| 1. |
- Abdul-Sattar Aljabery, Firas, et al.
(author)
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Management and outcome of muscle-invasive bladder cancer with clinical lymph node metastases. A nationwide population-based study in the bladder cancer data base Sweden (BladderBaSe)
- 2019
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In: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 53:5, s. 332-338
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Journal article (peer-reviewed)abstract
- Purpose: To investigate the clinical management and outcome of patients with muscle-invasive bladder cancer with clinical lymph node involvement, using longitudinal nationwide population-based data.Methods: In the Bladder Cancer Data Base Sweden (BladderBaSe), treatment and survival in patients with urinary bladder cancer clinical stage T2-T4 N + M0 diagnosed between 1997 and 2014 was investigated. Patients´ characteristics were studied in relation to TNM classification, curative or palliative treatment, cancer-specific (CSS) and overall survival (OS). Age at diagnosis was categorised as ≤60, 61-70, 71-80 and >80 years, and time periods were stratified as follows: 1997-2001, 2002-2005, 2006-2010 and 2011-2014.Results: There were 786 patients (72% males) with a median age of 71 years (interquartile range = 64-79 years). The proportion of patients with high comorbidity increased over time. Despite similar low comorbidity, curative treatment was given to 44% and to 70% of those in older (>70 years) and younger age groups, respectively. Curative treatment decreased over time, but chemotherapy and cystectomy increased to 25% during the last time period. Patients with curative treatment had better survival compared to those with palliative treatment, both regarding CSS and OS in the whole cohort and in all age groups.Conclusions: The low proportion of older patients undergoing treatment with curative intent, despite no or limited comorbidity, indicates missed chances of treatment with curative intent. The reasons for an overall decrease in curative treatment over time need to be analysed and the challenge of coping with an increasing proportion of node-positive patients with clinically significant comorbidity needs to be met.
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| 2. |
- Abrahamsson, Johan, et al.
(author)
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Circulating tumor cells in patients with advanced urothelial carcinoma of the bladder : Association with tumor stage, lymph node metastases, FDG-PET findings, and survival
- 2017
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In: Urologic Oncology. - : Elsevier BV. - 1078-1439. ; 35:10, s. 9-606
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Journal article (peer-reviewed)abstract
- Background: There are currently no methods in clinical use that can detect early systemic dissemination of urothelial tumor cells. Objective: To evaluate measurement of circulating tumor cells (CTCs) as a biomarker for disseminated disease in patients with advanced bladder cancer. Design, setting, and participants: Between March 2013 and October 2015, 88 patients were prospectively included in the study: 78 were scheduled for radical cystectomy (RC) ± perioperative chemotherapy and 10 treated with palliative chemotherapy. The CellSearch CTC test was further assessed in this context by investigating expression of epithelial cell adhesion molecule (EpCAM) in primary tumors obtained at cystectomy from an independent cohort of 409 patients. Outcome measurements and statistical analysis: Presence of CTCs was tested for association with tumor stage, lymph node metastases, metastatic disease on [18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and cancer-specific and progression-free survival. Results: CTCs were detected in 17/88 patients (19%). In 61 patients who underwent FDG-PET-computed tomography (CT), a statistically significant association with presence of CTCs was found for radiological metastatic disease but not for normal PET-CT results (12/35 [34%] vs. 2/26 [8%], P = 0.014). After a median follow-up time of 16.5 months (95% CI: 9.6-21.4), presence of CTCs was associated with an increased risk of progression among patients treated with RC with or without perioperative chemotherapy (n = 75, P = 0.049). A multivariate analysis adjusted for clinical tumor stage, clinical lymph node status, and age showed that CTCs were an independent marker of progression (n = 75; hazard ratio = 2.78; 95% CI: 1.005-7.69; P = 0.049) but not of cancer-specific death (P = 0.596). In 409 cystectomised patients, more than 392 (96%) of the bladder tumors expressed EpCAM. Conclusions: CTCs were present in 19% of patients with advanced urothelial tumors and were associated with metastatic disease on FDG-PET-CT and with increased risk of disease progression after RC. A significant portion of urothelial cancer cells do express EpCAM and can thus be identified using EpCAM-antigen-based CTC detection methods.
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| 3. |
- Aine, Mattias, et al.
(author)
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Biological determinants of bladder cancer gene expression subtypes.
- 2015
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Journal article (peer-reviewed)abstract
- Molecular stratification of tumors by gene expression profiling has been applied to a large number of human malignancies and holds great promise for personalized treatment. Comprehensive classification schemes for urothelial carcinoma have been proposed by three separate groups but have not previously been evaluated simultaneously in independent data. Here we map the interrelations between the proposed molecular subtypes onto the intrinsic structure of a rich independent dataset and show that subtype stratification within each scheme can be explained in terms of a set of common underlying biological processes. We highlight novel biological and genomic drivers of urothelial carcinoma molecular subtypes and show that tumors carrying genomic aberrations characteristic of distinct molecular pathways converge on a common top level phenotype corresponding to the two major molecular subtypes of non-muscle invasive disease.
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| 4. |
- Aine, Mattias, et al.
(author)
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On Molecular Classification of Bladder Cancer: Out of One, Many.
- 2015
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In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 68:6, s. 921-923
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Journal article (peer-reviewed)abstract
- Comparative analysis showed that bladder cancer classification systems identify overlapping subtypes but at different levels. Muscle-invasive bladder cancer shows remarkable heterogeneity, and six subtypes were identified that differ in transcriptional networks, marker profiles, and expression of actionable targets.
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| 5. |
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| 6. |
- Anell, Anders, et al.
(author)
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A randomized comparison between league tables and funnel plots as an aid to health care decision-making
- 2017
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In: International Journal for Quality in Health Care. - : Oxford University Press (OUP). - 1464-3677 .- 1353-4505. ; 28:6, s. 816-823
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Journal article (peer-reviewed)abstract
- Objective Comparison of provider performance is commonly used to inform health care decision-making. Little attention has been paid to how data presentations influence decisions. This study analyzes differences in suggested actions by decision-makers informed by league tables or funnel plots.Design Decision-makers were invited to a survey and randomized to compare hospital performance using either league tables or funnel plots for four different measures within the area of cancer care. For each measure, decision-makers were asked to suggest actions towards 12–16 hospitals (no action, ask for more information, intervene) and provide feedback related to whether the information provided had been useful.Setting Swedish health care.Participants Two hundred and twenty-one decision-makers at administrative and clinical levels.Intervention Data presentations in the form of league tables or funnel plots.Main outcome measures Number of actions suggested by participants. Proportion of appropriate actions.Results For all four measures, decision-makers tended to suggest more actions based on the information provided in league tables compared to funnel plots (44% vs. 21%, P < 0.001). Actions were on average more appropriate for funnel plots. However, when using funnel plots, decision-makers more often missed to react even when appropriate.Conclusions The form of data presentation had an influence on decision-making. With league tables, decision-makers tended to suggest more actions compared to funnel plots. A difference in sensitivity and specificity conditioned by the form of presentation could also be identified, with different implications depending on the purpose of comparisons. Explanations and visualization aids are needed to support appropriate actions.
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| 7. |
- Bernardo, Carina, et al.
(author)
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Molecular pathology of the luminal class of urothelial tumors
- 2019
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In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 249:3, s. 308-318
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Journal article (peer-reviewed)abstract
- Molecular subtypes of urothelial carcinoma may be divided into luminal and nonluminal tumors. Nonluminal tumors are composed of cases with basal/squamous-like or small cell/neuroendocrine features, with a consensus on the molecular characteristics of the respective subtype. In contrast, luminal tumors are more disparate with three to five suggested subtypes and with definitions that do not always cohere. To resolve some of these disparities we assembled a cohort of 344 luminal tumors classified as urothelial-like (Uro), with the subtypes UroA, UroAp, UroB, and UroC, or genomically unstable (GU) according to the LundTax system. Cases were systematically analyzed by immunohistochemistry using antibodies for proteins representing important biological processes or cellular states: KRT5, EGFR, and CDH3 for the integrity of a basal cell layer; CCNB1, Ki67, and FOXM1 for proliferation; FGFR3 and ERBB2 for receptor tyrosine kinase status; CCND1, CDKN2A(p16), RB1, and E2F3 for cell cycle regulation; PPARG, GATA3, and TP63 for the differentiation regulatory system; and KRT20 and UPK3 for the differentiation readout. We show that Uro tumors form one, albeit heterogenous, group characterized by FGFR3, CCND1, and RB1 expression, but low or absence of CDKN2A(p16) and ERBB2 expression. The opposite expression pattern is observed in GU cases. Furthermore, Uro tumors are distinguished from GU tumors by showing a high RB1/p16 expression ratio. Class defining characteristics were independent of pathological stage and growth pattern, and thus intrinsic. In Uro tumors, proliferation was limited to a well-defined single layer of basal-like cells in UroA tumors but occurred throughout the tumor parenchyma, independent of the basal layer, in the more progressed UroAp and UroC tumors. A similar change in proliferation topology was not observed in GU. We conclude that luminal urothelial carcinomas consist, at the molecular pathology level, of two major subtypes, the larger heterogenous Uro and the biologically distinct GU subtype.
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| 8. |
- Böös, Malin, et al.
(author)
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Who should record surgical complications? : Results from a third-party assessment of complications after radical cystectomy
- 2019
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In: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 53:5, s. 339-343
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Journal article (peer-reviewed)abstract
- Objective: In Sweden complications after radical cystectomy have been reported to the nationwide population-based Swedish Cystectomy Registry since 2011. Here, validation of the reporting was assessed in two healthcare regions.Materials and methods: Complications were ascertained from patient records by a third party not involved in the care delivered to 429 randomly selected patients from 949 who had undergone radical cystectomy since 2011 in four hospitals. Without knowledge of the outcome in the primary registration, post-operative complications within 90 days post-operatively were assessed by an independent review of patient charts, and the results were compared with the primary reports in the Swedish Cystectomy Registry.Results: The third-party assessment identified post-operative complications in 310 patients (72%). Low-grade complications (Clavien-Dindo I-II) were noted in 110 (26%) of the patients in the primary registration, but increased to 182 (42%) in the validation (p < 0.00001). High-grade complications (Clavien-Dindo III-V) were reported in 113 (26%) patients in the primary registration, but in 128 (30%) of the patients in the validation (p = 0.02). According to the third-party assessment, 18 patients (4%) had Clavien-Dindo grade IV complications and 12 (3%) died within 90 days of surgery (Clavien-Dindo grade V); corresponding values in the primary registration were 15 (3%) and 9 (2%), respectively. The readmission rate within 90 days increased from 27 to 32% in the validation (p < 0.00001).Conclusions: Compared with registry data, third-party assessment revealed more complications and readmissions after radical cystectomy. Hence such evaluation may improve the validity of reported complication data.
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| 9. |
- Eriksson, Pontus, et al.
(author)
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HER2 and EGFR amplification and expression in urothelial carcinoma occurs in distinct biological and molecular contexts
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:30, s. 48905-48914
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Journal article (peer-reviewed)abstract
- We analyzed a cohort of 599 cases of urothelial carcinoma for EGFR, ERBB2, and ERBB3 gene expression and genomic alterations. The cohort consisted of a reference set (n = 292) comprising all stages and grades and one set (n = 307) of advanced tumors. All cases were previously classified into urothelial carcinoma molecular subtypes. Genomic amplifications were established by array-CGH or in-situ hybridization, and gene expression both at mRNA and protein levels. Clinical HER2 status was independently evaluated using standard clinical procedures. EGFR amplifications were observed in 14% and ERBB2 amplifications in 23% of the reference cohort. EGFR gains were enriched in the Basal/SCC-like and ERBB2 gains in the Genomically Unstable subtypes. The expression data suggests that the Genomically Unstable show high ERBB2/ERBB3 but low EGFR expression and that Basal/SCC-like tumors show high EGFR but low ERBB2/ERBB3 expression. Whereas the frequency of ERBB2 genomic amplification were similar for cases of the Genomically Unstable subtype in the two cohorts, the Urotheliallike subtype acquires ERBB2 amplifications and expression during progression. Even though a good correlation between gene amplification and ERBB2 gene expression was observed in the Urothelial-like and Genomically Unstable subtypes less than half of the Basal/SCC-like cases with ERBB2 amplification showed concomitant ERBB2 mRNA and protein expression. We conclude that clinical trials using ERBB2 (HER2) or EGFR as targets have not fully appreciated the molecular heterogeneity in which activated ERBB2 and EGFR systems operate. Proper tumor classification is likely to be critical for arriving at thorough conclusions regarding new HER2 and EGFR based treatment regimes.
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| 10. |
- Eriksson, Pontus, et al.
(author)
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Molecular subtypes of urothelial carcinoma are defined by specific gene regulatory systems.
- 2015
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In: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 8:1
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Journal article (peer-reviewed)abstract
- Molecular stratification of bladder cancer has revealed gene signatures differentially expressed across tumor subtypes. While these signatures provide important insights into subtype biology, the transcriptional regulation that governs these signatures is not well characterized.
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