Umeå University's logo

Background: Comorbidity alterations during neoadjuvant chemotherapy (NAC) in patients with muscle invasive bladder cancer (MIBC) are not well studied. Comorbidity-estimates are mainly based on calculations at diagnosis. It is unknown if comorbidities alter in this patient group. This study aimed to investigate if comorbidity alterations during treatment need to be considered, for scientific evaluations.

Methods: A retrospective study of comorbidity alterations on MIBC patients undergoing NAC using age adjusted Charlson Comorbidity Index (CACI). We identified 684 patients between 2007–2022 from four Swedish cystectomy centers, a total of 320 were enrolled in the study. Inclusion criteria were nondisseminated MIBC, cT2–4aN0M0, NAC-treatment or NAC-eligibility. Medical files were reviewed and CACI were assessed and graded at three checkpoints during treatment: At diagnosis, post-NAC and pre-surgery. The cohort was divided into three subgroups, NAC complete, NAC incomplete and NAC-eligible. Data was retrospectively analyzed in SPSS Statistics 29.0 using descriptive statistics, one-way analysis of variance (ANOVA) and t-test.

Results: The total cohort (n=320) had an increase in CACI, 0.11 CACI points, between diagnosis and prior to surgery [95% confidence interval (CI): 0.06–0.15, P<0.001]. The NAC-incomplete group had the highest increase in CACI, 0.21 CACI points from diagnosis to pre-surgery (95% CI: 0.03–0.39, P=0.01). The NAC-complete group also had an increase in CACI, 0.11 CACI points from diagnosis to pre-surgery (95% CI: 0.06–0.15, P<0.001). The NAC-eligible group had no significant CACI-alterations. The most common events causing an increase in CACI was suspected peptic ulcer (85.2%).

Conclusions: There is a statistically significant increase of comorbidity in the total cohort as well as for two of the three subgroups, the NAC complete group and the NAC incomplete group. However, the increases are subtle and of limited clinical significance. This suggests that regardless of adverse events, complications, or progression, comorbidities only slightly change over time in the patient group. All together, answering the primary question if a comorbidity measurement at any moment on the timeline is sufficient.

Background: High recurrence rates for non-muscle-invasive bladder cancer (NMIBC) remain a clinical challenge. Recommended post-operative treatments are underutilized, highlighting the need for alternative strategies. Given the variability in bladder cancer prognosis, personalized treatment approaches are highly relevant. In this study, we evaluated post-operative two-hour continuous sterile water bladder irrigation (CSWBI) regarding recurrence and safety, as a potential addition to the treatment arsenal for bladder cancer.

Method: In 2018, two-hour CSWBI was implemented as routine treatment after all transurethral resection procedures of the bladder (TURB), at the urology department of Sundsvall Hospital. All patients who underwent TURBs four years prior (control group) and four years after the implementation of CSWBI (intervention group) were analyzed. Primary NMIBC were included, MIBC and CIS were excluded. Data were collected retrospectively from patient records, including baseline characteristics, adverse events, and recurrence rates within 12 months follow-up. Statistical analyses included Chi-squared test, Wilcoxon rank-sum test, univariate and multivariate logistic regression analyses, Kaplan–Meier curves and log-rank test.

Results: A total of 168 patients were included (control group n = 90, irrigation group n = 78). Median age was 73 years, 23% were female, 77% were male, and 74% were active or previous smokers. The recurrence rate within twelve months for the intervention group vs. the control group was: 27% vs. 21% (p = 0.4) respectively. CSWBI had no statistically significant impact on recurrence (OR 1.25, 95% CI 0.58–2.68, p = 0.6). Adverse effects were limited and equal between groups. Conclusions: Post-operative two-hour CSWBI did not significantly reduce NMIBC recurrence within twelve months in this cohort.

Introduction: 

For the 3-5% of patients diagnosed with urinary bladder cancer presenting with distant metastases, the five-year survival probability remains below 10% (1–3).

Since the late 1980s, platinum-based combination chemotherapy has been the cornerstone of treatment for metastatic urinary bladder cancer (mUBC) (4, 5). For cisplatin-ineligible patients, carboplatin-gemcitabine was established as an alternative in 2011 (6, 7), and is currently used as first-line chemotherapy in approximately half of the patients treated systemically for mUBC (8). However, platinum-based regimens are associated with a high incidence of serious adverse events (5, 7). Consequently, a substantial proportion of patients with mUBC do not receive any systemic chemotherapy (9). Vinflunine was approved in Europe in 2009 as second-line chemotherapy, though with limited clinical benefit (10, 11).

A new era in the systemic treatment of mUBC was marked by the approval of immune checkpoint inhibitors (ICI) 2017 (12, 13). ICIs demonstrated not only an improved overall survival but also a more favorable toxicity profile. Recent population-based studies have reported improved survival among systemically treated patients with mUBC following the introduction of ICI (14).

Given the historically low uptake of systemic therapy in the real-world setting of mUBC, it remains unclear whether the introduction of immune checkpoint inhibitors (ICI) has translated into improved survival at the population level. As the treatment landscape for mUBC continues to evolve rapidly, benchmarking treatment patterns and survival outcomes in real-world populations is essential to guide clinical practice and policy.

We used the Bladder Cancer Data Base Sweden (BladderBase) 2.0 (15) to investigate survival trends among patients diagnosed with synchronous mUBC between 1997 and 2019 across calendar periods defined by the introduction of novel systemic therapies. We hypothesized that survival in the overall mUBC population improved after the introduction of ICI (2017–2019), due to both the availably of a novel treatment option and an increased proportion of patients eligible for systemic treatment due to ICIs favorable toxicity profile.

Background: The 5-year survival rate in muscle-invasive bladder cancer (MIBC) is approximately 50%, cross over computed tomography (CT) stage in chemo-naive patients. Studies indicate lower survival rates in females when compared to males. The theories that explain the sex disparity are hormonal factors and delayed diagnosis for females. New investigations suggest that neoadjuvant chemotherapy (NAC) might be a possible method for bridging the gender survival gap. The aim of this study was to investigate whether complete treatment with NAC (≥3 cycles) prior to cystectomy reduces the gender gap in survival rates for MIBC and improves the surrogate marker of downstaging.

Methods: A multicenter retrospective cohort from five Swedish urological centers, from 1st January 2005 to 17th July 2023 based on NAC-eligible patients divided in NAC-receiving and non-NAC-receiving subgroups and further divided by sex (males and females). Survival was analyzed based on the Kaplan-Meier method, using log-rank test and adjusted analyses were made with the Cox regression model. Outcome measurements were overall survival (OS), disease-free survival (DFS), and downstaging.

Results: In the analysis of the total cohort (n=412), we could not detect any statistically significant differences in OS between NAC and non-NAC, nor between sexes, in the unadjusted analysis. In the adjusted analysis, we did not observe any significant differences in OS between sexes, either in total or within the NAC subgroups. Further analyzing the NAC group, we could see a significant increased downstaging rate in the NAC group compared to the non-NAC group (P<0.001) which indicates an increased survival in those receiving NAC treatment. There was no relationship between sexes and downstaging (P=0.72). Neither could we see any significant difference in downstaging between males and females in the NAC/non-NAC subgroups (P=0.41 and P=0.92, respectively).

Conclusions: NAC-eligible female and male MIBC patients who underwent radical cystectomy (RC) after at least three cycles of NAC, demonstrated similar OS and DFS. NAC seems to obliterate survival differences between genders in MIBC patients.

Single particle profiling (SPP) is a unique methodology to study nanoscale bioparticles such as liposomes, lipid nanoparticles, extracellular vesicles, and lipoproteins in a single particle and high throughput manner. The initial version requires the single photon counting modules for data acquisition, which limits its adoptability. Here, we present imaging-based SPP (iSPP) that can be performed by imaging a spot over time in the common imaging mode with confocal detectors. We also provide user-friendly software with a graphical user interface to analyze such data and give quantitative insights on the content and properties of nanoscale bioparticles. We use iSPP to decipher lipid-protein interactions, membrane modifications by drugs, and the heterogeneity of extracellular vesicles isolated from cell lines and human urine. This easily applicable modality of the single particle profiler will facilitate nanoscale bioparticle research in laboratories with access to any confocal microscope.

Urinary Bladder Cancer (UBC) ranks among the most prevalent cancers worldwide, has a high recurrence rate and unpredictable treatment responses. Thus, biomarkers are urgently needed. Extracellular vesicles (EVs) are released from both cancer- and immune cells and provide a snapshot of the originating cell. They are abundant in urine and are therefore candidate biomarkers for UBC.

Isolated urinary EVs from 39 UBC patients were compared with EVs from healthy controls, prostate cancer patients and whole urine. Samples were from bladder urine at time of both transurethral resection of the bladder tumour (TURB) and cystectomy, as well as urine taken from the ureter at cystectomy. EVs were isolated by tangential flow filtration and differential ultracentrifugation and their protein composition was detected by Proximity Extension Assay (PEA; Olink, immuno-oncology panel).

In UBC patients, the proteomic signature of bladder urine EVs differed from ureter urine EVs from the same individuals, and from bladder urine derived EVs of both healthy and prostate cancer controls. Pairwise comparison was performed with matched whole urine revealing proteins solely detected in isolated vesicles. Additionally, a distinct signature was identified in bladder urine EVs correlating with muscle invasiveness, and a trained classifier could predict UBC with 92% accuracy. Some differentially expressed proteins, HO-1 and MMP7, were analysed by bead- based flow cytometry, where HO-1 was detected on the EV surface.

Taken together, these results strengthen the rationale of using EVs as non-invasive biomarkers and prognostic tools for UBC.

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.

BACKGROUND: Prospective interventional trials and retrospective observational analyses provide conflicting evidence regarding the relationship between propofol versus inhaled volatile general anesthesia and long-term survival after cancer surgery. In specific, bladder cancer surgery lacks prospective clinical trial evidence.

METHODS: Data on bladder cancer surgery performed under general anesthesia between 2014 and 2021 from The National Quality Registry for Urinary Tract and Bladder Cancer and the Swedish Perioperative Registry were record-linked. Overall survival was compared between patients receiving propofol or inhaled volatile for anesthesia maintenance. The minimum clinically important difference was defined as a five-percentage point difference in five-year survival.

RESULTS: Of 7,571 subjects, 4,519 (59.7%) received an inhaled volatile anesthetic and 3,052 (40.3%) received propofol for general anesthesia maintenance. The two groups were quite similar in most respects but differed in ASA physical status and tumor stage. Propensity score matching was used to address treatment bias. Survival did not differ during follow-up (median 45 months [interquartile range, 33 to 62]) in neither the full unmatched cohort, nor following 1:1 propensity score matching (3,052 matched pairs). The Kaplan-Meier adjusted five-year survival rates in the matched cohort were 898/3,052, 67.5% (65.7-69.3) for propofol and 852/3,052, 68.5% (66.7-70.4) for inhaled volatile general anesthesia, respectively (hazard ratio 1.05 [95% CI: 0.96 to 1.15], P = 0.332). A sensitivity analysis restricted to 1,766 propensity score matched pairs of patients who received only one general anesthetic during the study period did not demonstrate a difference in survival; Kaplan-Meier adjusted five-year-survival rates were 521/1,766, 67.1% (64.7-69.7) and 482/1,766, 68.9% (66.5-71.4) for propofol and inhaled volatile general anesthesia, respectively (hazard ratio 1.09 [95% CI: 0.97 to 1.23], P = 0.139).

CONCLUSIONS: Among patients undergoing bladder cancer surgery under general anesthesia, there was no statistically significant difference in long-term overall survival associated with the choice of propofol or an inhaled volatile maintenance.

Background: A previously published study at Norrland University Hospital, Umeå, Sweden, found that in 29.5% of patients with urinary bladder cancer (UBC) who underwent cystectomy, incorrect cT-stage (clinical T-stage) was registered in the Swedish National Register of Urinary Bladder Cancer (SNRUBC). Tumor in bladder diverticulum (TIBD) and tumor-associated hydronephrosis (TAH) were common causes for misclassification. Our aim was to further investigate cT-staging, as well as pathoanatomical markers, in the SNRUBC, compared to detailed data from medical records in a larger, retrospective multicenter cohort. Our secondary objective was to describe the frequency of pathoanatomical markers in pathology reports (PAD) after transurethral resection of the bladder (TURb): variant histology (VH), concomitant carcinoma in situ (CIS), lymphovascular invasion (LVI) and perineural invasion (PNI).

Methods: Medical records of 630 patients planned for radical cystectomy in the years 2009-2022 in the Northern Healthcare Region, Region of Gävleborg and Region of Västmanland were reviewed. Factors impacting risk of misclassification of cT-staging were identified through logistic regression. In TURb pathology reports, all comments on pathoanatomical markers were identified. For each pathoanatomical marker, respectively, comments were then registered as positive or negative. The absence of a comment on a marker was registered as "not commented".

Results: A total discrepancy rate of 36.5% was found between validated cT-staging and the SNRUBC, of which 13.3% were upstaged from <T2 to ≥T2. The results are presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Registrations with discrepancy were significantly associated with TIBD (OR: 10.28, 95% CI: 5.20-20.34), TAH (OR: 9.60, 95% CI: 6.12-15.10) and year of cystectomy 2009-2011 (OR: 3.38, 95% CI: 2.13-5.36). Incorrect CIS registration: 134 (35.8%); incorrect histology registration: 98 (25.6%). Total frequencies of recorded pathoanatomical markers in TURb-reports were for VH =23.8%, concomitant CIS =36.9%, LVI =30.4%, PNI =2.3%.

Conclusions: The SNRUBC has a significant prevalence of misclassification of cT-staging with a large proportion due to TAH and TIBD. Misclassification of VH and CIS is also common. Improved guidelines could increase consistency. Total rates of recorded pathoanatomical markers in TURb-reports are low.