Progression of stage T1 bladder tumors after intravesical bacillus Calmette-Guerin

Of 221 patients with superficial bladder tumors (stages Ta, Tis and T1) treated by transurethral resection and an initial 6-week course of intravesical bacillus Calmette-Guerin (BCG) 195 were evaluated after 3 months for local response. Of these patients 17 (8.7%) had a stage T1 tumor, of whom 14 (82%) subsequently had muscle invasion (7), uncontrolled local disease (6) or metastasis (1). The median interval to progression was 8.4 months, which was significantly (p = 0.0001) less than among the other 178 patients with a nonstage T1 lesion or no tumor found at 3 months, of whom 44 (25%) had progression (median more than 5 years). These data suggest that patients with stage T1 tumor 3 months after BCG therapy require additional therapy other than simple tumor resection and meticulous followup.     

Management of stage T1 superficial bladder cancer with intravesical bacillus Calmette-Guerin therapy.

We reviewed our results with 86 patients who had a pretreatment history of a stage T1 tumor. All patients were treated with transurethral resection of all visible tumor followed by intravesical bacillus Calmette-Guerin (BCG) and many patients received additional maintenance therapy. Local recurrences were treated with repeat transurethral resection followed by additional BCG. Median followup was 59 months, with a range of 9 to 149 months. Overall, 78 of 86 patients (91%) were free of tumor recurrence with BCG therapy. This result includes 69% of the patients who responded to the initial transurethral resection and intravesical BCG, and 22% who ceased having tumors after additional treatments for local recurrences. Only 7% of the patients had progression to stage T2 tumors after BCG therapy. Grade of the stage T1 tumor, concurrent carcinoma in situ and tumor multiplicity before BCG did not predict tumor recurrence or progression. Of patients with recurrences after BCG therapy, those with stage T1 tumors had a higher rate of progression compared to those with stage Ta tumors but the difference was not statistically significant (p = 0.086). These data clearly support the efficacy of transurethral resection plus intravesical BCG immunotherapy in the treatment of stage T1 tumors as well as in the prevention of disease progression.     

Clinicopathological Evaluation of Repeated Courses of Intravesical Bacillus Calmette-Guerin Instillation for Preventing Recurrence of Initially Resistant Superficial Bladder Cancer

Purpose

The efficacy of repeated courses of intravesical bacillus Calmette-Guerin (BCG) for superficial bladder cancer was assessed with particular attention to initially resistant cases.

Materials and Methods

A total of 75 patients with stages Ta to T1b superficial transitional cell bladder carcinoma received 6 weekly instillations of 80 mg. Tokyo strain BCG in 40 ml. saline followed by 6 instillations at monthly intervals. If tumors recurred, another course of treatment was given with surgery.

Results

Of 17 patients (22.7 percent) with recurrent tumor at followup periods of up to 84 months 12 received an additional course of BCG instillations according to the same protocol after transurethral resection of bladder tumors, and 10 (83.3 percent) showed no further recurrence with or without additional surgery and BCG therapy after a median followup of 42.9 months. Thus, the overall success rate with this approach was 90.7 percent (68 of 75 patients). Comparison of patients with and without recurrence revealed a significant difference in number of tumors before therapy (p less than 0.05), and a pronounced tendency (p = 0.00507) for recurrence after prior systemic chemotherapy or intravesical instillation.

Conclusions

The results suggest that up to 3 courses of repeated intravesical instillation of BCG are effective even for cases that initially did not respond, and that best results may be achieved if no other prior chemotherapy has been attempted.     

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.     

Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials

PURPOSE: We determine if intravesical bacillus Calmette-Guerin (BCG) reduces the risk of progression after transurethral resection to stage T2 disease or higher in patients with superficial (stage Ta, T1 or carcinoma in situ) bladder cancer. MATERIALS AND METHODS: A meta-analysis was performed of the published results of randomized clinical trials comparing transurethral resection plus intravesical BCG to either resection alone or resection plus another treatment other than BCG. RESULTS: We identified 24 trials with progression information on 4,863 patients. Based on a median followup of 2.5 years and a maximum of 15 years, 260 of 2,658 patients on BCG (9.8%) had progression compared to 304 of 2,205 patients in the control groups (13.8%), a reduction of 27% in the odds of progression on BCG (OR 0.73, p = 0.001). The percent of patients with progression was low (6.4% of 2,880 patients with papillary tumors and 13.9% of 403 patients with carcinoma in situ, reflecting the short followup and relatively low risk patients entered in many of the trials. The size of the treatment effect was similar in patients with papillary tumors and in those with carcinoma in situ. However, only patients receiving maintenance BCG benefited. There was no statistically significant difference in treatment effect for either overall survival or death due to bladder cancer. CONCLUSIONS: Intravesical BCG significantly reduces the risk of progression after transurethral resection in patients with superficial bladder cancer who receive maintenance treatment. Thus, it is the agent of choice for patients with intermediate and high risk papillary tumors and those with carcinoma in situ.     

Intravesical bacillus Calmette-Guerin therapy for stage T1 grade 3 transitional cell carcinoma of the bladder: recurrence,progression and survival in a study of 57 patients

PURPOSE: Stage T1 grade 3 transitional cell carcinoma of the bladder is associated with a high risk of tumor recurrence and progression. We report our experience with stage T1 grade 3 bladder tumors treated with bacillus Calmette-Guerin (BCG) therapy in the last 10 years. MATERIALS AND METHODS: We analyzed the outcome in 57 consecutive patients treated with intravesical BCG for stage T1 grade 3 bladder cancer between 1991 and 2001. After initial transurethral resection all patients received a 6-week course of BCG therapy consisting of 1 instillation weekly. All patients underwent systematic biopsies at the end of the first BCG course. Patients with negative biopsies received maintenance BCG therapy, consisting of intravesical instillations each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months after the first course. Patients with residual tumor received a second course of 6 weekly instillations. Time to tumor recurrence and progression, and the rate of patient survival were retrospectively analyzed. RESULTS: Median followup was 53 months (range 9 to 110). Minimum followup was 2 years in 36 cases (63.2%) and 5 years in 28 (49.1%). After the first BCG course 50 patients (87.7%) had no residual disease, while 7 (12.3%) had residual tumor. The recurrence and progression rates were 42.1% and 22.8%, respectively. The rate of delayed cystectomy was 14%. The rate of disease specific survival was 87.7%. CONCLUSIONS: Our study confirms that BCG therapy is effective conservative treatment for patients with stage T1 grade 3 bladder tumors.     

A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence,progression and survival

PURPOSE: We retrospectively evaluated the long-term outcome in patients with newly diagnosed stage T1 grade 3 bladder cancer treated with transurethral resection with or without intravesical bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: Of 153 patients with a median age of 67 years (range 36 to 88) and a male-to-female ratio of 4:1 we treated 92 with transurethral bladder resection and additional BCG, and 61 with transurethral bladder resection alone. BCG was administered intravesically as 120 mg. BCG Pasteur F dissolved in 50 ml. saline, retained for up to 2 hours weekly for 6 weeks and repeated as necessary. RESULTS: Median followup was 5.3 years (range 0.4 to 18.2). Disease recurred in 70% of the patients treated with BCG and in 75% treated with transurethral resection alone. Median time to recurrence was 38 and 22 months for BCG and resection alone (p = 0.19). Tumor progressed in 33% of patients with BCG and in 36% with resection alone. Deferred cystectomy was performed in 29% of the patients with BCG and in 31% with resection alone. Overall and disease specific survival did not differ significantly. CONCLUSIONS: Our results suggest that intravesical BCG therapy after transurethral bladder resection for stage T1 grade 3 bladder cancer may delay the time to recurrence and cystectomy but it does not substantially alter the final outcome. Our findings reflect the rule of 30% for stage T1 grade 3 cancer, namely approximately 30% of patients never have recurrence, 30% ultimately die of metastatic disease and 30% require deferred cystectomy.     

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.     

Nichtinvasives und invasives Harnblasenkarzinom

Therapy of superficial bladder tumors is transurethral resection (TUR), and in cases of pT1 or high-grade tumors a re-TUR is indicated. Patients with carcinoma in situ receive intravesical chemotherapy or BCG for at least 3 months. Persistent carcinoma in situ may be treated by radical cystectomy. With the provision of a functionally adequate urinary diversion, cystectomy represents an effective treatment for patients with muscle-invasive bladder cancer without metastatic spread. Regional lymph node metastases can be found in up to 15% of stage T1 disease and are present in 33% of stage T3/4 lesions. Thus, lymphadenectomy gains diagnostic and possibly also therapeutic importance. For selected patients, who cannot be treated by radical cystectomy, multimodal concepts aiming to preserve the bladder are discussed. After or prior to cystectomy systemic chemotherapy may become necessary for some patients to positively affect the course of the disease in cases of locally advanced or metastatic lesions.     

Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.     

Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy

PURPOSE: This study was an evaluation of whether restaging transurethral resection (TUR) of superficial bladder cancer improves the early response to bacillus Calmette-Guerin (BCG) therapy. MATERIALS AND METHODS: A total of 347 patients with high risk superficial bladder cancer (high grade Ta and T1 tumors associated with carcinoma in situ) underwent a single transurethral resection (TUR, 132 patients) or restaging TUR (215 patients) before receiving 6 weekly intravesical BCG treatments. The patients were evaluated for response (presence or absence of tumor) at first followup cystoscopy, at 6 and 12 months after treatment, and evaluated for disease stage progression within 3 years of followup. RESULTS: Of the 132 patients who underwent a single TUR before BCG therapy, 75 (57%) had residual or recurrent tumor at the first cystoscopy and 45 (34%) later had progression, compared with 62 of 215 patients (29%) who had residual or recurrent tumors and 16 (7%) who had progression after undergoing restaging TUR (p = 0.001). CONCLUSIONS: Restaging TUR of high risk superficial bladder cancer improves the initial response rate to BCG therapy, reduces the frequency of subsequent tumor recurrence and appears to delay early tumor progression.     

Recurrence and progression of stage T1, grade 3 transitional cell carcinoma of the bladder following intravesical immunotherapy with bacillus Calmette-Guerin

PURPOSE: We prospectively examined the incidence of recurrence and progression in patients with stage pT1, grade 3 carcinoma of the bladder following complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: Between July 1987 and March 1999, 123 patients presenting to our clinic with superficial urothelial carcinoma (stage pT1, grades 1 to 3) received adjuvant intravesical immunotherapy with BCG after histologically confirmed complete transurethral tumor resection. Disease was stage pT1, grade 3 in 44 patients (36%). Median followup was 28 months (mean 43, range 5 to 141). RESULTS: Of the patients 36 (82%) with bladder preservation remained tumor-free during followup after 1 or 2 cycles of BCG. Superficial tumor recurred in 5 patients (11%) and muscle invasive progression was noted in 7 (16%). Radical cystectomy was performed in 4 cases (9%). Of the patients 5 (11%) died of cancer. Tumor-free survival for all patients was 89% (39 of 44). CONCLUSIONS: Adjuvant immunotherapy with BCG after complete transurethral resection of bladder tumor represents a highly effective primary treatment of stage pT1, grade 3 carcinoma of the bladder. Immediate radical cystectomy does not appear necessary.     

Does early cystectomy improve the survival of patients with high risk superficial bladder tumors?

PURPOSE: We compared survival after early versus delayed cystectomy in patients with high risk superficial bladder tumors. MATERIALS AND METHODS: Of 307 patients with high risk superficial bladder tumors who were treated initially with transurethral resection and bacillus Calmette-Guerin (BCG) therapy 90 (29%) underwent cystectomy for recurrent tumor during a followup of 15 to 20 years. Disease specific survival distribution of these 90 patients was determined relative to the indications for and time of cystectomy. RESULTS: Of the 90 patients who underwent cystectomy 44 (49%) survived a median of 96 months. Of 35 patients with recurrent superficial bladder tumors 92% and 56% survived who underwent cystectomy less than 2 years after initial BCG therapy and after 2 years of followup, respectively. Of 55 patients with recurrent muscle invasive bladder disease 41% and 18% survived when cystectomy was performed within and after 2 years, respectively. Multivariate analysis showed that survival was improved in patients who underwent earlier rather than delayed cystectomy for nonmuscle invasive tumor relapse. CONCLUSIONS: Earlier cystectomy improves the long-term survival of patients with high risk superficial bladder tumors in whom BCG therapy fails.     

LOCAL MICROWAVE HYPERTHERMIA AND INTRAVESICAL CHEMOTHERAPY AS BLADDER SPARING TREATMENT FOR SELECT MULTIFOCAL AND UNRESECTABLE SUPERFICIAL BLADDER TUMORS

Purpose

The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neodjuvant organ sparing clinical study.

Materials and Methods

A total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system,* based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas.*Boston Scientific Corp., Natick, Massachusetts.

Results

After treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved.

Conclusions

Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.     

Reassessment of Conservative Management for Stage T1N0M0 Transitional Cell Carcinoma of the Bladder

Purpose

We evaluated the outcome of stage T1 transitional cell carcinoma of the bladder treated with local tumor resection and intravesical therapies.

Materials and Methods

Of 42 patients with stage T1 bladder cancer seen at our clinic during a 10-year period 38 were treated conservatively with local tumor resection, intravesical therapy and long-term followup. Bacillus Calmette-Guerin (BCG) was used as the primary intravesical agent since 1986.

Results

Of the 38 patients 15 had initial grade 2 or 2 to 3 tumors, including 9 (60 percent) who had at least 1 or more local recurrences but without disease progression. The remaining 23 patients had grade 3 or grades 3 to 4 stage T1 tumors, with local recurrence in 17 (74 percent) and disease progression in 8 (35 percent). Furthermore, 5 patients (22 percent) died of the metastasis despite salvage therapies.

Conclusions

For patients with initial grade 2 or grades 2 to 3, stage T1 disease the risk of disease progression is low. Current management with local tumor resection and intravesical BCG is appropriate and should be continued. Patients with high grade, stage T1 disease are at particularly high risk for disease progression and BCG does not seem to decrease this risk effectively. Therefore, immediate cystectomy is appropriate and should be recommended.     

Therapy of superficial bladder carcinomas

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

A systematic review of intravesical bacillus Calmette-Guérin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer

OBJECTIVE: To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-Guérin (BCG) in preventing tumour recurrence in patients with medium/high risk Ta and T1 bladder cancer. PATIENTS AND METHODS: An electronic database search of Medline, Embase, DARE, the Cochrane Library, Cancerlit, Healthstar and BIDS was undertaken, plus hand searching of the Proceedings of ASCO, for randomized controlled trials, in any language, comparing transurethral resection (TUR) alone with TUR followed by intravesical BCG in patients with Ta and T1 bladder cancer. RESULTS: The search identified 26 publications comparing TUR with TUR + BCG. Six trials were considered acceptable, representing 585 eligible patients, 281 in the TUR-alone group and 304 in the TUR + BCG group. The major clinical outcome chosen was tumour recurrence. The weighted mean log hazard ratio for the first recurrence, taken across all six trials, was -0.83 (95% confidence interval -0.57 to -1.08, P < 0.001), which is equivalent to a 56% reduction in the hazard, attributable to BCG. The Peto odds ratio for patients recurring at 12 months was 0.3 (95% confidence interval of 0.21-0.43, P < 0.001), significantly favouring BCG therapy. Manageable toxicities associated with intravesical BCG were cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported. CONCLUSION: TUR with intravesical BCG provides a significantly better prophylaxis of tumour recurrence in Ta and T1 bladder cancer than TUR alone. Randomized trials are still needed to address the issues of BCG strain, dose and schedule, and to better quantify the effect on progression to invasive disease.     

Stage T1 bladder cancer: grade is the primary determinant for risk of muscle invasion

Tumor characteristics believed to predict for deep muscle invasion after transurethral resection of superficial bladder cancer alone were analyzed in 51 patients with stage T1 (stage A) transitional cell carcinoma of the bladder. All patients were treated at Stanford University Medical Center and none had intravesical chemotherapy at any time during the median followup of 78 months. No patient had carcinoma in situ. A total of 14 patients (27%) had deep muscle invasion. None of the patients with grade 1, 5 (22%) with grade 2 and 9 (50%) with grade 3 to 4 tumors had deep muscle invasion. Comparison of the risk of muscle invasion using pathological tumor grade at diagnosis, highest grade at any cystoscopic biopsy before the diagnosis of muscle invasion or highest grade at cystoscopic biopsy immediately antecedent to the cystoscopy at which muscle invasion was diagnosed all showed similar probability of muscle invasion. Mean interval to development of muscle invasion was 6 and 12 months in the grades 2 and 3 to 4 groups, respectively. At 36 months the cumulative probability of invasion-free survival was 62% for grade 2, compared to 50% for grades 3 to 4 cancer patients (p less than 0.005, Gehan). Univariate regression analysis demonstrated grade to be the only significant factor in predicting for invasive disease (p = 0.005), with tumors in the bladder neck to be of borderline significance (p = 0.159). On multivariate logistic regression analysis, grade remained the single tumor variable predicting for invasive bladder cancer (p = 0.004). These data suggest that of routinely available data at diagnosis and during subsequent followup cystoscopic examinations, tumor grade is the most important biological predictor of progression to muscle invasive cancer.     

Recurrence, progression and success in stage Ta grade 3 bladder tumors treated with low dose bacillus Calmette-Guerin instillations

PURPOSE: Bacillus Calmette-Guerin (BCG) therapy is considered to be an effective prophylactic and therapeutic agent for high risk superficial transitional cell carcinoma of the bladder. Nevertheless, in a select uncommon population of stage Ta grade 3 superficial lamina-free tumors the results of this treatment have not yet been well established. We evaluated recurrence and progression rates, and the success of BCG therapy in a population with stage Ta grade 3 transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Of the 605 patients treated at our institution from 1982 to 1996 for the histopathological diagnosis of primary bladder cancer 32 (5.3%) with stage Ta grade 3 noninvasive primary bladder tumor were treated with intravesical instillations of 75 mg. Pasteur strain BCG in 50 ml. saline weekly for 6 weeks. At a followup of 2 to 13 years (mean 58.4 months) patients were evaluated with urinary cytology, cystoscopy, transurethral resection and random mucosal biopsies. Recurrence, grade and stage progression, death and causality were analyzed. RESULTS: Of the 32 patients 9 (28%) responded positively to BCG without recurrence, while disease recurred as stage Ta in 8 (25%) and T1 in 7 (22%), and progressed to muscle layer infiltration in 8 (25%). Four patients (12%) died of bladder cancer. The number of tumors at primary resection, gross examination, the mitotic index or an association with carcinoma in situ did not appear to be predictive factors of progression to muscle invasion. Urine cytology (I to II versus III to IV) appeared to correlate highly with progression and BCG response (p<0.001) with excellent sensitivity (1) but low specificity (0.67). CONCLUSIONS: Our study demonstrates the high progression potential of stage Ta grade 3 tumors, since nearly 50% recurred and 25% progressed to invasive disease. These results may be closely compared with the results of previous trials of stage T1 grade 3 disease. We suggest that recurrence should be detected at an early stage using long-term followup with strict observance of the surveillance protocols during a minimum 5-year tumor-free period.     

Cystectomy in patients with high risk superficial bladder tumors who fail intravesical BCG therapy: pre-cystectomy prostate involvement as a prognostic factor

PURPOSE: To review understaging and outcome of patients who underwent radical cystectomy (RC) for high risk superficial bladder cancer after bacillus Calmette-Guérin (BCG) failure. PATIENTS AND METHODS: We carried out a retrospective study of 62 cases in which RC was indicated for clinical stage Tis, Ta, T1 transitional cell bladder tumors that failed transurethral resection (TUR) and BCG treatment. We used BCG (81 mg/Connaught BCG) in patients with superficial grade 3 tumors and CIS. We considered BCG failure a high-grade recurrence at 3 months of the first BCG course or after 2 courses. RC indications, correlation between their clinical and pathological stage and the ensuing progress were analyzed. We assessed the existence of any pre-cystectomy clinical or pathological factor related to understaging and survival. RESULTS: RC was performed in 22 patients with carcinoma in situ (CIS) (35%), 7 with Ta (11,2%), 31 with T1 (50%), and 2 with Tx tumors (3%). All 62 but one were high-grade tumors (grade 3 and/or CIS). Tumor was clinically understaged with stages pT2 or greater on the RC specimen in 17 patients (27%). The presence of tumor in the prostatic urethra at the moment of endoscopic staging before RC was the only factor associated with clinical understaging (p=0.003) and shorter survival (p<0.0002). Five-year disease-specific survival rate was significantly lower in understaged (38%) as compared with not-understaged patients (90%) after a median follow-up of 40-months (range 1-142) (p=0.006). Overall five-year disease-specific survival was 79%. CONCLUSIONS: RC should be performed prior to progression in high risk superficial tumors that fail after TUR and BCG. In patients with clinical and pathological nonmuscle invasive disease, RC provides an excellent disease-free survival. One third of patients with HRSBT who underwent RC after BCG failure were understaged and had a shorter survival. Tumor in the prostatic urethra at endoscopic staging was the only factor associated to understaging and shorter survival.