Pronostic factors on recurrence and progression of superficial bladder cancer. Risk groups (part II)

IntroductionWe try to establish risk groups combining the characteristics of each bladder tumour, for a better monitoring of these patients.Material and MethodsOnce known the variables implied in recurrence and progression we analyze the data to establish the extreme groups, so, the one with the worse and the one with the better prognostic, remaining a residual group that would correspond of the tumours of intermediate prognostic.ResultsFrom the results obtained, we can establish three risk groups: bad prognostic group (high risk) : high grade tumours (g3), isolated or associated tis and multiple or recurrent grade 2 tumours that were recurred in less than 6 months; intermediate prognostic group: multiple tag1 tumours, as well as not multiple ta-1g2 and t1g1 (less than 3 tumours) and group of low risk: single tag1 tumours.discussionAccording to these results the group of badly risk, involves a high risk of recurrence and progression. The most effective treatment was the BCG (bacillus Calmette-Guerin) with maintenance, requiring a long-term control, more intense in the 2 first years after the RTU. In the group of intermediate risk, the rates of long-term superficial recurrence were as high as those of the high risk group, being needed a long-term control, in this group was effective the treatment with chemotherapy or BCG being preferably the maintenance. Finally in the group of good risk we don’t objectify progressions being the time to the recurrence the longest one, with stabilization of the rate of recurrences after one year.     

Clinical study of prognostic factors of superficial bladder cancer treated with intravesical bacillus Calmette-Guerin

Intravesical instillation of Tokyo 172 strain Bacillus Calmette-Guérin (BCG) was performed in 96 patients with initial superficial bladder cancer (Ta and T1) after transurethral resection (TUR) of tumour as a prophylaxis against tumour recurrence. The recurrence rate of tumours was estimated by the person-years method, comparing it with that of historical controls. There were statistically significant decreases in recurrent tumours following BCG therapy. To clarify the efficacy of intravesical BCG therapy, the prognostic significance of several factors was evaluated in patients with bladder cancer treated with TUR and instillation of BCG. The prophylactic effects were statistically better for those with multiple tumours, grade 3 lesions or Ta lesions than for control patients. No correlation between purified protein derivative (PPD) responsiveness and favourable results could be observed. Our results suggest that intravesical BCG instillation can alter the biological behaviour that affects the recurrence of superficial bladder cancer, especially for multiple, high grade or Ta tumours.     

Bacillus Calmette-Guérin therapy in stage Ta/T1 bladder cancer: prognostic factors for time to recurrence and progression

OBJECTIVE: To report prognostic factors for time to recurrence and progression after bacillus Calmette-Guérin (BCG) prophylaxis in patients with stage Ta/T1 papillary bladder cancer. PATIENTS AND METHODS: The clinical records were assessed retrospectively for 236 patients with papillary stage Ta/T1 bladder cancer treated with BCG between 1986 and 2000. Patients with known carcinoma in situ were excluded. The median (range) follow-up was 44 (4-155) months. The effect of 13 variables on the time to recurrence and progression was evaluated using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS: The recurrence rate was markedly reduced for all grades and stages. Patients with a negative first cystoscopy and maintenance BCG had a significantly longer time to recurrence than those treated with an induction course alone (P < 0.001). Thirty-seven patients (16%) progressed in stage. The result of the first cystoscopy (P < 0.001), tumour grade (P = 0.003) and six or fewer initial instillations (P = 0.002) had prognostic importance for the time to progression. Twenty-eight patients (12%) had a history of an upper tract tumour, which was 3-10 times the expected rate. Age, number of tumours, number of positive cystoscopies, length of tumour history before BCG, BCG strain and treatment year had no influence on time to recurrence and progression. CONCLUSIONS: Maintenance treatment does not seem to be necessary among patients with TaG1-G2 disease after a negative first cystoscopy, as the progression rate was very low. One new finding was that BCG seemed to be equally effective among patients with or with no history of an upper tract tumour. Another new and surprising finding was that patients treated with fewer than six induction instillations, because of very bothersome side-effects, had an increased risk of tumour progression and of local failure.     

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.     

Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study

PURPOSE: Bacillus Calmette-Guerin (BCG) immunotherapy has been widely accepted as the optimal treatment for carcinoma in situ and high grade superficial transitional cell carcinoma. However, controversy remains regarding the role of maintenance therapy, and its long-term effect on recurrence and progression. MATERIALS AND METHODS: All patients in the study had transitional cell carcinoma of the bladder with carcinoma in situ or an increased risk of recurrence. The criteria for increased risk were 2 or more episodes of tumor within the most recent year, or 3 or more tumors within 6 months. At least 1 week following biopsy of carcinoma in situ and resection of any stage Ta or T1 transitional cell tumors 660 patients were started on a 6-week induction course of intravesical and percutaneous Connaught BCG. Three months following initiation of BCG induction therapy 550 consenting patients were stratified by purified protein derivative skin test and the presence of carcinoma in situ, and then randomized by central computer to receive BCG maintenance therapy (maintenance arm) or no BCG maintenance therapy (no maintenance arm). Maintenance therapy consisted of intravesical and percutaneous BCG each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months from initiation of induction therapy. The 384 eligible patients who were disease-free at randomization constitute the primary intent to treat analytic group because they could be followed for disease recurrence. All patients were followed for adverse effects of treatment, recurrence, disease worsening and survival. RESULTS: No toxicities above grade 3 were noted in the 243 maintenance arm patients. The policy of withholding maintenance BCG from patients with increased side effects may have diminished the opportunity to observe severe toxicity. Estimated median recurrence-free survival was 35.7 months (95% confidence interval 25.1 to 56.8) in the no maintenance and 76.8 months (64.3 to 93.2) in the maintenance arm (log rank p<0.0001). Estimated median time for worsening-free survival, defined as no evidence of progression including pathological stage T2 disease or greater, or the use of cystectomy, systemic chemotherapy or radiation therapy, was 111.5 months in the no maintenance and not estimable in the maintenance arm (log rank p = 0.04). Overall 5-year survival was 78% in the no maintenance compared to 83% in the maintenance arm. CONCLUSIONS: Compared to standard induction therapy maintenance BCG immunotherapy was beneficial in patients with carcinoma in situ and select patients with Ta, T1 bladder cancer. Median recurrence-free survival time was twice as long in the 3-week maintenance arm compared to the no maintenance arm, and patients had significantly longer worsening-free survival.     

Treatment of high-risk superficial bladder cancer with maintenance bacille Calmette-Guérin therapy: preliminary results

OBJECTIVE: To evaluate, in a prospective study, the effects and results of maintenance therapy with bacille Calmette-Guérin (BCG) in treating patients with high-risk superficial bladder cancer. PATIENTS AND METHODS: In all, 155 patients were enrolled in a randomized study of transurethral resection alone (53) or combined with intravesical BCG (102) as a treatment for superficial bladder cancer. BCG was administered for six consecutive weeks followed by three weekly instillations in months 3, 6, 12, 18, 24, 30 and 36 after resection. Recurrence, progression, prognostic factors and side-effects were assessed and analysed. RESULTS: After a median (range) follow-up of 23 (6-42) months, 83 of the 102 patients treated with BCG (81%) were disease-free, compared with 24 of the 53 treated with resection alone (45%). There was also a significant difference in tumour progression and time to progression between the trial arms. The disease progressed in eight patients (8%) treated with BCG and in 12 (23%) of those treated by resection alone. Independent risk factors for progression were DNA ploidy status and stage. Only the completion of treatment was predictive of outcome (risk of recurrence) for patients treated with BCG. CONCLUSION: Maintenance BCG therapy was better than resection alone in reducing the incidence of recurrence and progression in patients with high-risk superficial bladder cancer.     

Intravesical Bacillus Calmette-Guérin treatment for superficial bladder tumours

Intravesical instillations of Tokyo 172 strain BCG were given to 56 patients with superficial bladder cancer during the 24-month period after transurethral tumour resection as a prophylaxis against tumour recurrence. The recurrence rate of tumours was compared with that of historical controls. Results were estimated by the person-years method and there were statistically significant decreases in recurrent tumours following BCG therapy. Our results suggest that the intravesical Tokyo 172 strain BCG is effective and safe as a prophylaxis against the recurrence of superficial bladder tumours.     

The Treatment of Non–Muscle-Invasive Bladder Cancer with Intravesical Chemotherapy and Immunotherapy

ObjectivesTo determine the efficacy, best indications, and regimens of intravesical adjuvant instillations in case of non–muscle-invasive bladder tumours.MethodsThe authors analyse the most significant articles of the literature to draw recommendations.ResultsThe three main factors that appear to determine a patient's ultimate prognosis are tumour size at presentation, the grade, and the prior recurrence rate per year. Bacillus Calmette-Guérin (BCG) has a beneficial effect in preventing progression, especially in patients with pT1G3 disease and carcinoma in situ. It seems to be important to improve the results achieved so that at least maintenance, whatever it is, may occur. The effectiveness of mitomycin C with relation to progression may, in fact, be diluted because of its lack of effective usage. The recommendation seems to indicate one single early mitomycin C postoperative instillation in patients with superficial low- and intermediate-risk tumours.ConclusionsMitomycin C and BCG are effective agents in both preventing recurrence and progression. It is customary to use mitomycin C in the perceived less aggressive lesions and BCG for patients at higher risk.     

The management of T1G3 bladder cancer

INTRODUCTION: The treatment of T1G3 bladder cancer is still a controversial issue. Nowadays, intravesical bacillus Calmette-Guérin (BCG) instillation is considered to be the treatment of choice for patients with high-grade superficial bladder tumour after transurethral resection of all visible tumour. The aim of this retrospective study was to determine the effects and results of this approach, recurrence and progression rates in patients with T1G3 superficial bladder tumours. MATERIALS AND METHODS: 43 patients (28 male, 15 female; mean age 65.5 years, range 21-82) with T1G3 TCC (transitional cell carcinoma) bladder tumour underwent transurethral resection and subsequent intravesical BCG according to Morales protocol, in the period 1993-1998 at our institution. The mean follow-up period was 52.5 (range 30-96) months. RESULTS: After one or more initial courses of therapy, 33 patients were disease-free. Twelve patients (27.90%) had recurrent tumour after a median of 7 (range 3-46) months. After a second course of BCG treatment, 6 patients had no evidence of disease, 3 patients had progression and 3 had recurrence. Progression occurred in 7 (16.27%) patients after a median of 19 (range 3-43) months. Five patients underwent radical cystectomy and the remaining 2 underwent bladder-preserving therapies. Two patients died of TCC and 3 due to disease-unrelated conditions. CONCLUSION: Intravesical BCG instillation can be recommended as treatment modality for responders with T1G3 TCC bladder tumour. The benefit of the second course of intravesical BCG therapy has to be confirmed in further investigations.     

T1G3 transitional cell carcinoma of the bladder: recurrence, progression and survival

OBJECTIVES: To report our experience with T1G3 bladder tumours over the last 10 years. PATIENTS AND METHODS: We analysed the outcome of 74 consecutive patients treated for a T1G3 bladder cancer between 1991 and 2001. Fifty-seven patients (77%) were treated with transurethral resection (TUR) plus six weekly instillations of bacillus Calmette-Guérin (BCG) therapy. Ten patients (13.5%) with contraindications to BCG or with a small T1a tumour were treated with TUR plus mitomycin-C, and seven (9.5%) were treated with TUR alone because of their age. Patients treated with BCG had systematic biopsies taken at the end of the first course. Patients with residual tumour received a second course of six weekly instillations. 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. RESULTS: The median follow-up was 53 months. The overall recurrence rate was 46% and the overall progression rate 19%. The rate of delayed cystectomy was 8% and that of disease-specific survival 91%. In patients who received BCG therapy, the recurrence and progression rates were 42% and 23%, respectively. In this group the rate of disease-specific survival was 88%. CONCLUSION: This study confirms that maintenance BCG therapy is an effective treatment for T1G3 bladder tumours, with an acceptable rate of bladder preservation.     

Case report: differential diagnosis of isolated iliac lymphadenopathy following Bacillus Calmette-Guérin treatment for high-risk superficial bladder cancer

We report the unusual case of a patient with G3 pT1 transitional cell carcinoma (TCC) of the bladder, which was treated with repeated transurethral resection and maintenance intravesical Bacillus Calmette-Guérin (BCG) therapy. At 30 months follow-up, a symptomatic, solitary iliac lymph node mass was identified and biopsied. Histology demonstrated granulomatous tissue only, in the absence of any intravesical bladder tumour recurrence. Following 6 months of anti-tuberculous medication, the mass had progressed, and repeat biopsy revealed undifferentiated carcinoma (of a bladder primary). This is a rare case of metastatic superficial bladder cancer progression without local recurrence after BCG therapy. As such, it can be viewed as a diagnostic challenge.     

Results of adjuvant intravesical Bacillus Calmette-Guérin therapy for grade 3 superficial bladder cancer

To examine the incidence of recurrence, progression and survival in patients with grade 3 superficial bladder cancer after transurethral resection (TUR) and adjuvant intravesical instillation of Bacillus Calmette-Guérin (BCG), we retrospectively studied 39 patients with grade 3 superficial bladder cancer. Nineteen patients with high-grade superficial bladder cancer (pTa, pT1) and 5 patients with grade 3 carcinoma in situ (CIS) received intravesical instillation of BCG after transurethral resection of the bladder tumor (BCG group and CIS-BCG group). The Tokyo 172 strain BCG was given for 8 weeks, as a rule, in a dose of 80 mg in 40 ml of saline instilled into the bladder. As a control, 15 patients with grade 3 superficial bladder cancer who did not receive BCG therapy after TUR were compared (non-BCG group). Of the BCG group (n=19), 4 patients (21.1%) had recurrent tumor and 3 had invasive progression after BCG therapy and died as a result of tumor progression, while in the non-BCG group (n=15), 8 cases (53.3%) developed recurrence, only one case had progression and died of cancer. In the CIS-BCG group (n=5), 3 patients (60.0%) had recurrent tumor and 2 had invasive progression. Univariate analysis (Logrank test) demonstrated that tumor size and adjuvant instillation of BCG were associated with tumor recurrence except for carcinoma in situ, but tumor progression and survival did not differ significantly. Our results suggest that BCG therapy prevents grade 3 superficial bladder cancer (pT1, pTa) recurrence.     

¿Es necesario resecar siempre las recidivas de los tumores vesicales superficiales en el momento del diagnostico?: comunicación preliminar

ObjectiveTo asses the expectant management superficial recurrent bladder tumours.Material and methodsBetween Jan 1998 and Dec 2003, 112 patients were diagnosed of superficial bladder tumour. 13 patients were observed after the diagnosis of tumour relapse until the decision to perform a transurethral resection. We analysed the clinical and pathological features. The patients were controlled with flexible cystoscopy every 3 months approximately. Of the 13 patients we count 15 observation events,(2 times in 2 patients).The decision between to treat or continue with observation was based in changes of appearance, size or number of tumours and presence of hematuria.ResultsWith a mean age of 74,6 years (47-91). The mean observation time was 5,76 months (3-71).In the group of tumours previous to the observation period, in 12 events (10 patients) that means 80% any progression in grade or stage was observed. In the other 3 events we observed progression in grade and stage in 2 and only stage in 1. In any case we observed progression to invasive bladder tumour neither upper urinary tract tumour.ConclusionsDue to the low risk of progression, we believe that immediate eradication is not always necessary, thus reducing the adverse impact of repeat resections.     

Defining bacillus Calmette-Guerin refractory superficial bladder tumors

PURPOSE: We define bacillus Calmette-Guerin (BCG) refractory, high risk, superficial bladder cancer. MATERIALS AND METHODS: A total of 93 patients received a 6-week induction course of BCG. They were evaluated for response after 3 and 6 months. Half of the patients received monthly maintenance BCG for 2 years and half did not. In both groups the initial responses to BCG at 3 and 6 months were correlated with subsequent tumor recurrence and progression. RESULTS: Of the 93 cases 57% were negative for tumor at 3 months and 43% had residual tumor resected. At 6 months 80% of the patients were tumor-free and 20% had persistent or recurrent tumor. Maintenance BCG did not decrease tumor recurrence further than induction BCG. Subsequent tumor-free interval during 24 months of followup were best predicted by response to BCG after 6 months. CONCLUSIONS: A minimum treatment and followup time of 6 months is required to identify high risk, superficial bladder tumors as truly BCG refractory.     

The best management of superficial bladder tumours: Comparing TUR alone versus TUR combined with intravesical chemotherapy modalities?

To compare retrospectively the recurrence rates of TUR alone versus different intravesical chemotherapy modalities in superficial bladder cancer cases, 187 patients with stage Ta and T₁ bladder tumours were treated with transurethral resection followed by adjuvant intravesical chemotherapy with mitomycin, BCG or epirubicin or by transurethral resection alone. All patients in this study had historically proven transurethrally resectable primary, category Ta and T₁ transitional cell carcinoma (TCC) of the bladder. Group I included transurethral resection alone, and the other groups included intravesical mitomycin-C(Group II), BCG (Group III) and epirubicin (Group IV) therapies after transurethral resection. 146 male and 41 female patients (78% male and 22% female patients) in this study were diagnosed as primary TCC bladder tumours. Only 52 of them were stage Ta and 135 of them were stage T₁ bladder tumours. Examining the histological grade of the bladder tumours, 88 (47%) of the patients had grade I, 53 (28%) had grade IIa, 30 (16%) had grade IIb and remaining 16 (9%) had grade III bladder cancers. The recurrence rates were 25% for Group I, 23.8% for Group II, 26.2% for Group III and 22.7% for Group IV. These values were given with disregarding the grade and volume of the bladder tumours. For solitary, less than 3 cm low grade tumours (grade I, IIa) recurrence rates were 16% for Group I, 15.4% for Group II, 17.8% for Group III, 17.2% for Group IV (p> 0.05). As a result of this retrospective study, for patients with low grade, stage Ta and T₁ tumours TUR alone may be the best treatment modality. Although intravesical chemotherapy is effective in decreasing short-term incidences of tumour recurrence, it has not decreased long-term incidences of tumour recurrence. The high cost and adverse side effects of intravesical chemotherapy should also be taken into consideration in superficial, single, low grade tumours of bladder. This revised version was published online in August 2006 with corrections to the Cover Date.     

Management and prognosis of transitional cell carcinoma superficial recurrence in muscle-invasive bladder cancer after bladder preservation

PURPOSE: To assess the bladder preservation rate and cancer-specific survival after conservative treatment of superficial relapses in invasive tumors after bladder preservation. MATERIAL AND METHODS: Fifty-one patients with invasive bladder tumor (T2) were treated using transurethral resection (TUR) followed by three cycles of systemic chemotherapy (carboplatin-vinblastine). After three weeks, an endoscopic reappraisal was made including deep TUR of the site of the original tumor and multiple cold cup biopsies. Forty-two patients retained their bladder (33 complete responses and 9 partial responses). RESULTS: With a median follow-up of 63 months, 18 patients recurred as superficial TCC tumor (43%). Fourteen patients with high grade superficial recurrence were treated with TUR and Bacillus Calmette-Guerin (BCG) instillations; two patients (G2-3 T1) with TUR as well as endovesical mytomicine, and two patients with low grade recurrence with only TUR. With a median follow-up of 44 months after TUR of first superficial relapse, there was only one case with progression of the disease without any evidence of bladder tumor. Two cystectomies were made due to carcinoma in situ (Cis) persistence and high grade superficial recurrence. Eighty-three percent of the patients who had superficial recurrence retained their bladders, with 94% cancer-specific survival. CONCLUSIONS: A very strict follow-up is mandatory due to the high rate of superficial relapses (43%). Cis is the most frequent type of superficial recurrence. Superficial recurrences in bladder preservation may be treated with TUR and BCG instillations when they are high grade and and/or associated with Cis. Superficial recurrences do not imply a worse prognosis for bladder preservation or cancer-specific survival.     

Superficial papillary urothelial carcinomas in young and elderly patients: a comparative study

OBJECTIVE: To compare the clinicopathological and immunohistochemical findings of superficial papillary transitional cell carcinomas in "young" and "elderly" patients, as the natural history and prognosis of bladder tumours in young patients remains a matter of debate. PATIENTS AND METHODS: Tumours from 50 patients with superficial urothelial tumours of the bladder diagnosed before 45 years old ("young" group, follow-up 25-119 months) were compared with 90 similar tumours developed in patients aged >55 years ("elderly", follow-up 24-102 months). All the patients had a transurethral resection with curative intent, and none had received any therapy before surgery. After surgery only patients diagnosed with pT1 tumours were treated by intravesical bacille Calmette-Guérin (BCG) instillations; all received intravesical BCG if there was a recurrence. The clinicopathological variables, recurrence and disease-free interval to recurrence were assessed. Proliferative activity (MIB-1) and expression of cell-cycle regulation proteins cyclin D1, p53 and p27(kip1) were detected by immunohistochemistry in the tumours of both groups. RESULTS There were statistically significant differences in tumour grade, stage and occurrence between the "young" and "elderly" groups. The 'young' group had a longer disease-free interval to recurrence. Among the immunohistochemical markers analysed, only MIB-1 and cyclin D1 were associated with an increased risk of recurrence in the "young" group (P < 0.04 and <0.01, respectively) in a univariate analysis. CONCLUSIONS Superficial papillary urothelial tumours of the bladder in "young" patients had a better prognosis than those in the "elderly" group, showing a lower grade and stage at diagnosis, and a lower recurrence rate. Proliferative activity and cyclin D1 expression levels were of prognostic significance for the risk of recurrence in these patients.     

Bacillus Calmete-Guérin plus interferon-alpha2B intravesical therapy maintains an extended treatment plan for superficial bladder cancer with minimal toxicity

Bacillus Calmette-Guérin (BCG) and interferon-alpha2B (IFN-alpha2B) have both been individually used for the intravesical treatment of superficial bladder cancer. We report our experience on the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-alpha2B for treating superficial bladder cancer, including patients failing previous BCG therapy. Thirty-two patients with superficial bladder cancer underwent 6 weekly treatments with full-, one-third, or one-tenth-dose of BCG plus 50 or 100 MU of IFN-alpha2B based on prior BCG exposure and tolerance. Patients with no evidence of disease proceeded onto maintenance therapy of 3 weekly treatments at 3 months followed by 2 additional maintenance cycles given 6 months apart. Response was assessed by cystoscopy/biopsy every 3 months after treatment. Before BCG plus IFN-alpha2B treatment, 20 patients (63%) had previously failed intravesical BCG therapy, 27 (84%) had aggressive disease (stage T1, grade 3, or carcinoma in situ), 27 (84%) had recurrent disease, 14 (44%) had multifocal disease, and 6 (19%) had disease of over 4 years duration. At median follow-up of 22 months, 21 patients (66%) remain disease-free and 11 patients (34%) had disease-recurrence. Nineteen of 32 patients (59%) were disease-free after the initial induction cycle. Six of 11 patients 55% ultimately failing combination therapy did so at the first 3 to 4 month evaluation. Four of 7 patients (57%) benefited from salvage re-induction therapy. Of the 20 patients previously treated with BCG, 12 patients (60%) remain disease-free. Combination BCG plus IFN-alpha2B intravesical therapy was well tolerated. Combination intravesical BCG plus IFN-alpha2B is an effective and tolerable alternative for patients with superficial bladder cancer, including those patients in whom intravesical BCG therapy had previously failed. Benefits of this combination therapy may include potentially less morbidity, improved clinical efficacy, and in the long term, fewer patients undergoing radical therapy. However, radical treatment options should be pursued for early failures of this combination regimen in those patients with risk factors for recurrence and progression.     

Diagnostic and Prognostic Factors in Non-Muscle-Invasive Bladder Cancer and Their Influence on Treatment and Outcomes

ObjectivesThis paper explores the diagnostic and staging procedures available for bladder cancer, the prognostic factors for recurrence and progression of non-muscle-invasive tumours, and the indications for intravesical therapy and cystectomy in patients with non-muscle-invasive, recurrent disease.MethodsThe authors reviewed the literature on diagnosis of bladder cancer, prognostic factors for recurrence and progression of non-muscle-invasive disease, and the indications for intravesical therapy and cystectomy.ResultsThe presence of malignant cells at urinary cytology suggests a high-grade tumour in the urinary tract, but negative urinary cytology does not exclude a low-grade cancer. Transurethral resection of the bladder (TURB) is undertaken in non-muscle-invasive bladder tumours to aid diagnosis and to remove visible lesions and is more effective when guided by blue-light fluorescence than by white light. Repeated TURB may be required because of the risk of residual tumour after initial TURB. A tool from the European Organisation for Research and Treatment of Cancer (EORTC) can be used to assess an individual patient's risk of bladder cancer recurrence and progression. Further treatment options are intravesical chemotherapy, intravesical bacille Calmette-Guérin (BCG) immunotherapy, and cystectomy. Immediate cystectomy is advocated by many specialists for patients with non-muscle-invasive tumour who are at high risk of progression or who do not respond to BCG therapy.ConclusionsUrinary cytology and TURB (preferably under the guidance of fluorescence cystoscopy if carcinoma in situ is suspected) are the mainstays of bladder cancer diagnosis and staging. The likelihood of recurrence or progression can be assessed using a tool developed by the EORTC that is based on common prognostic factors. Patients with disease progression can be offered cystectomy.     

Intravesical prevention of recurrence of superficial urinary bladder cancer with BCG and KLH. A prospective randomized study

In a prospective randomized trial intravesical prophylaxis for recurrence of superficial bladder cancer with BCG versus KLH was performed in 42 patients, 38 of whom were then evaluable. After a mean observation period of 20 +/- 7 months (8-32 months) 41.2% (7/17) of the patients in the KLH and 14.3% (3/21) of the patients in the BCG group developed recurrent bladder tumours. The recurrence rate according to EORTC was 1.95 in the KLH group versus 0.76 in the BCG group. Among the BCG treated patients, 60% (15/25) had cystitis and 28% (7/25) fever, whereas only 1 of 19 (5.3%) patients treated with KLH had cystitis. BCG is a highly effective prophylactic against recurrence of superficial bladder cancer. Intravesical instillation therapy with KLH has only a slight prophylactic effect if treatment is started 6 weeks postoperatively.