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Objectives: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC)., Patients and Methods: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs., Results: The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk., Conclusions: These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

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.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

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.

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., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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.

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.

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.

Apolipoprotein (Apo) D is an important protein produced in many parts of the body. It is necessary for the development and repair of the brain and protection from oxidative stress. The purpose of this study was to investigate the extent to which apoD interacts with lipoproteins in human plasma. By using detergent-free ELISA, we show that immobilized monoclonal antibodies against apoD very efficiently bind to low density lipoprotein (LDL) from plasma; this binding is as equally efficient as binding to an anti-apoB monoclonal antibody. Adding detergent to the plasma inhibited the binding, suggesting that the binding is dependent on the presence of intact lipoprotein particles. Reversing the system by using immobilized anti-apoB revealed that the affinity of apoD for LDL is rather low, suggesting that multiple bindings are needed for a durable connection. Biosensor experiments using purified lipoproteins also showed that purified apoD and high density lipoprotein 3 (HDL3), a lipoprotein fraction rich in apoD, were both able to bind LDL very efficiently, indicating that the HDL3-LDL interaction may be a physiological consequence of the affinity of apoD for LDL. Furthermore, we found that apoD increases the binding of HDL to actively growing T24 bladder carcinoma cells but not to quiescent, contact-inhibited, confluent T24 cells. This result is especially intriguing given that the T24 supernatant only contained detectable levels of apoD after growth inhibition, raising the possibility that alternating the expression of apoD and a putative apoD-receptor could give direction to the flow of lipids. In the current paper, we conclude that apoD mediates binding of HDL to LDL and to growing T24 carcinomas, thereby highlighting the importance of apoD in lipid metabolism.

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., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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.

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.

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., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: This study evaluated the impact of hospital volume on local recurrence and distant metastasis in a population-based series of radical cystectomy patients in Sweden., Material and Methods: All patients who underwent cystectomy for bladder cancer in 1997-2002 in Sweden and were reported to the National Bladder Cancer Registry were included. A high-volume hospital (HVH) was defined as one with ≥10 cystectomies/year and a low-volume hospital (LVH) as one with <10 cystectomies/year. Information on preoperative tumour, node, metastasis (TNM) classification, operative procedure, postoperative course and follow-up was obtained from medical records., Results: Of the 1126 patients, 827 (74%) were males. The mean age was 66 years and median follow-up 47 months. Of the 610 (54%) HVH patients, 68 (11%) were pT0, 123 (20%) < pT2, 177 (29%) pT2, 242 (40%) > pT2 and 69 (11%) were microscopic non-radical. Corresponding figures for the 516 (46%) LVH patients were 35 (7%), 68 (13%), 191 (37%), 222 (43%) and 96 (19%). Local recurrence was observed in 245 patients (22%): 113 (19%) at HVHs and 132 (26%) at LVHs. Distant metastasis was found in 363 (32%): 203 (33%) at HVHs and 160 (31%) at LVHs. Perioperative chemotherapy was given to 193 (17%). Multivariate Cox proportional hazards analysis showed that local recurrence was associated with LVHs and non-organ-confined disease, whereas distant metastasis was correlated with non-organ-confined disease and lymph-node metastases., Conclusions: In this retrospective analysis, local tumour recurrence after cystectomy was common, particularly in patients with non-organ-confined disease. Furthermore, local recurrence was more frequent at LVHs than HVHs, and overall survival was better at HVHs. These findings suggest that concentrating cystectomies in HVHs may improve outcomes such as local recurrence and overall survival.

Purpose: An increasing body of evidence suggests gender differences in the presentation and prognosis of bladder cancer. We aimed to assess the impact of gender on outcomes in patients with primary T1 high-grade (HG) urothelial carcinoma of the bladder (UCB)., Methods: We retrospectively analysed the data from 916 patients with primary T1HG UCB from 7 tertiary care centres. Patients were treated with transurethral resection of the bladder with or without intravesical instillation therapy (IVT). Univariable and multivariable Cox regression analyses assessed the effect of gender on outcomes., Results: Within a median follow-up of 42.8 months, 365 (39.8 %) patients experienced disease recurrence, 104 (11.4 %) progression, 59 (6.4 %) cancer-specific mortality and 190 (20.7 %) mortality of any cause. Overall, 634 (69.2 %) patients received IVT of which 234 (25.5 %) received BCG therapy. Female gender (n = 190, 20.7 %) was associated with higher risk of disease recurrence (HR:1.359;1.071-1.724, p = 0.012) in all patients and in a subgroup of patients treated with BCG therapy (HR:1.717;1.101-2.677, p = 0.017). There was no difference between genders with regard to disease progression, cancer-specific mortality and any-cause mortality. In multivariable analyses that adjusted for the effects of concomitant carcinoma in situ (CIS), tumour size, number of tumours, and IVT, gender remained an independent predictor for disease recurrence (p = 0.026) when analysed in all patients, but not in the subgroup of BCG treated patients (p = 0.093)., Conclusions: In patients with T1HG UCB, female gender is associated with higher risk of disease recurrence, but not with disease progression. This gender disparity may be due to differences in care and/or biology of UCB.

Objective: According to current European Association of Urology (EAU) guidelines, a routine second transurethral resection (TUR) is mandatory in TaG3 and T1 tumours, but the scientific evidence is weak. The aim of this study was to report outcome data for patients not subjected or subjected to a routine second resection., Material and Methods: This retrospective study included 221 patients with a newly diagnosed TaG3 or T1 bladder cancer treated with intravesical bacillus Calmette-Guérin (BCG)., Results: A routine second resection or a repeat resection was done in 57 out of 221 patients (25.8%). During the first year, progression was diagnosed in 0/10 patients with TaG3, 2/12 with T1G2 and 5/35 with T1G3. Among 164 not subjected to a second resection, the progression rate during the first year was 0/56 for patients with TaG3, 1/30 for T1G2 and 8/78 for T1G3. The median age among all 16 patients with T1 tumours who progressed during the first year was 77.5 years (27-94 years). Twenty-five TURs (25/164, 15.2%) were performed among the 164 patients because of a tumour at the first cystoscopy. The majority (84/164, 51.2%) had no recurrences during a median follow-up of 45 months., Conclusions: The initial outcome was very good for TaG3 patients, so a routine re-resection may be unnecessary. However, progression among T1 patients was common, and therefore a re-resection should be strongly considered. The potential benefit of a second TUR should be weighed against costs and morbidity in a predominantly elderly population. The absence of prospective randomized studies is problematic.

Background: Characterising responders to neoadjuvant chemotherapy (NAC) is important to minimise overtreatment and the unnecessary delay of definitive treatment of urothelial urinary bladder cancer., Objective: To assess the effect of NAC on tumour downstaging and overall survival., Design, Setting, and Participants: A total of 449 patients from the randomised prospective Nordic Cystectomy Trials 1 and 2 were analysed retrospectively. Eligible patients were defined as T2-T4aNXM0 preoperatively and pT0-pT4aN0-N+M0 postoperatively. The median follow-up time was 5 yr., Intervention: The experimental arm consisted of cisplatin-based NAC; the control arm consisted of cystectomy only., Measurements: The primary outcome was tumour downstaging defined as pathologic TNM less than clinical TNM. Different downstaging thresholds were applied: complete downstaging (CD) (pT0N0), noninvasive downstaging (NID) (pT0/pTis/pTaN0), and organ confinement (OC) (≤ pT3aN0). Downstaging rates and nodal status were compared between the study arms using the chi-square test. Secondary outcome was overall survival (OS) stratified by treatment arm, downstaging categories, and clinical stages, analysed by the Kaplan-Meier method. The following covariates were tested as prognostic factors in univariate and multivariate analyses using the Cox regression method: age, sex, clinical stage, pN status, NAC, CD, NID, and OC., Results and Limitations: Downstaging rates increased significantly in the NAC arm independent of the downstaging threshold. The impact was more prominent in clinical T3 tumours, with a near threefold increase in CD tumours. The combination of CD and NAC showed an absolute risk reduction of 31.1% in OS at 5 yr compared with CD controls. The combination of NAC and CD revealed a hazard ratio of 0.32 compared with 1.0 for the combination of no NAC and no CD. Limitations were the retrospective approach and uncertain clinical TNM staging., Conclusions: Survival benefits of NAC are reflected in downstaging of the primary tumour. Chemo-induced downstaging might be a potential surrogate marker for OS., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: It is not known how long follow-up cystoscopy in tumour-free bacillus Calmette-Guérin (BCG)-treated patients should continue., Objective: Determine the incidence of late recurrences and progression after a tumour-free period of >5 yr after BCG treatment., Design, Setting, and Participants: Data on 542 patients with non-muscle-invasive bladder cancer treated with BCG between 1986 and 2003 were analysed. Of 542 patients, 204 patients (37.6%) were tumour-free for ≥5 yr. The median tumour-free period was 105.5 mo (range: 60-252 mo)., Measurements: To compare the tumour-free group with patients who were not tumour-free for 5 yr, traditional variables (tumour grade, tumour stage, age, gender, tumour number and size, primary or recurrent tumour, BCG strain, previous chemotherapy, previous upper tract tumour, number of earlier resections, and European Organisation for Research and Treatment of Cancer recurrence and progression risk groups) were analysed using the Fisher exact test for dichotomous variables, the Mantel-Haenszel chi-square test for ordered categorical variables, and the Mann-Whitney U-test for continuous variables. Kaplan-Meier curves for time to recurrence were constructed using Statistica software (StatSoft, Tulsa, Oklahoma, USA). Differences between groups were tested with the log-rank test. For continuous variables, Cox proportional hazard regression was performed to find significant effect on the time to recurrence., Results and Limitations: Twenty-two of 204 patients (10.8%) had a recurrence after being tumour-free for ≥5 yr. The Kaplan-Meier estimated risk for recurrence was 12.5% at 10 yr and 20.5% at 15 yr. Among patients with TaG1-TaG2 before BCG, 11 of 79 patients (13.9%) had recurrences, including three patients with invasive extravesical tumours. Among the bladder recurrences were seven TaG1s and one carcinoma in situ (CIS). Among the 125 patients with TaG3/CIS/T1 before BCG, 11 patients (8.8%) had recurrences, including 2 patients with invasive ureter tumours. The bladder recurrences were one T2, four CIS, and four TaG1. Late recurrences were 8.5 times more common among patients with recurrent tumours before BCG compared with patients treated after their first tumour episode. The study was retrospective and nonrandomised but unselected and population-based., Conclusions: A tumour-free period of 5 yr after BCG treatment is a good prognostic sign, but recurrences after >10 yr are not unusual. Literature data and the present report support cystoscopy follow-up for ≥10-15 tumour-free years, at least among patients with recurrent tumours and/or high-grade lesions before BCG treatment., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate outcome after radical cystectomy for primary bladder cancer in a large population-based material., Material and Methods: Between 1997 and 2002 all patients treated with radical cystectomy within 3 months after diagnosis of primary bladder cancer without distant metastasis were retrieved through the Swedish Bladder Cancer Registry. A follow-up questionnaire was distributed to all units where the primary registration of patients was performed. Follow-up data on recurrence date were retrieved from the patient charts and causes of death were obtained from the Swedish Cause of Death Registry until 2003., Results: During the study period radical cystectomy was performed in 39 units in Sweden, of which only five units were considered high-volume hospitals performing 10 or more procedures annually. Mean blood loss was 2300 ml (median 2000 ml) and the 90-day mortality rate was 5.7%. Blood loss was higher in high-volume units than in hospitals with lower hospital volumes, but the 90-day mortality rates were similar. During a median follow-up of 3.5 years, 24% of the patients were submitted to a reoperation. Reoperation rates were significantly higher in patients who received a continent urinary diversion (29%) compared with an ileal conduit (22%, p < 0.015)., Conclusions: Radical cystectomy was associated with a reoperation rate of 24% in Sweden during the study period. The reoperation rates were higher in patients receiving a continent cutaneous diversion or bladder substitution. Blood loss was higher in high-volume units; otherwise, surgical volume did not affect mortality rates, cancer-specific survival or reoperation rates.

Objective: • To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions., Patients and Methods: • During their follow-up we attempted to contact all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. • During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with free-hand comments. The patients completed the questionnaire at home. • Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval., Results: • The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). • A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively., Conclusions: • Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). • Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: • To report a late bacille Calmette-Guérin (BCG) complication previously not described in the literature., Patients and Methods: • We reviewed our database with 858 patients treated with BCG from 1986 to 2008 and identified 13 male patients (1.8% of all male patients) who had a large tuberculous-like bladder ulcer., Results: • All patients had high-grade tumours and seven had tumours invading lamina propria before BCG treatment. A solitary ulceration or inflammatory lesion, 10-50 mm in diameter, was seen at routine follow-up cystoscopy 2-34 months (median 8 months) after the first instillation. Significantly more patients had been treated with BCG-RIVM than with BCG-Tice (10/320 vs. three of 454, P < 0.01). BCG was cultured from urine 3-34 months (median 14 months) after the last instillation. • So far, eight patients have been successfully treated with rifampicin and isoniazid. Nine patients are still tumour-free 15-66 months (median 44 months) after the last transurethral resection before BCG treatment. • Another three patients had one to two non-invasive recurrences. One patient had an invasive recurrence and underwent cystectomy. The present study is limited by biases associated with its retrospective design., Conclusions: • This is the first report on persisting BCG infections with large inflammatory lesions in the bladder. Treatment is effective and the oncological outcome is good. • Mycobacterial cultures of the urine should be performed in BCG-patients with unclear inflammatory lesions in the bladder since a delayed diagnosis of a persistent BCG infection could result in a permanently reduced bladder capacity. • Large studies are warranted to study differences in efficacy and side-effects between different BCG strains., (© 2010 THE AUTHORS; BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Purpose: Patients with Lynch syndrome are much more likely to have generally rare upper urinary tract urothelial carcinoma but not bladder urothelial carcinoma. While the risk has been quantified, to our knowledge there is no description of how this population of patients with Lynch syndrome and upper urinary tract cancer differs from the general population with upper urinary tract cancer., Materials and Methods: We obtained retrospective data on a cohort of patients with Lynch syndrome from the Hereditary Cancer Center in Omaha, Nebraska and compared the data to those on a control general population from western Sweden. These data were supplemented by a new survey about exposure to known risk factors., Results: Of the patients with Lynch syndrome 91% had mutations in MSH2 rather than in MSH1 and 79% showed upper tract urothelial carcinoma a mean of 15.85 years after prior Lynch syndrome-type cancer. Median age at diagnosis was 62 years vs 70 in the general population (p <0.0001). Only half of our patients had a significant smoking history and the male-to-female ratio was 0.95. Of patients with Lynch syndrome 51% had urothelial carcinoma in the ureter while it occurred in the renal pelvis in 65% of the general population (p = 0.0013). Similar numbers of high grade tumors were found in the Lynch syndrome and general populations (88% and 74%, respectively, p = 0.1108)., Conclusions: Upper urinary tract tumors develop at a younger age and are more likely to be in the ureter with an almost equal gender ratio in patients with Lynch syndrome. It has high grade potential similar to that in the general population., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine whether or not an improved hygiene can lessen the incidence of symptomatic urinary tract infections (UTIs) in patients treated by cystectomy for urinary bladder cancer., Patients and Methods: We attempted to contact during their follow-up all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified hygienic measures and included them in a study-specific questionnaire. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results presented as relative risks (RR) with 95% confidence interval., Results: We received the questionnaire from 452 (92%) of 491 identified patients. The proportion of patients who had a symptomatic UTI in the previous year was 22% for orthotopic neobladder and cutaneous continent reservoir, and 23% for non-continent urostomy diversion. The RR for a UTI was 1.1 (0.5-2.5) for 'never washing hands' before handling with catheters or ostomy material. Patients with diabetes mellitus had a RR of 2.1 (1.4-3.2) for having a symptomatic UTI., Conclusions: We could not confirm lack of hygiene measures as a cause of UTI for men and women who had a cystectomy with urinary diversion. Patients with diabetes mellitus have a greater risk of contracting a UTI., (© 2009 THE AUTHORS. JOURNAL COMPILATION © 2009 BJU INTERNATIONAL.)

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.

Background: Fluorescent light (FL)-guided cystoscopy induced by 5-aminolevulinic acid (5-ALA) has been reported to detect more tumours compared with standard white-light (WL) cystoscopy. Most reports are from single centres with relatively few patients., Objective: To evaluate whether 5-ALA-induced FL and WL cystoscopy at transurethral resection (TUR) is superior compared with standard procedures under WL only with respect to tumour recurrence and progression in patients with non-muscle-invasive bladder cancer., Design, Setting, and Participants: This randomised, multicentre, observer- and pathologist-blinded, prospective phase 3 clinical trial enrolled 300 patients, and of those patients, 153 were randomised to FL cystoscopy and 147 were randomised to standard WL cystoscopy., Intervention: All patients were first inspected under WL and all lesions were recorded. Patients randomised to FL underwent a second inspection. TUR was carried out in both groups., Measurements: Control cystoscopy under WL was performed in all patients every 3 mo during the first year after randomisation and biannually thereafter., Results and Limitations: At the first TUR, the mean number of resection specimens per patient was 2.5 (FL: 2.5; WL: 2.4; p=0.37) and the resulting mean number of resected tumours was 1.7 with FL and 1.8 with WL (p=0.85). More patients were diagnosed with carcinoma in situ (CIS) in the WL group (13%) than in the FL group (4.2%). Within-patient comparison of FL patients only showed that FL detected more lesions than WL. Tumour lesions solely detected by FL cystoscopy that would not otherwise be detected by WL cystoscopy included 52% dysplasia, 33% CIS, 18% papillary neoplasms, 13% pT1, and 7% pTa. Outcome at 12 mo did not show any difference between groups with regard to recurrence-free and progression-free survival rates., Conclusions: In this prospective, randomised, multi-institutional study, we found no clinical advantage of FL cystoscopy compared with WL cystoscopy and TUR., (Copyright 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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.

Purpose: We studied whether a single instillation of epirubicin after transurethral bladder tumor resection would influence the interval to and size of the first recurrence., Materials and Methods: A total of 404 patients from 13 hospitals were randomized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors., Results: Of 155 evaluable patients in the epirubicin group 79 (51.0%) had recurrence compared to 95 of 152 (62.5%) in the placebo group (p = 0.04). Of the recurrences 63.3% were small (1 to 5 mm). Tumor size was unknown in 5 patients. Of 79 patients with recurrence in the epirubicin arm 33 (42.9%) vs 29 (31.5%) of 95 in the placebo arm had larger (more than 5 mm) first recurrences (p = 0.12). Approximately half of the patients with first recurrences were treated as outpatients and the other half spent a total of 145 days in the hospital with no difference between the groups., Conclusions: We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent 1 recurrence. Furthermore, our data may indicate that only small recurrences are prevented, which could easily be fulgurated using local anesthesia at followup cystoscopy. The benefit of single instillations can be questioned if this finding is confirmed by others.

Objectives: We studied the prognostic factors for progression and disease-specific survival in patients with Stage T1 bladder cancer to identify subgroups with different prognoses., Methods: All 121 patients with Stage T1 bladder cancer at first diagnosis in 1987 to 1988 in a large region were prospectively registered. The histopathologic material and the clinical records were reviewed. We performed univariate and multivariate analyses of the clinical and pathologic factors of potential significance for the time to progression and disease-specific survival. At the end of the study, only 18 patients (15%) were alive and had been followed up for a median of 15 years., Results: On univariate analysis, vascular invasion, solid tumor pattern, deep invasion, grade 3 disease, and carcinoma in situ were associated with an increased risk of progression. The multivariate analysis showed that only vascular invasion and tumor pattern had independent prognostic value for progression. Vascular invasion and a solid tumor pattern also had independent prognostic value for disease-specific survival., Conclusions: Patients who have Stage T1 bladder cancer with a solid tumor pattern and/or vascular invasion have a very poor prognosis when treated with transurethral resection only. It is unknown whether intravesical bacille Calmette-Guérin treatment can improve the poor prognosis in such cases.

Objective: To report the side-effects after a reduction in the dwell-time in patients who had pronounced symptoms after intravesical bacillus Calmette-Guèrin (BCG) treatment, as side-effects such as fever, haematuria, and frequency are common and sometimes severe after BCG treatment in patients with bladder cancer., Patients and Methods: The dwell-time was reduced to < or = 30 min in 51 patients who had pronounced side-effects after the preceding BCG instillation. All patients self-reported side-effects after each instillation in a questionnaire., Results: After reducing the BCG dwell-time, fever, chills, dysuria and the overall time-to-recovery were significantly reduced but frequency and haematuria were not influenced. Patients with carcinoma in situ had significantly less dysuria than patients with papillary tumours. There was no difference in the treatment results between patients who had a normal dwell-time and a reduced dwell-time, determined at the first and second follow-up cystoscopy., Conclusion: Reducing the BCG dwell-time to < or = 30 min could be an alternative to a dose reduction in patients who experience pronounced side-effects after BCG instillations. The long-term outcome after reducing dwell-time and after dose reduction has not been studied and warrants further investigation.

Objective: It is routine procedure to obtain a urogram or retrograde stentogram 1-2 weeks after urinary diversion. The purpose of this is to diagnose silent urinary leakage and obstruction of the anastomosis. We registered the frequency of significant findings at routine postoperative urography in patients with bladder cancer treated with radical cystectomy and urinary diversion., Material and Methods: We identified a total of 200 consecutive patients who were treated with radical cystectomy and urinary diversion between 1994 and 2002. Eight patients were never evaluated radiologically and another 14 were examined earlier than planned due to symptoms or signs from the urinary tract and abdomen. The remaining 178 patients underwent a routine radiological examination. The methods of deviation in these patients were Bricker conduit (n=119), continent abdominal reservoir (n=24) and orthotopic bladder reconstruction (n=35). A total of 170 patients underwent urography, seven underwent bilateral retrograde pyelographies and one was examined by means of antegrade pyelography., Results: Not a single significant finding was identified with urography in 170 patients. Minimal leakage was identified at retrograde pyelography in one patient with a Bricker conduit, which resulted in treatment for 2 weeks with a pyelostomy catheter., Conclusion: Routine postoperative urography is not necessary in patients who have a normal postoperative course after cystectomy and urinary diversion.

Objective: The total costs of radical cystectomy comprise a significant part of the total costs of bladder cancer treatment. The aims of this study were to determine the costs of cystectomy, with and without complications, and to investigate related prognostic factors., Material and Methods: The clinical records and relevant economic files of 70 consecutive patients operated on between 1994 and 1998 were studied. Uni- and multivariate analyses were performed on 22 variables of possible prognostic significance to high total costs., Results: The total (median) costs for 53 uncomplicated and 17 complicated cystectomies were 181,096 and 290,625 SEK, respectively. The preoperative variables (patient characteristics) had no or minimal prognostic significance for high total costs. High peri-operative blood loss was the most important factor associated with high total hospital costs for radical cystectomy., Conclusions: Total costs may be very high for a cystectomy with complications. Peri-operative blood loss was the most important factor associated with high total hospital costs for radical cystectomy due to bladder cancer. If the amount of bleeding can be influenced then substantial reductions in the total costs of cystectomy would seem possible.

Objectives: A Nordic collaborative group assessed the effectiveness of cisplatinum based combination chemotherapy prior to cystectomy in two consecutive trials. We analyzed overall survival in all patients and in prespecified subgroups defined by preoperative T-stage, gender and age., Methods: The studies included in 1985-1997 620 patients with clinically T1G3, T2-T4aNXM0 urothelial bladder cancer and WHO performance

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.

Purpose: We recorded initial symptoms and evaluated the frequency and intensity of hematuria in patients with newly diagnosed bladder cancer. We also evaluated and compared the sensitivity of bladder wash cytology, NMP22 (Matritech, Newton, Massachusetts), BTA Stat (Bion Diagnostic Sciences, Redmond, Washington) and UBC antigen (IDL Biotech, Sollentona, Sweden) with hematuria dipsticks and flow cytometry for determining the size of erythrocytes in urine., Materials and Methods: Urine samples were collected from 92 patients with newly diagnosed bladder cancer, 64 with idiopathic microhematuria and 42 with nephritis. Urine was analyzed for NMP22, BTA Stat, UBC and erythrocytes size using flow cytometry. Bladder wash cytology was done at cystoscopy. Urine was analyzed for microhematuria with hematuria dipsticks at home for 7 consecutive days immediately before the operation and in the hospital on the day of surgery., Results: Sensitivity was 75% for NMP22, 78% for BTA Stat, 64% for UBC and 61% for flow cytometry at 73% specificity. Cytology had 42% sensitivity at 97% specificity. Tumor size, grade and stage had a statistically significant influence on NMP22, BTA Stat, UBC and cytology. Of the patients 75% had microhematuria on the day of the operation and 75% had hematuria at least 1 of 7 days when tested at home the last week before transurethral bladder resection. The 70% of all patients with macroscopic hematuria as the initial symptom did not seem to differ from those without the condition in tumor size, grade, stage or tumor marker levels., Conclusions: Flow cytometry was not well enough able to distinguish patients with bladder cancer from controls. The sensitivity of all tested markers, including hematuria dipsticks, was high for large and high grade, high stage tumors. Further studies are needed to evaluate whether a marker could be used to determine priority among patients referred due to microhematuria.

Purpose: We studied the relationship of first cystoscopy findings with recurrence and progression rates in a large, population based series of patients with bladder cancer., Materials and Methods: All 463 patients with an initial diagnosis of stage Ta-T1 bladder cancer in western Sweden in 1987 to 1988 were followed at least 5 years. The 355 patients who were treated with transurethral resection only until repeat cystoscopy or longer were selected for this report., Results: Negative first cystoscopy findings were associated with significantly decreased recurrence and progression rates for all grades, and for stage Ta and T1 tumors. However, some patients with initial high grade carcinoma (WHO 2 to 3) had stage progression despite negative first cystoscopy. On multivariate analyses first cystoscopy findings and papillary urothelial neoplasm of low malignant potential versus grades 1 to 3 but not stage and the number of tumors had prognostic significance for time to recurrence. Only first cystoscopy findings and grade had prognostic significance for time to stage progression., Conclusions: Our data support other groups who recommend a less intense cystoscopy followup schedule in patients with negative cystoscopy findings 3 months after initial transurethral bladder resection. We recommend that patients with initial papillary urothelial neoplasm of low malignant potential and low grade carcinoma (WHO 1) with negative first cystoscopy findings undergo repeat cystoscopy at month 12. In our opinion followup should not be less intense in patients with high grade carcinoma (WHO 2-3), even in those with stage pTa disease.

Background: In a previous study we reported on a new approach describing intravesical instillation of charged dextran in patients with superficial bladder carcinoma. The cationic derivative showed a strong tumor-selective accumulation. To develop this approach, the present study investigates the cytotoxic effect of cationic dextran derivatives on two urinary bladder cancer cell lines (J82 and 5637)., Methods: The dextran conjugates were prepared by periodate activation and subsequent coupling by reductive amination. A fluorimetric cytotoxicity assay (FMCA) was used for the cytotoxicity assay. The tumor cells were seeded into 96-well microtiter plates and different cationic dextran derivatives were added and incubated for 72 hours., Results: The results showed that cationic epirubicin-dextran had a clear inhibitory effect on the growth in both cell lines (40-95% growth inhibition). The corresponding values for epirubicin (the reference) was 90-100% inhibition. Interestingly, cationic dextran had, by itself, a growth inhibitory effect. This cytotoxic effect could be strongly enhanced to be almost equal to the reference by changing the cationic sidegroup to aminohexane. Dextran alone showed no effect., Conclusion: The finding that cationic dextran by itself can be made cytotoxic, together with its capacity to accumulate in superficial bladder cancer, suggests possibilities for new therapeutic constructs. Cationic dextran with different cationic side-groups and in combination with cytotoxic drugs will be studied further. The cytotoxic mechanism needs to be elucidated.

Background: In the first Nordic cystectomy trial (1986-1989) a chemotherapy combination of cisplatin-doxorubicin and external radiation seemed to improve the long-term survival after cystectomy in patients with stage T3-T4a bladder carcinomas. The aim of this study was to investigate if solely neoadjuvant chemotherapy could influence survival in patients with advanced urothelial bladder cancer undergoing cystectomy., Methods: The study (1991-1997) recruited 317 patients with T2-T4aNXM0 urothelial bladder tumours. The patients were randomly allocated to three courses of cisplatin-methotrexate or no pretreatment before cystectomy, eight were subsequently excluded due to protocol violation., Results: Chemotherapy according to protocol was administered to 74% (115/155) of the patients in the experimental arm. No chemotherapy related mortality was observed. Of remaining patients in the experimental arm, 14 did not receive any chemotherapy, nine discontinued after one course and 14 after two courses due to side effects. Median follow-up time among censored patients was 5.3 years. Estimated 5-year overall survival was 53% in the experimental arm and 46% in the control arm (n.s. log-rank test). The proportion of patients with pathological stage pT0 was 26.4% in the experimental arm and 11.5% in the control arm (p = 0.001). Risk of locoregional relapse and distant metastases was similar in the study arms., Conclusions: The chemotherapy regimen was well tolerated. Despite substantial downstaging no statistically significant survival benefit with the neoadjuvant therapy could be seen after 5 years of follow-up.

Objective: To evaluate the costs of bladder tumour treatment and follow-up., Material and Methods: The incidence of bladder tumours, both new and recurrences, and the cost of bladder tumour treatments with curative intent were registered during a 4-year period (1994-97)., Results: The incidence of new tumours varied from year to year, in contrast to the number of recurrent tumours, which remained remarkably stable. The total cost of bladder cancer diagnosis, treatment and follow-up was almost 7,000,000 SEK per year (2,800,000 SEK per 100,000 inhabitants per year). The number of therapeutic events per year remained stable at 256 +/- 17 (102 per 100,000 inhabitants per year). Cystectomies were responsible for 34% of the expenditure and transurethral procedures for 40%. Follow-up cystoscopies accounted for only 13% of the total cost. One-third of the routine follow-up cystoscopies resulted in a therapeutic procedure. The cost of transurethral resections and extirpations was approximately five times higher when performed with the patient hospitalized compared to when performed as day-care surgery., Conclusions: A reduction in the number of follow-up cystoscopies will only produce marginal economic savings. Further savings could be made if more transurethral resections and extirpations/fulgurations were performed on an outpatient basis. Another important goal is to reduce the median cost per cystectomy.

Purpose: We determine the sensitivity and specificity of 3 bladder tumor markers in urine, including NMP22 assay (Matritech, Newton, Massachusetts), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and UBC antigen (IDL Biotech, Sollentuna, Sweden), and bladder wash cytology for new and recurrent bladder cancer. We examine whether tumor size, grade, and stage influence sensitivity and specificity of the markers., Materials and Methods: A total of 304 samples in 250 patients were studied. There were 174 patients who had a history of bladder cancer, including 93 with and 81 without recurrent tumor at cystoscopy. The other group of patients consisted of 66 with newly diagnosed bladder tumor and 64 investigated for microscopic hematuria that was found to be idiopathic. BTA stat was assayed according to manufacturer instructions. NMP22 and UBC were measured in urine with an enzyme-linked immunosorbent assay. A cutoff level of 4 for NMP22 and 1 for UBC was chosen to get the same specificity for new tumors as BTA stat (75%), Results: There was a highly significant difference (p <0.001) in all markers between patients with new bladder tumors and those without. The difference was less pronounced for tumor recurrence for NMP22, UBC and BTA stat (p=0.002, 0.016 and 0.244, respectively). The difference between new and recurrent tumors disappeared when corrected for tumor size, grade and stage. The sensitivity for new tumors was 65%, 75% and 60% for NMP22, BTA stat and UBC, respectively. Cytology had a sensitivity of 41% for new tumors at a specificity of 94%. The specificity for recurrence was 64% for NMP22, 54% BTA stat and 72% UBC. The sensitivity was 45% for NMP22, 55% BTA stat and 40% UBC., Conclusions: Tumor size, grade and stage have a strong impact on sensitivity, and specificity for all 3 tested tumor markers as well as bladder wash cytology. The tumor markers or any combination of them cannot replace followup cystoscopy, mainly because most recurrences are small. The role of the markers for screening high risk populations and as a complement to followup cystoscopy remains to be evaluated.