The 2022 guideline provides the current best evidence base for renal cell carcinoma management. Changes in medical management in recent years include the use of immune checkpoint inhibitors (ICIs), ...ICI–ICI combinations, and ICI-targeted therapy combinations. Surgery remains the mainstay for lower-grade tumours, with increasing use of minimally invasive approaches. More robust data are needed to identify optimal follow-up schedules.
The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC.
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.
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.
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.
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.
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.
The European Association of Urology Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC.
To provide an updated RCC ...guideline based on standardised methodology including systematic reviews, which is robust, transparent, reproducible, and reliable.
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.
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.
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.
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.
The 2019 European Association of Urology renal cell cancer guidelines have been updated by a multidisciplinary panel of experts, based on the highest methodological standards. These guidelines provide the most reliable contemporaneous evidence base for the management of patients with renal cell cancer in 2019.
Abstract Objective To present a summary of the 2016 version of the European Association of Urology (EAU) – European Society for Radiotherapy & Oncology (ESTRO) – International Society of Geriatric ...Oncology (SIOG) Guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC). Evidence acquisition The working panel performed a literature review of the new data (2013–2015). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature. Evidence synthesis Relapse after local therapy is defined by a rising prostate-specific antigen (PSA) level >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir after radiation therapy (RT).11 C-choline positron emission tomography/computed tomography is of limited importance if PSA is <1.0 ng/ml; bone scans and computed tomography can be omitted unless PSA is >10 ng/ml. Multiparametric magnetic resonance imaging and biopsy are important to assess biochemical failure following RT. Therapy for PSA relapse after RP includes salvage RT at PSA levels <0.5 ng/ml and salvage RP, high-intensity focused ultrasound, cryosurgical ablation or salvage brachytherapy of the prostate in radiation failures. Androgen deprivation therapy (ADT) remains the basis for treatment of men with metastatic prostate cancer (PCa). However, docetaxel combined with ADT should be considered the standard of care for men with metastases at first presentation, provided they are fit enough to receive the drug. Follow-up of ADT should include analysis of PSA, testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Level 1 evidence for the treatment of metastatic CRPC (mCRPC) includes, abiraterone acetate plus prednisone (AA/P), enzalutamide, radium 223 (Ra 223), docetaxel at 75 mg/m2 every 3 wk and sipuleucel-T. Cabazitaxel, AA/P, enzalutamide, and radium are approved for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with mCRPC and osseous metastases to prevent skeletal-related complications. Conclusions The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2016 EAU-ESTRO-SIOG Guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are the first endorsed by the European Society for Therapeutic Radiology and Oncology and the International Society of Geriatric Oncology and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online ( http://uroweb.org/guideline/prostate-cancer/ ). Patient summary In men with a rise in their PSA levels after prior local treatment for prostate cancer only, it is important to balance overtreatment against further progression of the disease since survival and quality of life may never be affected in many of these patients. For patients diagnosed with metastatic castrate-resistant prostate cancer, several new drugs have become available which may provide a clear survival benefit but the optimal choice will have to be made on an individual basis.
Abstract Context There is controversy regarding the therapeutic role of pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy for prostate cancer (PCa). Objective To ...systematically review the relevant literature assessing the relative benefits and harms of PLND for oncological and non-oncological outcomes in patients undergoing radical prostatectomy for PCa. Evidence acquisition MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2015. Comparative studies evaluating no PLND, limited, standard, and (super)-extended PLND that reported oncological and non-oncological outcomes were included. Risk-of-bias and confounding assessments were performed. A narrative synthesis was undertaken. Evidence synthesis Overall, 66 studies recruiting a total of 275,269 patients were included (44 full-text articles and 22 conference abstracts). Oncological outcomes were addressed by 29 studies, one of which was a randomized clinical trial (RCT). Non-oncological outcomes were addressed by 43 studies, three of which were RCTs. There were high risks of bias and confounding in most studies. Conflicting results emerged when comparing biochemical and clinical recurrence, while no significant differences were observed among groups for survival. Conversely, the majority of studies showed that the more extensive the PLND, the greater the adverse outcomes in terms of operating time, blood loss, length of stay, and postoperative complications. No significant differences were observed in terms of urinary continence and erectile function recovery. Conclusions Although representing the most accurate staging procedure, PLND and its extension are associated with worse intraoperative and perioperative outcomes, whereas a direct therapeutic effect is still not evident from the current literature. The current poor quality of evidence indicates the need for robust and adequately powered clinical trials. Patient summary Based on a comprehensive review of the literature, this article summarizes the benefits and harms of removing lymph nodes during surgery to remove the prostate because of PCa. Although the quality of the data from the studies was poor, the review suggests that lymph node removal may not have any direct benefit on cancer outcomes and may instead result in more complications. Nevertheless, the procedure remains justified because it enables accurate assessment of cancer spread.
Summary Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of ...various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment. The results suggest that patients treated with complete metastasectomy have better survival and symptom control (including pain relief in bone metastases) than those treated with either incomplete or no metastasectomy. Nevertheless, the available evidence was marred by high risks of bias and confounding across all studies. Although the findings presented here should be interpreted with caution, they and the identified gaps in knowledge should provide guidance for clinicians and researchers, and directions for further research.
Abstract Context It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. ...Objective To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa. Evidence acquisition The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer. Evidence synthesis A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range IQR, 36.4–57.7%) for overall cancer and 32.9% (IQR, 28.1–37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0–92.4%) for overall cancer and 88.1% (IQR, 85.7–92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer ( r = –0.64, p < 0.0001) and csPCa ( r = –0.75, p = 0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval 95% CI, 77–99%) to 67% (95% CI, 56–79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%. Conclusions The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative. Patient summary This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer.
Abstract Context For the treatment of localised renal cell carcinoma (RCC), uncertainties remain over the perioperative and quality-of-life (QoL) outcomes for the many different surgical techniques ...and approaches of nephrectomy. Controversy also remains on whether newer minimally invasive nephron-sparing interventions offer better QoL and perioperative outcomes, and whether adrenalectomy and lymphadenectomy should be performed simultaneously with nephrectomy. These non-oncological outcomes are important because they may have a considerable impact on localised RCC treatment decision making. Objective To review systematically all the relevant published literature comparing perioperative and QoL outcomes of surgical management of localised RCC (T1–2N0M0). Evidence acquisition Relevant databases including Medline, Embase, and the Cochrane Library were searched up to January 2012. Randomised controlled trials (RCTs) or quasi-randomised controlled trials, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The outcome measures were QoL, analgesic requirement, length of hospital stay, time to normal activity level, surgical morbidity and complications, ischaemia time, renal function, blood loss, length of operation, need for blood transfusion, and perioperative mortality. 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. Evidence synthesis A total of 4580 abstracts and 380 full-text articles were assessed, and 29 studies met the inclusion criteria (7 RCTs and 22 NRSs). There were high risks of bias and low-quality evidence for studies meeting the inclusion criteria. There is good evidence indicating that partial nephrectomy results in better preservation of renal function and better QoL outcomes than radical nephrectomy regardless of technique or approach. Regarding radical nephrectomy, the laparoscopic approach has better perioperative outcomes than the open approach, and there is no evidence of a difference between the transperitoneal and retroperitoneal approaches. Alternatives to standard laparoscopic radical nephrectomy (LRN) such as hand-assisted, robot-assisted, or single-port techniques appear to have similar perioperative outcomes. There is no good evidence to suggest that minimally invasive procedures such as cryotherapy or radiofrequency ablation have superior perioperative or QoL outcomes to nephrectomy. Regarding concomitant lymphadenectomy during nephrectomy, there were low event rates for complications, and no definitive difference was observed. There was no evidence to base statements about concomitant ipsilateral adrenalectomy during nephrectomy. Conclusions Partial nephrectomy results in significantly better preservation of renal function over radical nephrectomy. For tumours where partial nephrectomy is not technically feasible, there is no evidence that alternative procedures or techniques are better than LRN in terms of perioperative or QoL outcomes. In making treatment decisions, perioperative and QoL outcomes should be considered in conjunction with oncological outcomes. Overall, there was a paucity of data regarding QoL outcomes, and when reported, both QoL and perioperative outcomes were inconsistently defined, measured, or reported. The current evidence base has major limitations due to studies of low methodological quality marked by high risks of bias.
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.
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.
Longer follow-up data 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. A recent update of Keynote-426 demonstrated an ongoing overall survival benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a progression-free survival benefit seen across all International Metastatic RCC Database Consortium (IMDC) subgroups. The RCC Guidelines Panel continues to recommend this combination across IMDC risk groups in advanced first-line RCC.
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.
Abstract Objective To present a summary of the 2016 version of the European Association of Urology (EAU) - European Society for Radiotherapy & Oncology (ESTRO) - International Society of Geriatric ...Oncology (SIOG) Guidelines on screening, diagnosis, and local treatment with curative intent of clinically localised prostate cancer (PCa). Evidence acquisition The working panel performed a literature review of the new data (2013–2015). The guidelines were updated and the levels of evidence and/or grades of recommendation were added based on a systematic review of the evidence. Evidence synthesis BRCA2 mutations have been added as risk factors for early and aggressive disease. In addition to the Gleason score, the five-tier 2014 International Society of Urological Pathology grading system should now be provided. Systematic screening is still not recommended. Instead, an individual risk-adapted strategy following a detailed discussion and taking into account the patient's wishes and life expectancy must be considered. An early prostate-specific antigen test, the use of a risk calculator, or one of the promising biomarker tools are being investigated and might be able to limit the overdetection of insignificant PCa. Breaking the link between diagnosis and treatment may lower the overtreatment risk. Multiparametric magnetic resonance imaging using standardised reporting cannot replace systematic biopsy, but robustly nested within the diagnostic work-up, it has a key role in local staging. Active surveillance always needs to be discussed with very low-risk patients. The place of surgery in high-risk disease and the role of lymph node dissection have been clarified, as well as the management of node-positive patients. Radiation therapy using dose-escalated intensity-modulated technology is a key treatment modality with recent improvement in the outcome based on increased doses as well as combination with hormonal treatment. Moderate hypofractionation is safe and effective, but longer-term data are still lacking. Brachytherapy represents an effective way to increase the delivered dose. Focal therapy remains experimental while cryosurgery and HIFU are still lacking long-term convincing results. Conclusions The knowledge in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2016 EAU-ESTRO- SIOG Guidelines on PCa summarise the most recent findings and advice for the use in clinical practice. These are the first PCa guidelines endorsed by the European Society for Radiotherapy and Oncology and the International Society of Geriatric Oncology and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office and online ( http://uroweb.org/guideline/prostate-cancer/ ). Patient summary The 2016 EAU–ESTRO–SIOG Prostate Cancer (PCa) Guidelines present updated information on the diagnosis, and treatment of clinically localised prostate cancer. In Northern and Western Europe, the number of men diagnosed with PCa has been on the rise. This may be due to an increase in opportunistic screening, but other factors may also be involved (eg, diet, sexual behaviour, low exposure to ultraviolet radiation). We propose that men who are potential candidates for screening should be engaged in a discussion with their clinician (also involving their families and caregivers) so that an informed decision may be made as part of an individualised risk-adapted approach.
PDF
