Urinary diversion after cystectomy for bladder cancer: a population-based study in Sweden.

OBJECTIVE: To investigate the type of urinary diversion performed after cystectomy in patients with muscle-invasive bladder cancer in Sweden, using data from a population-based national register. MATERIAL AND METHODS: Since 1997, the Swedish Bladder Cancer Register has included more than 90% of all patients with newly diagnosed bladder cancer. The different types of urinary diversion performed in 1997-2003 were analysed, comparing non-continent diversion (ileal conduit) with continent reconstruction (bladder substitution or continent cutaneous diversion). RESULTS: During the study period, 3463 patients were registered with clinical T2-T4 non-metastatic bladder cancer. Cystectomy was performed in 1141 patients with ileal conduit in 732 (64%) and continent reconstruction in 409 (36%). Ileal conduit was used more frequently in females than males (p = 0.019), in patients older than 75 years (p < 0.00001), and in those with less favourable TNM classification. Continent reconstruction was done more often at university hospitals than at county hospitals (p < 0.00001), but rarely in the northern and western healthcare regions compared with other regions (p < 0.00001). Nationwide, the proportion of registered continent reconstructions decreased, although the absolute number was relatively stable (50-60 per year). CONCLUSIONS: Continent reconstruction after cystectomy for muscle-invasive bladder cancer is performed more often in some healthcare regions and in patients at university hospitals than in county hospitals, indicating a substantial provider influence on the choice of urinary diversion. Over time, the proportion of these procedures has decreased, while the absolute number has remained low and stable; therefore, concentration in high-volume hospitals specialized in bladder cancer and continent reconstruction seems appropriate.

A population-based study of patterns of care for muscle-invasive bladder cancer in Sweden.

OBJECTIVE: To analyse the management of muscle-invasive bladder cancer in a population-based national register, and specifically to investigate the role of curative therapy (i.e. cystectomy or radiotherapy) in relation to patient, tumour and hospital characteristics. MATERIAL AND METHODS: The Swedish Bladder Cancer Register covers more than 90% of all patients in the country who have been diagnosed with such disease since 1997. Results from 1997-2003 were analysed regarding curative-intent treatment given within 3-6 months of diagnosis of muscle-invasive bladder cancer. RESULTS: In total, 3463 patients with clinical T2-T4 bladder cancer were included in the analysis. Of those patients, 1426 (41%) received curative-intent treatment in the form of radiotherapy (285, 20%) or cystectomy (1141, 80%). Male gender, age < 76 years, favourable TNM category and registration at a high-volume hospital were associated with such treatment. Curative-intent treatment was given to significantly more patients registered at high-volume hospitals (1003/2227, 45%) than at low-volume hospitals (423/1235, 34%) (chi(2)=37.7, p<0.00001). Cystectomy was performed more often in those registered at high-volume than at low-volume hospitals (826/2227, 37%, and 316/1235, 26%, respectively, chi(2)=47.3, p<0.00001). CONCLUSIONS: Lower rates of curative-intent treatment were found in patients registered at low-volume than at high-volume facilities, and the same was seen when comparing females with males, and patients aged 76-80 years with younger patients. Since many of these bladder cancer patients were registered at and eventually treated at hospitals handling fewer than 10 such cases annually, it seems desirable to concentrate treatment of this disease at more specialized centres.

Bacillus Calmette-Guérin is superior to a combination of epirubicin and interferon-alpha2b in the intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective, randomized, Nordic study.

BACKGROUND: Bacillus Calmette-Guérin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed. OBJECTIVE: To compare BCG to the combination of epirubicin and interferon-alpha2b as adjuvant therapy of T1 tumours. DESIGN, SETTING, AND PARTICIPANTS: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr. MEASUREMENTS: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented. RESULTS AND LIMITATIONS: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p=0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p=0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination. CONCLUSIONS: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

Analysis of clinical characteristics, management and survival of patients with Ta T1 bladder tumours in Sweden between 1997 and 2001.

OBJECTIVE: To analyse the management and outcome of patients with Ta T1 urinary bladder cancer in a population-based national database. MATERIAL AND METHODS: Between 1997 and 2001, 94% of all newly diagnosed cases of urinary bladder cancer were registered in the Swedish National Bladder Cancer Register. Data were analysed regarding gender, healthcare region, stage and grade for patients with Ta T1 tumours. The choice of initial treatment in different regions was reviewed. Survival was analysed by calculating relative survival. RESULTS: Out of 9859 registered patients, there were 4442 Ta tumours and 2139 T1 tumours. The median age at diagnosis was 72 and 73 years for patients with Ta and T1 tumours, respectively. Seventy-six percent of the patients were men. The choice of treatment varied between different healthcare regions. A significant trend towards an increased use of intravesical therapy was seen over time. Significantly fewer older than younger patients received such therapy. There was also a tendency towards more intensive therapy in men. The bladder cancer relative 5-year survival rate was 93% for Ta and 75% for T1 tumours. Survival was similar for men and women. CONCLUSIONS: Our analysis revealed a regional variation in the treatment of bladder cancer. A large group of patients, even those at high risk, were still undertreated. However, the recent publication of guidelines may have contributed to an increased use of intravesical treatment. Urologists tended to treat TaG3 and T1G3 tumours more aggressively than T1G2 tumours. Therapeutic aggressiveness decreased as the age of the patients increased. The survival rate of patients with bladder cancer in Sweden seems to remain at the levels previously reported for the 1980s.

T1 G1 urinary bladder carcinoma: fact or fiction?

OBJECTIVES: To record the occurrence of well-differentiated bladder carcinoma reported as T1 G1 to the Swedish Urinary Bladder Cancer Registry, to review the staging and grading of the carcinomas and to scrutinize the validity of the data on T1 G1 tumours reported to the registry during the period 1997-2000. MATERIAL AND METHODS: The primary histopathological diagnoses of 98 cases of well-differentiated bladder carcinoma reported to the Registry were compared with the data delivered by the local urologists. Also, the histopathology slides were obtained from the local laboratories and re-examined. RESULTS: Fifty-five cases had been erroneously reported to the Registry as T1 tumours by the urologists, even though they were clearly described as non-infiltrating G1 tumours by the pathologists. The results of the re-examination of the pathology slides were concordant with the judgements of the local pathologists in only 50% of cases (20 stage T and 29 grade G tumours). Most importantly, the re-evaluation did not reveal a single invasive G1 tumour. Simply by providing the urologists with information about this problem, it was possible to reduce the number of errors in the reports from 27 in 1997 to only five in 2000. CONCLUSIONS: Well-differentiated urothelial carcinoma (G1) has no propensity to infiltrate the bladder mucosa. For investigating specific problems the data collected in the Swedish Urinary Bladder Cancer Registry have to be validated.

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.

A systematic overview of radiation therapy effects in urinary bladder cancer.

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for urinary bladder cancer is based on data from 3 meta-analyses and 33 randomized trials. The studies include 4333 patients. The results were compared with those of a similar overview from 1996 including 15,042 patients. The conclusions reached can be summarized as these points: There is moderate evidence for an overall survival benefit with preoperative radiotherapy followed by cystectomy compared to curative radiotherapy based on early studies (1964-1986). Since that time surgical as well as radiation techniques have developed considerably. Therefore, the conclusion may not be relevant to modern treatment of invasive urinary bladder carcinoma. There is only one small study reporting on curative radiotherapy where increased dose per fraction is compared with conventionally fractionated radiotherapy to the same total dose. Thus, no conclusions can be drawn concerning optimal fraction dose. A meta-analysis based on two studies on hyperfractionated radiotherapy gives moderate evidence of a survival benefit at 5 and 10 years and an increased local control rate compared with conventional fractionation. The documentation of local control and overall survival rate after split-course radiation treatment compared to continuous therapy is conflicting. No firm conclusions can be drawn. Four small and early studies have compared radiation treatment using neutrons with photon treatment. The reports favour therapy with photons with respect to overall treatment results. There is moderate evidence for this conclusion. There is fairly strong evidence in early studies that radiation treatment in combination with hyperbaric oxygen does not confer a treatment benefit compared to radiation in normal atmosphere. There is no indication of a treatment benefit with the addition of either hyperthermia or misonidazole. A large number of phase II studies, suggesting an increased possibility for bladder preservation with concomitant chemoradiotherapy compared to radiotherapy alone, have been reviewed in a previous SBU report on chemotherapy. Only one small randomized study has been reported where concomitant chemoradiotherapy with cisplatin is compared to radiation alone. No conclusion on the therapeutic benefit of combined treatment can be drawn. Large randomized studies are needed. There is some evidence that preoperative radiotherapy followed by cystectomy does not confer any significant survival benefit compared to cystectomy alone. There is moderate evidence that palliative radiotherapy of invasive bladder carcinoma can rapidly induce tumour-related symptom relief. There is moderate evidence that palliative hypofractionated radiotherapy, 3 fractions during one week, gives the same relief of symptoms as 10 fractions during 2 weeks.

Alternating mitomycin C and BCG instillations versus BCG alone in treatment of carcinoma in situ of the urinary bladder: a nordic study.

OBJECTIVES: To evaluate whether, in patients with carcinoma in situ (CIS) of the urinary bladder, alternating instillation therapy with mitomycin C (MMC) and bacillus Calmette-Guerin (BCG) was more effective and less toxic than conventional BCG monotherapy. METHODS: Patients were stratified prospectively for primary, secondary, and concomitant CIS and randomized to one of two regimens. Patients in the alternating group received six weekly intravesical instillations of MMC 40 mg, followed by alternating monthly instillations of BCG 120 mg and MMC for one year. In the monotherapy group, only BCG was instilled on the same schedule. RESULTS: Of 323 enrolled patients, 304 were eligible for analysis. After an overall median follow-up of 56 months, the Kaplan-Meier disease-free estimate for BCG monotherapy was significantly better than that for alternating therapy (p=0.03; log rank test). Risk for progression appeared lower in the BCG monotherapy group (p=0.07), but no differences existed in survival. Besides the regimen, CIS category also predicted outcome to some extent. BCG monotherapy caused significantly more local side-effects and premature cessation of instillation treatment than did the alternating therapy. However, no differences were observed in the number of serious side-effects. CONCLUSION: One-year BCG monotherapy was more effective than the alternating therapy for reducing recurrence and compared well with the best regimens reported from substantially smaller series. The alternating therapy was better tolerated.