PURPOSE: We evaluate the prognostic factors of recurrence, progression and disease specific mortality in patients with primary superficial Ta and T1 transitional cell carcinoma of the bladder.
MATERIALS AND METHODS: We studied a cohort of 1,529 patients with primary superficial transitional cell carcinoma of the bladder treated with transurethral resection and random bladder biopsies. Mean followup was 4.2 years. Statistical analysis was performed using the Kaplan-Meier method and multivariate analysis was done with the Cox proportional hazards model with stepwise forward selection. All p values were 2-sided, with odds ratios and 95% confidence intervals.
RESULTS: Multiple tumors (odds ratio 2), tumor greater than 3 cm. (1.65) and carcinoma in situ (1.6) increased, whereas intravesical bacillus Calmette-Guerin (BCG) instillations (0.39) decreased the risk of recurrence. Grade 3 disease (odds ratio 19.9), multiple tumors (1.9), tumor greater than 3 cm. (1.7) and carcinoma in situ (2.1) increased, whereas BCG (0.3) decreased the risk of progression. Grade 3 disease (odds ratio 14) and carcinoma in situ (odds ratio 3) increased the risk of disease specific mortality.
CONCLUSIONS: Neither tumor stage nor dysplasia influenced tumor evolution. Multiple tumors, tumor greater than 3 cm. and intravesical BCG instillations were risk factors of recurrence and progression. Carcinoma in situ influenced recurrence, progression and disease specific mortality. Finally, the main predictor of progression and mortality was grade 3 disease.
PURPOSE: We report the 5-year followup of a randomized comparison of mitomycin C and bacillus Calmette-Guerin (BCG) in patients with superficial bladder carcinoma. Recurrence, progression and survival rates, crossover results, prognostic factors and long-term side effects were analyzed.
MATERIALS AND METHODS: A total of 261 patients were enrolled in the study, and the inclusion criteria were primary Tis, dysplasia G2, T1 G3 and multiple recurrent Ta/T1 G1-2 disease. Intravesical instillations of 40 mg. mitomycin C and 120 mg. Pasteur BCG, Danish strain 1331, were given for 2 years.
RESULTS: After a median followup of 64 months 101 of the 250 evaluable patients (42%) were disease-free. A significant difference was noted in disease-free survival with BCG (p = 0.04), which was most pronounced for stage Tis disease. No difference in tumor progression, or crude or corrected survival was found between the 2 arms. Crossover treatment was successful in 39% of patients with second line BCG and 19% with second line mitomycin C. Independent risk factors for progression were initial p53 status and stage. Only the completion of treatment was predictive of outcome for patients treated with BCG. Bladder shrinkage occurred in 2.4% of patients.
CONCLUSIONS: Therapy with BCG was superior to mitomycin C for recurrence prophylaxis but no difference was found for progression and survival.
OBJECTIVES: Evaluation of a protocol of intravesical BCG therapy using 75 mg of Pasteur strain BCG with 2 years of maintenance treatment, and a follow-up of up to 60 months.
MATERIAL AND METHODS: 189 patients treated by transurethral resection (TUR) for a pTa (N = 80) or pT1 (N = 109) bladder tumour were included in the study. The local and general safety was excellent. We retrospectively compared this series to a group of patients treated by TUR alone (N = 42) another group treated with TUR and Mitomycin C (MMC) (N = 81). The 3 groups were statistically comparable.
RESULTS: At 48 months, 62% of patients treated with BCG were recurrence-free, versus only 18% for patients treated with TUR alone and 38% for patients treated with TUR and MMC (p = 0.001). At 42 months, 11% of pT1 tumours treated with BCG had progressed to invasive carcinoma, and this progression occurred during the first 18 months in every case. In comparison, this progression was observed in 25% of pT1 tumours treated by TUR alone and 21% of tumours treated with TUR and MMC.
CONCLUSIONS: Our study confirms the efficacy of our BCG protocol ro reduce the potential for recurrence and progression of superficial bladder tumours, despite reduction of the dose to 75 mg. It also suggests the superiority of BCG compared to MMC in terms of recurrence and progression.
PURPOSE: A randomized multicenter trial was done to compare transurethral resection only to transurethral resection plus adjuvant mitomycin C and bacillus Calmette Guerin (BCG) instillation for treatment of superficial bladder cancer (stage pTa/1 grades 1 to 3 except primary stage pTa grade 1).
MATERIALS AND METHODS: Included in the study were 337 patients with superficial stage pTa/1 grades 1 to 3 bladder cancer except primary stage pTa grade 1 tumors. One group underwent transurethral resection alone. Mitomycin C (20 mg./50 ml. sodium chloride) was given every 2 weeks during year 1 and once a month during year 2. BCG (120 mg/50 ml. sodium chloride was instilled once a week for 6 weeks and once a month for 4 months.
RESULTS: At a median followup of 20.2 months, a decrease in recurrence rate was noted for both drug instillations compared to transurethral resection only. The relative risk of recurrence was 0.508 after mitomycin C and 0.618 after BCG instillation compared to transurethral resection alone. There was no significant difference between the mitomycin C and BCG instillations. The progression rate was comparable in all 3 therapy groups, with an estimated common progression rate of 4.22% per year. Side effects occurred most frequently during or after BCG instillation, most often consisting of cystitis. One patient required cystectomy because of ulcerating cystitis and a prostatic abscess subsequent to unsuccessful tuberculostatic therapy. There were no systemic complications.
CONCLUSIONS: Our study showed a positive effect of adjuvant chemotherapy and immunotherapy on decreasing tumor recurrence rate. No influence was observed concerning progression rate, which was low overall.
To compare the toxicity and efficacy of intravesical bacillus Calmette-Guérin (BCG) immunotherapy and mitomycin C (MMC) chemotherapy in the prophylaxis of recurrent transitional cell carcinoma, 469 patients with completely resected stage Ta or TI transitional cell carcinoma were enrolled in a randomized Southwest Oncology Group Phase III study. All patients were judged to be at increased risk for tumor recurrence due to having had two occurrences of tumor within 56 weeks, stage T I tumor or three or more tumors within 16 weeks, or concurrent carcinoma in situ. Three hundred and seventy-seven evaluable patients received either 50 mg of Tice BCG in 50 cc saline or 20 mg MMC in 20 cc water weekly for 6 weeks and then monthly to one year. Local and systemic grade I and 2 toxicity was seen significantly more frequently following BCG treatment (P = 0.003), but no life threatening toxicity was seen with either treatment. Recurrence-free survival was significantly prolonged (P = 0.017, proportional hazard regression) in patients randomized to the BCG arm compared to the MMC arm, but there were no statistically significant differences at this analysis for worsening-free survival and overall survival, although the number of these events is too low for a definitive analysis of these long-term outcomes. Therefore, when compared to MMC chemotherapy, BCG immunotherapy is associated with a significantly higher frequency of grade 1 and 2 adverse reactions and a significantly lower first recurrence hazard rate.
Results of a randomized prospective study are reported in which mitomycin C, Tice bacillus Calmette-Guerin (BCG) and RIVM-BCG were compared in 437 patients with primary or recurrent pTa and pT1 bladder tumors, including carcinoma in situ. The followup (or time in study) varied from 2 to 81 months (mean 36 months). After complete transurethral resection of all visible tumors the patients were treated with 30 mg. mitomycin C once a week for 4 consecutive weeks and thereafter every month for a total of 6 months, and 5 x 10(8) colony-forming units Tice BCG or RIVM-BCG once a week for 6 consecutive weeks. For papillary tumors mitomycin C and RIVM-BCG treatments were equally effective (p = 0.53), and mitomycin C was more effective than Tice BCG therapy (p = 0.01).
The results of a randomized, prospective, two-arm study are reported in which treatment with bacillus Calmette-Guérin (BCG) was compared with mitomycin therapy in patients with primary or recurrent superficial bladder tumors, including carcinoma in situ. Mean follow-up time was 21.25 months. After complete transurethral resection of all visible tumors, the following therapeutic regimens were given: in group 1, BCG (5 × 108 bacilli in 50 mL saline) was instilled once a week for six consecutive weeks; in group 2, mitomycin (30 mg in 50 mL saline) was instilled once a week for one month (weeks 1 to 4) and thereafter once a month for a total of six months. The incidence of side effects in 338 patients and the tumor recurrence rate in 325 patients are presented. Local side effects of treatment, classified as drug-induced (chemical) cystitis, were observed in 30 of 165 treated patients (18 %) in group 1 and in 36 of 173 treated patients (21 %) in group 2. Bacterial cystitis occurred in 43 (26 %) and 35 (20 %) of the patients in each group, respectively. Systemic side effects were observed in 10 patients (6 %) in group 1 and in 5 patients (3 % ) in group 2. Treatment was stopped due to systemic side effects in 5 patients (3 %) in group 1 and in none in group 2. Of the patients treated with BCG (n = 158), disease recurred in 66 patients (42 %), whereas, of those patients who received mitomycin (n = 167), 60 (36%) had disease recurrence. The recurrence rate is 0.28 for group 1 and 0.24 for group 2, which was not significant (P = 0.40, two-tailed test). No statistically significant difference between the two arms of this study was noted with regard to toxicity or tumor recurrence.
