 (48 per cent) had a complete response with a median followup of 43.7 months without recurrence. Progression of some type (local, muscle invasion or metastasis) occurred in 10 patients (44 per cent); none occurred in the prostatic urethra. Median interval free of progression was 55.7 months; 7 of 10 patients required cystectomy for progression or refractory disease in the bladder (prostate negative for transitional cell carcinoma). A trial of complete transurethral resection plus intravesical bacillus Calmette-Guerin is a viable alternative to immediate radical cystectomy for patients with mucosal and/or ductal involvement of the prostatic urethra with in situ transitional cell carcinoma.     

Prognostic value of purified protein derivative skin test and granuloma formation in patients treated with intravesical bacillus Calmette-Guerin

We evaluated the prognostic value of purified protein derivative skin test reactivity and a granulomatous response in intravesical bacillus Calmette-Guerin therapy. We treated 62 patients with intravesical bacillus Calmette-Guerin once a week for 6 weeks. Purified protein derivative skin tests were performed before and after therapy. Cold cup bladder biopsies were examined in a blind retrospective manner for the presence of granulomas 6 weeks after completion of therapy. A significant correlation between status free of tumor and the presence of either granulomas or positive purified protein derivative skin tests was observed for the total patient population. Of 25 patients whose purified protein derivative test was converted from negative to positive 19 (77 per cent) remained free of tumor, while only 11 of 32 (34 per cent) whose test did not convert to purified protein derivative positive remained free of tumor (p equals 0.0006, chi-square). Similarly, 28 of 37 patients (77 per cent) who had a granulomatous response remained free of tumor, while only 8 of 25 (32 per cent) without a granulomatous response remained free of tumor (p less than 0.003, chi-square). The correlation was similar for each parameter when the total patient population was subdivided into patients treated for carcinoma in situ, residual tumor or prophylaxis. Calculation of predictive values showed that neither purified protein derivative responsiveness, granuloma formation nor a combination of both provided a highly accurate predictive index of therapeutic response in individual patients. False positive or negative rates, ranging from 23 to 24 per cent and 32 to 39 per cent, respectively, were observed. These results suggest that a link between immunological responsiveness and response to therapy exists but that neither the purified protein derivative skin test nor the granulomatous response exhibits sufficient immunological specificity to serve as accurate prognostic indicators in individual patients.     

Intraluminal interleukin 2 and bacillus Calmette-Guerin for treatment of bladder cancer: a preliminary report

The authors treated 13 patients who had undergone resection of transitional cell carcinoma of the bladder with a combination of 3,500 units of interleukin 2 and half the recommended dose of bacillus Calmette-Guerin. Of the patients 11 (85 per cent) remained free of tumor for a mean of 13 months (range 6 to 24 months). These results are comparable to those with bacillus Calmette-Guerin therapy alone. However, a longer followup with a large number of patients is needed to assess the efficacy of this modality compared to conventional bacillus Calmette-Guerin therapy. Side effects after treatment were minor, self limiting (fever, hematuria and bladder irritability) and lasted for 24 hours.     

Monitoring intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma by postoperative urinary cytology

We studied 51 patients with superficial bladder carcinoma who had been treated with transurethral resection of all gross tumor followed by intravesical bacillus Calmette-Guerin weekly for 6 weeks. Within 72 hours of either the first or second quarterly cystoscopic surveillance examination after bacillus Calmette-Guerin therapy, a conventional cytology study was obtained. Of these patients 8 (15.7 per cent) had positive, 9 (17.6 per cent) suspicious and 34 (66.7 per cent) negative postoperative cytology studies. Subsequent tumor recurrence was defined as a positive biopsy or visible papillary tumors on cystoscopic examination. All 8 patients with a positive postoperative cytology study had tumor recurrence at a median interval of 4 months. Of the 9 patients with a suspicious study 7 (77.8 per cent) had recurrent tumor at a median interval of 7 months and 2 (22.2 per cent) had no evidence of disease at 16 and 19 months, respectively. Of the 34 patients with a negative postoperative cytology study 13 (38.2 per cent) had tumor recurrence after a median interval of 4 months and 21 (67.8 per cent) had no evidence of disease after a median of 25 months. The tumor recurrence rate in patients with a positive or suspicious postoperative cytology study was significantly greater than that of patients with a negative study (p equals 0.001, Fisher's exact test). Postoperative cytology appears to be a significant prognostic indicator following transurethral resection and intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma.     

Superficial bladder cancer treated with bacillus Calmette-Guerin: a multivariate analysis of factors affecting tumor progression

A multivariate analysis was performed on data from 221 patients with superficial bladder tumors (papilloma in 30, grade II to III stage Ta in 51, grade II to III stage Tis in 111 and grade II to III stage T1 in 29) who were treated with intravesical bacillus Calmette-Guerin and followed for a minimum of 24 months or until progression. The purpose of this analysis was to identify prognostic variables predictive of tumor progression defined as muscle invasion, metastasis or endoscopically uncontrolled superficial bladder carcinoma involving the bladder and/or prostatic urethra. Variables examined before bacillus Calmette-Guerin, and at 3 and 6 months after bacillus Calmette-Guerin included age, sex, race, purified protein derivative reaction, duration of disease, tumor category, tumor grade, multifocality, results of cytology, flow cytometry, cystoscopy, biopsy, prior chemotherapy and bacillus Calmette-Guerin treatment regimen. Significant variables (Cox regression analysis, p less than 0.07) for tumor progression were before bacillus Calmette-Guerin--stage T1 tumors and duration of disease less than 1 year, at 3 months after bacillus Calmette-Guerin--stage T1 tumor, duration of disease less than 1 year, positive cytology studies and multifocality, and at 6 months after bacillus Calmette-Guerin--stage T1 tumor, positive cytology and positive biopsy other than stage T1 tumors. Prognostic risk groups were best defined at 6 months after bacillus Calmette-Guerin, the probability of tumor progression thereafter being at 1, 3 and 5 years, respectively, as follows: for risk group 1 (T1 tumor)--71, 100 and 100 per cent, for risk group 2 (positive biopsy other than T1 plus positive cytology)--25, 79 and 100 per cent, for risk group 3 (either positive biopsy other than stage T1 or positive cytology studies)--18, 40 and greater than 81 per cent, and for risk group 4 (negative biopsy and negative cytology studies)--2, 11 and 26 per cent, respectively. Evaluation of patients with superficial bladder carcinoma at 6 months after intravesical bacillus Calmette-Guerin therapy identifies the probability of tumor progression. Patients at high risk for tumor progression require alternative treatment strategies, whereas low risk patients can be observed for further therapy if necessary.     

Adverse impact of fibrin clot inhibitors on intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors

Although intravesical bacillus Calmette-Guerin therapy has proved to be efficacious in the treatment and prophylaxis against tumor recurrence of superficial bladder tumors, its mechanism of action has not been fully elucidated. Previous work has suggested that bacillus Calmette-Guerin organisms attach to the matrix protein, fibronectin, during fibrin clot formation at sites of urothelial disruption and that this attachment was required for the antitumor effect of bacillus Calmette-Guerin to be expressed. Furthermore, drugs inhibiting clot formation were found to abrogate the antitumor effect of intravesical bacillus Calmette-Guerin therapy in a murine bladder tumor model. To examine the effect of inhibitors of fibrin clot formation on the results of intravesical bacillus Calmette-Guerin therapy, a retrospective analysis of 149 evaluable patients receiving intravesical bacillus Calmette-Guerin for superficial bladder tumors was performed. The over-all response rate free of tumor for 29 patients who concomitantly received inhibitors of fibrin clot formation with bacillus Calmette-Guerin therapy was 48%, as compared with 67% for 120 patients who were not receiving these medications (p = 0.0655, chi-square). The most striking difference was noted for patients who failed with recurrent superficial disease. Of the patients who received fibrin clot inhibitors during intravesical bacillus Calmette-Guerin therapy 35% had recurrent superficial tumors compared to only 8% of those who did not receive these drugs during a mean followup of 29.8 plus or minus 11 months (p = 0.005, chi-square). Our study suggests that inhibitors of fibrin clot formation may have an adverse influence on the results of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors.     

Oral or intravesical bacillus Calmette-Guerin immunoprophylaxis in bladder carcinoma

A total of 71 patients with superficial transitional cell carcinoma underwent transurethral resection of bladder tumor. All patients had stage pTa or pT1 transitional cell carcinoma or carcinoma in situ without other concurrent malignancies. The patients were assigned to 3 treatment groups: control group--transurethral resection discontinued within the study, oral bacillus Calmette-Guerin (BCG) group--transurethral resection of bladder tumor plus BCG (Moreau) and intravesical BCG group--transurethral resection of bladder tumor plus BCG. Of 9 patients in the control group 8 (89%) experienced tumor recurrence during a mean followup of 20 months. Of the 28 patients in the oral BCG group 11 (39.3%) had recurrence during a mean followup of 36 months. Of the 34 patients in the intravesical group 6 (18%) had recurrence in a 24-month mean followup. The incidence of complications was higher in the intravesical (41.2%) than in the oral BCG group (28.5%). These results show that intravesical BCG is a more effective immunotherapy; however, oral BCG can be used in patients who do not accept intravesical BCG administration.     

Bacillus Calmette-Guerin for treatment of superficial transitional cell carcinoma of the bladder in patients who have failed thiotepa and/or mitomycin C

Thirty patients with stage Ta carcinoma in situ or T1 superficial bladder cancer received 6 weeks of intravesical bacillus Calmette-Guerin. All patients had persistent or recurrent tumor despite thiotepa and/or mitomycin C. Response was determined by the results of endoscopy, bladder wash cytology and biopsy performed 4 weeks after the last dose of bacillus Calmette-Guerin. Of the 30 patients 15 (50 per cent) had a complete response. The likelihood of a complete response was better for those with initial Ta lesions (62 per cent) and carcinoma in situ (56 per cent) than for patients with an initial T1 lesion (25 per cent). Although the longest followup is only 36 months (mean 16 months) patients with a complete response have a much better prognosis in terms of subsequent tumor, need for cystectomy and death of bladder cancer.     

Bacillus Calmette-Guerin immunotherapy for bladder cancer

Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. While the optimal protocol for bacillus Calmette-Guerin remains to be determined, experience with 92 randomized and 30 nonrandomized (high risk) patients followed for up to 5 years provides information that may improve future protocols. Side effects of bacillus Calmette-Guerin are observed to increase with increasing frequency and duration of treatment. The protection from tumor recurrence has persisted: only 6 of 30 patients (20 per cent) treated with bacillus Calmette-Guerin have had recurrent tumor compared to 14 of 27 controls (52 per cent, p equals 0.008, chi-square test), and mean time to recurrence increased from 24 to 48 months (p less than 0.005, Savage). Skin test reactivity to purified protein derivative is particularly useful in predicting response to bacillus Calmette-Guerin immunotherapy. Currently, 60 patients have been randomized to receive bacillus Calmette-Guerin immunotherapy and only 1 of 22 patients (4.5 per cent) in whom the purified protein derivative skin test results converted from negative to positive has had recurrent tumor, compared to 12 recurrences (32 per cent) in patients whose skin tests were positive before treatment or failed to convert following treatment (p equals 0.014, chi-square). Seven recurrences (33 per cent) developed in 21 patients whose skin tests remained negative (p equals 0.015) and 5 recurrences (29 per cent) developed in 17 patients whose tests previously were positive (p equals 0.068, Fisher's test, not significant). The benefit of percutaneous bacillus Calmette-Guerin is suggested by the observations that the recurrence rate in patients treated with intravesical bacillus Calmette-Guerin alone is 40 per cent, and all 7 patients whose purified protein derivative skin tests were negative continued to have negative results when percutaneous bacillus Calmette-Guerin was omitted (p equals 0.003). Among high risk patients a marked decrease in or complete prevention of recurrent tumor was observed in 82 per cent of 22 patients treated previously with chemotherapy and 11 of 14 (78 per cent) with carcinoma in situ have had a complete response.     

Control group and maintenance treatment with bacillus Calmette-Guerin for carcinoma in situ and/or high grade bladder tumors

PURPOSE: Intravesical instillations of bacillus Calmette-Guerin have demonstrated satisfactory results in the treatment of vesical carcinoma in situ and high grade superficial bladder tumors. We designed a protocol to evaluate the decrease in tumor recurrence with maintenance therapy. MATERIALS AND METHODS: Between June 1989 and May 1995 an initial course of 6 intravesical instillations of Connaught strain bacillus Calmette-Guerin was administered in patients with carcinoma in situ and/or high grade superficial bladder tumors. Six months later 131 disease-free patients were randomly assigned to a control group or a maintenance therapy group that received 6 instillations every 6 months (6 x 6) for a 2-year period. RESULTS: Of the 126 evaluable patients at a mean followup of 79 months there were no significant differences in recurrence nor progression. A total of 16 patients (26.2%) in the control and 10 (15.1%) in the maintenance group had superficial relapse at a mean of 24 and 20 months, respectively (p = 0.07). Eight patients underwent radical cystectomy due to bladder contraction in 1, high grade superficial recurrence in 4 and disease progression in 3. Of the 65 patients on maintenance therapy 22 (33.85%) completed the planned 2-year treatment. CONCLUSIONS: Six-month maintenance therapy in patients treated initially for carcinoma in situ and/or high grade superficial bladder tumors who are disease-free at 6 months did not significantly decrease recurrence or progression.     

Intravesical bacillus Calmette-Guerin in the treatment of superficial transitional cell carcinoma of the bladder

Pasteur strain bacillus Calmette-Guerin was used to treat 145 patients with superficial transitional cell carcinoma of the bladder: 47 had established residual disease (therapeutic group) and 130 received prophylactic/adjuvant therapy (including 32 who had a complete response in the therapeutic group and then were placed into the prophylactic group). Among the patients in the therapeutic group a complete response rate of 68 per cent (32 of 47 patients, 95 per cent confidence limits 55 to 81 per cent) was achieved. Of those in the prophylactic/adjuvant group 85 per cent (111 of 130 patients, 95 per cent confidence limits 73 to 91 per cent) remain free of disease. The median followup for the therapeutic group was 17 months (range 3 to 49 months). In the prophylactic/adjuvant therapy group the followup was greater than 3 years in 7 per cent, 2 to 3 years in 23 per cent, 1 to 2 years in 29 per cent and up to 1 year in 41 per cent (median 18 months). Our study confirms that Pasteur strain bacillus Calmette-Guerin is safe and efficacious in the treatment and prevention of recurrent superficial bladder carcinoma.     

Long-term results and complications of intracavitary bacillus Calmette-Guerin therapy for bladder cancer

Clinical studies on intracavitary bacillus Calmette-Guerin therapy for bladder cancer have been conducted at this institution for more than 10 years. The 82 patients treated for prophylaxis of multiple superficial recurrences, residual tumors or carcinoma in situ have been followed for 2 to 7 years after treatment. The long-term results confirm previous studies showing the effectiveness of bacillus Calmette-Guerin in the prophylaxis and therapy of superficial vesical neoplasms. However, some decrease is observed in the population free of disease with a prolonged followup. Recent modifications in the original protocol have been introduced to enhance the effectiveness of the vaccine. Side effects during or shortly after treatment were minor and self-limiting in the large majority of patients (fever, bladder irritability and hematuria). Mild, transient hepatic dysfunction was noted in 2 patients. Hematological disturbances were insignificant. No patient had permanent structural or functional alterations of the bladder.