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Westergren, D.-O., Gardmark, T., Lindhagen, L., Chau, A. & Malmström, P.-U. (2019). 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. Journal of Urology, 202(5), 905-912
Open this publication in new window or tab >>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
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2019 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 202, no 5, p. 905-912Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
urinary bladder neoplasms, palliative care, survival analysis, mortality, Sweden
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-398416 (URN)10.1097/JU.0000000000000350 (DOI)000496924200062 ()31144594 (PubMedID)
Funder
Swedish Cancer Society, CAN 2016/470Swedish Cancer Society, CAN 2017/278
Available from: 2019-12-11 Created: 2019-12-11 Last updated: 2019-12-11Bibliographically approved
Lotan, Y., Bivalacqua, T. J., Downs, T., Huang, W., Jones, J., Kamat, A. M., . . . Daneshmand, S. (2019). Blue light flexible cystoscopy with hexaminolevulinate in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on optimal use in the USA - update 2018. Nature reviews. Urology, 16(6), 377-386
Open this publication in new window or tab >>Blue light flexible cystoscopy with hexaminolevulinate in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on optimal use in the USA - update 2018
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2019 (English)In: Nature reviews. Urology, ISSN 1759-4812, E-ISSN 1759-4820, Vol. 16, no 6, p. 377-386Article, review/survey (Refereed) Published
Abstract [en]

Blue light cystoscopy (BLC) with hexaminolevulinate (HAL) during transurethral resection of bladder cancer improves detection of non-muscle-invasive bladder cancer (NMIBC) and reduces recurrence rates. Flexible BLC was approved by the FDA in 2018 for use in the surveillance setting and was demonstrated to improve detection. Results of a phase III prospective multicentre study of blue light flexible cystoscopy (BLFC) in surveillance of intermediate-risk and high-risk NMIBC showed that 20.6% of malignancies were identified only by BLFC. Improved detection rates in the surveillance setting are anticipated to lead to improved clinical outcomes by reducing future recurrences and earlier identification of tumours that are unresponsive to therapy. Thus, BLFC has a role in surveillance cystoscopy, and determining which patients will benefit from BLFC and optimal and cost-effective ways of incorporating this technology into surveillance cystoscopy must be developed.

National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-387986 (URN)10.1038/s41585-019-0184-4 (DOI)000470118100010 ()31019310 (PubMedID)
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-06-27Bibliographically approved
Malmström, P.-U., Gårdmark, T., Sherif, A., Ströck, V., Hosseini-Aliabad, A., Jahnson, S., . . . Liedberg, F. (2019). Incidence, survival and mortality trends of bladder cancer in Sweden 1997-2016. Scandinavian journal of urology, 53(4), 193-199
Open this publication in new window or tab >>Incidence, survival and mortality trends of bladder cancer in Sweden 1997-2016
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2019 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 4, p. 193-199Article in journal (Refereed) Published
Abstract [en]

Objective: To evaluate trends in bladder cancer incidence, survival and mortality in Sweden from 1997-2016.

Patients and methods: The Swedish National Registry of Urinary Bladder Cancer is a nation-wide quality register that started in 1997. It includes information on initial tumor characteristics and treatment; 41,097 new cases were registered up to 2016. Patients were stratified into four time periods. Deaths were monitored through the national death register. Overall and relative survival in time periods were studied with respect to differences in stage, age and gender.

Results: The number of new cases increased by 38% for men and 39% for women from 1997 to 2016. The corresponding age-standardized incidence per 100,000 was less dramatic, with increases of 6% and 21%, respectively, and the increase was most evident in the oldest age group. The survival rate was stable until 2012, but thereafter a significant improvement occurred. The survival trends in stage-groups show that this improvement is found in all categories as well as irrespective of age and gender. The mortality rate during this period was stable for women, but showed a slight decrease for men. The main limitation of this study is the use of administrative data for defining some of the endpoints.

Conclusion: The most recent Swedish bladder cancer statistics show an increased incidence, improved survival, but stable mortality.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Bladder cancer, population-based, incidence, survival and mortality
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-395926 (URN)10.1080/21681805.2019.1632380 (DOI)000473940600001 ()31262208 (PubMedID)
Available from: 2019-10-30 Created: 2019-10-30 Last updated: 2019-11-08Bibliographically approved
Turker, P., Segersten, U., Malmström, P.-U. & Hemdan, T. (2019). Is Bcl-2 a predictive marker of neoadjuvant chemotherapy response in patients with urothelial bladder cancer undergoing radical cystectomy?. Scandinavian journal of urology, 53(1), 45-50
Open this publication in new window or tab >>Is Bcl-2 a predictive marker of neoadjuvant chemotherapy response in patients with urothelial bladder cancer undergoing radical cystectomy?
2019 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 1, p. 45-50Article in journal (Refereed) Published
Abstract [en]

Background: Response to neoadjuvant cisplatin treatment in bladder cancer has been linked to expression of Bcl-2 protein by cancer cells. The objective of this study was to test Bcl-2 as a predictive marker of neoadjuvant cisplatin chemotherapy response in a patient cohort from randomized cystectomy trials.Methods: Tumor samples were taken from 247 patients with T2-T4 bladder cancer enrolled in two randomized trials comparing cystectomy with or without neoadjuvant chemotherapy. Tissue microarrays from pre-intervention transurethral resection specimens were assessed for Bcl-2 protein status by immunohistochemistry. Extension of staining above 10% was regarded as positive. Downstaging and survival ratios in relation to Bcl-2 immunoreactivity and neoadjuvant chemotherapy utilization were calculated using the log rank test and multivariate Cox proportional hazards regression analyses.Results: Bcl-2 expression was positive in 38% and negative in 62% of the 236 evaluable patients. Bcl-2 negative patients receiving neoadjuvant chemotherapy had a significant increase in survival (p=0.009), while Bcl-2 positive patients showed no difference (p=0.4). However, the interaction variable between neoadjuvant chemotherapy and biomarker status was not significant (p=0.38). When the prognostic value was assessed in the no-chemotherapy group, 5-year overall survival times were significantly better among Bcl-2 positive patients than among Bcl-2 negative patients (42 months vs 33 months, p=0.04), but again Bcl-2 status did not remain independent when other factors were adjusted. Also, in a multivariate analysis with all patients, Bcl-2 was not significant.Conclusions: Bcl-2 status is not an independent predictor of neoadjuvant cisplatin chemotherapy response and is not prognostic in muscle-invasive bladder cancer.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Urothelial bladder cancer, Bcl-2, neoadjuvant cisplatin, predictive
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-389984 (URN)10.1080/21681805.2019.1575467 (DOI)000471933500010 ()30806186 (PubMedID)
Funder
Swedish Cancer SocietyErik, Karin och Gösta Selanders Foundation
Available from: 2019-08-02 Created: 2019-08-02 Last updated: 2019-08-02Bibliographically approved
Jahnson, S., Gårdmark, T., Hosseini, A., Jedström, T., Liedberg, F., Malmström, P.-U., . . . Aljabery, F. (2019). Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe). Scandinavian journal of urology, 53(4), 200-205
Open this publication in new window or tab >>Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe)
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2019 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 4, p. 200-205Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate the management of TaG3 tumours of the urinary bladder using nationwide population-based data in relation to the prevailing guidelines, patients' characteristics, and outcome. Materials and methods: The Bladder Cancer Data Base Sweden (BladderBaSe), including data from the Swedish National Register for Urinary Bladder Cancer (SNRUBC), was used to study all patients with TaG3 bladder cancer diagnosed from 2008 to 2014. Patients were divided into the following management groups: (1) transurethral resection (TUR) only, (2) TUR and intravesical instillation therapy (IVIT), (3) TUR and second-look resection (SLR), and (4) TUR with both SLR and IVIT. Patient and tumour characteristics and outcome were studied. Results: There were 831 patients (83% males) with a median age of 74 years. SLR was performed more often on younger patients, on men, and less often in the Western and Uppsala/orebro Healthcare regions. IVIT was performed more often with younger patients, with men, in the Western Healthcare region, and less often in the Uppsala/orebro Healthcare region. Death from bladder cancer occurred in 6% of cases within a median of 29 months (0-84 months) and was lower in the TUR/IVIT and TUR/SLR/IVIT groups compared to the other two groups. Conclusion: In the present study, there was, according to the prevailing treatment guidelines, an under-treatment with SLR for older patients, women, and in some healthcare regions and, similarly, there was an under-treatment with IVIT for older patients. Cancer-specific survival and relative survival were lower in the TUR only group compared to the TUR/IVIT and TUR/SLR/IVIT groups.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2019
Keywords
Bladder cancer, population-based, TaG3, second-look resection, intravesical instillation treatment
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-398723 (URN)10.1080/21681805.2019.1621377 (DOI)000471561600001 ()31144582 (PubMedID)
Funder
Swedish Cancer Society, CAN 2016/470Swedish Cancer Society, CAN 278
Available from: 2019-12-10 Created: 2019-12-10 Last updated: 2019-12-12Bibliographically approved
Russell, B., Sherif, A., Häggström, C., Josephs, D., Kumar, P., Malmström, P.-U. & Van Hemelrijck, M. (2019). Neoadjuvant chemotherapy for muscle invasive bladder cancer: a nationwide investigation on survival. Scandinavian journal of urology, 53(4), 206-212
Open this publication in new window or tab >>Neoadjuvant chemotherapy for muscle invasive bladder cancer: a nationwide investigation on survival
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2019 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 4, p. 206-212Article in journal (Refereed) Published
Abstract [en]

Objectives: Randomised controlled trials (RCTs) have investigated the use of neoadjuvant chemotherapy (NAC) and its effect on survival patients with non-metastatic muscle-invasive bladder cancer (MIBC). However, these RCTs have limited external validity and generalisability and, therefore, the current study aims to use real world evidence in the form of observational data to identify the effect that NAC may have on survival, compared to the use of radical cystectomy (RC) alone. Materials and methods: The study cohort (consisting of 944 patients) was selected as a target trial from the Bladder Cancer Data Base Sweden (BladderBaSe). This study calculated 5-year survival and risk of bladder cancer (BC)-specific and overall death by Cox proportional hazard models for the study cohort and a propensity score (PS) matched cohort. Results: Those who had received NAC had higher 5-year survival proportions and decreased risk of both overall and BC specific death (HR = 0.71, 95% CI = 0.52-0.97 and HR = 0.67, 95% CI = 0.48-0.94), respectively, as compared to patients who did not receive NAC. The PS matched cohort showed similar estimates, but with larger statistical uncertainty (Overall death: HR = 0.76, 95% CI = 0.53-1.09 and BC-specific death: HR = 0.73, 95% CI = 0.50-1.07). Conclusion: Results from the current observational study found similar point estimates for 5-year survival and of relative risks as previous studies. However, the results based on real world evidence had larger statistical variability, resulting in a non-statistically significant effect of NAC on survival. Future studies with detailed validated data can be used to further investigate the effect of NAC in narrower patient groups.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Muscle invasive bladder cancer, neoadjuvant chemotherapy, radical cystectomy, survival
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-396072 (URN)10.1080/21681805.2019.1624611 (DOI)000472425500001 ()31174452 (PubMedID)
Available from: 2019-10-30 Created: 2019-10-30 Last updated: 2019-12-12Bibliographically approved
Liedberg, F., Hagberg, O., Aljabery, F., Gardmark, T., Hosseini, A., Jahnson, S., . . . Holmberg, L. (2019). Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study. BJU International, 124(3), 449-456
Open this publication in new window or tab >>Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study
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2019 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 124, no 3, p. 449-456Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
hospital volume, radical cystectomy, survival, quality of care, #blcsm, #BladderCancer
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-394256 (URN)10.1111/bju.14767 (DOI)000482452800019 ()30950568 (PubMedID)
Funder
Swedish Cancer Society, CAN 2016/470Swedish Cancer Society, CAN 2017/278
Available from: 2019-10-11 Created: 2019-10-11 Last updated: 2019-12-12Bibliographically approved
Malmström, P.-U., Skaaheim, E., Boström, P. J., Gudjonsson, S. & Jensen, J. B. (2019). Progress towards a Nordic standard for the investigation of hematuria: 2019. Scandinavian journal of urology, 53(1), 1-6
Open this publication in new window or tab >>Progress towards a Nordic standard for the investigation of hematuria: 2019
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2019 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 1, p. 1-6Article in journal (Refereed) Published
Abstract [en]

Objective: To describe the management of patients with hematuria in the Nordic countries in relation to bladder cancer epidemiology, especially in the context of introducing fast track pathways with the aim of proposing a common guideline.

Materials and methods: Epidemiological data on bladder cancer from each country, and the combined cancer registry, Nordcan, were analyzed. The evolution of the different national recommendations and the introduction of fast track pathways were assessed. Patients' demographics, type of hematuria and cancer detection rates were analysed if available.

Results: The crude incidence of bladder cancer has increased substantially since the 1960s, while the age standardized incidence has been stable during recent decades. The relative survival has increased in all countries, while the mortality has been stable. For those with microscopic hematuria there has been a clear trend towards less rigorous investigations. In the fast track pathways, introduced in three of five countries, about one in five patients with macroscopic hematuria had a cancer diagnosis. Data show that time to diagnosis has been reduced.

Conclusions: The number of patients with bladder cancer is increasing in the Nordic region. The introduction of fast track pathways has been important in improving the management of patients with suspicion of the disease. Our recommendation is to focus on macroscopic hematuria in the fast track pathways. Microhematuria without any symptoms should not be an indication for cystoscopy. However, urinary tract symptoms accompanied by microhematuria can still be investigated according to respective guidelines but not necessarily within fast track pathways.

 

Keywords
Hematuria, bladder cancer, investigation, population study
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-389983 (URN)10.1080/21681805.2018.1555187 (DOI)000471933500001 ()30636472 (PubMedID)
Available from: 2019-08-02 Created: 2019-08-02 Last updated: 2019-10-30Bibliographically approved
Roupret, M., Malmström, P.-U. & Black, P. (2019). Recurrent Ta Low-grade Non-muscle-invasive Bladder Cancer: What Are the Options?. EUROPEAN UROLOGY ONCOLOGY, 2(6), 723-729
Open this publication in new window or tab >>Recurrent Ta Low-grade Non-muscle-invasive Bladder Cancer: What Are the Options?
2019 (English)In: EUROPEAN UROLOGY ONCOLOGY, ISSN 2588-9311, Vol. 2, no 6, p. 723-729Article in journal (Refereed) Published
Abstract [en]

Recurrent low-grade Ta tumours, classified as intermediate-risk non-muscle-invasive bladder cancer (NMIBC), have a high risk of recurrence but a low risk of progression. This case presents a 60-yr-old female with intermediate-risk NMIBC who has been treated with sequential courses of mitomycin C followed by bacillus Calmette-Guerin (BCG). She continued to develop multiple episodes of recurrence. The discussion addresses whether the best course is repeat transurethral resection of the bladder with continued monitoring, more of the same intravesical treatments, new methods of applying these treatments, or novel treatments that might involve enrolling the patient in a clinical trial. The biggest unmet need in the field comes from the lack of a molecular marker that could help select patients for aggressive strategies. Patient summary: Following treatment of intermediate-risk non-muscle-invasive bladder cancer with a fairly standard course of intravesical drug therapy, the patient, a relatively young woman, continued to develop recurrences of the bladder cancer. The authors discuss whether the best next course is "more of the same", device-assisted application of these treatments, or perhaps one of the new, still investigatory treatment approaches. Radical surgery (removal of the bladder) should not be necessary unless the recurrences show signs of disease progression. .

Place, publisher, year, edition, pages
ELSEVIER, 2019
Keywords
Surveillance, Mutation, Immune checkpoint blockade, Urothelial cancer, Bladder, Neoplasm, Progression, Recurrence
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-398023 (URN)10.1016/j.euo.2019.06.003 (DOI)000496493400015 ()31239237 (PubMedID)
Available from: 2019-12-05 Created: 2019-12-05 Last updated: 2019-12-05Bibliographically approved
Häggström, C., Garmo, H., de Luna, X., Van Hemelrijck, M., Söderkvist, K., Aljabery, F., . . . Holmberg, L. (2019). Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study. Cancer Medicine, 8(5), 2196-2204
Open this publication in new window or tab >>Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study
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2019 (English)In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, no 5, p. 2196-2204Article in journal (Refereed) Published
Abstract [en]

Background: Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC.

Methods: We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period.

Results: The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29.

Conclusion(s): Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
bladder cancer, muscle-invasive, radical cystectomy, radiotherapy, urothelial carcinoma
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-387973 (URN)10.1002/cam4.2126 (DOI)000469272500024 ()30938068 (PubMedID)
Funder
Swedish Cancer Society, CAN 2013/472
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-12-12Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8572-9957

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