Clinical outcome of high-grade non-muscle-invasive bladder cancer: A long-term single center experience

Objectives:   To report on the long-term clinical outcome of high-grade (G3) non-muscle-invasive bladder cancer (NMIBC) patients treated at a single institution.
Methods:   A retrospective analysis of 93 patients with NMIBC treated between January 1991 and September 2005 was performed. Patients were divided into three groups on the basis of treatment they received after transurethral resection (TUR) of the bladder. Forty-seven patients received adjuvant intravesical epirubicine after TUR of the bladder (Group 1). Twenty-four patients received intravesical bacillus Calmette–Guérin (BCG) (Group 2). A radical cystectomy (RC) was performed on twenty-two patients (Group 3).
Results:   Median follow up was 68.7 months. Overall, thirty patients (33%) experienced tumor recurrence. The survival rates of Group 3 were significantly higher than the 71 patients undergoing conservative therapy (Group 1 and 2). There was no statistically significant difference between Group 1 and 2, but treatment failure in patients treated with epirubicine was significantly higher than in those with BCG. Cases without concomitant carcinoma in situ (CIS) showed statistically significantly higher survival rates than those with concomitant CIS.
Conclusions:   RC provides excellent survival rates in patients with high-grade NMIBC. Adjuvant therapy with BCG after a complete TUR of the bladder may be an effective treatment for high-grade NMIBC. If a conservative treatment is preferred to RC, co-existence of a concomitant CIS should be considered with caution.     

Bacillus Calmette-Guerin versus epirubicin for primary, secondary or concurrent carcinoma in situ of the bladder: results of a European Organization for the Research and Treatment of Cancer--Genito-Urinary Group Phase III Trial (30906)

PURPOSE: We compared the efficacy and side effects of intravesical instillations of bacillus Calmette-Guerin (BCG) and epirubicin in patients with carcinoma in situ (CIS) of the bladder. MATERIALS AND METHODS: Patients with primary, secondary or concurrent CIS of the bladder were randomized to 81 mg BCG-Connaught (6 weekly instillations) or 50 mg epirubicin (8 weekly instillations). When a complete response (CR), defined as no Ta/T1 or CIS on biopsy and negative cytology, was obtained, patients in the 2 groups received maintenance instillations at months 3, 6, 12, 18, 24, 30 and 36. When no complete response was observed, the original treatment was repeated, followed again by cystoscopy and biopsies plus cytology. RESULTS: A total of 168 patients were randomized between March 1993 and April 1999 to receive BCG (84) or epirubicin (84), while 4 on epirubicin and 3 on BCG were ineligible. The majority (52%) had concurrent CIS. Primary and secondary CIS was found in 23% and 24% of cases, respectively. The overall CR rate was 56% for epirubicin and 65% for BCG (p = 0.21, 90% CI 21.5 to -2.9). When tumor was found following 2 instillation courses, further treatment was left to the investigator (BCG in 29 cases and epirubicin in 37). Time to bladder tumor recurrence after CR was longer in patients treated with BCG vs epirubicin (median 5.1 vs 1.4 years). CIS recurrences were more frequently observed in complete responders to epirubicin (45% vs 16%). No differences in time to progression or duration of survival were observed. Side effects were more frequently seen in patients on BCG with 26 on BCG and 8 on epirubicin stopping treatment due to side effects. CONCLUSIONS: No significant difference in CR rates could be demonstrated with intravesical instillations of epirubicin or BCG. Time to recurrence was significantly longer in patients treated with BCG after having achieved a CR. More CIS recurrences were found in patients treated with epirubicin. For time to progression and survival longer followup is warranted. Side effects were more frequent in patients on BCG.     

Prognostic factors in patients with carcinoma in situ treated with intravesical bacille Calmette-Guérin

OBJECTIVE: To report prognostic factors and follow-up data for an unselected group of patients with carcinoma in situ (CIS) of the urinary bladder treated with bacille Calmette-Guérin (BCG). MATERIAL AND METHODS: The clinical records of patients with CIS treated with BCG were reviewed. All 173 patients treated between 1986 and 1997 in four hospitals in two Swedish cities were included. The median follow-up period was 72 months (range 6-154 months). The impact of 18 variables on the times to recurrence and progression was studied using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS: No pre-treatment variables, including type of CIS and T1G3 tumour, had prognostic value in terms of time to progression. The result of the first cystoscopy had a very strong prognostic importance: 44% of patients with a positive first cystoscopy progressed in stage, 59% were BCG failures and 35% died from urothelial cancer. The corresponding values for patients with a negative first cystoscopy were 11%, 18% and 8%. Fourteen patients (8%) were diagnosed with an upper urinary tract tumour but no variable had prognostic significance. The diagnoses of the upper urinary tract tumours were evenly distributed during follow-up. CONCLUSIONS: We were not able to predict which patients would respond favourably to BCG. Cystectomy should be strongly considered even after a positive first cystoscopy. The accumulated incidence of patients with bladder CIS and a subsequent upper urinary tract tumour is rather high but it is questionable whether the prognosis will improve if routine follow-up urographies are performed.     

Possible factors affecting response to intravesical bacillus Calmette-Guérin (Tokyo 172 Strain) therapy for carcinoma in situ of the bladder: A multivariate analysis

To evaluate clinicopathological factors affecting response to intravesical instillation therapy with the bacillus Calmette-Guérin (BCG) Tokyo 172 strain for carcinoma in situ (CIS) of the bladder, we reviewed data for 84 patients treated between 1985 and 1996. Median follow-up was 56 months. The patients comprised three groups: primary (only the in situ lesion, 31 patients), subsequent (found after treatment of a gross neoplasm, 20), and concomitant (found together with a gross neoplasm, 33). A complete response was found in 62 (74%) of the 84 patients. Intravesical BCG therapy eradicated tumour cells in 74% of the primary group, 70% of the subsequent group, and 76% of the concomitant group. Multivariate logistic regression analysis revealed that the presence of gross haematuria and patient age were significantly associated with a complete response to the intravesical BCG therapy (p<0.05). On the other hand, gender, irritative bladder symptoms, type of extent of CIS, histological grade of CIS, BCG dose, and number of times BCG was given did not exert any significant influence. The 5-year recurrence rate was 33% for the 62 patients for whom a complete response was once achieved. Patients aged 60 or older had a higher probability of recurrence than those less than 60 years of age (p<0.05). Disease progression was found in 13% of the 84 patients and total cystectomy was performed in 19%. The present finding that patient age is related to the response to intravesical BCG therapy may point to a role for the reduced host immunocompetence in elderly individuals.     

Initial high-grade T1 urothelial cell carcinoma: feasibility and prognostic significance of lamina propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-non-treated patients

OBJECTIVES: This study aimed to determine the prognostic value of depth of lamina propria invasion in initial high-grade T1 bladder tumors. Secondary aims were to evaluate the prognostic significance of concomitant carcinoma in situ (CIS) and the impact of bacillus Calmette-Guérin (BCG) treatment as well as to assess the feasibility of microstaging by pathologists in a community setting. PATIENTS AND METHODS: Ninety-seven tumors were available for study and were substaged according to invasion superficial to, into or beyond the muscularis mucosae (MM) (T1a, T1b, T1c). Outcomes were compared by chi-square analysis. Recurrence-free and progression-free survival estimates were obtained by Kaplan-Meier analysis. BCG treatment impact and prognostic significance of CIS were also evaluated (Cox regression). RESULTS: T1 subclassification was possible in 87% (85/97) of cases: 38 (39.1%) T1a, 10 (10.3%) T1b, and 37 (38.1%) T1c; in 12 patients (12.4%) substaging was not possible. Mean age was 66.4 years and mean follow-up was 53 months. Recurrence rates were similar for all groups. By contrast, the progression rate for deep lamina propria-invasive tumors, i.e. T1b and T1c, was 34% (16/47) in comparison to 8% (3/38) for T1a (p=0.016). Progression-free intervals were significantly different in patients with (T1b, T1c) or without (T1a) deep lamina propria involvement (p=0.003), regardless of BCG treatment (p=0.02). BCG-treated patients (67 cases) showed a slight trend towards a better outcome, but differences were not significant. CIS was associated with more than 50% of cases that progressed. On multivariate analysis, depth of invasion and CIS remained two independent prognostic factors, increasing the hazards ratio of progression to 4.47 and 3.19 respectively. CONCLUSIONS: The depth of invasion in the TURB specimens is an independent prognostic factor for T1 bladder cancer even in BCG-treated patients. Associated CIS significantly increases the risk of progression in these patients. The percentage of cases that can be substaged according to the depth of lamina propria involvement increases over time with the collaboration between urologists and pathologists. Consequently, we support that routine pathological assessment of the level of MM invasion in patients with stage T1 bladder cancer should be included in the histopathological report.     

Risk of concomitant carcinoma in situ determining biopsy candidates among primary non-muscle-invasive bladder cancer patients: Retrospective analysis of 173 Japanese cases

Objectives:   To determine candidates for bladder biopsies among Japanese primary non-muscle-invasive bladder cancer patients according to the risk of concomitant carcinoma in situ (CIS).
Methods:   Between January 1992 and August 2006, 173 primary non-muscle-invasive bladder cancer cases underwent transurethral resection of the bladder tumor with bladder biopsies for the detection of CIS. Correlations between biopsy results and preoperative/pathological features were retrospectively analyzed.
Results:   Positive cytology was statistically associated with the presence of concomitant CIS in multivariate analysis ( P  < 0.01). Abnormal cystoscopic appearance outside the tumor almost achieved statistical significance in multivariate analysis among preoperative factors ( P  = 0.06). In our series, one (12.5%) of eight low-risk, 18 (24.7%) of 73 intermediate-risk and 41 (59.4%) of 69 high-risk cases had CIS in normal-looking sites, respectively. In cases with a single papillary tumor and negative cytology, one of 16 (6.3%) had concomitant CIS in their biopsy specimens at the normal-looking sites.
Conclusions:   All non-muscle-invasive bladder cancer patients with positive cytology are candidates for additional random biopsies. Targeted biopsies should be performed for all suspicious areas in the bladder mucosa. Random biopsies should be considered in cases with the macroscopic types of cancer for predicting intermediate- and high-risk cancer.     

Is second course intravesical Bacillus Calmette-Guerin therapy for recurrent carcinoma in situ of the bladder useful?

We evaluated the usefulness of second course intravesical bacillus Calmette-Guerin (BCG) therapy for carcinoma in situ (CIS) of the bladder that failed to respond to the initial BCG therapy. Between January 1995 and December 2000, 185 patients with CIS of the bladder underwent an initial 6- or 8-week course of intravesical BCG instillation with an average follow-up period of 40.9 months (range: 3.8 to 94.8 months). Of the 185 patients, 160 (86.5%) completely responded to an initial course of BCG therapy. During follow up, 49 (30.6%) of the complete responders had recurrent transitional cell carcinoma. Overall, 9 (36.0%) of the 25 patients who did not respond completely to the initial 6- or 8-week course of BCG therapy and 22 (44.9%) of the 49 who had recurrent tumor after initial complete response, a total of 31 patients received the second course intravesical BCG therapy. Of the 9 incomplete responders, 8 (88.9%) achieved a complete response after the second course BCG therapy. With an average follow-up period of 39.6 months (range: 2.8 to 62.2 months), 2 (22.2%) of the 8 had recurrence. On the other hand, 17 (77.3%) of the 22 with recurrent tumor after the initial complete response developed recurrence with an average follow-up period of 14.1 months (range: 2.8 to 55.2 months). Seven (31.8%) of the 17 patients had disease progression to muscle invasion. Subsequently, cystectomy was done in 10 (58.8%) and radiation in 1 (5.9%). Our results suggest that a selected group of incomplete responders with initial BCG therapy may benefit from continued second course BCG. However, in patients who had recurrence after initial BCG success, the benefits of second course BCG therapy are limited. Careful surveillance and aggressive therapy on optimal timing are mandatory.     

Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and disease-specific mortality in T1G3 bladder cancer patients treated with bacillus Calmette-Guérin

Background

Controversy exists over the most important prognostic factors in T1 high-grade non–muscle-invasive bladder cancer (NMIBC) patients treated with bacillus Calmette-Guérin (BCG).

Objective

Evaluate prognostic factors for recurrence, progression, and disease-specific mortality after adjuvant intravesical BCG immunotherapy in patients with T1G3 NMIBC and long-term follow-up.

Design, setting, and participants

A single-institution retrospective analysis of 146 patients with primary stage T1G3 NMIBC.

Intervention

All patients were treated with complete transurethral resection (TUR) plus multiple bladder biopsies that included the prostatic urethra. No second TUR was done. Patients underwent an induction course of intravesical BCG (Connaught strain, 81 mg) without maintenance therapy.

Measurements

The variables analysed for time to recurrence, progression, and death due to bladder cancer (BCa) were gender, age, tumour multiplicity, diameter, aspect, substaging, concomitant carcinoma in situ (CIS), and CIS in the prostatic urethra. Cox regression models were used to assess the univariate and multivariate prognostic importance of these factors and estimate hazard ratios (HRs). Time-to-event distributions were estimated using cumulative incidence functions.

Results and limitations

The median follow-up was 8.7 yr. Sixty-five patients (44.5%) had recurrence, 25 patients (17.1%) had progression, and 18 patients (12.3%) died because of BCa. Female gender and presence of CIS in the prostatic urethra were associated with an increased risk of recurrence (p = 0.0003, HR: 2.53), progression (p = 0.001, HR: 3.59), and death due to BCa (p = 0.004, HR: 3.53).

Conclusions

In primary T1G3 bladder tumours treated with induction BCG, female gender or having CIS in the prostatic urethra were the only prognostic factors for time to recurrence, progression, and disease-related mortality. It is very important to perform a biopsy of the prostatic urethra in patients with primary high-grade NMIBC as a first step to obtain this prognostic information.     

Prognostic Markers of Intravesical Bacillus Calmette-Guérin Therapy for Multiple, High-Grade, Stage T1 Bladder Cancers

Background :
Prediction of a response to intravesical bacillus Calmette-Guérin (BCG) therapy for bladder cancer is clinically important. We determined whether several molecular markers have prognostic value in intravesical BCG therapy for multiple, high-grade, stage T1 bladder cancers. Methods: The expressions of p53 (clone D07), bcl-2 (100-D5), cathepsin-D (C5), c-myc(9E11), c-erbB-2 (CB11) and Ki-67 (MM1) were determined by immunohistochemistry in paraffin-embedded tissues from 32 multiple, T1, grade II–III bladder cancer patients (1 5 BCG responders, 1 7 nonresponders) who had undergone a single course of BCG therapy (Pasteur strain, 5 × 10⁸ CFU weekly for 6 weeks) after complete removal of the tumors. The association between the expression of these markers and the response to BCG was assessed by univariate and multivariate analyses.
Results :
There was no difference in patient and tumor characteristics between the 2 groups. Using multivariate analysis, the only useful marker was p53, with the overexpression of the p53 protein inversely related to the response to BCG therapy (P = 0.0182).
Conclusion :
Our results suggest that the status of p53 expression offers significant clinical information and may be a useful tool in the selection of suitable candidates for BCG therapy in multiple, high-grade stage T1 bladder cancer patients.     

Intravesical instillations with bacillus calmette-guérin for the treatment of carcinoma in situ involving prostatic ducts

OBJECTIVES: Bacillus Calmette-Guérin (BCG) has proven its efficacy in the treatment of carcinoma in situ (CIS) of the prostatic urethra. We performed a retrospective study to evaluate the use of intravesical instillations of BCG in patients with carcinoma in situ involving prostatic ducts after complete transurethral resection (TUR). MATERIAL AND METHODS: Eligibility for the study was CIS of the prostatic urethra involving prostatic ducts. Previous instillation with BCG was an exclusion criterion. Patients were treated with intravesical BCG Connaught (81 mg) administered once a week, over a 6-wk period. TUR loop biopsies of the prostate were performed only when a macroscopic tumor was present. RESULTS: In this retrospective study of 11 patients, 8 (73%) presented with macroscopic tumor in the prostatic urethra. Ten patients (91%) had a simultaneous superficial bladder carcinoma. Eight patients (73%) had tumoral involvement of the bladder neck region. After a median follow-up of 27 mo (n=10 patients), the response in the prostatic urethra was 82%, and the response in the bladder due to superficial tumor recurrence was 64%. Two patients with residual ductal disease in the prostatic urethra were subsequently treated with cystoprostatectomy and are currently free of disease. In one of those patients, the cystoprostatectomy specimen did show prostatic stromal invasion. Another patient developed distant metastatic disease and died a few months after diagnosis. Thus, progression was encountered in two patients (18%). Currently, 90% of patients are alive without evidence of disease and 72.7% have benefitted from this bladder preservation strategy. CONCLUSION: Intravesical BCG is a feasible treatment option for patients with CIS involving prostatic ducts. In this retrospective study, bladder preservation was successful in 8 of 11 patients (70%) and there was only one oncologic death. Obviously, these patients need a careful follow-up with cystoscopy and cytology to detect either recurrence or progression and in those with persistent disease after the initial BCG induction therapy, prompt cystectomy is indicated.     

Efficacy of intravesical bacillus Calmette-Guerin for carcinoma in situ of bladder

Three months after an initial 6-week course ofintravesical bacillus Calmette-Guerin (BCG) given between January 1990 and March 2005, 94 (90%) out of 104 patients with carcinoma in situ (CIS) of the bladder achieved a complete response (CR). The 5- and 10-year recurrence-free rates were 67 and 60%, respectively (median follow-up 42 months). Three months after a second course ofintravesical BCG given to 23 patients who failed the initial induction course for CIS was evaluated. Of these, 96% achieved a CR, and the 5- and 10-year recurrence-free rates were 56 and 28%,respectively (median follow-up 23 months). Only one patient who received a second course of BCG therapy showed disease progression. Two of the 4 patients with BCG-refractory CIS of the bladder achieved CR after intravesical gemcitabine therapy and maintained a tumor-free status beyond 6 months. Five of the 16 patients showing disease progression had upper urinary tract cancer, 4 had recurrent or muscle invasive bladder cancer, 6 had prostatic involvement of CIS, and one patient had urethral recurrence. Three of the 16 patients died. Bladder preservation was achieved in 97 of the 104 patients, although 7 patients ultimately underwent radical cystectomy and urinary diversion for aggressive disease. In conclusion, some patients may be managed safely by repeated endoscopic resection and intravesical therapy with cystectomy postponed until objective evidence of progression exists.     

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.     

Clinical outcome of tumor recurrence for Ta, T1 non-muscle invasive bladder cancer from the data on registered bladder cancer patients in Japan: 1999–2001 report from the Japanese Urological Association

Objective:   To characterize the clinical outcome in a large contemporary series of Japanese patients with newly diagnosed Ta, T1 non-muscle invasive bladder cancer who underwent transurethral bladder tumor resection with or without intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) therapy.
Methods:   We developed a database incorporating newly diagnosed non-muscle invasive bladder cancer data and outcomes from a Japanese bladder cancer registry between 1999 and 2001 and identified a study population of 3237 consecutive patients who had complete data based on pathological features. Median patient age was 69.9 years.
Results:   The 1-year, 3-year, and 5-year overall recurrence-free survival rates were 77.0%, 61.3%, and 52.8%, respectively. In multivariate analyses, the multiplicity of bladder tumors, tumor size greater than 3 cm, pathological stage T1, tumor grade G3, and the absence of adjuvant intravesical instillation were independent risk factors for tumor recurrence. Overall, 1710 patients (52.8%) received intravesical instillation; chemotherapy in 1314 (76.8%) and BCG treatment in 396 (23.2%). In patients treated with intravesical chemotherapy in which an anthracycline chemo-agent was used in 90.5% of the cases, multivariate analyses demonstrated that male gender, multiple bladder tumors, a tumor size greater than 3 cm, and pathological stage T1 were associated with tumor recurrence.
Conclusions:   The accumulation and analysis of data from the Japanese National Bladder Cancer Registry made it possible to determine the clinical characteristics, management trends, and survival rates for the period studied. Further study with a dataset created from longer follow-up data would be warranted to analyze tumor progression and disease survival.     

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.     

Bacillus calmette-guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: a meta-analysis of the published results of randomized clinical trials

PURPOSE: We determined the short-term and long-term efficacy of bacillus Calmette-Guerin (BCG) and chemotherapy in the treatment of patients with carcinoma in situ (CIS). MATERIALS AND METHODS: A meta-analysis was performed on published results of randomized clinical trials comparing intravesical BCG to intravesical chemotherapy. RESULTS: Nine randomized trials including 700 patients with CIS compared BCG to either mitomycin C (MMC), epirubicin, adriamycin, or sequential MMC/adriamycin. Of 298 patients on BCG 203 (68.1%) had a complete response compared with 158 of 307 patients on chemotherapy (51.5%), a reduction of 47% in the odds of nonresponse on BCG (OR 0.53, p =0.0002). Based on a median followup of 3.6 years, 161 of 345 patients on BCG (46.7%) had no evidence of disease compared with 93 of 355 patients on chemotherapy (26.2%), a reduction of 59% in the odds of treatment failure on BCG (OR 0.41, p <0.0001). Although the long-term benefit of BCG was smaller in trials with MMC, BCG was superior to MMC in trials with maintenance BCG (OR 0.57, p =0.04). The reduction of 26% in the risk of progression on BCG (p =0.20) is consistent with the reduction of 27% (p =0.001) previously reported in a larger superficial bladder cancer meta-analysis. CONCLUSIONS: Intravesical BCG significantly reduces the risk of short and long-term treatment failure compared with intravesical chemotherapy. Therefore, it is considered to be the intravesical agent of choice in the treatment of CIS.     

Multivariate evaluation of factors affecting recurrence,progression, and survival in patients with superficial bladder cancer treated with intravesical bacillus Calmette-Guérin (Tokyo 172 strain) therapy: Significance of concomitant carcinoma in situ

To evaluate the relative importance of clinicopathological factors affecting recurrence, progression, and survival in patients with superficial bladder cancer (pTa and pT1) undergoing bacillus Calmette-Guérin (BCG) therapy (Tokyo 172 strain), we reviewed data for 146 patients treated between 1985 and 1998. The median follow-up period was 64.7 months. Tumour recurrence, progression, and death were evaluated as endpoints using Cox's proportional hazards model. The 5-year recurrence-free rate was 56% for all 146 patients. Those with a past history of bladder cancer (n = 73) had significantly earlier recurrence than those without (n = 73, p = 0.017) and this tended to be the case for concomitant CIS (n = 34) although this did not reach statistical significance. The 5-year progression rate was 15% for all 146 patients and univariate analysis revealed that the presence of concomitant CIS was significantly associated with disease progression (p = 0.002). Multivariate analysis using the proportional hazards model confirmed the finding that only one factor, concomitant CIS, was significantly associated with progression. The 5-year survival rate was 84% for all 146 patients. Furthermore, univariate and multivariate analyses revealed that patient age, history of bladder cancer, and concomitant CIS were variables significantly related to patient survival. The present findings suggest that careful follow-up is mandatory after BCG instillation therapy for patients with superficial bladder cancer and concomitant CIS because of their relatively poor prognosis.     

Risk factors for urothelial carcinoma of the prostate in patients undergoing radical cystoprostatectomy for bladder cancer

OBJECTIVE

To examine the risk factors for urothelial carcinoma (UC) involvement of the prostate in patients undergoing radical cystoprostatectomy (RCP) for bladder cancer, as such involvement has both prognostic and therapeutic implications.

PATIENTS AND METHODS

We examined 308 consecutive men from 1998 to 2005 who had RCP for UC of the bladder, with whole‐mount processing of their prostate. Prostatic involvement was categorized by site of origin (the bladder or the prostatic urethra) and, in the case of prostatic urethral origin, by depth of invasion, i.e. dysplasia/carcinoma in situ (CIS), involving the prostatic urethra, prostatic ductal invasion or prostatic stromal invasion. The impact of pathological characteristics was evaluated.

RESULTS

In all, 121 (39.3%) patients had some form of urothelial involvement of the prostate, of whom 59 (48.8%) had dysplasia/CIS of the prostatic urethra, 20 (16.5%) had ductal involvement and 32 (26.4%) had stromal involvement. Multivariate analysis showed that bladder CIS (odds ratio 2.0, 95% confidence interval, 1.2–3.6, P = 0.012) and trigonal involvement of bladder tumours (2.0, 1.1–3.7, P = 0.028) were independent risk factors for urothelial involvement of the prostate.

CONCLUSION

There was prostatic involvement with UC in nearly 40% of patients undergoing RCP. In this study CIS and trigonal involvement were independent predictors of risk, but were not adequate enough to accurately identify most patients who have UC within their prostate; further prospective studies are needed to more accurately predict risk factors and depth of invasion.     

Bladder sparing approach for initial T1G3 bladder cancer: Do multifocality,size of tumor or concomitant carcinoma in situ matter? A long‐term analysis of 132 patients

OBJECTIVES: In T1 bladder cancer (BC) multifocality, size of tumor (> or =3 cm) and concomitant carcinoma in situ (CIS) are used to stratify patients' risk. We compared the long-term results in patients with initial T1G3 bc treated with transurethral resection of the bladder (TURB), bacille Calmette-Guérin (BCG) instillations and repeat resection with special regard to these clinical risk factors. The aim was to determine if they influence the outcome in the bladder sparing approach for initial T1G3 bc. METHODS: One hundred and thirty-two consecutive patients with initial T1G3 and no prior history of BC were identified. All patients completed six weekly adjuvant BCG instillations followed by control TURB. Follow-up consisted of cystoscopy with bladder wash cytology every 3 months for 2 years and every 6 months thereafter. RESULTS: Forty-two percent of patients had residual disease, 65% developed recurrence of any stage and 41% had progression to muscle-invasive disease. Cancer-specific survival was 89% and 78% at 5 and 10 years, respectively. Only CIS was significantly correlated with all end points on multivariate analysis. While the presence of one or two risk factors was not related to recurrence, progression or cancer-related death, the presence of all three risk factors predicted the latter. CONCLUSIONS: While no guideline has been established for the decision between cystectomy and bladder sparing, concomitant CIS and the presence of all three risk factors together seem to predict an adverse oncological outcome in the bladder sparing approach.     

Intravesical Bacillus Calmette-Guérin with the Danish Strain for Treatment of Carcinoma In situ of the Bladder

Summary We report our experience of the treatment of carcinoma in situ (CIS) using intravesical therapy with the Danish Bacillus Calmette-Guérin (BCG) strain 331 (SSI). Forty-two patients received treatment, 11 had primary and 31 secondary CIS. The median follow-up period was 26 months (range 3–68). Patients received 6 weekly instillations (1 course) and non-responders an additional 6 instillations at 2-week intervals (2 courses). The complete response rate was 59% for 1 -course patients, 33% for the 2-course patients and 68% for the entire series. Patients were considered treatment failures if they suffered progression to invasive cancer, metastasis or died from transitional cell carcinoma. BCG treatment was more effective in primary than in secondary CIS, with a complete response rate of 80% versus 65% and with no failures versus 35%. Patients with persistent CIS after the first course of BCG had a greater risk of failure than responders: 50% versus 17%. Patients with persistent CIS after the second course had a 75% failure rate. This suggests that cystectomy should be considered for non-responders following a 6-week course and recommended to those not responding to 2 courses. Ten patients had CIS in the prostatic urethra. All responded to BCG treatment; 2 suffered from recurrent CIS 1 associated with invasive urethral tumour. The incidence and severity of side effects were similar to those reported with other strains of BCG. One patient with primary CIS failed to complete the treatment owing to “BCG-itis”.     

Discrepancies between cytology, cystoscopy and biopsy in bladder cancer detection after Bacille Calmette-Guerin intravesical therapy

Objectives:   To evaluate discrepancies in the detection of Bacille Calmette-Guerin (BCG)-resistant bladder cancer by cystoscopy, bladder biopsy and urinary cytology.
Methods:   Between January 1992 and August 2006, 127 bladder cancer patients underwent a cycle of eight weekly BCG instillations. Four weeks after the last BCG instillation, urinary cytological analysis and cystoscopy with targeted biopsy in addition to eight–nine selected-site biopsies were performed.
Results:   Biopsy-proven cancer was found in 11/27 (40.7%), 5/42 (11.9%), and 11/58 (19.0%) of positive, suspicious, and negative cytology cases, respectively. Abnormal and normal cystoscopic findings correlated with a biopsy-proven cancer in 13/53 (24.5%) and 14/74 (18.9%) cases, respectively. The combination of a macroscopic cystoscopic suspicion and a positive cytology missed malignant cases in 15.9% of the cases. In 100 cases without biopsy-proven cancer, the rates of denuded urothelium at biopsy in the cases with positive and non-positive cytology were 7/16 (43.8%) and 16/84 (19.0%), respectively
Conclusions:   According to our study, routine biopsy is recommended in the evaluation of BCG treatment, even if the timing, limitations and disadvantages of the procedure should be taken into account.