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.
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.
Pembrolizumab plus axitinib are recommended as a new standard of care in all International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups. For treatment-naïve IMDC intermediate- and poor-risk patients, ipilimumab plus nivolumab remains the standard treatment. Sunitinib, pazopanib, and cabozantinib (in IMDC intermediate- and poor-risk disease) are alternative treatment options in patients who cannot receive or tolerate immune checkpoint inhibition in a first-line setting.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
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Global survival studies have shown favorable development in renal cell carcinoma (RCC) treatment but few studies have considered extended periods or covered populations for which medical care is ...essentially free of charge. We analyzed RCC survival in Finland and Sweden over a 50-year period (1967-2016) using data from the NORDCAN database provided by the local cancer registries. While the health care systems are largely similar in the two countries, the economic resources have been stronger in Sweden. In addition to the standard 1- and 5-year relative survival rates, we calculated the difference between these as a measure of how well survival was maintained between years 1 and 5. Relative 1- year survival rates increased almost linearly in both countries and reached 90% in Sweden and 80% in Finland. Although 5-year survival also developed favorably the difference between 1- and 5-year survival rates did not improve in Sweden suggesting that the gains in 5-year survival were entirely due to gains in 1-year survival. In Finland there was a gain in survival between years 1 and 5, but the gain in 1-years survival was the main contributor to the favorable 5-year survival. Age group specific analysis showed large survival differences, particularly among women. Towards the end of the follow-up period the differences narrowed but the disadvantage of the old patients remained in 5-year survival. The limitations of the study were lack of information on performed treatment and clinical stage in the NORDCAN database. In conclusion, the available data suggest that earlier diagnosis and surgical treatment of RCC have been the main driver of the favorable change in survival during the past 50 years. The main challenges are to reduce the age-specific survival gaps, particularly among women, and push survival gains past year 1.
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Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized ...controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment.
To explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis.
The trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management.
ClinicalTrials.gov NCT03977571 June 6, 2019.
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Background The dominant risk factor for urinary bladder cancer has been cigarette smoking, but, as smoking prevalence is decreasing in many populations, other risk factors may become uncovered. Such ...new risk factors could be responsible for halting the declining incidence of bladder cancer. We hypothesize that snuff use by Swedish men may increase the rate for bladder cancer, as snuff contains carcinogenic nitrosamines. Methods We carried out an ecological study by comparing incidence trends in lung and bladder cancers between Danish, Finnish and Swedish men in order to test if the Swedish bladder cancer rate deviates from the Danish and Finnish ones. We used the NORDCAN database for cancer data from 1960 through 2016 to test the hypothesis. Results In the three countries, the incidence of lung cancer started to decrease after a peak incidence, and this was later followed by declining incidence in bladder cancer in Denmark from 1990 to 2016 by 14.3%, in Finland by 8.3% but not in Sweden (the decline of 1.4% was not significant). The difference in trends can be partly explained by the increasing incidence in Swedish men aged 70 or more years. Sweden differs from the two other countries by low male smoking prevalence but increasing use of snuff recorded by various surveys. Conclusion The stable bladder cancer trend for Swedish men was opposite to the declining trends in Denmark, Finland and globally. We suggest that this unusual finding may be related to the increasing use of snuff by Swedish men. Average users of snuff are exposed to at least 3 times higher levels of carcinogenic tobacco-specific nitrosamines than a smoker of one daily pack of cigarettes. Keywords: Risk factors, Sex difference, Incidence trend, Tobacco products, Snuffing
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This study aimed to assess the cellular localization and expression levels of hypoxia-inducible factor (HIF) -α proteins (specifically HIF-1α, HIF-2α, and HIF-3α) that play a role in the hypoxia ...pathway and to determine their correlation with clinicopathological parameters and patient survival in renal cell carcinoma (RCC).
Tissue microarray (TMA) with cores from 150 clear cell RCCs and 31 non-ccRCC samples. HIF-1α, HIF-2α, and HIF-3α antibodies were used for immunohistochemistry (IHC) of TMA to evaluate the cellular localization and expression levels of HIF-α proteins, specifically in relation to the hypoxia pathway.
The expression levels of the HIF-α proteins were higher in the nucleus than in the cytoplasm. Furthermore, the nuclear expression levels of all HIF-α proteins were significantly higher in clear cell RCC (ccRCC) than in non-ccRCC. Cytoplasmic HIF-3α expression was also higher in ccRCC than in non-ccRCC, whereas cytoplasmic HIF-1α and HIF-2α expression levels were similar between the different RCC types. In ccRCC, nuclear HIF-1α expression levels correlated with both nuclear HIF-2α and HIF-3α levels, whereas cytoplasmic HIF-3α expression levels were associated with HIF-1α only.In non-ccRCC, there was a positive correlation observed between nuclear HIF-1α and HIF-3α expression, but no correlation was found with HIF-2α. In patients with ccRCC, the nuclear expressions of HIF-1α and HIF-3α was significantly associated with cancer-specific survival (CSS) in univariate analysis. This association was no longer evident in multivariate analysis. Notably, there was no correlation observed between nuclear HIF-2α expression and CSS in these patients. In contrast, cytoplasmic expression levels showed no association with CSS.
The expression levels of the three primary HIF-α proteins were found to be higher in the nucleus than in the cytoplasm. Furthermore, the results indicated that HIF-3α and HIF-1α expression levels were significant univariate factors associated with CSS in patients with clear cell RCC. These results highlight the critical role that HIF-3α and HIF-1α play in the hypoxia pathway.
Tumors in the human prostate are usually stiffer compared to surrounding non-malignant glandular tissue, and tactile resonance sensors measuring stiffness can be used to detect prostate cancer. To ...explore this further, we used a tactile resonance sensor system combined with a rotatable sample holder where whole surgically removed prostates could be attached to detect tumors on, and beneath, the surface ex vivo. Model studies on tissue phantoms made of silicone and porcine tissue were performed. Finally, two resected human prostate glands were studied. Embedded stiff silicone inclusions placed 4 mm under the surface could be detected in both the silicone and biological tissue models, with a sensor indentation of 0.6 mm. Areas with different amounts of prostate cancer (PCa) could be distinguished from normal tissue (
< 0.05), when the tumor was located in the anterior part, whereas small tumors located in the dorsal aspect were undetected. The study indicates that PCa may be detected in a whole resected prostate with an uneven surface and through its capsule. This is promising for the development of a clinically useful instrument to detect prostate cancer during surgery.
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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.
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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.
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