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.     

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.     

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)     

Prophylactic maltose tetrapalmitate and bacillus Calmette-Guerin immunotherapy of recurrent superficial bladder tumors: preliminary report

We divided randomly into 3 groups 47 patients with recurrent superficial transitional cell carcinoma of the bladder: group 1-15 controls who underwent transurethral resection only, group 2-17 patients who underwent transurethral resection and bacillus Calmette-Guerin therapy, and group 3-15 patients treated by transurethral resection and maltose tetrapalmitate. Mean followup was 22.93 months for the controls, 28.0 months for group 2 and 24.4 months for group 3. The recurrence rate per 100 patient-months was 11.34 in the controls, 7.4 in group 2 and 7.19 in group 3, and the recurrence index per month was 0.113, 0.070 and 0.072, respectively. The recurrence rate and recurrence index per month were significantly decreased in the treated groups compared to the controls (p less than 0.005). There was no significant difference between the bacillus Calmette-Guerin and maltose tetrapalmitate groups. Invasive carcinoma developed in 60 per cent of the controls, 29.4 per cent of group 2 and 20 per cent of group 3. Invasive carcinoma required cystectomy or definitive radiotherapy. Bacillus Calmette-Guerin caused irritation of the bladder mucosa, while maltose tetrapalmitate did not have any side effects.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

A comparison of treatment methods for the prophylaxis of recurrent superficial bladder tumors

We assigned 55 patients with superficial transitional cell carcinoma of the bladder by rotation to 1 of 3 treatment categories. Group 1 patients were treated by transurethral resection alone, group 2 by transurethral resection followed by topical thiotepa and group 3 by transurethral resection followed by orally administered bacillus Calmette-Guerin. Recurrent bladder tumors developed subsequently in 80 per cent of the patients in group 1, 42.9 per cent in group 2 and 6.2 per cent in group 3.     

Flow cytometry as a predictor of response and progression in patients with superficial bladder cancer treated with bacillus Calmette-Guerin

Simultaneous bladder wash flow cytometry, voided urinary cytology and cystoscopic examinations were performed at 3-month intervals during a median of 18 months (range 5.5 to 50 months) in 65 patients receiving intravesical bacillus Calmette-Guerin treatment for superficial bladder cancer. Of the 65 patients treated 36 (56 per cent) had a complete response, 12 (18 per cent) had no response and 17 (26 per cent) had progression. Results of examinations at 6 months suggested that a negative bladder wash flow cytometry (29 of 36 patients, r equals 0.73, p less than 10(-7) is a strong predictor of response to bacillus Calmette-Guerin, comparable with cytological (r equals 0.60, p less than 10(-7) or cystoscopic (r equals 0.38, p less than 0.005) examinations alone or combined with cytology (r equals 0.74, p less than 10(-7)). At 6 months a positive bladder wash flow cytometry (r equals 0.44, p less than 0.0005) is as strong a predictor of disease progression as a positive cystoscopic examination (r equals 0.43, p less than 0.0005). The combination of bladder wash flow cytometry and voided urinary cytology is not superior to positive bladder wash flow cytometry alone. Median estimated interval to progression for these patients treated with bacillus Calmette-Guerin was 38 months. In the subgroup with positive bladder wash flow cytometry at 6 months the median interval to progression was 30 months. With a negative bladder wash flow cytometry at 6 months the probability of survival free of progression at 30 months was 85 per cent (p less than 0.01). Thus, negative bladder wash flow cytometry at 6 months is a strong predictor of response to bacillus Calmette-Guerin and also survival free of progression.     

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.     

The response of patients with superficial bladder cancer to a second course of intravesical bacillus Calmette-Guerin

Of 347 patients who received an initial 6-week course of intravesical bacillus Calmette-Guerin for superficial transitional cell carcinoma of the bladder 28 (8%) were treated with another course. Subsequent progression of disease (muscle infiltration, metastasis or local progression) occurred in 13 patients (46%). Of the 15 patients (54%) without progression 10 (36%) had a complete response and 5 (33%) had new tumors, and they were rendered free of disease after transurethral resection. The median duration of response to course 1 of bacillus Calmette-Guerin was shorter for patients with disease progression after course 2 than for those with no progression (15 and 27 months, respectively, p equals 0.05). The median followup after course 2 was 31.2 months (range 15.6 to 56.4 months). The median interval between courses 1 and 2 of intravesical bacillus Calmette-Guerin was 21.6 months (range 3.6 to 78.8 months). The interval from course 2 of bacillus Calmette-Guerin to progression correlated with the duration of response to course 1 of treatment (p equals 0.01). It appears that a subsequent treatment with bacillus Calmette-Guerin is most likely to be useful in patients who have a sustained response to the initial treatment.     

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.     

The Treated Natural History of High Risk Superficial Bladder Cancer: 15-year Outcome

Purpose

The long-term outcome of patients with high risk superficial bladder cancer is unknown. We report the results of 15 years of followup of high risk patients treated initially with aggressive local therapy, including transurethral resection alone or combined with intravesical bacillus Calmette-Guerin.

Materials and Methods

Between 1978 and 1981, 86 high risk patients enrolled in a randomized study of transurethral resection alone or with intravesical bacillus Calmette-Guerin for superficial bladder cancer. Of these patients 81% had diffuse carcinoma in situ and 44% had stage T1 tumors before entry into the study. Patients were followed until death (61%) or until the present time (median followup 184 months).

Results

Disease stage progressed in 46 patients (53%) and 31 (36%) eventually underwent cystectomy for progression reference 28 or refractory carcinoma in situ reference 3, while 18 (21%) had upper tract tumors at a median of 7.3 years. The 10 and 15-year disease specific survival rates were 70 and 63%, respectively. At 15 years 34% of patients overall were dead of bladder cancer, 27% were dead of other causes and 37% were alive, including 27% with an intact functioning bladder.

Conclusions

Despite aggressive local therapy patients with high risk superficial bladder cancer are at lifelong risk for development of stage progression and upper tract tumors. A third of patients are at risk for death from bladder cancer, justifying careful and vigilant long-term followup. These results support the use of initial aggressive local therapy in patients with high risk superficial bladder cancer.