| 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. |
- 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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| 3. |
- Enkovaara, J., et al.
(författare)
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Electronic structure calculations with GPAW : a real-space implementation of the projector augmented-wave method
- 2010
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 22:25, s. 253202-
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Forskningsöversikt (refereegranskat)abstract
- Electronic structure calculations have become an indispensable tool in many areas of materials science and quantum chemistry. Even though the Kohn-Sham formulation of the density-functional theory (DFT) simplifies the many-body problem significantly, one is still confronted with several numerical challenges. In this article we present the projector augmented-wave (PAW) method as implemented in the GPAW program package (https://wiki.fysik.dtu.dk/gpaw) using a uniform real-space grid representation of the electronic wavefunctions. Compared to more traditional plane wave or localized basis set approaches, real-space grids offer several advantages, most notably good computational scalability and systematic convergence properties. However, as a unique feature GPAW also facilitates a localized atomic-orbital basis set in addition to the grid. The efficient atomic basis set is complementary to the more accurate grid, and the possibility to seamlessly switch between the two representations provides great flexibility. While DFT allows one to study ground state properties, time-dependent density-functional theory (TDDFT) provides access to the excited states. We have implemented the two common formulations of TDDFT, namely the linear-response and the time propagation schemes. Electron transport calculations under finite-bias conditions can be performed with GPAW using non-equilibrium Green functions and the localized basis set. In addition to the basic features of the real-space PAW method, we also describe the implementation of selected exchange-correlation functionals, parallelization schemes, Delta SCF-method, x-ray absorption spectra, and maximally localized Wannier orbitals.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Hofmann, Fabian, et al.
(författare)
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Targeted therapy for metastatic renal cell carcinoma
- 2020
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Ingår i: Cochrane Database of Systematic Reviews. - : John Wiley & Sons. - 1469-493X. ; :10
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Forskningsöversikt (refereegranskat)abstract
- Background: Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors since the publication of a Cochrane Review on targeted therapy for metastatic renal cell carcinoma (mRCC) in 2008. This review represents an update of that original review.Objectives: To assess the effects of targeted therapies for clear cell mRCC in patients naïve to systemic therapy.Search methods: We performed a comprehensive search with no restrictions on language or publication status. The date of the latest search was 18 June 2020.Selection criteria: We included randomised controlled trials, recruiting patients with clear cell mRCC naïve to previous systemic treatment. The index intervention was any TKI‐based targeted therapy.Data collection and analysis: Two review authors independently assessed the included studies and extracted data for the primary outcomes: progression‐free survival (PFS), overall survival (OS) and serious adverse events (SAEs); and the secondary outcomes: health‐related quality of life (QoL), response rate and minor adverse events (AEs). We performed statistical analyses using a random‐effects model and rated the certainty of evidence according to the GRADE approach.Main results: We included 18 RCTs reporting on 11,590 participants randomised across 18 comparisons. This abstract focuses on the primary outcomes of select comparisons.
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| 7. |
- 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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| 8. |
- Ljungberg, Börje, Professor, 1949-, et al.
(författare)
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European Association of Urology Guidelines on Renal Cell Carcinoma : the 2022 Update
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 82:4, s. 399-410
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Forskningsöversikt (refereegranskat)abstract
- Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC.Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC.Evidence acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines.Evidence synthesis: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence.Conclusions: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022. Patient summary: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer.
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| 9. |
- MacLennan, Steven, et al.
(författare)
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Systematic Review of Oncological Outcomes Following Surgical Management of Localised Renal Cancer
- 2012
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 61:5, s. 972-993
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Forskningsöversikt (refereegranskat)abstract
- Context: Renal cell carcinoma (RCC) accounts for 2-3% of adult malignancies. There remain uncertainties over the oncological outcomes for the surgical management of localised RCC. Objective: Systematically review relevant literature comparing oncological outcomes of surgical management of localised RCC (T1-2N0M0). Evidence acquisition: Relevant databases including Medline, Embase, and the Cochrane Library were searched up to October 2010, and an updated scoping search was performed up to January 2012. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The main outcomes were overall survival, cancer-specific survival, recurrence, and metastases. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Evidence synthesis: A total of 4580 abstracts and 389 full-text articles were assessed. Thirty-four studies met the inclusion criteria (6 RCTs and 28 NRSs). Meta-analyses were planned but were deemed inappropriate due to data heterogeneity. There were high risks of bias and low-quality evidence across the evidence base. Open radical nephrectomy and open partial nephrectomy showed similar cancer-specific and overall survival, but when both open and laparoscopic approaches are considered together, the evidence showed improved survival for partial nephrectomy for tumours <= 4 cm. The overall evidence suggests either equivalent or better survival with partial nephrectomy. Laparoscopic radical nephrectomy offered equivalent survival to open radical nephrectomy, and all laparoscopic approaches achieved equivalent survival. Open and laparoscopic partial nephrectomy achieved equivalent survival. The issue of ipsilateral adrenalectomy or complete lymph node dissection with radical nephrectomy or partial nephrectomy remains unresolved. Conclusions: The evidence base suggests localised RCCs are best managed by nephron-sparing surgery where technically feasible. However, the current evidence base has significant limitations due to studies of low methodological quality marked by high risks of bias. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 10. |
- 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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