Risk of prostate cancer death in men diagnosed with prostate cancer at cystoprostat-ectomy. A nationwide population-based study.

BACKGROUND AND AIMS: One out of three men who undergo cystoprostatectomy for bladder cancer is diagnosed with incidental prostate cancer (PCa) at histopathological examination. Many of these men are PSA tested as part of their follow-up, but it is unclear if this is needed. The aim of this study was to assess the risk of PCa death in these men and the need of PSA-testing during follow-up. METHODS: Between 2002 and 2020, 1,554 men were diagnosed with PCa after cystoprostatectomy performed for non-metastatic bladder cancer and registered in the National Prostate Cancer Register (NPCR) of Sweden. We assessed their risk of death from PCa, bladder cancer and other causes up to 15 years after diagnosis by use of data in The Cause of Death Register. The use of androgen deprivation therapy (ADT) as a proxy for PCa progression was assessed by fillings in The Prescribed Drug Register. RESULTS: Fifteen years after diagnosis, cumulative incidence of death from PCa was 2.6% (95% CI 2.3%-2.9%), from bladder cancer 32% (95% CI: 30%-34%) and from other causes 40% (95% CI: 36%-44%). Only 35% of men with PCa recorded as primary cause of death in The Cause of Death Register had started ADT before date of death, indicating sticky-diagnosis bias with inflated risk of PCa death. CONCLUSIONS: For a large majority of men diagnosed with incidental PCa at cystoprostatectomy performed for bladder cancer, the risk of PCa death is very small so there is no rationale for PSA testing during follow-up.

Cystectomy for bladder cancer in Sweden - short-term outcomes after centralization.

OBJECTIVE: Radical cystectomy (RC) for bladder cancer is associated with an inherent risk of complications and even postoperative mortality. The number of hospitals performing RC has decreased in Sweden over time, and since a formal regional centralization in 2017 cystectomy care is currently provided by nine hospitals. MATERIAL AND METHODS: In the Swedish National Urinary Bladder Cancer Register (SNRUBC) 90-day complications after RC have been registered with high coverage since 2012. Descriptive data and short-term outcomes were compared in relation to centralization of the cystectomy care by stratifying data before (2012-2016) and after (2017-2023). RESULTS: Out of all 4,638 cystectomies, 2,738 (59%) were performed after the centralization in 2017 and onwards. The median age at RC increased from 71 (Inter Quartile Range [IQR] 65-76) to 73 (IQR 67-77) years, and the proportion of patients with comorbidity (American Society of Anesthesiologists [ASA] 3 or 4) increased from 32% to 37% after the centralization (p < 0.001). The number of patients suffering from high-grade complications within 90 days of surgery corresponding to Clavien grade three were 345 (18%) and 407 (15%), and corresponding to Clavien grade four 61 (3%) and 64 (2%) before and after centralization, respectively. Reoperations within 90 days of RC decreased from 234/1,900 (12%) to 208/2,738 (8%) (p < 0.001), and 90-day mortality decreased from 84/1,900 (4%) to 85/2,738 (3%) (p = 0.023) before and after centralization, respectively. CONCLUSION: After the centralization of the cystectomy-care in Sweden, older patients and individuals with more extensive comorbidity were offered RC whereas 90-day mortality and the proportion of patients subjected to reoperations within 90 days of surgery decreased without increasing waiting times.

Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations.

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.

Diagnostic value of repeated comprehensive investigation with CT urography and cystoscopy for recurrent macroscopic haematuria.

Objectives: To perform a descriptive analysis of a series of patients with recurrent macroscopic haematuria after a primary standard evaluation including computed tomography urography (CTU) and cystoscopy negative for urinary bladder cancer (UBC) and upper tract urothelial cancer (UTUC) and to identify potential factors associated with occurrence of recurrent macroscopic haematuria. Methods: All patients older than 50 years who underwent urological investigation for macroscopic haematuria with both cystoscopy and CTU 2015-2017 were retrospectively reviewed. A descriptive analysis of the primary and later investigations for recurrent macroscopic haematuria was performed. To investigate the association between explanatory variables and the occurrence of recurrent macroscopic haematuria, a Poisson regression analysis was performed. Results: A total of 1395 eligible individuals with primary standard investigation negative for UBC and UTUC were included. During a median follow-up of 6.2 (IQR 5.3-7) years, 248 (18%) patients had recurrent macroscopic haematuria, of whom six patients were diagnosed with UBC, two with prostate cancer, one with renal cell carcinoma and one had a suspected UTUC at the repeated investigation. Within 3 years, 148 patients (11%) experienced recurrent macroscopic haematuria, of whom two patients were diagnosed with low-grade UBC (TaG1-2), one with T2G3 UBC and one with low-risk prostate cancer. The presence of an indwelling catheter, use of antithrombotic medication, pathological findings at CTU or cystoscopy or history of pelvic radiotherapy were all statistically significant independent predictors for increased risk for recurrent macroscopic haematuria. Conclusion: In the case of recurrent macroscopic haematuria within 3 years of primary standard evaluation for urinary tract cancer, there was a low risk of later urological malignancies in patients initially negative for UBC and UTUC. Therefore, waiting 3 years before conducting another complete investigation in cases of recurrent macroscopic haematuria might be appropriate.

[Radical cystectomy for bladder cancer is a complex procedure]. / Cystektomi för blåscancer ­ har utfallet förbättrats?

Radical cystectomy (RC) for bladder cancer is a complex procedure with an inherent risk of complications and even postoperative mortality. Historically, RC was performed in 44 hospitals in Sweden, which gradually decreased over time, and since a formal regional centralisation of these operations in 2017, cystectomy care is currently provided by nine hospitals. In the Swedish national urinary bladder cancer register (SNRUBC), complications after RC has been registered with high coverage since 2012, with data presented in an interactive online data resource (RODRET). Over time, an increased median age and proportion of patients with significant comorbidity (ASA 3 or 4) were observed between 2012 and 2022. A simultaneous decrease in 90-day mortality from 7 percent to 2 percent was noted, as well as a decreased need for reoperations within 90 days of RC from 11 percent to 7 percent. It is likely that the regionalization of the cystectomy care in Sweden has contributed to these improved outcomes.

Diagnostic pathways and treatment strategies in upper tract urothelial carcinoma in Sweden between 2015 and 2021: a population-based survey.

OBJECTIVE: To report national data on diagnostics and treatment of upper tract urothelial carcinoma (UTUC) from the Swedish National Registry of Urinary Bladder Cancer (SNRUBC). PATIENTS AND METHODS: Data from 2015 to 2021 were retrieved, and descriptive analyses were performed regarding incidence, diagnostic modalities, preoperative tumor staging, quality indicators for treatment including the use of standardized care pathways (SCP) and multidisciplinary tumor boards (MDTB). Time trends were explored for the study period. RESULTS: Registrations included 1,213 patients with renal pelvic cancer and 911 patients with ureteric cancer with a median age of 74 (interquartile range [IQR] 70-77) and 75 (IQR 71-78) years, respectively. Incidence rates of UTUC were stable, as were proportions of curative treatment intent. Median number of days from referral to treatment was 76 (IQR 57-99) and 90 (IQR 72-118) days, respectively, for tumors of the renal pelvis and ureter, which remained unchanged after introduction of SCP in 2016. Noticeable trends included stable use of kidney-sparing surgery and increased use of MDTB. For radical nephroureterectomy (RNU), robot-assisted technique usage increased even for non-organ-confined tumors (cT3-4) and in one out of three patients undergoing RNU a bladder cuff excision was not registered. CONCLUSIONS: The population-based SNRUBC with high coverage contributes to the knowledge about UTUC with granular and generalizable data. The present study reveals a high proportion of patients not subjected to curatively intended treatment and suggests unmet needs to shorten lead times to treatment and use of bladder cuff excision when performing radical surgery for UTUC in Sweden.

International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer: Working Group 3: Subcategorization of T1 Bladder Cancer.

Emerging data on T1 bladder cancer subcategorization (aka substaging) suggests a correlation with oncological outcomes. The International Society of Urological Pathology (ISUP) organized the 2022 consensus conference in Basel, Switzerland to focus on current issues in bladder cancer and tasked working group 3 to make recommendations for T1 subcategorization in transurethral bladder resections. For this purpose, the ISUP developed and circulated a survey to their membership querying approaches to T1 bladder cancer subcategorization. In particular, clinical relevance, pathological reporting, and endorsement of T1 subcategorization in the daily practice of pathology were surveyed. Of the respondents of the premeeting survey, about 40% do not routinely report T1 subcategory. We reviewed literature on bladder T1 subcategorization, and screened selected articles for clinical performance and practicality of T1 subcategorization methods. Published literature offered evidence of the clinical rationale for T1 subcategorization and at the conference consensus (83% of conference attendants) was obtained to report routinely T1 subcategorization of transurethral resections. Semiquantitative T1 subcategorization was favored (37%) over histoanatomic methods (4%). This is in line with literature findings on practicality and prognostic impact, that is, a shift of publications from histoanatomic to semiquantitative methods or by reports incorporating both methodologies is apparent over the last decade. However, 59% of participants had no preference for either methodology. They would add a comment in the report briefly stating applied method, interpretation criteria (including cutoff), and potential limitations. When queried on the terminology of T1 subcategorization, 34% and 20% of participants were in favor of T1 (microinvasive) versus T1 (extensive) or T1 (focal) versus T1 (nonfocal), respectively.

Second TURB, restaging TURB or repeat TURB in primary T1 non-muscle invasive bladder cancer: impact on prognosis?

PURPOSE: A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. METHODS: Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. RESULTS: Median follow-up was 45.3 (IQR 22.7-81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). CONCLUSION: Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB.

Location of Retroperitoneal Lymph Node Metastases in Upper Tract Urothelial Carcinoma: Results from a Prospective Lymph Node Mapping Study.

Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC). Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND). Design setting and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node-positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates. Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used. Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates. Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited. Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.

Quinolone Prophylaxis in Conjunction with Bacillus Calmette-Guérin Instillations for Bladder Cancer: Time To Reconsider the Evidence and Open the Quinolone Box?

Adjuvant bacillus Calmette-Guérin (BCG) instillations represent a cornerstone in the treatment of non-muscle-invasive bladder cancer. Instillation schedule and dose modifications have been evaluated in efforts to reduce the incidence of adverse events (AEs), but none so far has the same treatment efficacy as the full-dose recommended schedule. It has been shown that prophylactic quinolone use in conjunction with BCG instillations reduces AE incidence and improves timely completion of instillation regimens and patient survival. However, the European Medicines Agency imposed restrictions on the use of quinolones in 2019 because of side effects. Nevertheless, rational use of quinolone prophylaxis could be considered for selected individuals treated with BCG without risk factors for quinolone-associated side effects in conjunction with patient information about side-effect symptoms. PATIENT SUMMARY: Bladder instillations of BCG (bacillus Calmette-Guérin) are used in the treatment of non-muscle-invasive bladder cancer. Antibiotics from the quinolone class can reduce the adverse effects of BCG and help patients in completing the treatment course; however, these antibiotics have their own side effects. Our mini review suggests that the antibiotics could be used in selective cases if patients are given adequate information on these side effects and their symptoms.

Health-related quality of life prior to and 1 year after radical cystectomy evaluated with FACT-G and FACT-VCI questionnaires.

OBJECTIVE: The aim of this study was to investigate health-related quality of life (HRQoL) before and 1 year after radical cystectomy in relation to age and gender. METHODS: This prospective study involves 112 men and 40 women with bladder cancer treated with radical cystectomy between 2015 and 2018. HRQoL was assessed preoperatively and 1 year post-surgery through Functional Assessment of Cancer Therapy Scale - General (FACT-G) and Functional Assessment of Cancer Therapy Scale - Vanderbilt Cystectomy Index (FACT-VCI) questionnaires. The median age of the 152 patients was 71.5 years. RESULTS: Preoperatively, emotional and functional well-being were negatively affected. Physical, emotional and functional well-being presented higher values 1 year after surgery compared to before radical cystectomy, that is, better HRQoL. Social well-being showed a reduction, especially regarding closeness to partner and support from family. Men and women were equally satisfied with their sex life before radical cystectomy, but less so 1 year after, where men were less satisfied compared to women. Additionally, one out of five patients reported that they had to limit their physical activities, were afraid of being far from a toilet and were dissatisfied with their body appearance after surgery. CONCLUSIONS: Recovery regarding HRQoL was ongoing 1 year after radical cystectomy. Patients recovered in three out of four dimensions of HRQoL, but social well-being was still negatively affected 1 year after treatment. Sexual function after radical cystectomy was exceedingly limited for both men and women. An individual sexual rehabilitation plan involving the couple with special intention to encourage intimacy, might not only improve sexual life but also have a positive effect on social well-being as a consequence.

FDG-PET/CT for lymph node staging prior to radical cystectomy.

BACKGROUND: 18F-Fluorodeoxyglucose positron emission combined with computed tomography (FDG-PET/CT) has been proposed to improve preoperative staging in patients with bladder cancer subjected to radical cystectomy (RC). OBJECTIVE: Our aim was to assess the accuracy of FDG-PET/CT for lymph node staging ascertained at the multidisciplinary tumour board compared to lymph node status in the surgical lymphadenectomy specimen obtained at RC, and to explore potential factors associated with false-positive FDG-PET/CT results. DESIGN, SETTING AND PARTICIPANTS: Consecutive patients with bladder cancer undergoing RC with extended lymph node dissection between 2011 and 2019 without preoperative chemotherapy in a tertial referral cystectomy unit were included in the study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated. Potential factors investigated for association with false-positive FDG-PET/CT were; bacteriuria within four weeks prior to FDG-PET/CT, Bacillus Calmette-Guerin (BCG) treatment within 12 months prior to FDG-PET/CT and transurethral resection of bladder tumour (TURB) within four weeks prior to FDG-PET/CT. RESULTS: Among 157 patients included for analysis, 44 (28%) were clinically node positive according to FDG-PET/CT. The sensitivity and specificity for detection of lymph node metastasis were 50% and 84%, respectively, and the corresponding positive predictive and negative predictive values were 61% and 76%. Positive and negative likelihood ratios were 3.0 and 0.6, respectively. No association was found between bacteriuria, previous BCG treatment or TURB within 28 days and false-positive FDG-PET/CT results. CONCLUSIONS: Preoperative FDG-PET/CT prior to RC had a clinically meaningful high specificity (84%) but lower sensitivity (50%) for detection of lymph node metastases compared to lymph node status in an extended pelvic lymphadenectomy template. We could not identify any factors associated with false-positive FDG-PET/CT outcomes.

International Opinions on Grading of Urothelial Carcinoma: A Survey Among European Association of Urology and International Society of Urological Pathology Members.

Background: Grade of non-muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1-3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinoma) are used. Objective: To ask the European Association of Urology (EAU) and International Society of Urological Pathology (ISUP) members regarding their current practice and preferences of grading systems. Design setting and participants: A web-based, anonymous questionnaire with ten questions on grading of NMIBC was created. The members of EAU and ISUP were invited to complete an online survey by the end of 2021. Thirteen experts had previously answered the same questions. Outcome measurements and statistical analysis: The submitted answers from 214 ISUP members, 191 EAU members, and 13 experts were analyzed. Results and limitations: Currently, 53% use only the WHO2004 system and 40% use both systems. According to most respondents, PUNLMP is a rare diagnosis with management similar to Ta-LG carcinoma. The majority (72%) would consider reverting back to WHO1973 if grading criteria were more detailed. Separate reporting of WHO1973-G3 within WHO2004-HG would influence clinical decisions for Ta and/or T1 tumors according the majority (55%). Most respondents preferred a two-tier (41%) or a three-tier (41%) grading system. The current WHO2004 grading system is supported by a minority (20%), whereas nearly half (48%) supported a hybrid three- or four-tier grading system composed of both WHO1973 and WHO2004. The survey results of the experts were comparable with ISUP and EAU respondents. Conclusions: Both the WHO1973 and the WHO2004 grading system are still widely used. Even though opinions on the future of bladder cancer grading were strongly divided, there was limited support for WHO1973 and WHO2004 in their current formats, while the hybrid (three-tier) grading system with LG, HG-G2, and HG-G3 as categories could be considered the most promising alternative. Patient summary: Grading of non-muscle-invasive bladder cancer (NMIBC) is a matter of ongoing debate and lacks international consensus. We surveyed urologists and pathologists of European Association of Urology and International Society of Urological Pathology on their preferences regarding NMIBC grading to generate a multidisciplinary dialogue. Both the "old" World Health Organization (WHO) 1973 and the "new" WHO2004 grading schemes are still used widely. However, continuation of both the WHO1973 and the WHO2004 system showed limited support, while a hybrid grading system composed of both the WHO1973 and the WHO2004 classification system may be considered a promising alternative.

Treatment Patterns and Efficacy of Chemotherapy After Pembrolizumab in Advanced Urothelial Cancer-a Real-World Study in the pre-Antibody-Drug Conjugate Era.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been established as a routine treatment in patients with metastatic urothelial cancer (mUC). However, there has been no standard of care after progression on ICIs. We investigated real-world treatment patterns and efficacy of chemotherapy (CHT) after pembrolizumab, in the era before introduction of maintenance avelumab and antibody-drug conjugates (ADC). PATIENTS AND METHODS: An observational, retrospective study was conducted at twelve Nordic centers. Patients with mUC were treated according to investigator´s choice of CHT after pembrolizumab. Primary endpoint was overall response (ORR) and disease control rate (DCR); secondary endpoints were progression-free (PFS) and overall survival (OS). RESULTS: In total, 102 patients were included whereof 23 patients received CHT after pembrolizumab as second line treatment (subcohort A) and 79 patients in third line (subcohort B). Platinum-gemcitabine combinations were the most common regimens in subcohort A, and vinflunine in subcohort B. The ORR and DCR were 36% and 47%, respectively. Presence of liver metastases was independently associated with lower ORR and DCR. The PFS and OS were 3.3 months and 7.7 months, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG PS) and number of previous cycles of pembrolizumab were found to be independent prognostic factors associated with OS. CONCLUSION: In a real-world setting, CHT showed clinically meaningful response rates and survival in mUC patients after progression with pembrolizumab. Clinical benefit may primarily be achieved in patients with favorable ECOG PS, in patients treated with > 6 cycles pembrolizumab as well as in patients without presence of liver metastases.

Urodrill - a novel MRI-guided endoscopic biopsy technique to sample and molecularly classify muscle-invasive bladder cancer without fractionating the specimen during transurethral resection.

The current diagnostic pathway for patients with muscle-invasive bladder cancer (MIBC), which involves with computed tomography urography, cystoscopy, and transurethral resection of the bladder (TURB) to histologically confirm MIBC, delays definitive treatment. The Vesical Imaging-Reporting and Data System (VI-RADS) has been suggested for MIBC identification using magnetic resonance imaging (MRI), but a recent randomized trial reported misclassification in one-third of patients. We investigated a new endoscopic biopsy device (Urodrill) for histological confirmation of MIBC and assessment of molecular subtype by gene expression in patients with VI-RADS 4 and 5 lesions on MRI. In ten patients, Urodrill biopsies were guided by MR images to the muscle-invasive portion of the tumor via a flexible cystoscope under general anesthesia. During the same session, conventional TURB was subsequently performed. A Urodrill sample was successfully obtained in nine of ten patients. MIBC was verified in six of nine patients, and seven of nine samples contained detrusor muscle. In seven of eight patients for whom a Urodrill biopsy sample was subjected to RNA sequencing, single-sample molecular classification according to the Lund taxonomy was feasible. No complications related to the biopsy device occurred. A randomized trial comparing this new diagnostic pathway for patients with VI-RADS 4 and 5 lesions and the current standard (TURB) is warranted. Patient summary: We report on a novel biopsy device for patients with muscle-invasive bladder cancer that facilitates histology analysis and molecular characterization of tumor samples.

Urosymphyseal fistula after pelvic radiotherapy in a tertial referral centre - a rare entity with significant comorbidity requiring multidisciplinary management.

OBJECTIVE: To report population-based clinical presentation and outcomes in patients with urosymphyseal fistula (USF) after pelvic radiotherapy (RT). PATIENTS AND METHODS: A retrospective chart review was performed in 33 consecutive patients diagnosed with suspicion of USF in a tertial referral center from 2014-2022 to ascertain information about diagnostic delay, clinical presentation, precipitating causes, treatments received and outcomes during the median 22 months follow-up. Out of 33 consecutive patients with suspicion of USF, one female with vesicovaginal fistula, one patient developing RT-associated bladder angiosarcoma, four patients with short follow-up (<3 months), and three patients that during chart review not were considered to have a USF were excluded. RESULTS: In all, 24 males with a median age of 77 years were diagnosed with USF. Local pain was the predominating symptom in 17/24 (71%) patients. Endourologic manipulations preceded the diagnosis of USF in 16 patients. Five patients had a diagnostic delay of more than 3 months. At diagnosis, 20/24 patients had radiological signs of osteomyelitis, and five had a concomitant rectourethral fistula. Due to comorbidity, five patients were not amenable to any other interventions than urinary catheter or suprapubic tube in conjunction with long-term antibiotics, of which three died from infections related to the USF. Out of the remaining 19 patients receiving some form of urinary diversion, five had recurrent osteomyelitis, of which four did not undergo cystectomy in conjunction with surgery for the USF. CONCLUSIONS: Urethral endourologic interventions in patients previously subjected to pelvic RT should be performed cautiously.

Latent heterogeneity of muscle-invasive bladder cancer in patient characteristics and survival: A population-based nation-wide study in the Bladder Cancer Data Base Sweden (BladderBaSe).

BACKGROUND: Patients with muscle-invasive bladder cancer (MIBC) constitute a heterogenous group in terms of patient and tumour characteristics ('case-mix') and prognosis. The aim of the current study was to investigate whether differences in survival could be used to separate MIBC patients into separate classes using a recently developed latent class regression method for survival analysis with competing risks. METHODS: We selected all participants diagnosed with MIBC in the Bladder Cancer Data Base Sweden (BladderBase) and analysed inter-patient heterogeneity in risk of death from bladder cancer and other causes. RESULTS: Using data from 9653 MIBC patients, we detected heterogeneity with six distinct latent classes in the studied population. The largest, and most frail class included 50% of the study population and was characterised by a somewhat larger proportion of women, higher age at diagnosis, more advanced disease and lower probability of curative treatment. Despite this, patients in this class treated with curative intent by radical cystectomy or radiotherapy had a lower association to risk of death. The second largest class included 23% and was substantially less frail as compared to the largest class. The third and fourth class included each around 9%-10%, whereas the fifth and sixth class included each 3%-4% of the population. CONCLUSIONS: Results from the current study are compatible with previous research and the method can be used to adjust comparisons in prognosis between MIBC populations for influential differences in the distribution of sub-classes.

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update.

CONTEXT: The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial carcinoma (UTUC) has updated the guidelines to aid clinicians in evidence-based management of UTUC. OBJECTIVE: To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. EVIDENCE ACQUISITION: The recommendations provided in these guidelines are based on a review of the literature via a systematic search of the PubMed, Ovid, EMBASE, and Cochrane databases. Data were searched using the following keywords: urinary tract cancer, urothelial carcinomas, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, (neo)adjuvant treatment, instillation, recurrence, risk factors, metastatic, immunotherapy, and survival. The results were assessed by a panel of experts. EVIDENCE SYNTHESIS: Even though data are accruing, for many areas there is still insufficient high-level evidence to provide strong recommendations. Patient stratification on the basis of histology and clinical examination (including imaging) and assessment of patients at risk of Lynch syndrome will aid management. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk UTUC and two functional kidneys. In particular, for patients with high-risk or metastatic UTUC, new treatment options have become available. In high-risk UTUC, platinum-based chemotherapy after radical nephroureterectomy, and adjuvant nivolumab for unfit or patients who decline chemotherapy, are options. For metastatic disease, gemcitabine/carboplatin chemotherapy is recommended as first-line treatment for cisplatin-ineligible patients. Patients with PD-1/PD-L1-positive tumours should be offered a checkpoint inhibitor (pembrolizumab or atezolizumab). CONCLUSIONS: These guidelines contain information on the management of individual patients according to the current best evidence. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen according to the risk stratification of these tumours. PATIENT SUMMARY: Cancer of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, timely and appropriate diagnosis is most important. A number of known risk factors exist.

Tumor Biomarkers for Bacillus Calmette-Guérin Response: What We Get Is Not What We Want.

Studies to date on biomarkers predictive of response to bacillus Calmette-Guérin (BCG) treatment for non-muscle-invasive bladder cancer have only identified markers with prognostic potential. There is an urgent need for larger study cohorts and for control arms comprising BCG-untreated patients to identify biomarkers with true ability to predict BCG response in classifying this patient population.