Is bladder tumour fulguration under local anaesthesia more painful than cystoscopy only?

Objectives: To prospectively register self-reported pain levels associated with office cystoscopy with or without bladder tumour biopsy and fulguration.Patients and methods: During a 15-month period, patients examined with cystoscopy under local anaesthesia graded their pain level using the Visual Analogue Scale (VAS). All patients were examined in the lithotomy position and lidocaine gel was used in all. A bladder instillation or a submucosal injection of lidocaine was given mainly in patients treated with extirpation of larger tumours.Results: The pain perception was graded by the patients as none (VAS = 0) or mild (VAS = 1-3) in 86% of the 1,314 cystoscopies. Fewer patients (65% out of 258) reported VAS 0-3 when cystoscopy with biopsy and fulguration of bladder tumour was performed. More than 97% of all patients stated that they would prefer treatment under local anaesthesia in the case of a future recurrence.Conclusion: The VAS-scores after diagnostic cystoscopy are in accordance with those previously reported, with the absolute majority reporting no or mild pain. Patients treated with extirpation of bladder tumours reported higher levels of pain but still within acceptable limits. This confirms the potential of treating most patients with small-sized bladder tumour recurrences under local anaesthesia.

Impact of age on outcomes of patients with non-muscle-invasive bladder cancer treated with immediate postoperative instillation of mitomycin C.

OBJECTIVES: To evaluate whether age affects the clinical benefit afforded by immediate postoperative intravesical instillation of mitomycin C in a contemporary cohort of patients with NMIBC. PATIENTS AND METHODS: A total of 4,258 patients with NMIBC treated with transurethral resection of the bladder with (n = 2,605, 61%) or without (n = 1,652, 39%) one immediate instillation of mitomycin C from 5 institutions (study period: 2000-2007) were included. No patients received adjuvant instillations. A multivariable Cox proportional hazards regression model adjusting for standard clinical and pathological features tested the potential interaction term between age and administration of mitomycin C with regard to disease recurrence. RESULTS: A total of 2,063 patients experienced disease recurrence with a median follow-up of 48 months for those who did not recur. In multivariable Cox regression analysis, immediate postoperative instillation of mitomycin C (HR: 0.62; 95% CI: 0.56-0.68; P<0.0001) and age (HR: 1.04; 95% CI: 1.00-1.09; P = 0.036) were associated with disease recurrence. We observed only slight decreases in recurrence-free survival with age irrespective of treatment administration of mitomycin C or not. CONCLUSION: We confirmed reduced disease recurrence rates associated with 1 immediate postoperative intravesical instillation of mitomycin C in NMIBC patients. The benefit on recurrence-free survival of a postoperative intravesical instillation was preserved across all ages and therefore age by itself should not be taken into consideration when deciding to use it.

Second-look resection for primary stage T1 bladder cancer: a population-based study.

OBJECTIVE: This study aimed to evaluate the use of second-look resection (SLR) in stage T1 bladder cancer (BC) in a population-based Swedish cohort. MATERIALS AND METHODS: All patients diagnosed with stage T1 BC in 2008-2009 were identified in the Swedish National Registry for Urinary Bladder Cancer. Registry data on TNM stage, grade, primary treatment and pathological reports from the SLR performed within 8 weeks of the primary transurethral resection were validated against patient charts. The endpoint was cancer-specific survival (CSS). RESULTS: In total, 903 patients with a mean age of 74 years (range 28-99 years) were included. SLR was performed in 501 patients (55%), who had the following stages at SLR: 172 (35%) T0, 83 (17%) Ta/Tis, 210 (43%) T1 and 26 (5%) T2-4. The use of SLR varied from 18% to 77% in the six healthcare regions. Multiple adjuvant intravesical instillations were given to 420 patients (47%). SLR was associated with intravesical instillations, age younger than 74 years, discussion at multidisciplinary tumour conference, G3 tumour and treatment at high-volume hospitals. Patients undergoing SLR had a lower risk of dying from BC (hazard ratio 0.62, 95% confidence interval 0.45-0.84, p < .0022). Five-year CSS rates were as follows, in patients with the indicated tumours at SLR (p = .001): 82% in those with T1, 90% in T0, 90% in Ta/Tis and 56% in T2-4. CONCLUSIONS: There are large geographical differences in the use of SLR in stage T1 BC in Sweden, which are presumably related to local treatment traditions. Patients treated with SLR have a high rate of residual tumour but lower age, which suggests that a selection bias affects CSS.

Gender-related differences in urothelial carcinoma of the bladder: a population-based study from the Swedish National Registry of Urinary Bladder Cancer.

OBJECTIVE: The aim of this investigation was to describe tumour characteristics, treatments and survival in patients with urinary bladder cancer (UBC) in a national population-based cohort, with special reference to gender-related differences. MATERIAL AND METHODS: All primary UBC patients with urothelial pathology reported to the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) from 1997 to 2011 were included in the study. Groups were compared regarding tumour, node, metastasis classification, primary treatment and survival. RESULTS: In total, 30,310 patients (74.9% male, 25.1% female) with UBC were analysed. A larger proportion of women than men had stage T2-T4 (p < 0.001), and women also had more G1 tumours (p < 0.001). However, compared to women, a larger proportion of men with carcinoma in situ or T1G3 received intravesical treatment with bacillus Calmette-Guérin or intravesical chemotherapy, and a larger proportion of men with stage T2-T4 underwent radical cystectomy (38% men vs 33% women, p < 0.0001). The cancer-specific survival at 5 years was 77% for men and 72% for women (p < 0.001), and the relative survival at 5 years was 72% for men and 69% for women (p < 0.001). CONCLUSIONS: In this population-based cohort comprising virtually all patients diagnosed with UBC in Sweden between 1997 and 2011, female gender was associated with inferior cancer-specific and relative survival. Although women had a higher rate of aggressive tumours, a smaller proportion of women than men received optimal treatment.

Swedish National Registry of Urinary Bladder Cancer: No difference in relative survival over time despite more aggressive treatment.

OBJECTIVE: The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. MATERIALS AND METHODS: All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. RESULTS: The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. CONCLUSIONS: This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.

Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation?

CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial. OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation. EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out. EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5. CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended. PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.

Patients with High Grade Bladder Cancer, and Tumor-Free 3 and 6-Month Cystoscopy after bacillus Calmette-Guérin have a Good Prognosis without Further Maintenance bacillus Calmette-Guérin.

INTRODUCTION: The benefit of 3 years of maintenance bacillus Calmette-Guérin has been questioned. The outcome is reported for bacillus Calmette-Guérin treated patients who had negative 3 and 6-month cystoscopy results and were subsequently not treated with maintenance bacillus Calmette-Guérin. METHODS: A retrospective, population based study of patients with high grade nonmuscle invasive bladder cancer treated with bacillus Calmette-Guérin was performed. Patients were included in analysis who had tumor-free cystoscopy findings 3 and 6 months after the start of treatment. No patient was treated with maintenance bacillus Calmette-Guérin after the 6-month cystoscopy. The Kaplan-Meier estimated 5-year survival rates were calculated. RESULTS: Three and 6-month cystoscopy revealed no tumor in 196 patients with a median age of 72 years. Of the patients 84% had carcinoma in situ or multiple and/or recurrent high grade tumors. Five-year recurrence-free, progression-free and disease specific survival was 69%, 95% and 98%, respectively. Median followup in 119 patients who were alive at the last contact was 79 months. Recurrence developed in 62 of 196 patients (32%), disease stage progressed to at least T2 in 13 (7%) and 7 (3%) died of bladder cancer. CONCLUSIONS: Patients without maintenance bacillus Calmette-Guérin after tumor-free 3 and 6-month cystoscopy have a low rate of progression and bladder cancer death. An alternative to 1 to 3 years of bacillus Calmette-Guérin maintenance may be no maintenance after the second tumor-free cystoscopy with re-treatment with bacillus Calmette-Guérin in case of recurrence.

Local recurrence and progression of non-muscle-invasive bladder cancer in Sweden: a population-based follow-up study.

OBJECTIVE: The aim of this study was to investigate recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) in a large population-based setting. MATERIALS AND METHODS: Patients with bladder cancer (stage Ta, T1 or carcinoma in situ) diagnosed in 2004-2007 (n = 5839) in Sweden were investigated 5 years after diagnosis using a questionnaire. Differences in time to recurrence and progression were analysed in relation to age, gender, tumour stage and grade, intravesical treatment, healthcare region, and hospital volume of NMIBC patients (stratified in three equally large groups). RESULTS: Local bladder recurrence and progression occurred in 50 and 9% of the patients, respectively. The rate of local recurrence was 56% in the southern healthcare region compared to 37% in the northern region. A multivariate Cox proportional hazards model, adjusting for age, gender, tumour stage and grade, intravesical treatment, healthcare region and hospital volume, showed that recurrence was associated with TaG2 and T1 disease, no intravesical treatment and treatment in the southern healthcare region, but indicated a lower risk of recurrence in the northern healthcare region. Adjusting for the same factors in a multivariate analysis suggested that increased relative risk of progression correlated with older age, higher tumour stage and grade, and diagnosis in the Uppsala/Örebro healthcare region, whereas such risk was decreased by intravesical treatment (relative risk 0.72, 95% confidence interval 0.55-0.93, p = 0.012). CONCLUSIONS: The incidence of NMIBC recurrence and progression was found to be high in Sweden, and important disparities in outcome related to care patterns appear to exist between different healthcare regions.

A Prospective Study of the Size, Number and Histopathology of New and Recurrent Bladder Tumors.

INTRODUCTION: We prospectively registered the grade, stage, number and size of bladder tumor recurrences as to our knowledge this has not yet been done. New tumors were included in the study for comparative purposes. METHODS: All 581 transurethral resections, random biopsies and fulgurations for a suspected bladder tumor were prospectively registered during a 15-month period at a single institution. Tumor size was determined using the size of the resection loop or biopsy forceps as a reference. RESULTS: Of all suspected new and recurrent bladder tumors 22% were benign or inflammatory lesions. A total of 167 patients with a new urothelial tumor and 214 recurrences in 166 patients were registered during the study period. Compared to new tumors, recurrences were more often noninvasive (88% vs 67%, p <0.001), more often 10 mm or less in diameter (63% vs 18%, p <0.001) and more often multifocal (55% vs 38%, p <0.01). New and recurrent tumors had a median size of 20 and 8 mm, respectively. CONCLUSIONS: The absolute majority of suspected bladder tumor recurrences are benign or low grade noninvasive malignant tumors and are less than 10 mm in diameter. This finding suggests that there is great potential for cost reductions when a significant proportion of patients with suspected recurrences after treatment of low grade tumors could undergo biopsy and fulguration using local anesthesia in the office instead of general anesthesia.

Use of bacillus Calmette-Guérin in stage T1 bladder cancer: Long-term observation of a population-based cohort.

OBJECTIVE: The aim of this study was to analyse the rate of use of bacillus Calmette-Guérin (BCG) at a population-based level, and the overall mortality and bladder cancer mortality due to stage T1 bladder cancer in a national, population-based register. MATERIALS AND METHODS: In total, 3758 patients with primary stage T1 bladder cancer, registered in the Swedish Bladder Cancer Register between 1997 and 2006, were included. Age, gender, tumour grade and primary treatment in the first 3-6 months were registered. High-volume hospitals registered 10 or more T1 tumours per year. Date and cause of death were obtained from the National Board of Health and Welfare Cause of Death Register. RESULTS: BCG was given to 896 patients (24%). The use of BCG increased from 18% between 1997 and 2000, to 24% between 2001 and 2003, and to 31% between 2004 and 2006. BCG was given more often to patients with G3 tumours, patients younger than 75 years and patients attending high-volume hospitals. BCG treatment, grade 2 tumours and patient age younger than 75 years were associated with lower mortality due to bladder cancer. Hospital volume, gender and year of diagnosis were not related to bladder cancer mortality. However, selection factors might have affected the results since comorbidity, number of tumours and tumour size were unknown. CONCLUSIONS: Intravesical BCG is underused at a population-based level in stage T1 bladder cancer in Sweden, particularly in patients 75 years or older, and in those treated at low-volume hospitals. BCG should be offered more frequently to patients with stage T1 bladder cancer in Sweden.

Urinary bladder cancer treated with radical cystectomy: perioperative parameters and early complications prospectively registered in a national population-based database.

OBJECTIVE: Cystectomy combined with pelvic lymph-node dissection and urinary diversion entails high morbidity and mortality. Improvements are needed, and a first step is to collect information on the current situation. In 2011, this group took the initiative to start a population-based database in Sweden (population 9.5 million in 2011) with prospective registration of patients and complications until 90 days after cystectomy. This article reports findings from the first year of registration. MATERIAL AND METHODS: Participation was voluntary, and data were reported by local urologists or research nurses. Perioperative parameters and early complications classified according to the modified Clavien system were registered, and selected variables of possible importance for complications were analysed by univariate and multivariate logistic regression. RESULTS: During 2011, 285 (65%) of 435 cystectomies performed in Sweden were registered in the database, the majority reported by the seven academic centres. Median blood loss was 1000 ml, operating time 318 min, and length of hospital stay 15 days. Any complications were registered for 103 patients (36%). Clavien grades 1-2 and 3-5 were noted in 19% and 15%, respectively. Thirty-seven patients (13%) were reoperated on at least once. In logistic regression analysis elevated risk of complications was significantly associated with operating time exceeding 318 min in both univariate and multivariate analysis, and with age 76-89 years only in multivariate analysis. CONCLUSIONS: It was feasible to start a national population-based registry of radical cystectomies for bladder cancer. The evaluation of the first year shows an increased risk of complications in patients with longer operating time and higher age. The results agree with some previously published series but should be interpreted with caution considering the relatively low coverage, which is expected to be higher in the future.

The economics of bladder cancer: costs and considerations of caring for this disease.

CONTEXT: Due to high recurrence rates, intensive surveillance strategies, and expensive treatment costs, the management of bladder cancer contributes significantly to medical costs. OBJECTIVE: To provide a concise evaluation of contemporary cost-related challenges in the care of patients with bladder cancer. An emphasis is placed on the initial diagnosis of bladder cancer and therapy considerations for both non-muscle-invasive bladder cancer (NMIBC) and more advanced disease. EVIDENCE ACQUISITION: A systematic review of the literature was performed using Medline (1966 to February 2011). Medical Subject Headings (MeSH) terms for search criteria included "bladder cancer, neoplasms" OR "carcinoma, transitional cell" AND all cost-related MeSH search terms. Studies evaluating the costs associated with of various diagnostic or treatment approaches were reviewed. EVIDENCE SYNTHESIS: Routine use of perioperative chemotherapy following complete transurethral resection of bladder tumor has been estimated to provide a cost savings. Routine office-based fulguration of small low-grade recurrences could decrease costs. Another potential important target for decreasing variation and cost lies in risk-modified surveillance strategies after initial bladder tumor removal to reduce the cost associated with frequent cystoscopic and radiographic procedures. Optimizing postoperative care after radical cystectomy has the potential to decrease length of stay and perioperative morbidity with substantial decreases in perioperative care expenses. The gemcitabine-cisplatin regimen has been estimated to result in a modest increase in cost effectiveness over methotrexate, vinblastine, doxorubicin, and cisplatin. Additional costs of therapies need to be balanced with effectiveness, and there are significant gaps in knowledge regarding optimal surveillance and treatment of both early and advanced bladder cancer. CONCLUSIONS: Regardless of disease severity, improvements in the efficiency of bladder cancer care to limit unnecessary interventions and optimize effective cancer treatment can reduce overall health care costs. Two scenarios where economic and comparative-effectiveness research is limited but would be most beneficial are (1) the management of NMIBC patients where excessive costs are due to vigilant surveillance strategies and (2) in patients with metastatic disease due to the enormous cost associated with late-stage and end-of-life care.

Long-term follow-up of patients with tumours of the renal pelvis and ureter: how often is a bladder tumour diagnosed after five tumour-free years?

OBJECTIVE: It is not known when cystoscopy follow-up should be terminated after surgery for tumours of the renal pelvis and ureter [upper urinary tract tumours (UUTTs)]. The aim of this study was to investigate the length of the interval from surgery to diagnosis of the first bladder tumour. MATERIAL AND METHODS: A review was performed of all 930 patients who were diagnosed with a UUTT from 1971 to 1998 in western Sweden. The time to the first bladder tumour was estimated using Kaplan--Meier analyses. Univariate and multivariate analyses of potential risk factors for bladder recurrence were performed. RESULTS: In total, 614 patients were treated surgically for a renal pelvic or ureteral tumour and underwent cystoscopy at least 3 months afterwards. Of these 614 patients,192 (31.3%) patients developed a bladder tumour after the upper tract surgery. The majority, 157 out of 192 patients (81.8%), were diagnosed during the first 2 years, an additional 24 patients (12.5%) during years 3--5 and 11 patients (5.7%) between years 5 and 20. A history of bladder tumours, large tumour diameter, carcinoma in situ and UUTT diagnosed during the last part of the study period were significant risk factors for bladder recurrence after upper tract surgery. CONCLUSION: Cystoscopy should be performed at short intervals during the first 2 years after surgery for a UUTT, in particular among patients with a history of bladder tumours. Late bladder recurrences are unusual; therefore, as a rule, follow-up cystoscopy should be terminated after 5 tumour-free years.

Long-term cancer-specific outcomes of TaG1 urothelial carcinoma of the bladder.

BACKGROUND: Few studies have investigated the natural history of TaG1 urothelial carcinoma of the bladder (UCB). OBJECTIVE: To assess the long-term outcomes of patients with TaG1 UCB and the impact of immediate postoperative instillation of chemotherapy (IPIC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 1447 patients with TaG1 UCB treated between 1996 and 2007 at eight centers. Median follow-up was 67.2 mo (interquartile range: 67.9). Patients were stratified into three European Association of Urology (EAU) guidelines risk categories; high-risk patients (n=11) were excluded. INTERVENTION: Transurethral resection of the bladder with or without IPIC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression models addressed factors associated with disease recurrence, disease progression, death of disease, and any-cause death. RESULTS AND LIMITATIONS: Of the 1436 patients, 601 (41.9%) and 835 (58.1%) were assigned to low- and intermediate-risk categories, respectively. The actuarial estimate of 5-yr recurrence-free survival was 56% (standard error: ± 1). Advancing age (p=0.04), tumor >3 cm (p=0.001), multiple tumors (p<0.001), and recurrent tumors (p<0.001) were independently associated with increased risk of disease recurrence, whereas IPIC was associated with decreased risk (p=0.001). The actuarial estimate of 5-yr progression-free survival was 95% ± 1. Advancing age (p<0.001) and multiple tumors (p=0.01) were independent risk factors for disease progression. Five-year cancer-specific survival was 98% ± 1. Advancing age (p=0.001) and previous recurrence (p=0.04) were associated with increased risk, whereas female gender (p=0.02) was associated with decreased risk of cancer-specific mortality. Compared with low-risk patients, intermediate-risk patients were at significantly higher risk of disease recurrence, disease progression, and cancer-specific mortality (all p<0.01). Limitations include the retrospective design of the study and the lack of a central pathology review. CONCLUSIONS: TaG1 UCB patients experience heterogeneous risks of disease recurrence. We validated the EAU guidelines risk stratification in TaG1 UCB patients. IPIC was associated with a reduced risk of disease recurrence in patients with low- and intermediate-risk TaG1 UCB.