| 41. |
- Bedke, Jens, et al.
(författare)
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2021 Updated European Association of Urology Guidelines on the Use of Adjuvant Pembrolizumab for Renal Cell Carcinoma
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:2, s. 134-137
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Tidskriftsartikel (refereegranskat)abstract
- Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy.Patient summary: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery.
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| 42. |
- Bedke, Jens, et al.
(författare)
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The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma : Immune Checkpoint Inhibitor–based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care
- 2021
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 80:4, s. 393-397
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. Patient summary: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.
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| 43. |
- Bedke, Jens, et al.
(författare)
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The 2022 updated European association of urology guidelines on the use of adjuvant immune checkpoint inhibitor therapy for renal cell carcinoma
- 2023
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:1, s. 10-14
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Tidskriftsartikel (refereegranskat)abstract
- In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient.Patient summary: New results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed.
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| 44. |
- Bedke, Jens, et al.
(författare)
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Updated European Association of Urology Guidelines on Renal Cell Carcinoma : Nivolumab plus Cabozantinib Joins Immune Checkpoint Inhibition Combination Therapies for Treatment-naïve Metastatic Clear-Cell Renal Cell Carcinoma
- 2021
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 79:3, s. 339-342
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Tidskriftsartikel (refereegranskat)abstract
- Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. PATIENT SUMMARY: New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.
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| 45. |
- Beijert, Irene J., et al.
(författare)
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The importance of being grade 3 : a plea for a three-tier hybrid classification system for grade in primary non–muscle-invasive bladder cancer
- 2024
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560.
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Tidskriftsartikel (refereegranskat)abstract
- Grade is an important determinant of progression in non–muscle-invasive bladder cancer. Although the World Health Organization (WHO) 2004/2016 grading system is recommended, other systems such as WHO1973 and WHO1999 are still widely used. Recently, a hybrid (three-tier) system was proposed, separating WHO2004/2016 high grade (HG) into HG/grade 2 (G2) and HG/G3 while maintaining low grade. We assessed the prognostic performance of HG/G3 and HG/G2. Three independent cohorts with 9712 primary (first diagnosis) Ta-T1 bladder tumors were analyzed. Time to progression was analyzed with cumulative incidence functions and Cox regression models. Harrell's C-index was used to assess discrimination. Time to progression was significantly shorter for HG/G3 than for HG/G2 in multivariable analyses (cohort 1: hazard ratio [HR] = 1.92; cohort 2: HR = 2.51, and cohort 3: HR = 1.69). Corresponding progression risks at 5 yr were 18%, 20%, and 18% for HG/G3 versus 7.3%, 7.5%, and 9.3% for HG/G2, respectively. Cox models using hybrid grade performed better than models with WHO2004/2016 (all cohorts; p < 0.001). For the three cohorts, C-indices for WHO2004/2016 were 0.69, 0.62, and 0.75, while, for hybrid grade, C-indices were 0.74, 0.68, and 0.78, respectively. Subdividing the HG category into HG/G2 and HG/G3 stratifies time to progression and supports the recommendation to adopt the hybrid grading system for Ta/T1 bladder cancers.
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| 46. |
- Bekema, Hendrika J., et al.
(författare)
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Systematic Review of Adrenalectomy and Lymph Node Dissection in Locally Advanced Renal Cell Carcinoma
- 2013
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 64:5, s. 799-810
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Forskningsöversikt (refereegranskat)abstract
- Context: Controversy remains over whether adrenalectomy and lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for locally advanced renal cell carcinoma (RCC) cT3-T4N0M0. Objective: To systematically review all relevant literature comparing oncologic, perioperative, and quality-of-life (QoL) outcomes for locally advanced RCC managed with RN with or without concomitant adrenalectomy or LND.Evidence acquisition: Relevant databases were searched up to August 2012. Randomised controlled trials (RCTs) and comparative studies were included. Outcome measures were overall survival, QoL, and perioperative adverse effects. Risks of bias (RoB) were assessed using Cochrane RoB tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.Evidence synthesis: A total of 3658 abstracts and 252 full-text articles were screened. Eight studies met the inclusion criteria: six LNDs (one RCT and five nonrandomised studies [NRSs]) and two adrenalectomies (two NRSs). RoB was high across the evidence base, and the quality of evidence from outcomes ranged from moderate to very low. Meta-analyses were not undertaken because of diverse study designs and data heterogeneity. There was no significant difference in survival between the groups, even though 5-yr overall survival appears better for the RN plus LND group compared with the no-LND group in one randomised study. There was no evidence of a difference in adverse events between the RN plus LND and no-LND groups. No studies reported QoL outcomes. There was no evidence of an oncologic difference between the RN with adrenalectomy and RN without adrenalectomy groups. No studies reported adverse events or QoL outcomes.Conclusions: There is insufficient evidence to draw any conclusions on oncologic outcomes for patients having concomitant LND or ipsilateral adrenalectomy compared with patients having RN alone for cT3-T4N0M0 RCC. The quality of evidence is generally low and the results potentially biased. Further research in adequately powered trials is needed to answer these questions.
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| 47. |
- Bergengren, Oskar, et al.
(författare)
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2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review
- 2023
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 84:2, s. 191-206
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Forskningsöversikt (refereegranskat)abstract
- Context: Prostate cancer (PCa) is one of the most common cancers worldwide. Understanding the epidemiology and risk factors of the disease is paramount to improve primary and secondary prevention strategies.Objective: To systematically review and summarize the current evidence on the descrip-tive epidemiology, large screening studies, diagnostic techniques, and risk factors of PCa.Evidence acquisition: PCa incidence and mortality rates for 2020 were obtained from the GLOBOCAN database of the International Agency for Research on Cancer. A systematic search was performed in July 2022 using PubMed/MEDLINE and EMBASE biomedical databases. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered in PROSPERO (CRD42022359728).Evidence synthesis: Globally, PCa is the second most common cancer, with the highest incidence in North and South America, Europe, Australia, and the Caribbean. Risk factors include age, family history, and genetic predisposition. Additional factors may include smoking, diet, physical activity, specific medications, and occupational factors. As PCa screening has become more accepted, newer approaches such as magnetic resonance imaging (MRI) and biomarkers have been implemented to identify patients who are likely to harbor significant tumors. Limitations of this review include the evidence being derived from meta-analyses of mostly retrospective studies.Conclusions: PCa remains the second most common cancer among men worldwide. PCa screening is gaining acceptance and will likely reduce PCa mortality at the cost of over-diagnosis and overtreatment. Increasing use of MRI and biomarkers for the detection of PCa may mitigate some of the negative consequences of screening.
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| 48. |
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| 49. |
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