The optimum timing of radical cystectomy for patients with recurrent high-risk superficial bladder tumour

OBJECTIVE: To establish the optimum time of radical cystectomy (RC) for patients with recurrent high-risk superficial bladder tumours after the failure of intravesical therapy. PATIENTS AND METHODS: Among 318 patients with transitional cell carcinoma treated with RC and with no neoadjuvant therapy, there were 46 with clinical stage Ta, T1 or Tis refractory to transurethral resection associated with intravesical therapy. These patients had at least one of: (i) high-risk superficial bladder tumours after failure of two consecutive induction courses of intravesical therapy; (ii) superficial bladder tumours with prostatic stromal invasion; (iii) superficial bladder tumours with mucosa/ducts involvement after failure of one course of intravesical therapy; (iv) uncontrolled superficial tumours with transurethral resection associated or not with intravesical therapy. Progression and cause-specific survival of these patients were compared to those with muscle-invasive tumours. Univariate and multivariate analyses of predictive factors for cause-specific survival were also used in patients with superficial tumours. The incidence of significant prognostic factors was compared in both superficial and muscle-invasive tumours, as were the progression pattern and survival. RESULTS: The progression-free and cause-specific survival of patients with superficial tumours was 54% and 67%, respectively, with no significant difference from those with muscle-invasive tumours. In multivariate analysis, positive lymph-nodes and prostatic stromal invasion were significant and independent variables for survival. The incidence of positive lymph nodes was 15% vs 30% (P < 0.05) and of stromal invasion was 32% vs 1.5% (P < 0.001) in patients with superficial and muscle-invasive tumours, respectively. Accounting for the progression pattern in patients with superficial tumours, extravesical urothelial recurrence prevailed over local or distant recurrences (30% vs 15%), whereas in patients with muscle-invasive tumours the opposite occurred (5% vs 33%, respectively). The cause-specific survival of patients with superficial tumour and prostatic stromal invasion was one of three, and in those who developed extravesical urothelial recurrence was 28.5%. CONCLUSION: In patients with recurrent high-risk superficial bladder cancer after intravesical therapy, our criteria for RC were inappropriate, and patients had a survival rate similar to those with muscle-invasive tumours. RC might have been used too late, as there was a high incidence of prostatic stromal invasion and extravesical urothelial recurrence after RC. Both events seem to be responsible of the low cause-specific survival. Predictive factors for progression are needed to indicate early RC in patients with recurrent high-risk superficial tumours. From a previous analysis the pathological pattern of the clinical lack of response (T1, G3, bladder carcinoma in situ and prostate involvement) to intravesical therapy evaluated at 3 months might be important for predicting progression, and an early RC at that time might be useful.     

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.     

Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guérin (Danish 1331 strain)

OBJECTIVE: To report recurrence and progression rates in patients with T1G3 superficial bladder carcinoma treated with intravesical bacille Calmette-Guérin (BCG, Danish 1331 strain) after complete transurethral resection. PATIENTS AND METHODS: Data from the records of 111 patients with T1G3 bladder carcinoma treated between January 1991 and December 1999 were analysed for recurrence, progression, salvage therapy and survival. RESULTS: Of the 111 patients with T1G3 bladder tumours, 69 had intravesical BCG therapy, 20 radical cystectomy and 22 only transurethral resection (TUR). Of the 69 patients receiving BCG therapy 37 (54%) had no recurrence, and 24 (35%) had a recurrence that was not muscle-invasive (Ta/T1) and were treated with TUR only. The remaining eight (12%) progressed to muscle invasion and had salvage cystectomy. During the follow-up six patients died, four from disease and three from other causes, while the remaining 63 are alive and well. Of the other 42 patients, 15 are alive after radical cystectomy and 18 after TUR. CONCLUSION: This series further confirms the benefits of intravesical BCG (Danish 1331) in an adjuvant setting; furthermore, this treatment facilitates bladder preservation by reducing recurrences and delaying the progression in many patients.     

A population-based study of 538 patients with newly detected urinary bladder neoplasms followed during 5 years

OBJECTIVE: To describe in detail the diagnosis and clinical course of an unselected population-based cohort of patients with newly diagnosed bladder neoplasms. MATERIAL AND METHODS: A total of 538 patients registered in the Stockholm region with newly diagnosed primary bladder neoplasms (transitional cell carcinomas) in 1995 and 1996 were followed for at least 5 years. All hospitals and urology units in the region participated in the study. Treatment and follow-up were performed according to a standard-of-care programme. Routine pathological reports were used. Original case records were scrutinized on location in 2001. In addition, a tumour bank of freshly frozen tumour tissue was established. RESULTS: The calculated 5-year cancer-specific survival rate for the 538 patients in the cohort was 78%. No patient (0/29) with TaG1 tumours showed progression or died of bladder cancer. Only 2/187 patients (1%) with stage Ta and grade 2A or 2B tumours died of bladder cancer. In contrast, after 5 years of follow-up, patients with TaG3 and T1G2B tumours had disease-specific death rates of 20% and 27%, respectively. The result of the first cystoscopy examination after the initial resection of non-invasive tumours was of prognostic value. Recurrent disease was present in 62% (248/402) of all patients with Ta and T1 tumours at diagnosis and patients with T1 tumours had recurrences earlier than those with Ta tumours. Moreover, 32% (35/110) of the patients who presented with T1 tumours at diagnosis progressed to muscle-invasive disease during the follow-up period. The overall prognosis for patients presenting with muscle-invasive tumours (T2+) was dismal, with 69% (80/116) of the patients dying of the disease. CONCLUSIONS: We analysed a population-based cohort of patients with urinary bladder neoplasms in order to establish a clearly defined and unselected clinical series, with the main aims of comparing and evaluating the clinical utility of new molecular biology techniques. In the present series, TaG1 tumours behaved benignly. The disease-specific mortality rate was low for initial TaG2 tumours, intermediate for initial TaG3 and T1 tumours and high for initial T2+ tumours.     

Results of second-look resection after primary resection of T1 tumour of the urinary bladder

OBJECTIVE: To study residual tumours at second-look resection in patients resected 4-8 weeks earlier for T1 tumours of the urinary bladder. MATERIAL AND METHODS: All patients randomized in the ongoing Nordic T1G2-G3 Bladder Sparing Study with monitored data available were included in the study. Data on residual tumours at second-look resection were compared to basic patient and tumour characteristics. RESULTS: There were 72 patients (56%) without and 57 with residual exophytic tumours. In the former group, 20 patients (28%) had carcinoma in situ, compared to 19 (33%) in the latter group. Potentially dangerous tumours (either carcinoma in situ, T1 or Ta grade 3) were observed in 55 patients (43%). Multiple tumours at primary resection were more prone to residual tumour at second-look resection than single tumours. No other tumour or patient characteristics could predict the occurrence of a residual tumour. CONCLUSIONS: Residual tumours are frequently observed at second-look resection 4-8 weeks after primary resection of T1 tumours. The majority of residual tumours detected at this stage are potentially dangerous; therefore, early second-look resection followed by intravesical instillation therapy is mandatory in patients with T1 tumours of the urinary bladder.     

Evaluation of a low-dose intravesical bacillus Calmette-Guérin (Tokyo strain) therapy for superficial bladder cancer

To examine whether intravesical instillation of low-dose bacillus Calmette-Guérin (BCG) therapy is effective with low toxicity, we reviewed data for 111 patients with superficial bladder cancer (stages Ta and T1). Among them, 74 received the BCG treatment for prophylaxis of intravesical recurrence after transurethral resection, and the remaining 37 therapeutically for Ta or T1 tumours. The patients were divided into two groups by instillation dose of BCG (Tokyo 172 strain): 40 mg (n=55) and 80 mg (n=56), and statistically compared for recurrence, antitumour effect and toxicity. The mean instillations were done 8.4 times in the 40 mg dose group and 8.6 times in the 80 mg dose group. Among the 74 patients with BCG therapy for prophylaxis those with a previous episode of bladder cancer treatment (n=47) experienced a significantly (p=0.006) shorter recurrence-free interval than those with no episode (n=27). Among 47 patients with a previous treatment episode, those receiving the 80 mg dose demonstrated a significantly longer recurrence-free interval than those given the 40 mg dose (p=0.03). Among the 27 patients without previous treatment no significant difference in recurrence-free intervals was found between the two dose groups. Univariate and multivariate aalyses using Cox's proportional hazards model confirmed the above findings. The drecurrence index was also significantly reduced after BCG therapy in the 80 mg and 40 mg groups and similar antitumour effects for Ta or T1 tumours were observed in the two dose groups. The degree of toxicity due to BCG therapy was significantly (p=0.02) lower with the 40 mg dose. The present study suggests that (1) a 40 mg BCG low-dose (Tokyo 172 strain) regimen is useful for preventing recurrence, with sufficient therapeutic efficacy and low frequency of toxicity, among patients without a previous treatment, and (2) prophylactic effects with the 80 mg dose regimen are much superior for previous treatment cases.     

Bladder cancer clinical guidelines panel summary report on the management of nonmuscle invasive bladder cancer (stages Ta, T1 and TIS). The American Urological Association.

PURPOSE: The American Urological Association convened the Bladder Cancer Clinical Guidelines Panel to analyze the literature regarding available methods of treating nonmuscle invasive bladder cancer, and to make practice policy recommendations based primarily on treatment outcomes data. MATERIALS AND METHODS: The panel searched the MEDLINE database for all articles related to nonmuscle invasive bladder cancer published from 1966 to January 1998. Outcomes data were extracted from articles accepted after panel review and meta-analyzed to produce comparative probability estimates for alternative treatments. RESULTS: All of the intravesical agents (thiotepa, bacillus Calmette-Guerin, mitomycin C and doxorubicin) when used as adjuvant therapy after transurethral resection resulted in a lower probability of recurrence compared to resection alone. However, there is no evidence that intravesical therapy affects long-term progression. CONCLUSIONS: For patients with no prior intravesical therapy adjuvant intravesical chemotherapy or immunotherapy is a treatment option after endoscopic removal of low grade Ta bladder cancers. Intravesical instillation of bacillus Calmette-Guerin or mitomycin C is recommended for carcinoma in situ, and after endoscopic removal of T1 and high grade Ta tumors.     

Analysis of factors predicting intravesical recurrence of superficial transitional cell carcinoma of the bladder without concomitant carcinoma in situ

BACKGROUND: The objective of this study was to investigate risk factors for intravesical recurrence in patients with superficial bladder cancer without concomitant carcinoma in situ (CIS). METHODS: In this series, we analyzed data from patients with newly diagnosed superficial Ta or T1 transitional cell carcinoma (TCC) of the bladder without concomitant CIS who underwent complete transurethral resection (TUR) without any adjuvant intravesical instillation therapies. Multivariate analysis was used to determine significant risk factors affecting intravesical recurrence after TUR. Differences in clinicopathological features between primary and recurrent tumors were also characterized. RESULTS: Among 341 patients undergoing TUR of Ta or T1 bladder cancer, 187 diagnosed as having concomitant CIS and/or treated with adjuvant intravesical therapy were excluded, and the remaining 154 were evaluated. Intravesical recurrence was detected in 64 of the 154 patients, showing a 5-year recurrence-free survival rate of 58.3%. Among several factors examined, only tumor size was significantly associated with intravesical recurrence. Multivariate analysis identified tumor size as an independent predictor for intravesical recurrence irrespective of other parameters including age, gender, multiplicity, growth pattern, grade and stage. Recurrent tumors were significantly smaller and of a lower grade and lower stage than primary tumors, despite the absence of differences in growth pattern and the multiplicity between them. CONCLUSIONS: These findings suggest that primary tumor size could be used as a potential risk factor for predicting intravesical recurrence following TUR of superficial TCC of the bladder without concomitant CIS, and that the pathological characteristics of recurrent tumors are more favorable than those of primary tumors.     

Role of routine transurethral biopsy and isolated upper tract cytology after intravesical treatment of high‐grade non‐muscle invasive bladder cancer

Objectives: To investigate whether random bladder, and prostatic urethral biopsies and individual upper tract cytologies (restaging) provide useful clinical information in addition to cystoscopy and bladder cytology in assessing initial intravesical therapy response for high‐grade non‐muscle invasive bladder cancer. Methods: We retrospectively reviewed records of all patients who underwent restaging at our institution after treatment for high‐grade non‐muscle invasive bladder cancer (Ta, T1 and Tis) between January 2000 and October 2009. A total of 78 patients undergoing 116 consecutive restagings were included. The presence of intravesical cancer at restaging was assessed by cystoscopy, bladder wash cytology and random bladder biopsies, whereas ureteral and prostatic urethral disease was determined using upper tract barbotage cytology and prostatic urethral biopsies. Results: Indication for intravesical treatment was carcinoma in situ in 86, high‐grade T1 in 16 and high‐grade Ta in 14 cases. A total of 48 patients had primary disease and 68 had recurrence. Overall, 59 of 116 (50.9%) restagings showed positive bladder or prostatic biopsy and/or a positive cytology localized to the upper tract. Of the total number of recurrences, 12.9% (15 of 116) showed a negative cystoscopy and negative bladder cytology, and would have been missed on routine surveillance. A total of 23 of 116 (19.8%) restagings showed evidence of prostatic urethral and or ureteral disease. Conclusion: Roughly 25% of high‐grade non‐muscle invasive bladder cancer early recurrences after induction intravesical therapy would go unnoticed without the addition of random and directed prostate biopsies, and isolated upper tract cytologies to standard cystoscopy and bladder cytology.     

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.     

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.     

Total cystectomy after intravesical bacillus Calmette-Guérin (Tokyo strain) therapy for superficial bladder cancer: Experience in Japan

To clarify which patients might most require total cystectomy after intravesical bacillus Calmette-Guérin (BCG) therapy, we reviewed data for 111 individuals with superficial bladder cancer. Of the 111 patients, 73 received the BCG treatment for prophylaxis of intravesical recurrence after transurethral resection (group 1), 24 therapeutically for Ta or T1 tumours (group 2), and 14 for eradicating carcinomas in situ (CIS, group 3). Although the BCG therapy significantly reduced frequencies of recurrence in group 1, 27 patients (37%) did develop tumours again. Tumours disappeared in 18 of 24 patients (75%) in group 2, and in 11 of 14 (79%) in group 3. The rate of disease progression was 6% for all 111 patients: 3% (2/73) for group 1, 17% (4/24) for group 2, and 7% (1/14) for group 3. A total of 16 of the 111 patients (14%) underwent total cystectomy, the respective figures being 7% in group 1, 29% in group 2, and 29% in group 3. Indications for total cystectomy were progression in 7, recurrent multiple tumours in 5, persistent CIS in 2, a contracted bladder in 1, and occurrence of bilateral renal pelvic cancer in 1. Thus, 4 of 6 patients (67%) who had tumours unresponsive to BCG therapy in group 2 demonstrated progression and necessitated total cystectomy. Because tumours persisting after BCG therapy are frequently of the muscle-invasive type, such cases should be regarded as candidates for immediate total cystectomy.     

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.     

Management of local bacillus Calmette-Guerin failures in superficial bladder cancer.

We attempt to define the treated natural history of patients with superficial bladder tumors (stages Ta, TIS and T1) managed with intravesical bacillus Calmette-Guerin (BCG) to determine the best form of treatment for locally recurrent tumors. The management and survival of 41 patients who failed BCG within the bladder or prostatic urethra and who subsequently were treated with a variety of secondary therapies are reviewed. Our aim was to assess the role of several independent clinical variables on the rate of death from bladder cancer. Of the 41 patients 6 (15%) died. Univariate statistical analysis identified early involvement of the prostatic urethra and the presence of superficially invasive (stage T1) tumor at initial treatment with BCG as factors having an adverse effect on survival. A multivariate statistical model revealed that patients with early prostatic urethral involvement and the presence of superficially invasive (stage T1) tumor at diagnosis had the highest risk of death from bladder cancer. The reason for change in therapy at failure of BCG, stage of the tumor at BCG failure, occurrence of upper tract tumors and early versus delayed radical cystectomy had no impact on survival. The results suggest that not all tumors that recur after BCG are destined to proceed to muscle invasion or metastases, and that some patients may be managed safely by repeated endoscopic resection and intravesical therapy with cystectomy delayed until objective progression is evident. Such an approach can yield survival equal to that in patients treated with early cystectomy and may result in longer intervals of bladder preservation in a select subset of patients who fail BCG locally.     

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.     

Recurrence, progression and survival in bladder cancer. A retrospective analysis of 232 patients with greater than or equal to 5-year follow-up

A retrospective study of 232 bladder tumours with minimum follow-up 5 years is presented. The carcinoma was superficial in 66%, muscle-invasive in 31% and could not be staged in 3%. Primary treatment was mainly transurethral resection for superficial tumour, but was cystectomy or radiotherapy in 22 of 29 T1 G3. Of the superficial tumours, 71% recurred. Progression to higher T stage occurred in 15% of Ta and 29% of T1 tumours, and half of these patients died of bladder cancer. The corrected 5-year survival rates in grades 1, 2A, 2B and 3-4 were 96, 84, 64 and 43%, and in stages Ta, T1, T2 and T3 they were 94, 69, 40 and 31%. All patients with T4 tumour died within 4 years. Among the 45 patients with 40 Gy irradiation + cystectomy, the corrected 5-year survival rate was 83% in superficial and 64% in muscle-invasive tumours, and among the 38 with radical radiotherapy the rates in T1-3 were 46, 36 and 13%. Transurethral resection was successful in most Ta cases. Most T1 tumours were, like T2-4, of higher grade than Ta. Prognosis was worse in T1 than in Ta. After progression to muscle-invasive disease, even during close follow-up the outlook was poor, as poor as for patients with primary muscle-invasive disease.     

Radical transurethral resection and chemotherapy in the treatment of muscle-invasive bladder cancer: a long-term follow-up

OBJECTIVE: To evaluate the treatment of patients with muscle-invasive bladder cancer (T2-T4a) by radical transurethral resection (TUR) and cisplatin-methotrexate systemic chemotherapy. PATIENTS AND METHODS: Fifty patients with transitional cell carcinoma (TCC) of the bladder (nine T2, 36 T3 and five T4a) were treated by 'complete' TUR of the bladder tumour followed by 2-6 cycles of cisplatin (70 mg/m2) and methotrexate (40 mg/m2) chemotherapy. The median (range) tumour size was 3 (1-7 cm). In six patients, attempted TUR at the dome of the bladder led to intraperitoneal perforation; the tumour was excised by partial cystectomy in these patients. The latest follow-up results from 57 patients treated by radical TUR and methotrexate alone, reported previously, are included. RESULTS: At the first evaluation cystoscopy immediately after completing chemotherapy, 38 patients were tumour-free, eight had persistent muscle-invasive TCC and four had Ta, T1+CIS disease. With an overall median follow-up of 47 months, 10 additional patients relapsed with muscle-invasive carcinoma in the bladder after a median interval of 15.6 months; three patients developed Ta, T1 tumours, three Ta, T1 + CIS, and six CIS only. Six of the 10 recurrent invasive tumours were at the same site, but four were at a different site in the bladder. Although during follow-up 12 patients developed superficial recurrence that required endoscopic treatment, the bladder was preserved (free of muscle-invasive cancer) in 37 of 50 patients. In 30 of these 37, this was achieved with no need for salvage radiotherapy or cystectomy. Six patients died from metastatic TCC with no tumour in the bladder. CONCLUSION: In this selected group of patients, muscle-invasive bladder cancer was controlled by TUR and systemic chemotherapy, preserving normal bladder function in 60% of patients without apparently comprising overall survival.     

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.     

5-aminolaevulinic acid-induced fluorescence cystoscopy during transurethral resection reduces the risk of recurrence in stage Ta/T1 bladder cancer

OBJECTIVE: To assess the influence of 5-aminolaevulinic acid-induced fluorescence cystoscopy (FC) during transurethral resection (TUR) on the recurrence rate and the length of tumour-free interval in stage Ta/T1 transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: In all, 122 patients with primary or recurrent stage Ta/T1 bladder TCC treated with TUR were enrolled in a prospective randomized study. In group A the TUR was performed with standard white-light endoscopy, and in group B with FC. The patients were followed using standard cystoscopy and urinary cytology. The recurrence-free interval was evaluated in whole groups, for single and multiple, and for primary and recurrent tumours separately. RESULTS: At the time of the first cystoscopy (10-15 weeks after TUR) tumour recurrence was detected in 23 of 62 patients (37%) in group A, but only in five of 60 patients (8%) in group B. The recurrence-free survival rates in group A were 39% and 28% after 12 and 24 months, compared to 66% and 40% respectively in group B (P = 0.008, log-rank test). In separate analyses, the recurrence-free survival rates were significantly higher using FC in multiple (P = 0.001) and in recurrent (P = 0.02) tumours. In solitary and primary tumours the median time to recurrence was also longer in group B, but the difference was not statistically significant. CONCLUSION: 5-aminolaevulinic acid-induced FC during TUR reduces the recurrence rate in stage Ta/T1 bladder TCC. The most significant benefit is in patients with multiple and recurrent tumours.     

Natural history of superficial bladder tumors: 10- to 20-year follow-up of treated patients

Summary Superficial bladder tumors (Ta, T1, Tis) account for 80% of primary bladder cancers. Transurethral resection and intravesical therapy are successful in controlling the majority of these tumors for up to 5 years. However, patients with multiple or recurrent Ta, T1 and Tis bladder cancer have a lifelong risk of developing stage progression and upper tract tumors. One-half are at risk of having cystectomy eventually and one-third are at risk over a 15-20 year period of dying of bladder cancer.