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.     

Ureteral carcinoma in situ after successful intravesical therapy for superficial bladder tumors: incidence, possible pathogenesis and management

A total of 66 patients with multifocal, progressive, flat carcinoma in situ of the bladder responded completely to intravesical bacillus Calmette-Guerin therapy for more than 1 year. Of the patients 19 (29 per cent) had clinical evidence of distal ureteral carcinoma in situ between 13 and 30 months (median 15 months) after bacillus Calmette-Guerin treatment. After evaluation of a positive urinary cytology study failed to reveal recurrent urothelial tumor of the bladder or prostatic urethral mucosa 6 patients underwent distal ureterectomy, 2 underwent nephroureterectomy, and 11 were managed by ureteroscopic resection and fulguration. In patients with carcinoma in situ of the bladder treated successfully with topical therapy the ureters represent a potential site of in situ carcinoma.     

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.     

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 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.     

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)     

Superficial transitional cell carcinoma of the bladder associated with mucosal involvement of the prostatic urethra: results of treatment with intravesical bacillus Calmette-Guerin

Intravesical Pasteur strain bacillus Calmette-Guerin was used to treat 8 patients with mucosal transitional cell carcinoma of the prostatic urethra associated with superficial transitional cell carcinoma of the bladder. Complete initial response in the prostatic urethra was obtained in 7 of the 8 patients. Two patients had progression of disease during intravesical bacillus Calmette-Guerin therapy (1 in the prostate and 1 in the bladder) and they received further surgical therapy. Of the 6 complete responders 1 patient had invasive ureteral, vesical and prostatic tumor 15 months after bacillus Calmette-Guerin therapy, and he underwent nephroureterectomy and cystoprostatourethrectomy. Two patients required additional transurethral therapy for recurrent superficial tumors in the bladder but they have shown no evidence of recurrence in the prostatic urethra. Three patients have remained free of disease at 8 to 36 months. Before radical cystoprostatourethrectomy and urinary diversion are recommended, our study supports a course of bacillus Calmette-Guerin therapy as initial treatment for patients with superficial transitional cell carcinoma of the bladder associated with mucosal involvement of the prostatic urethra.     

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.     

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.     

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.     

Topical mitomycin C therapy for carcinoma in situ of the bladder: a followup

We studied 15 patients with histologically proved multifocal carcinoma in situ of the bladder who were in remission at a mean followup of 21 months after induction intravesical chemotherapy with mitomycin C. These patients have been followed for a further 28 months, for a total mean duration of 49 months. Of the 15 patients 4 suffered new areas of carcinoma in situ, including 3 who subsequently required cystectomy (2 after unsuccessful intravesical bacillus Calmette-Guerin therapy and 1 with a simultaneous invasive tumor). One patient underwent transurethral resection of the prostate for carcinoma in situ of the prostatic urethra, which subsequently was shown to be limited to mucosa and not involving the deeper ducts nor the stroma. Of the remaining 11 patients 1 died of unrelated disease and 2 suffered recurrent papillary transitional cell carcinoma treated successfully with a combination of intravesical bacillus Calmette-Guerin therapy and resection. The other 8 patients have remained free of tumor. None of the 15 patients had metastatic cancer. We believe that these results support the durability of response after induction mitomycin C therapy. We stress the necessity for prolonged close followup to detect recurrent tumor and to avoid metastatic disease.     

Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results

We treated 40 patients with superficial bladder cancer via intravesical bacillus Calmette-Guerin for 1) prophylaxis against tumor recurrence, 2) residual carcinoma or 3) flat carcinoma in situ. A single course of intravesical bacillus Calmette-Guerin therapy was successful in 6 of 11 patients (55 per cent) treated for residual carcinoma and 6 of 12 (50 per cent) treated for carcinoma in situ. Of 17 patients receiving a single course of bacillus Calmette-Guerin for prophylaxis 11 remained free of tumor during short-term followup. A second course of therapy was administered to failures in each treatment category, which resulted in favorable responses in 5 of 6 patients treated for prophylaxis, 2 of 5 treated for residual tumor and 3 of 6 treated for carcinoma in situ. Over-all complete responses were achieved in 16 of 17 patients (94 per cent) treated for prophylaxis, 8 of 11 (73 per cent) for residual carcinoma and 8 of 12 (66 per cent) for carcinoma in situ, with a mean followup from the final treatment of 9.3, 12.3 and 7.9 months, respectively. Favorable results occurred more frequently among patients who exhibited a granulomatous inflammatory response in the bladder and delayed hypersensitivity skin test response to purified protein derivative. Marked variability in viability of bacillus Calmette-Guerin organisms was observed among different lots of bacillus Calmette-Guerin, and a direct relationship was observed between bacillus Calmette-Guerin vaccine viability and therapeutic efficacy. Most patients who failed initial therapy with a low viability lot of bacillus Calmette-Guerin responded favorably to re-treatment with a higher viability lot. The results suggest that the level of viability of each lot of bacillus Calmette-Guerin vaccine should be verified before clinical use.     

The use of bacillus Calmette-Guerin in the therapy of bladder carcinoma in situ

Intravesical instillations of Tice strain bacillus Calmette-Guerin were given to 33 patients with biopsy proved carcinoma in situ. An induction phase consisting of 12 weekly instillations was followed by a maintenance phase of instillations bimonthly for 3 months and then monthly for 18 months. A total of 6 patients did not complete the induction phase because of adverse reactions but 4 were rendered free of tumor and have had no recurrence. Of the remaining 27 patients 18 became free of tumor after 12 weeks of therapy (3 had recurrences during the maintenance period), 6 after 18 weeks (with 1 recurrence) and 3 after 24 weeks. Thus, 31 of 33 patients (94 per cent) were rendered free of carcinoma in situ. There were 4 recurrences in these patients (13 per cent). The 27 patients who have remained free of disease have been followed for 1.75 to 8.5 years, with an average of 5.25 years. Side effects, principally bladder irritability, were a problem early in the study. With the use of isoniazid, nonsteroidal anti-inflammatory agents and bladder antispasmodics, the treatment has been safe and tolerated well. The study indicates that bacillus Calmette-Guerin is effective in eliminating carcinoma in situ in most patients, although prolonged treatment may be necessary. Maintenance therapy appears to be of value in reducing the incidence of recurrent tumor.     

Expression of blood group precursor T antigen as a prognostic marker for human bladder cancer treated by bacillus Calmette-Guerin and interleukin-2

The relationship between T antigen expression in transitional cell carcinoma of the bladder and response to bacillus Calmette-Guerin plus interleukin-2 treatment was studied. A total of 25 patients received combined treatment with bacillus Calmette-Guerin and interleukin-2 at weekly instillations for 6 consecutive weeks and then monthly for 1 year. T antigen expression in all patients was studied before treatment. Of the patients 16 had positive T antigen expression in the tumors: 13 (81%) remained free of tumor for an average of 28 months, 3 had a noninvasive recurrence each at 8 to 27 months (mean 18 months) and all responded well to a repeated treatment cycle. Nine patients were negative for T antigen: 1 (11%) remained free of tumor for 11 months, while 8 had recurrence within 12 months. Of the latter 8 patients 2 had noninvasive recurrence each at 4 to 5 months but they responded to a repeated treatment cycle and remained free of tumor for 4 to 22 months (mean 13 months), 4 had subsequent repeated recurrences at 12 to 41 months (mean 22 months) and 2 had progression to deep invasion resulting in cystectomy at 11 to 12 months. Thus, the disease-free rate (continuous complete response) in patients with tumors positive for T antigen was 81%, while that in patients with tumors negative for T antigen was 11% (p less than 0.005, chi-square test). The over-all response rate in patients with positive and negative tumors to bacillus Calmette-Guerin and interleukin-2 treatment was 100 and 33%, respectively, and that for the total patients was 76%. T antigen may serve as a target recognition structure for effector cells generated by bacillus Calmette-Guerin plus interleukin-2 treatment. This study suggests that T antigen is useful to predict the response of bladder tumors to treatment with bacillus Calmette-Guerin and interleukin-2.     

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.     

Bacillus Calmette-Guerin for superficial transitional cell carcinoma of the bladder

Pasteur strain bacillus Calmette-Guerin was used to treat superficial transitional cell carcinoma of the bladder in 28 patients. Patients selected for treatment had an incomplete resection, positive selected site biopsies and/or post-resection positive cytology findings. Complete response required negative histology and cytology findings at cystoscopic followup 4 to 8 weeks after completion of treatment. Of the patients 20 (71 per cent) demonstrated a complete response, including all 6 with carcinoma in situ. Results converted to negative in 16 of 17 patients with positive urine cytology findings and 4 with positive prostatic urethral biopsies. Of the responders 8 had received prior treatment with thiotepa. The treatment regimen of 120 mg. Pasteur strain bacillus Calmette-Guerin weekly for 6 weeks was well tolerated. It was necessary to limit the number of treatments to 5 because of local irritative effects in only 3 patients. No chronic bladder disability has been noted during followup of 3 to 30 months. This experience supports the efficacy of bacillus Calmette-Guerin as a cost-effective, well tolerated treatment modality for patients with superficial transitional cell carcinoma of the bladder.     

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.     

Percutaneous Bacillus Calmette-Guerin perfusion of the upper urinary tract for carcinoma in situ]

We performed percutaneous perfusion of the upper urinary tract with Bacillus Calmette-Guerin (BCG) in 3 patients. Two of them had undergone unilateral nephrectoureterectomy for ureter carcinoma in situ and one had undergone radical cystectomy with bilateral ureterocutaneostomy for invasive bladder carcinoma. However, they suffered recurrent upper urinary tract carcinoma in situ within 2 years after their operation. Under ultrasound control a percutaneous nephrostomy tube was placed in the patient. Before BCG perfusion unobstructed flow from the renal pelvis to the bladder was confirmed and pyelovenous or pyelolymphatic back flow was excluded under fluoroscopy. A dose of 240 mg BCG was dissolved in 150 ml 0.9% saline. The flask was placed 20 cm above the kidney of the resting patient. A continuous flow of approximately 1 ml per minute was maintained. The perfusion was stopped after 2 hours and the nephrostomy tube was closed. Therapy was repeated at weekly intervals for a total of 6 perfusions (1 treatment course). In each of them urine cytology results became negative after 1 treatment course. No severe side effects were observed. Further investigation is also needed to determine whether BCG perfusion of the upper urinary tract could become a conservative treatment for carcinoma in situ of the upper urinary tract.     

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.     

Phase 1 trial of oral bropirimine in superficial bladder cancer.

A total of 34 patients with measurable superficial transitional cell cancer of the bladder entered into a phase 1, nonrandomized, noncomparative trial to assess the toxicity of the oral interferon inducer bropirimine. Of the patients 26 were also evaluable for response. The toxicity of bropirimine was minimal. At the 3-month evaluation 6 patients had experienced complete regression of tumor and had negative cytology studies, and 2 had partial responses. The majority of complete responses were in patients with carcinoma in situ only, with most responses seen at higher dose levels. One patient with papillary tumor and carcinoma in situ had a complete response. Some early responses appear to be durable. Most importantly, a high rate of complete response was noted at higher dose levels among patients who had failed prior therapy with bacillus Calmette-Guerin. Further clinical trials of bropirimine in bladder cancer appear warranted.