To Örebro University

The European Association of Urology (EAU) 2021 prognostic model for non-muscle-invasive bladder cancer (NMIBC) is based on the World Health Organization (WHO) 1973 and/or WHO 2004/2022 grading systems for patients who did not receive bacillus Calmette-Gu & eacute;rin (BCG) instillations and is widely used to assess the risk of progression. The estimated risk of progression affects the type of adjuvant intravesical instillation (chemotherapy or BCG), with primary radical cystectomy recommended for patients with the highest risk of progression. We applied the EAU 2021 prognostic model in a population-based setting for 3392 patients with primary NMIBC diagnosed in 2013-2014 according to the BladderBaSe 2.0 database. We assessed the model calibration by comparing the 5-yr progression probability observed in our cohort with the predicted progression probability assigned for the risk groups in the original EAU study, and evaluated the discrimination according to Harrell's C index. At 5-yr follow-up, 394 patients had experienced disease progression. The progression probability observed was 4.9% (95% confidence interval [CI] 3.5-6.3%), 8.6% (95% CI 6.9-10%), 25% (95% CI 22-28%), and 23% (95% CI 14-30%) for the low-, intermediate-, high-, and very high-risk groups, respectively. The discrimination at 5 yr was 0.72 (95% CI 0.69-0.78) for the overall cohort and 0.74 (95% CI 0.70-0.80) in the group excluding the 811 patients who received BCG instillations. Showing moderate predictive ability, the EAU 2021 prognostic model has clinical utility in population-based settings despite underestimation of the observed progression risk in the low-and high-risk groups in the current study. Patient summary: W of non-muscle-invasive bladder cancer using results for a group of Swedish patients. Approxim more advanced dis e looked at how well a model predicted the risk of progression ately one in four patients in the high-risk category progress to ease within 5 yr. Doctors and patients need to consider the probability of progr on which treatment ess ion in the high-risk category when making shared decisions is best for an individual patient. (c) 2025 The Author(s). Urology. This is an op Published by Elsevier B.V. on behalf of European Association of en access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

OBJECTIVE: To estimate the probability of vaginal events (diagnosis and/or surgery) following radical cystectomy (RC) and explore possible risk factors in a nationwide population-based observational registry based study.

PATIENTS AND METHODS: Women undergoing RC for urinary bladder cancer in Sweden, from 1 January 1997 to 31 December 2019, were identified within national registries. Women with any postoperative vaginal event (PVE), either a diagnosis or surgical repair related to a vaginal complication, were identified using diagnostic and treatment codes. The probability of developing a PVE was estimated based on the cumulative incidence proportion using a competing risk model. Additionally, a multivariable Cox proportional hazards model was used to explore the risk factors for PVEs. Subgroup analysis was performed in patients operated from 2011 to 2019, where additional perioperative variables were registered.

RESULTS: The study encompassed 1914 women with a median age of 69 years at the time of bladder cancer diagnosis. The 5-year cumulative risk of PVEs in the entire cohort was 11% (95% confidence interval [CI] 9.5-12.5%). Subgroup analysis showed that robot-assisted RC and a body mass index (BMI) >30 kg/m2 were more often associated with PVEs after RC (hazard ratio [HR] 2.82, 95% CI 1.81-4.40; and HR 1.71, 95% CI 1.05-2.79, respectively).

CONCLUSIONS: A clinically relevant cumulative incidence of PVEs following RC was identified. An association between robot-assisted RC or high BMI with increased risk of a PVE indicate the need for further studies on risk assessment of vaginal complications.

BACKGROUND AND PURPOSE: The Measure of Case-Discussion Complexity (MeDiC) tool was created to gauge case complexity at multidisciplinary team meetings (MDTM) for case selection and prioritization. We aimed to assess applicability and association with MeDiC score and non-compliance with national guideline-recommendations for MDTM referral in a bladder cancer setting.

MATERIAL AND METHODS: A modified MeDiC scoring system was applied in 8955 subjects with localized (T1-T4N0M0) or metastasized disease as per the Bladder Cancer Data Base Sweden (BladderBaSe) 2.0. Association between MeDiC score and not being discussed at MDTM was investigated by multivariable logistic regression, and further explored in relation to calendar time period, healthcare region, age at diagnosis and hospital volume.

RESULTS AND INTERPRETATION: Median total MeDiC score was lower in individuals not being discussed at an MDTM (7.0 Inter Quartile Range [IQR] 6.0-9.0) compared to those who were (8.0 IQR 6.0-10.0). Adjusted odds ratio for not being discussed at an MDTM was 2.1 (95% confidence interval [CI] 1.8-2.4) for a MeDiC score in the lower quartile, as compared to the highest quartile, with higher estimates when performing stratified analyses in later calendar years and in specific healthcare regions. Our data indicate that the MeDiC score is applicable in bladder cancer patients, and we identified an association between lower MeDiC score and not being discussed at an MDTM.

The reliability of molecular diagnostic and prognostic tools is contingent on the quality of biospecimens, which are often collected during surgical procedures. This study investigated the impact of surgical manipulation on gene expression in the urinary bladder mucosa during radical cystectomy. Seventeen patients with urinary bladder cancer were enrolled, and paired pre- and post-surgery biopsies were analyzed. Pre-surgical biopsies were obtained in situ under anesthesia, while post-surgical biopsies were collected ex vivo following bladder removal. Total RNA was extracted, and gene expression was assessed using qPCR arrays, measuring the expression of 374 inflammation-related genes. The findings from the exploratory phase were further validated by analyzing key genes in an independent patient cohort using TaqMan® gene-specific assays. Exploratory analysis revealed significant differential expression in 27 genes, with key genes such as IL6, FOS, and PTGS2 being upregulated post-surgery. Validation of five selected genes in an independent cohort confirmed these findings. This study reinforces the necessity of accounting for surgery-induced alterations in gene expression when analyzing tissue samples collected intraoperatively. By elucidating the molecular impact of surgical interventions, this work provides critical insights for refining experimental methodologies and enhancing the interpretability of gene expression studies in clinical and research settings.

OBJECTIVES: To investigate the risk of upper urinary tract urothelial carcinoma (UTUC) in patients with non-muscle-invasive bladder cancer (NMIBC), in relation to the primary NMIBC tumour risk categories, calendar time trends and intravesical Bacillus Calmette-Guerin (BCG) treatment.

PATIENT AND METHODS: All patients with primary NMIBC diagnosed 1997-2019 registered in Bladder Cancer Data base Sweden (BladderBaSe) 2.0 were included in the study. Risk of UTUC was calculated by cumulative incidence proportion using competing risk analysis. Associations with risk of UTUC by tumour stage category, calendar time, and intravesical BCG treatment was estimated by hazard ratios from multivariable Cox regression analyses.

RESULTS: Of 36 038 NMIBC patients, 537 (1.5%) were diagnosed with UTUC during a mean time of 7 years in follow-up. The risk of UTUC within 10 years from NMIBC diagnosis was 1.7% (95% 1.6-1.9) with highest estimates for TaG3/CIS. Stage T1 and TaG3/CIS, as compared with TaG1-2 was associated to risk, with stronger associations during later calendar times. Within high-risk NMIBC patients (CIS/TaG3/T1), intravesical BCG treatment was associated with higher risk of UTUC.

CONCLUSIONS: This large study of more than 36 000 patients with NMIBC found 1.7% (95% 1.6-1.9) risk of UTUC within 10 years of diagnosis. Differences by tumour stage category indicate the need for refined studies accounting for tumour characteristics, location in the bladder and given treatment to optimise follow-up routines in NMIBC.

OBJECTIVE: To overview and summarise the Swedish National Guidelines on Urothelial Carcinoma 2024.

METHODS: A narrative review of the updated guidelines was performed, highlighting new treatment recommendations for advanced and metastasized disease. 

Results: Compared to the previous guideline version, the current update includes recommendations for standardised radiological reporting when urothelial carcinomas are detected at CT-urography (CTU), to early identify locally advanced patients and accelerate the care pathway for these patients. The Swedish guidelines apply a more structured and liberal recommendation for the use of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in patients with locally advanced urothelial carcinomas compared to the EAU-guidelines and recommend such examinations prior to transurethral resection. Improved outcomes for radical cystectomy in Sweden after centralised cystectomy care have led to a recommendation for performing more than six nephroureterectomies (NUs) per year for upper tract urothelial carcinomas (UTUC)-based associations with decreased use of invasive diagnostic modalities and better survival outcomes. Additionally, updated recommendations regarding adjuvant systemic therapies for muscle-invasive disease have been included. Whilst awaiting national regulatory approval for enfortumab vedotin/pembrolizumab, the present guideline version aligns with EAU-guidelines by endorsing cisplatin-gemcitabine-nivolumab as a new first-line treatment option in cisplatin-fit patients with unresectable or metastatic urothelial carcinoma.

CONCLUSIONS: The current version of the Swedish national guidelines on urothelial carcinoma introduces standardised reporting at CTU to facilitate early identification of advanced disease, includes recommendations for centralisation of NU for UTUC and updated recommendations for adjuvant systemic treatment of muscle-invasive disease and endorses cisplatin-gemcitabine-nivolumab as a new first-line treatment option for non-resectable locally advanced and metastatic disease.

BACKGROUND AND OBJECTIVE: It has been suggested that urinary tract infections (UTIs) are associated with delayed diagnosis of bladder cancer (BC). Our aim was to investigate prediagnostic treatments related to UTI and the relation to BC diagnostic delay, reflected by advanced disease at diagnosis. METHODS: We used data from the BladderBaSe 2.0 with data of treatments related to UTI up to 3 yr before BC diagnosis (2008-2019) for BC patients in comparison to a matched reference population. We investigated the association between UTI treatments and more advanced disease at diagnosis in the BC cohort. We used generalized ordered logistic regression to calculate odds ratios (ORs) for more advanced disease as an ordered outcome: non-muscle-invasive BC (NMIBC), muscle-invasive BC (MIBC), and metastatic BC (MBC). KEY

FINDINGS AND LIMITATIONS: The study population included 29 921 BC patients and 149 467 matched reference subjects. The proportions of individuals receiving UTI treatment were higher in the patient groups than in the corresponding reference groups, with the greatest differences observed for the MIBC and MBC subgroups. The OR for the risk of more advanced disease (MIBC or MBC) with at least one UTI treatment versus none was 1.28 (95% confidence interval [CI] 1.19-1.37) for men and 1.42 (95 % CI 1.27-1.58) for women. The association to risk of more advanced disease increased with the number of UTI treatments for both sexes.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Further studies on the effects of treatments related to UTI in combination with other factors are needed to identify reasons for possible delays in the BC diagnostic pathway. PATIENT SUMMARY: We found that for patients with bladder cancer, previous antibiotic treatment for a urinary tract infection was linked to more advanced disease at diagnosis. Further studies are needed to identify reasons for possible delays in the diagnosis of bladder cancer.

OBJECTIVES: To investigate the association between waiting time and outcomes in patients with upper tract urothelial carcinomas (UTUC).

PATIENTS AND METHODS: We studied a population-based cohort of 858 patients in BladderBaSe 2.0 subjected to extirpative surgery for UTUC 2015-2019 in Sweden. Diagnostic waiting time (from referral to diagnosis, reference <1 week), treatment waiting time (from diagnosis to surgery, reference <5 weeks) and total waiting time (reference <10 weeks) were investigated in relation to disease-specific (DSS) and overall survival (OS) by multivariable Cox regression models. To further explore these associations, stage progression from preoperatively recorded clinical tumour stage to pathological tumour stage in the extirpated specimen was assessed by logistic regression.

RESULTS: Total waiting time was not associated with DSS, OS or stage progression. A diagnostic waiting time between 1 and 4 weeks was associated with better DSS (HR 0.57 [95% CI 0.35-0.94]) and OS (HR 0.60 [95% CI 0.41-0.87]). In the strata of patients with UTUC in the renal pelvis, a diagnostic waiting time > 4 weeks was associated with stage progression (OR 2.44 [95% CI 1.00-5.95]), and in patients with UTUC in the ureter, a treatment waiting time between 5 and 10 weeks was associated to worse DSS (HR 2.85 (95% CI 1.03-7.89).

CONCLUSIONS: In general, shorter care pathways were linked to beneficial survival estimates, yet some estimates may be influenced by selection bias due to prioritizing short waiting times for patients with advanced and/or overt symptomatic tumours. Stage progression with increased waiting time may indicate an underlying causal mechanism.

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.