| 1. |
- Abu-Ghanem, Yasmin, et al.
(författare)
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Limitations of Available Studies Prevent Reliable Comparison Between Tumour Ablation and Partial Nephrectomy for Patients with Localised Renal Masses : A Systematic Review from the European Association of Urology Renal Cell Cancer Guideline Panel
- 2020
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 3:4, s. 423-442
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Forskningsöversikt (refereegranskat)abstract
- The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel performed a protocol-driven systematic review (SR) on thermal ablation (TA) compared with partial nephrectomy (PN) for T1N0M0 renal masses, in order to provide evidence to support its recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed, and only comparative studies published between 2000 and 2019 were included. Twenty-six nonrandomised comparative studies were included, recruiting a total of 167 80 patients. Risk of bias (RoB) assessment revealed high or uncertain RoB across all studies, with the vast majority being retrospective, observational studies with poorly matched controls and short follow-up. Limited data showed TA to be safe, but its long-term oncological effectiveness compared with PN remains uncertain. A quality assessment of pre-existing SRs (n = 11) on the topic, using AMSTAR, revealed that all SRs had low confidence rating, with all but two SRs being rated critically low. In conclusion, the current data are inadequate to make any strong and clear conclusions regarding the clinical effectiveness of TA for treating T1N0M0 renal masses compared with PN. Therefore, TA may be cautiously considered an alternative to PN for T1N0M0 renal masses, but patients must be counselled carefully regarding the prevailing uncertainties. We recommend specific steps to improve the evidence base based on robust primary and secondary studies.Patient summary: In this report, we looked at the literature to determine the effectiveness of thermoablation (TA) in the treatment of small kidney tumours compared with surgical removal. We found that TA could cautiously be offered as an option due to many remaining uncertainties regarding its effectiveness.
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| 2. |
- Albiges, Laurence, et al.
(författare)
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Updated European Association of Urology Guidelines on Renal Cell Carcinoma : Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 76:2, s. 151-156
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Tidskriftsartikel (refereegranskat)abstract
- Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma. The European Association of Urology Guidelines Panel has updated its recommendations based on these studies. Patient summary: Pembrolizumab plus axitinib is a new standard of care for patients diagnosed with kidney cancer spread outside the kidney and who did not receive any prior treatment for their cancer (treatment naïve). This applies to all risk groups as determined by the International Metastatic Renal Cell Carcinoma Database Consortium criteria.
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| 3. |
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| 4. |
- Bex, Axel, et al.
(författare)
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Updated European Association of Urology Guidelines for Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Clear-cell Renal Cell Carcinoma
- 2018
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 74:6, s. 805-809
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Tidskriftsartikel (refereegranskat)abstract
- Cytoreductive nephrectomy (CN) has been the standard of care in patients with metastatic clear-cell renal cancer who present with the tumour in place. The CARMENA trial compared systemic therapy alone with CN followed by systemic therapy. This article outlines the new guidelines based on these data.Patient summary: The CARMENA trial demonstrates that immediate cytoreductive nephrectomy should no longer be considered the standard of care in patients diagnosed with intermediate and poor risk metastatic renal cell carcinoma when medical treatment is required. However, the psychological burden poor risk patients experience hearing that removal of their primary tumour will not be beneficial, should be carefully considered.
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| 5. |
- Bex, Axel, et al.
(författare)
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Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:5, s. 719-722
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Tidskriftsartikel (refereegranskat)abstract
- The European Association of Urology Renal Cell Carcinoma (RCC) guidelines panel updated their recommendation on adjuvant therapy in unfavourable, clinically nonmetastatic RCC following the recently reported results of a second randomised controlled phase 3 trial comparing 1-yr sunitinib to placebo for high-risk RCC after nephrectomy (S-TRAC). On the basis of conflicting results from the two available studies, the panel rated the quality of the evidence, the harm-to-benefit ratio, patient preferences, and costs. Finally, the panel, including representatives from a patient advocate group (International Kidney Cancer Coalition) voted and reached a consensus to not recommend adjuvant therapy with sunitinib for patients with high-risk RCC after nephrectomy. Patient summary: In two studies, sunitinib was given for 1 yr and compared to no active treatment (placebo) in patients who had their kidney tumour removed and who had a high risk of cancer coming back after surgery. Although one study demonstrated that 1 yr of sunitinib therapy resulted in a 1.2-yr longer time before the disease recurred, the other study did not show a benefit and it has not been shown that patients live longer. Despite having been diagnosed with high-risk disease, many patients remain without recurrence, and the side effects of sunitinib are high. Therefore, the panel members, including patient representatives, do not recommend sunitinib after tumour removal in these patients.
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| 6. |
- Chi, Kim N, et al.
(författare)
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Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer
- 2019
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 381:1, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined.METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival.RESULTS: A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.CONCLUSIONS: In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).
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| 7. |
- Chi, Kim N., et al.
(författare)
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Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer : Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study
- 2021
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 39:20, s. 2294-2303
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover. METHODS: Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed. RESULTS: With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached v 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; P < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance (P < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports. CONCLUSION: The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.
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| 8. |
- Fernández-Pello, Sergio, et al.
(författare)
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A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:3, s. 426-436
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Forskningsöversikt (refereegranskat)abstract
- Context While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown. Objective To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC. Evidence acquisition Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken. Evidence synthesis The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03–1.92 and 1.41, 95% CI: 0.88–2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67–2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9–2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91–1.86). Sunitinib was associated with more Grade 3–4 adverse events than everolimus, although this was not statistically significant. Conclusions This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed. Patient summary We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need.
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| 9. |
- Fernández-Pello, Sergio, et al.
(författare)
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Management of Sporadic Renal Angiomyolipomas : A Systematic Review of Available Evidence to Guide Recommendations from the European Association of Urology Renal Cell Carcinoma Guidelines Panel
- 2020
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 3:1, s. 57-72
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Forskningsöversikt (refereegranskat)abstract
- Context: Little is known about the natural history of sporadic angiomyolipomas (AMLs); there is uncertainty regarding the indications of treatment and treatment options. Objective: To evaluate the indications, effectiveness, harms, and follow-up of different management modalities for sporadic AML to provide guidance for clinical practice. Evidence acquisition: A systematic review of the literature was undertaken, incorporating Medline, Embase, and the Cochrane Library (from 1 January 1990 to 30 June 2017), in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. No restriction on study design was imposed. Patients with sporadic AML were included. The main interventions included active surveillance, surgery (nephron-sparing surgery and radical nephrectomy), selective arterial embolisation, and percutaneous or laparoscopic thermal ablations (radiofrequency, microwaves, or cryoablation). The outcomes included indications for active treatment, AML growth rate, AML recurrence rate, risk of bleeding, post-treatment renal function, adverse events of treatments, and modalities of followup. Risk of bias assessment was performed using standard Cochrane methods. Evidence synthesis: Among 2704 articles identified, 43 were eligible for inclusion (zero randomised controlled trials, nine nonrandomised comparative retrospective studies, and 34 single-arm case series). Most studies were retrospective and uncontrolled, and had a moderate to high risk of bias. Conclusions: In active surveillance series, spontaneous bleeding was reported in 2% of patients and active treatment was undertaken in 5%. Active surveillance is the most chosen option in 48% of the cases, followed by surgery in 31% and selective arterial embolisation in 17% of the cases. Selective arterial embolisation appeared to reduce AML volume but required secondary treatment in 30% of the cases. Surgery (particularly nephron-sparing surgery) was the most effective treatment in terms of recurrence and need for secondary procedures. Thermal ablation was an infrequent option. The association between AML size and the risk of bleeding remained unclear; as such the traditional 4-cm cut-off should not per se trigger active treatment. In spite of the limitations and uncertainties relating to the evidence base, the findings may be used to guide and inform clinical practice, until more robust data emerge. Patient summary: Sporadic angiomyolipoma (AML) is a benign tumour of the kidney consisting of a mixture of blood vessels, fat, and muscle. Large tumours may have a risk of spontaneous bleeding. However, the size beyond which these tumours need to be treated remains unclear. Most small AMLs can be monitored without any active treatment. For those who need treatment, options include surgical removal of the tumour or stopping its blood supply (selective embolisation). Surgery has a lower recurrence rate and lower need for a repeat surgical procedure.
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| 10. |
- Lardas, Michael, et al.
(författare)
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Systematic Review of Surgical Management of Nonmetastatic Renal Cell Carcinoma with Vena Caval Thrombus
- 2016
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 70:2, s. 265-280
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Overall, 4-10% of patients with renal cell carcinoma (RCC) present with venous tumour thrombus. It is uncertain which surgical technique is best for these patients. Appraisal of outcomes with differing techniques would guide practice.OBJECTIVE: To systematically review relevant literature comparing the outcomes of different surgical therapies and approaches in treating vena caval thrombus (VCT) from nonmetastatic RCC.EVIDENCE ACQUISITION: Relevant databases (Medline, Embase, and the Cochrane Library) were searched to identify relevant comparative studies. Risk of bias and confounding assessments were performed. A narrative synthesis of the evidence was presented.EVIDENCE SYNTHESIS: The literature search identified 824 articles. Fourteen studies reporting on 2262 patients were included. No distinct surgical method was superior for the excision of VCT, although the method appeared to be dependent on tumour thrombus level. Minimal access techniques appeared to have better perioperative and recovery outcomes than traditional median sternotomy, but the impact on oncologic outcomes is unknown. Preoperative renal artery embolisation did not offer any oncologic benefits and instead resulted in significantly worse perioperative and recovery outcomes, including possibly higher perioperative mortality. The comparison of cardiopulmonary bypass versus no cardiopulmonary bypass showed no differences in oncologic outcomes. Overall, there were high risks of bias and confounding.CONCLUSIONS: The evidence base, although derived from retrospective case series and complemented by expert opinion, suggests that patients with nonmetastatic RCC and VCT and acceptable performance status should be considered for surgical intervention. Despite a robust review, the findings were associated with uncertainty due to the poor quality of primary studies available. The most efficacious surgical technique remains unclear.PATIENT SUMMARY: We examined the literature on the benefits of surgery to remove kidney cancers that have spread to neighbouring veins. The results suggest such surgery, although challenging and associated with high risk of complications, appears to be feasible and effective and should be contemplated for suitable patients if possible; however, many uncertainties remain due to the poor quality of the data.
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| 11. |
- Ljungberg, Börje, et al.
(författare)
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EAU Guidelines on Renal Cell Carcinoma : 2014 Update
- 2015
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 67:5, s. 913-924
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Tidskriftsartikel (refereegranskat)abstract
- Context: The European Association of Urology Guideline Panel for Renal Cell Carcinoma (RCC) has prepared evidence-based guidelines and recommendations for RCC management. Objectives: To provide an update of the 2010 RCC guideline based on a standardised methodology that is robust, transparent, reproducible, and reliable. Evidence acquisition: For the 2014 update, the panel prioritised the following topics: percutaneous biopsy of renal masses, treatment of localised RCC (including surgical and nonsurgical management), lymph node dissection, management of venous thrombus, systemic therapy, and local treatment of metastases, for which evidence synthesis was undertaken based on systematic reviews adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Relevant databases (Medline, Cochrane Library, trial registries, conference proceedings) were searched (January 2000 to November 2013) including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm. Risk of bias (RoB) assessment and qualitative and quantitative synthesis of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. Evidence synthesis: All chapters of the RCC guideline were updated. For the various systematic reviews, the search identified a total of 10 862 articles. A total of 151 studies reporting on 78 792 patients were eligible for inclusion; where applicable, data from RCTs were included and meta-analyses were performed. For RCTs, there was low RoB across studies; however, clinical and methodological heterogeneity prevented data pooling for most studies. The majority of studies included were retrospective with matched or unmatched cohorts based on single or multi-institutional data or national registries. The exception was for systemic treatment of metastatic RCC, in which several RCTs have been performed, resulting in recommendations based on higher levels of evidence. Conclusions: The 2014 guideline has been updated by a multidisciplinary panel using the highest methodological standards, and provides the best and most reliable contemporary evidence base for RCC management. Patient summary: The European Association of Urology Guideline Panel for Renal Cell Carcinoma has thoroughly evaluated available research data on kidney cancer to establish international standards for the care of kidney cancer patients.
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| 12. |
- Ljungberg, Börje, 1949-, et al.
(författare)
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European Association of Urology Guidelines on Renal Cell Carcinoma : The 2019 Update
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 75:5, s. 799-810
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Tidskriftsartikel (refereegranskat)abstract
- Context: The European Association of Urology Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC. Objective: To provide an updated RCC guideline based on standardised methodology including systematic reviews, which is robust, transparent, reproducible, and reliable. Evidence acquisition: For the 2019 update, evidence synthesis was undertaken based on a comprehensive and structured literature assessment for new and relevant data. Where necessary, formal systematic reviews adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were undertaken. Relevant databases (Medline, Cochrane Libraries, trial registries, conference proceedings) were searched until June 2018, including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm, systematic reviews, and meta-analyses. Where relevant, risk of bias (RoB) assessment, and qualitative and quantitative syntheses of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. Clinical practice recommendations were developed and issued based on the modified GRADE framework. Evidence synthesis: All chapters of the RCC guidelines were updated based on a structured literature assessment, for prioritised topics based on the availability of robust data. For RCTs, RoB was low across studies. For most non-RCTs, clinical and methodological heterogeneity prevented pooling of data. The majority of included studies were retrospective with matched or unmatched cohorts, based on single- or multi-institutional data or national registries. The exception was for the treatment of metastatic RCC, for which there were several large RCTs, resulting in recommendations based on higher levels of evidence. Conclusions: The 2019 RCC guidelines have been updated by the multidisciplinary panel using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2019. Patient summary: The European Association of Urology Renal Cell Carcinoma Guideline Panel has thoroughly evaluated the available research data on kidney cancer to establish international standards for the care of kidney cancer patients.
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| 13. |
- Marconi, Lorenzo, et al.
(författare)
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Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy
- 2016
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 69:4, s. 660-673
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Forskningsöversikt (refereegranskat)abstract
- Context: The role of percutaneous renal tumour biopsy (RTB) remains controversial due to uncertainties regarding its diagnostic accuracy and safety.Objective: We performed a systematic review and meta-analysis to determine the safety and accuracy of percutaneous RTB for the diagnosis of malignancy, histologic tumour subtype, and grade.Evidence acquisition: Medline, Embase, and Cochrane Library were searched for studies providing data on diagnostic accuracy and complications of percutaneous core biopsy (CB) or fine-needle aspiration (FNA) of renal tumours. A meta-analysis was performed to obtain pooled estimates of sensitivity and specificity for diagnosis of malignancy. The Cohen kappa coefficient (κ) was estimated for the analysis of histotype/grade concordance between diagnosis on RTB and surgical specimen. Risk of bias assessment was performed (QUADAS-2).Evidence synthesis: A total of 57 studies recruiting 5228 patients were included. The overall median diagnostic rate of RTB was 92%. The sensitivity and specificity of diagnostic CBs and FNAs were 99.1% and 99.7%, and 93.2% and 89.8%, respectively. A good (κ = 0.683) and a fair (κ = 0.34) agreement were observed between histologic subtype and Fuhrman grade on RTB and surgical specimen, respectively. A very low rate of Clavien ≥2 complications was reported. Study limitations included selection and differential-verification bias.Conclusions: RTB is safe and has a high diagnostic yield in experienced centres. Both CB and FNA have good accuracy for the diagnosis of malignancy and histologic subtype, with better performance for CB. The accuracy for Fuhrman grade is fair. Overall, the quality of the evidence was moderate. Prospective cohort studies recruiting consecutive patients and using homogeneous reference standards are required.Patient summary: We systematically reviewed the literature to assess the safety and diagnostic performance of renal tumour biopsy (RTB). The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes, and it appears to be safe. However, the quality of evidence was moderate, and better quality studies are required to provide a more definitive answer.
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| 14. |
- Merseburger, Axel S., et al.
(författare)
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Renal cell carcinoma
- 2016
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Ingår i: World journal of urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 34:8, s. 1051-1052
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 15. |
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| 16. |
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| 17. |
- Powles, Thomas, et al.
(författare)
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Updated European Association of Urology Guidelines : Recommendations for the Treatment of First-line Metastatic Clear Cell Renal Cancer
- 2018
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 73:3, s. 311-315
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Tidskriftsartikel (refereegranskat)abstract
- The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metastatic/advanced clear cell renal cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-naive advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. LBA5, ESMO 2017, 2017). These results change the frontline standard of care for this disease and have implications for the selection of subsequent therapies. For this reason the European Association of Urology RCC guidelines have been updated. Patient summary: The European Association of Urology guidelines will be updated based on the results of the phase III Checkmate-214 clinical trial. The trial showed superior survival for a combination of ipilimumab and nivolumab (IN), compared with the previous standard of care, in intermediate-and poor-risk patients with metastatic clear cell renal cell carcinoma. When IN is not safe or feasible, alternative agents such as sunitinib, pazopanib, and cabozantinib should be considered. Furthermore, at present, the data from the trial are immature in favourable-risk patients. Therefore, sunitinib or pazopanib remains the favoured agent for this subgroup of patients.
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| 18. |
- Ueckert, Stefan, et al.
(författare)
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Phosphodiesterase type 5 (PDE5) is co-localized with key proteins of the nitric oxide/cyclic GMP signaling in the human prostate
- 2013
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Ingår i: World journal of urology. - : Springer Verlag (Germany). - 0724-4983 .- 1433-8726. ; 31:3, s. 609-614
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Tidskriftsartikel (refereegranskat)abstract
- Experimental studies have provided the basis for the evaluation of inhibitors of the phosphodiesterase type 5 (PDE5) in the treatment of lower urinary tract symptomatology (LUTS) secondary to benign prostatic hyperplasia (BPH). It has been speculated that the clinical efficacy of PDE5 inhibitors in patients with LUTS/BPH can be explained by their effects on the urinary bladder rather than on the prostate. Hence, the significance of the nitric oxide (NO)/cyclic GMP signaling in the control of the human prostate requires further clarification. less thanbrgreater than less thanbrgreater thanThe present study aimed to investigate by means of immunohistochemistry in the human prostate the expression and distribution of key mediators of the NO pathway, namely cyclic GMP, the neuronal nitric oxide synthase (nNOS), and cyclic GMP-binding protein kinases type I (cGKI alpha, cGKI), in relation to PDE5, protein kinase A (cAK), and the vasoactive intestinal polypeptide (VIP). less thanbrgreater than less thanbrgreater thanIn the smooth muscle portion of the transition zone, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKI alpha, and cGKI, as well as with the cyclic cAMP-binding protein kinase A. Smooth muscle bundles were seen innervated by slender varicose nerves characterized by the expression of nNOS. Some of these nerves also presented staining related to the neuropeptide VIP. less thanbrgreater than less thanbrgreater thanThe findings give hints that the cyclic GMP- and cyclic AMP-dependent signal transduction may synergistically work together in regulating muscle tension in the transition zone. This might be of significance for the identification of new pharmacological avenues to treat patients with symptomatic BPH.
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| 19. |
- Vogel, Christian, et al.
(författare)
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Imaging in Suspected Renal-Cell Carcinoma : Systematic Review
- 2019
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Ingår i: Clinical Genitourinary Cancer. - : Elsevier. - 1558-7673 .- 1938-0682. ; 17:2, s. E345-E355
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Forskningsöversikt (refereegranskat)abstract
- Objective: To systematically assessed the diagnostic performance of contrast-enhanced computed tomography (CT) compared to other imaging modalities for diagnosing and staging renal-cell carcinoma in adults.Methods: A comprehensive literature search was conducted through various electronic databases. Data from the selected studies were extracted and pooled, and median sensitivity and specificity were calculated wherever possible. Forty studies analyzing data of 4354 patients were included. They examined CT, magnetic resonance imaging (MRI), positron emission tomography-CT, and ultrasound (US).Results: For CT, median sensitivity and specificity were 88% (interquartile range [IQR] 81%-94%) and 75% (IQR 51%-90%), and for MRI they were 87.5% (IQR 75.25%-100%) and 89% (IQR 75%-96%). Staging sensitivity and specificity for CT were 87% and 74.5%, while MRI showed a median sensitivity of 90% and specificity of 75%. For US, the results varied greatly depending on the corresponding technique. Contrast-enhanced US had a median diagnostic sensitivity of 93% (IQR 88.75%-98.25%) combined with mediocre specificity. The diagnostic performance of unenhanced US was poor. For positron emission tomography-CT, diagnostic accuracy values were good but were based on only a small amount of data. Limitations include the strong heterogeneity of data due to the large variety in imaging techniques and tumor histotypes. Contrast-enhanced CT and MRI remain the diagnostic mainstay for renal-cell carcinoma, with almost equally high diagnostic and staging accuracy.Conclusion: For specific questions, a combination of different imaging techniques such as CT or MRI and contrast-enhanced US may be useful. There is a need for future large prospective studies to further increase the quality of evidence.
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| 20. |
- Agarwal, Neeraj, et al.
(författare)
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Apalutamide plus Androgen Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer : Analysis of Pain and Fatigue in the Phase 3 TITAN Study
- 2021
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Ingår i: The Journal of urology. - 1527-3792. ; 206:4, s. 914-923
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We performed an exploratory analysis of prostate cancer-related pain and fatigue on health-related quality of life in patients with metastatic castration-sensitive prostate cancer receiving apalutamide (240 mg/day) or placebo, with continuous androgen deprivation therapy (ADT), in the phase 3, randomized, double-blind, placebo controlled TITAN trial (NCT02489318). MATERIALS AND METHODS: Patient-reported outcomes for pain and fatigue were evaluated using the Brief Pain Inventory-Short Form and Brief Fatigue Inventory. Time to deterioration (TTD) was estimated by Kaplan-Meier method; hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards model. General estimating equations for logistic regression estimated treatment-related differences in the likelihood of worsening pain or fatigue. RESULTS: Compliance for completing the Brief Pain Inventory-Short Form and Brief Fatigue Inventory was high (96% to 97%) in the first year. Median followup times were similar between treatments (19 to 22 months). Median pain TTD was longer with apalutamide than placebo for "pain at its least in the last 24 hours" (28.7 vs 21.8 months, respectively; p=0.0146), "pain interfered with mood" (not estimable vs 22.4 months; p=0.0017), "pain interfered with walking ability" (28.7 vs 20.2 months; p=0.0027), "pain interfered with relations" (not estimable vs 23.0 months; p=0.0139) and "pain interfered with sleep" (28.7 vs 20.9 months; p=0.0167). Likelihood for fatigue and worsening fatigue were similar between groups. CONCLUSIONS: Patients with metastatic castration-sensitive prostate cancer receiving apalutamide plus ADT vs placebo plus ADT reported consistently favorable TTD of pain. No difference for change in fatigue was observed with apalutamide vs placebo.
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| 21. |
- Agarwal, Neeraj, et al.
(författare)
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Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN) : a randomised, placebo-controlled, phase 3 study
- 2019
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Ingår i: The Lancet Oncology. - 1470-2045. ; 20:11, s. 1518-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue. Methods: In this randomised, placebo-controlled, double-blind, phase 3 study, patients with metastatic castration-sensitive prostate cancer (defined as not receiving ADT at the time of metastatic disease progression) aged 18 years and older, receiving continuous ADT (selected at the investigator's discretion), and with an Eastern Cooperative Oncology Group performance status score of 0 or 1 were randomly assigned (1:1), using an interactive web response system, to receive oral apalutamide (four 60 mg tablets, once daily) or matching placebo. Previous localised disease treatment or previous docetaxel for metastatic castration-sensitive prostate cancer were allowed. Randomisation was stratified by Gleason score at diagnosis, region, and previous docetaxel treatment. Randomisation was done using randomly permuted blocks (block size of four). Investigators, research staff, sponsor study team, and patients were masked to the identities of test and control treatments. Patient-reported outcomes were prespecified exploratory endpoints and were the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5D questionnaire 5 level (EQ-5D-5L). BPI and BFI were completed for 7 consecutive days (days −6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1–7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Missing patient-reported outcome assessments were calculated as the expected number of assessments for a visit minus the actual number of assessments received for that visit. For time-to-event endpoints, when median values could not be calculated because less than 50% of patients had degradation, 25th percentiles were compared. This study is registered with ClinicalTrials.gov, number NCT02489318, and is ongoing. Findings: Between Dec 9, 2015, and July 25, 2017, 1052 eligible patients were enrolled randomly assigned to apalutamide (n=525) or placebo (n=527). Data cutoff for this analysis of patient-reported outcomes was Nov 23, 2018. Median follow-up for time to pain-related endpoints ranged from 19·4 to 22·1 months. Patients were mostly asymptomatic at baseline: on the BPI-SF pain severity scale of 0–10, median pain scores (indicating worst pain in the past 24 h) were 1·14 (IQR 0–3·17) in the apalutamide group and 1·00 (0–2·86) in the placebo group, and median worst fatigue scores on the BFI were 1·29 (IQR 0–3·29) in the apalutamide group and 1·43 (0·14–3·14) in the placebo group. Patient experience of pain and fatigue (intensity and interference) did not differ between the groups for the duration of treatment. Median time to worst pain intensity progression was 19·09 months (95% CI 11·04–not reached) in the apalutamide group versus 11·99 months (8·28–18·46) in the placebo group (HR 0·89 [95% CI 0·75–1·06]; p=0·20). Median time to pain interference progression was not reached in either group (95% CI 28·58–not reached in the apalutamide group; not reached–not reached in the placebo group). 25th percentiles for time to pain interference progression were 9·17 months (5·55–11·96) in the apalutamide group and 6·24 months (4·63–7·43) in the placebo group (HR 0·90 [95% CI 0·73–1·10]; p=0·29). FACT-P total scores and EQ-5D-5L data showed preservation of HRQOL in both groups. The median time to deterioration as determined by FACT-P total score was 8·87 months (95% CI 4·70–11·10) in the apalutamide group and 9·23 months (7·39–12·91) in the placebo group (HR 1·02 [95% CI 0·85–1·22]; p=0·85). Interpretation: Apalutamide with ADT is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with ADT alone while maintaining HRQOL despite additive androgen blockade. Funding: Janssen Research & Development.
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| 22. |
- Braegelmann, Johannes, et al.
(författare)
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Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer
- 2017
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research Inc.. - 1078-0432 .- 1557-3265. ; 23:7, s. 1829-1840
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches.Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer (n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq.Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancerwasmarked by high expression of CDK19. In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8were present inmetastases. In vitro, inhibition ofCDK19 and CDK8 by knockdown or treatment with a selective CDK8/ CDK19 inhibitor significantly decreased migration and invasion.Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer.
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| 23. |
- Ljungberg, Börje, et al.
(författare)
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EAU guidelines on renal cell carcinoma : the 2010 update
- 2010
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 58:3, s. 398-406
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Tidskriftsartikel (refereegranskat)abstract
- Context and objectives The European Association of Urology Guideline Group for renal cell carcinoma (RCC) has prepared these guidelines to help clinicians assess the current evidence-based management of RCC and to incorporate the present recommendations into daily clinical practice. Evidence acquisition The recommendations provided in the current updated guidelines are based on a thorough review of available RCC guidelines and review articles combined with a systematic literature search using Medline and the Cochrane Central Register of Controlled Trials. Evidence synthesis A number of recent prospective randomised studies concerning RCC are now available with a high level of evidence, whereas earlier publications were based on retrospective analyses, including some larger multicentre validation studies, meta-analyses, and well-designed controlled studies. Conclusions These guidelines contain information for the treatment of an individual patient according to a current standardised general approach. Updated recommendations concerning diagnosis, treatment, and follow-up can improve the clinical handling of patients with RCC. Take Home Message This review of the 2010 European Association of Urology renal cell carcinoma guidelines is intended to help clinicians access knowledge of current evidence-based management according to a standardised general approach. Structured literature searches were carried out in different databases of systematic reviews and clinical trials. Grade of recommendation was assigned based on the underlying evidence.
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| 24. |
- Ljungberg, Börje, et al.
(författare)
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Renal cell carcinoma guideline.
- 2007
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Ingår i: Eur Urol. - 0302-2838. ; 51:6, s. 1502-10
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Tidskriftsartikel (refereegranskat)
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| 25. |
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