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.

Treatment and prognosis of patients with urinary bladder cancer with other primary cancers: a nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe).

OBJECTIVE: To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis. PATIENTS AND METHODS: Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patient's characteristics, UBC tumour stage at diagnosis, and site of OPC. RESULTS: There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis. CONCLUSIONS: OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.

No increased risk of short-term complications after radical cystectomy for muscle-invasive bladder cancer among patients treated with preoperative chemotherapy: a nation-wide register-based study.

PURPOSE: Preoperative chemotherapy is underused in conjunction with radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) due to concerns for complications and delay of surgery. Prospective data on short-term complications from population-based settings with frequent use of preoperative chemotherapy and standardised reporting of complications is lacking. METHODS: We identified 1,340 patients who underwent RC between 2011 and 2015 in Sweden due to MIBC according to the Swedish Cystectomy Register. These individuals were followed through linkages to several national registers. Propensity score adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for complications and death within 90 days of surgery, comparing patients receiving preoperative chemotherapy or not. RESULTS: Minimum two cycles of preoperative chemotherapy were given to 519 (39%) of the patients, who on average tended to be younger, have higher education, better physical status, and more advanced bladder cancer than patients not receiving chemotherapy. After adjusting for these and other parameters, there was no association between treatment with preoperative chemotherapy and short-term complications (OR 1.06 95% CI 0.82-1.39) or mortality (OR 0.75 95% CI 0.36-1.55). We observed a risk reduction for gastrointestinal complications among patients who received preoperative chemotherapy compared with those who did not (OR 0.49 95% CI 0.30-0.81). CONCLUSION: This nation-wide population-based observational study does not suggest that preoperative chemotherapy, in a setting with high utilisation of such treatment, is associated with an increased risk of short-term complications in MIBC patients treated with radical cystectomy.

A Nationwide, Population Based Analysis of Patients with Organ Confined, Muscle Invasive Bladder Cancer Not Receiving Curative Intent Therapy in Sweden from 1997 to 2014.

PURPOSE: While radical cystectomy remains the standard treatment of muscle invasive bladder cancer, the natural history of patients unable or unwilling to receive therapy with curative intent is not well understood. The study objective was to identify these patients in a population based cohort, investigate the clinical profile and describe time to mortality. MATERIALS AND METHODS: We analyzed the Bladder Cancer Data Base Sweden, a database collected from 1997 to 2014, and identified 9,811 patients with stage T2-T4 disease. Median overall and cancer specific survival was estimated by the Kaplan-Meier method. Relative risks due to prognostic factors were estimated using Cox proportional hazards models. RESULTS: Of the 5,592 patients who did not receive therapy with curative intent 68% were male and 32% were female with a median age of 79 and 81 years, respectively. After 1 year patients had been hospitalized an average of 2.1 times for an average of 18.8 days. Major and minor urological surgeries were the most commonly registered procedures during these hospitalizations. Median overall survival was worse in women than in men (7 vs 8 months). Risk factors for death from bladder cancer were higher tumor stage, age greater than 80 years, later year of diagnosis and female gender. Organ confined disease (T2-T3 M0) was diagnosed in 1,352 patients (24%). These patients had a median of 2.4 hospitalizations per patient during the first 12 months after diagnosis. Half of these hospitalizations were due to cancer or genitourinary symptoms. Median overall survival in the organ confined subgroup was 11 months. Most of these patients had stage N0 disease. They had 2-month longer median overall survival but otherwise similar outcomes. CONCLUSIONS: These patients experience substantial disease specific morbidity. They are hospitalized frequently during the final year of life and primarily die of bladder cancer progression.

Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study.

OBJECTIVE: To investigate the association between hospital volume and overall survival (OS), cancer-specific survival (CSS), and quality of care of patients with bladder cancer who undergo radical cystectomy (RC), defined as the use of extended lymphadenectomy (eLND), continent reconstruction, neoadjuvant chemotherapy (NAC), and treatment delay of <3 months. PATIENTS AND METHODS: We used the Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent RC for primary invasive bladder cancer stage T1-T3 in Sweden between 1997 and 2014. The period-specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level, and NAC. PSMAV was either categorised in tertiles, dichotomised (at ≥25 RCs annually), or used as a continuous variable for every increase of 10 RCs annually. RESULTS: PSMAV in the highest tertile (≥25 RCs annually) was associated with improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.75-1.0), whereas the corresponding HR for CSS was 0.87 (95% CI 0.73-1.04). With PSMAV as a continuous variable, OS was improved for every increase of 10 RCs annually (HR 0.95, 95% CI 0.90-0.99). Moreover, higher PSMAV was associated with increased use of eLND, continent reconstruction and NAC, but also more frequently with a treatment delay of >3 months after diagnosis. CONCLUSIONS: The current study supports centralisation of RC for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral.

EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides.

BACKGROUND: There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder cancer and these methods are therefore not routinely used. Targeting radio-nuclides to the extracellular domain of the receptors is potentially a better possibility. METHODS: EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. RESULTS: EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. CONCLUSIONS: At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.

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.

[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.

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.

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.

Short term outcomes after robot assisted and open cystectomy - A nation-wide population-based study.

INTRODUCTION: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population. MATERIALS AND METHODS: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary outcomes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models. RESULTS: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multivariable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0). CONCLUSION: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.

Preoperative upper tract invasive diagnostic modalities are associated with intravesical recurrence following surgery for upper tract urothelial carcinoma: A population-based study.

BACKGROUND: Intravesical recurrence (IVR) after surgery for upper tract urothelial carcinoma (UTUC) is a clinical problem. We investigated if preoperative invasive diagnostic modalities (IDM) such as antegrade/retrograde uretero-pyelography and/or selective urine cytology/barbotage, and URS with or without concomitant biopsy are associated with IVR after radical surgery for UTUC. Risk of death from urothelial cancer and all causes was investigated as secondary outcomes. METHODS: We investigated a population-based cohort of 1038 consecutive patients subjected to radical surgery for UTUC 2015-2019 in Sweden, using the Bladder Cancer Data Base Sweden (BladderBaSe 2.0), comprising all patients in the Swedish National Registry of Urinary Bladder Cancer. Risk estimates of IVR, death from urothelial cancer, and all causes was assessed using multivariable Cox regression models. RESULTS: The study included 536 cases with and 502 without preoperative IDM. IDM was associated with increased risk of IVR (HR 1.24, 95% CI 1.03-1.52) and risk of urothelial cancer death (HR 1.56, CI 1.12-2.18), compared to no IDM after a median follow-up of 1.3 yrs. Stratified analysis for tumor location showed that IDM was associated with risk of IVR in ureteric cancer (HR 1.66, 95% CI 1.21-2.28) but not in renal pelvic cancer (HR 1.07, 95% CI 0.81-1.41). Limitations included the observational setting and the lack of variables such as tumour grade, multifocality and preoperative hydronephrosis. CONCLUSIONS: Worse outcomes for patients subjected to preoperative IDM highlight the need for carefully considering diagnostic decisions for UTUC patients, specifically in tumours located in the ureter.

Improved long-term outcome of patients with non-muscle invasive, low and intermediate risk bladder cancer between 1997 and 2014; a Swedish population-based study.

OBJECTIVE: The most common form of urinary bladder cancer is the low and intermediate risk categories of stage Ta. This patient group has a high recurrence rate, but progression is rare. The aim of this study was to investigate recurrence and survival in a large population-based setting, with respect to possible prognostic factors and during different time periods. PATIENTS AND METHODS: BladderBaSe is a database which links information from the Swedish National Register of Urinary Bladder Cancer with national healthcare and demographic registers. Between 1997 and 2014, 16,599 were diagnosed with low and intermediate risk of Ta cancer in Sweden. The times to recurrence and cancer-specific death were analysed concerning the differences in age, gender, grade, region and hospital type. For temporal analysis, we divided the material into 6-year periods. RESULTS: The mean age was 70 years and 75% were males. Low risk according to grade constituted 56%, whilst 44% had intermediate risk. With a median follow-up time of 63 months the recurrence rates were 47% and 59% for the respective categories and overall 52%. The rate was similar between the first two time periods, but became substantially lower in the most recent period. Five percent of patients died of the disease and risk category was the main prognostic variable. CONCLUSIONS: The risk of recurrence decreased in the last time period. Risk category based on grade was the most important prognostic indicator for outcome.

Standardized care pathways for patients with suspected urinary bladder cancer: the Swedish experience.

OBJECTIVES: To compare time intervals to diagnosis and treatment, tumor characteristics, and management in patients with primary urinary bladder cancer, diagnosed before and after the implementation of a standardized care pathway (SCP) in Sweden. MATERIALS AND METHODS: Data from the Swedish National Register of Urinary Bladder Cancer was studied before (2011-2015) and after (2016-2019) SCP. Data about time from referral to transurethral resection of bladder tumor (TURBT), patients and tumor characteristics, and management were analyzed. Subgroup analyses were performed for cT1 and cT2-4 tumors. RESULTS: Out of 26,795 patients, median time to TURBT decreased from 37 to 27 days after the implementation of SCP. While the proportion of cT2-T4 tumors decreased slightly (22-21%, p < 0.001), this change was not stable over time and the proportions cN + and cM1 remained unchanged. In the subgroups with cT1 and cT2-4 tumors, the median time to TURBT decreased and the proportions of patients discussed at a multidisciplinary team conference (MDTC) increased after SCP. In neither of these subgroups was a change in the proportions of cN + and cM1 observed, while treatment according to guidelines increased after SCP in the cT1 group. CONCLUSION: After the implementation of SCP, time from referral to TURBT decreased and the proportion of patients discussed at MDTC increased, although not at the levels recommended by guidelines. Thus, our findings point to the need for measures to increase adherence to SCP recommendations and to guidelines.

Risk of bladder cancer death in patients younger than 50 with non-muscle-invasive and muscle-invasive bladder cancer.

INTRODUCTION AND OBJECTIVES: Bladder cancer is primarily a disease of older age and little is known about the differences between patients diagnosed with bladder cancer at a younger versus older age. Our objectives were to compare bladder cancer specific survival in patients aged <50 versus those aged 50-70 at time of diagnosis. MATERIALS AND METHODS: The Swedish bladder cancer database provided data on patient demographics, clinical characteristics and treatments for this observational study. Cox proportional hazard regression models were adjusted for appropriate variables. All analyses were stratified by disease stage (non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Furthermore, we compared the frequency of lower urinary tract infections within 24 months prior to bladder cancer diagnosis by sex and age groups. RESULTS: The study included 15,452 newly-diagnosed BC patients (1997-2014); 1,207 (8%) patients were <50 whilst 14,245 (92%) were aged 50-70. Patients aged <50 at diagnosis were at a decreased risk of bladder cancer death (HR = 0.82, 95%CI: 0.68-0.99) compared to those aged 50-70. When stratified by non-muscle-invasive and muscle-invasive bladder cancer, this association remained in non-muscle-invasive patients only (<50, HR = 0.43, 95% CI: 0.28-0.64). The frequency of lower urinary tract infection diagnoses did not differ between younger and older patients in either men or women. CONCLUSIONS: Patients diagnosed with non-muscle-invasive bladder cancer when aged <50 are at decreased risk of bladder cancer-specific death when compared to their older (50-70) counterparts. These observations raise relevant research questions about age-related differences in diagnostic procedures, clinical decision-making and, not least, potential differences in tumour biology.

Cohort profile: Bladder Cancer Data Base Sweden (BladderBaSe) 2.0.

PURPOSE: We constructed Bladder Cancer Data Base Sweden (BladderBaSe) 2.0 to expand studies in BladderBaSe on incidence, treatment outcomes, side effects, survival and health economic aspects of men and women with cancer in the urinary bladder, upper tract urothelial carcinoma (UTUC) (renal pelvis and ureter) and urethral carcinoma. PARTICIPANTS: BladderBaSe 2.0 includes 53 298 patients with cancer in the urinary bladder, diagnosed from 1 January 1997 to 31 December 2019, and 961 patients with UTUC in the renal pelvis and 792 in the ureter, and 146 patients with urethral urothelial carcinoma, diagnosed from 1 January 2015 to 31 December 2019, and in total 275 816 participants in reference groups, free of cancer in the urinary tract, matched 1:5 on sex, age and county. FINDINGS TO DATE: To date, 18 published studies based on data from the BladderBaSe have investigated calendar time trends in survival; impact of gender, socioeconomic factors, tumour aggressiveness and hospital volume for radical cystectomy on prognosis; survival after radical cystectomy compared with radical radiotherapy; risk factors for complications and side effects after radical cystectomy such as thromboembolism, strictures of ureteroenterostomies and incisional hernia. FUTURE PLANS: The BladderBaSe initiators are currently investigating gender-dependent detection delays due to urinary tract infections; survival after non-muscle invasive bladder cancer with respect to the number of transurethral resections; short-term outcomes comparing open and robot-assisted radical cystectomy; studies on risk for intravesical recurrence after different diagnostic measures in UTUC, and suicide risk after bladder cancer diagnosis. The BladderBaSe project group is open for collaborations with national and international colleagues.

Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancer.

BACKGROUND: Previous research has associated repeated transurethral procedures after a diagnosis of non-muscle invasive bladder cancer (NMIBC) with increased risk of death of causes other than bladder cancer. AIM: We investigated the overall and disease-specific risk of death in patients with NMIBC compared to a background population sample. METHODS: We utilized the database BladderBaSe 2.0 containing tumor-specific, health-related and socio-demographic information for 38,547 patients with NMIBC not primarily treated with radical cystectomy and 192,733 individuals in a comparison cohort, matched on age, gender, and county of residence. The cohorts were compared using Kaplan-Meier curves and Hazard ratios (HR) from a Cox regression models. In the NMIBC cohort, we analyzed the association between number of transurethral procedures and death conditioned on surviving two or five years. RESULTS: Overall survival and survival from causes other than bladder cancer estimated with Kaplan-Meier curves was 9.3% (95% confidence interval (CI) (8.6%-10.0%)) and 1.4% (95% CI 0.7%-2.1%) lower respectively for the NMIBC cohort compared to the comparison cohort at ten years. In a Cox model adjusted for prognostic group, educational level and comorbidity, the HR was 1.03 (95% CI 1.01-1.05) for death from causes other than bladder cancer comparing the NMIBC cohort to the comparison cohort. Among the NMIBC patients, there was no discernible association between number of transurethral procedures and deaths of causes other than bladder cancer after adjustment. The number of procedures were, however, associated with risk of dying from bladder cancer HR 3.56 (95% CI 3.43-3.68) for four or more resections versus one within two years of follow-up. CONCLUSION: The results indicate that repeated diagnostic or therapeutic transurethral procedures under follow-up do not increase of risk dying from causes other than bladder cancer. The modestly raised risk for NMIBC patients dying from causes other than bladder cancer is likely explained by residual confounding.

Bladder cancer recurrence in papillary urothelial neoplasm of low malignant potential (PUNLMP) compared to G1 WHO 1999: a population-based study.

OBJECTIVE: Papillary urothelial neoplasm of low malignant potential (PUNLMP) and stage TaG1 non-muscle invasive bladder cancer (NMIBC) represent separate categories in current WHO 1999 grade definitions. Similarly, PUNLMP and Ta low-grade are separate entities in the WHO 2004/2016 grading system. However, this classification is currently questioned by reports showing a similar risk of recurrence and progression for both categories. PATIENTS AND METHODS: In this population-based study, risk estimates were evaluated in patients diagnosed with PUNLMP (n = 135) or stage TaG1 (n = 2176) NMIBC 2004-2008 with 5-year follow-up registration in the nation-wide Bladder Cancer Data Base Sweden (BladderBaSe). The risk of recurrence was assessed using multivariable Cox regression with adjustment for multiple confounders (age, gender, marital status, comorbidity, educational level, and health care region). RESULTS: At five years, 28/135 (21%) patients with PUNLMP and 922/2176 (42%) with TaG1 had local recurrence. The corresponding progression rates were 0.7% (1/135) and 4.0% (86/2176), respectively. A higher relative risk of recurrence was detected in patients with TaG1 tumours compared to PUNLMP (Hazard Ratio 1.6, 95% CI 1.2-2.0) at 5-year follow-up, while progression events were too few to compare. CONCLUSIONS: The difference in risk of recurrence between primary stage TaG1 and PUNLMP stands in contrast to the recently adapted notion that treatment and follow-up strategies can be merged into one low-risk group of NMIBC.

Radical cystectomy compared to intravesical BCG immunotherapy for high-risk non-muscle invasive bladder cancer - is there a long-term survival difference? A Swedish nationwide analysis.

OBJECTIVES: High-risk non-muscle invasive urinary bladder cancer (NMIBC) presents an increased risk of progression and cancer death. To reduce these risks, two different treatments are recommended - BCG or radical cystectomy (RC). The purpose of this study is to analyze cancer-specific survival of these two initial treatments. MATERIALS AND METHODS: BladderBaSe links information from the SNRUBC from 1997 to 2014, with a number of national healthcare and demographic registers. BCG was used for 3,862 patients (399 had delayed RC), while 687 had initial RC. Propensity scores were used to match the patients treated with RC and with relevant variables such as age, gender, and tumor stage with the same number treated with BCG (673 each arm). In a further comparison, an instrumental variable analysis using hospital strategy as the instrument was used. RESULTS: The 5-year cancer-specific survival chance was higher for the BCG group than it was for the initial RC group, 87 vs 71%, respectively. In the population with propensity score matching, 78 died from cancer in the BCG group during follow-up and 162 in the RC group. In the instrumental variable analysis, the multivariate adjusted risk difference of cancer-specific death 2 years after diagnosis was 32 per 100 treated patients, in favor of the BCG group. CONCLUSIONS: BCG therapy had better cancer-specific survival than RC also when two different statistic methods were used to try to control for confounding. A prospective randomized trial will be necessary to rule out that selection is a major factor for the outcome.