Alfredo Distante, Riccardo Bertolo, R. Campi, S. Erdem, Anna Caliò, Carlotta Palumbo, N. Pavan, Chiara Ciccarese, U. Carbonara, M. Marchioni, E. Roussel, Zhenjie Wu, Peter F.A. Mulders, Constantijn H. J. Muselaers
BACKGROUND: The role of active surveillance (AS) has been recognized as a management strategy for localized small renal masses (SRMs). The EAU guidelines suggest AS can be offered to frail and/or comorbid patients diagnosed with SRM due to the low cancer-specific-mortality (CSM) and higher competing-cause mortality. As specific cut-offs defining the characteristics of frail and comorbid patients who may benefit from AS remain less clear, our objective is to conduct a systematic review aiming to identify potential characteristics that could assist physicians in shared decision-making. METHODS: The systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Two authors independently screened the literature according to the PICOs criteria previously outlined in our registered review protocol (via Pubmed, Embase, and the Cochrane Central Register of Controlled Trials), extracted data, and assessed the risk of bias, using Newcastle-Ottawa Scale. Studies that analyzed differences in patient’s tumor-related and molecular characteristics associated with any differences in growth rate (GR), overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS), were considered eligible. RESULTS: Nineteen studies comprising a total of 5105 patients were analyzed. Patient-specific factors such as age and cardiovascular index, which demonstrated a predominant impact on OS, exhibited a high degree of consistency across the analyzed studies. Less concordance was found when exploring GR, with the main predictors being ethnicity, age, sex, comorbidity, symptoms, and eGFR. The analysis of tumor-related characteristics, such as tumor size, nephrometry score, and mass histology, among others, yielded contradictory outcomes concerning their impact on GR and CSS. CONCLUSION: Age, cardiovascular index, and chronic kidney disease have shown to be reliable predictors of OS. Nonetheless, significant debates persist regarding tumor characteristics or molecular markers that may influence survival and GR. Further research is awaited to shed light on the potential to identify prognostic factors. This would aid in pinpointing the subgroup of patients who could experience additional benefits from AS, potentially leading to a reduced risk of progression. It is imperative to standardize approaches to AS and reporting of results, as this will be pivotal for future quantitative analyses.
背景：主动监测（AS）作为局部肾小肿块（SRM）的一种管理策略，其作用已得到认可。由于癌症特异性死亡率（CSM）较低，而竞争性病因死亡率较高，EAU指南建议可为诊断为SRM的体弱和/或合并症患者提供主动监测。由于界定可能从 AS 中获益的体弱和合并症患者特征的具体临界值仍不太明确，我们的目标是进行一项系统性综述，旨在确定有助于医生共同决策的潜在特征。方法：系统性文献综述按照《系统性综述和元分析首选报告项目》声明进行。两位作者根据我们注册的综述协议（通过 Pubmed、Embase 和 Cochrane Central Register of Controlled Trials）中概述的 PICOs 标准独立筛选文献，提取数据，并使用纽卡斯尔-渥太华量表评估偏倚风险。符合条件的研究包括：分析患者肿瘤相关特征和分子特征的差异与生长率（GR）、总生存期（OS）、癌症特异性生存期（CSS）和无转移生存期（MFS）差异的相关性。结果：共分析了 19 项研究，包括 5105 名患者。年龄和心血管指数等患者特异性因素对OS有主要影响，这些因素在所分析的研究中表现出高度的一致性。在探讨GR时，发现一致性较低，主要预测因素是种族、年龄、性别、合并症、症状和eGFR。对肿瘤相关特征（如肿瘤大小、肾功能评分和肿块组织学等）的分析结果显示，这些特征对GR和CSS的影响相互矛盾。结论：年龄、心血管指数和慢性肾病已被证明是预测 OS 的可靠指标。尽管如此，关于肿瘤特征或分子标记物可能影响生存率和GR的争论依然存在。我们期待进一步的研究来揭示确定预后因素的潜力。这将有助于确定哪些亚组患者可从 AS 中获得额外益处，从而降低病情恶化的风险。当务之急是实现 AS 和结果报告方法的标准化，因为这对未来的定量分析至关重要。
{"title":"Patient Selection for Active Surveillance for Small Renal Masses: A Systematic Review of the Literature","authors":"Alfredo Distante, Riccardo Bertolo, R. Campi, S. Erdem, Anna Caliò, Carlotta Palumbo, N. Pavan, Chiara Ciccarese, U. Carbonara, M. Marchioni, E. Roussel, Zhenjie Wu, Peter F.A. Mulders, Constantijn H. J. Muselaers","doi":"10.3233/kca-230025","DOIUrl":"https://doi.org/10.3233/kca-230025","url":null,"abstract":"BACKGROUND: The role of active surveillance (AS) has been recognized as a management strategy for localized small renal masses (SRMs). The EAU guidelines suggest AS can be offered to frail and/or comorbid patients diagnosed with SRM due to the low cancer-specific-mortality (CSM) and higher competing-cause mortality. As specific cut-offs defining the characteristics of frail and comorbid patients who may benefit from AS remain less clear, our objective is to conduct a systematic review aiming to identify potential characteristics that could assist physicians in shared decision-making. METHODS: The systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Two authors independently screened the literature according to the PICOs criteria previously outlined in our registered review protocol (via Pubmed, Embase, and the Cochrane Central Register of Controlled Trials), extracted data, and assessed the risk of bias, using Newcastle-Ottawa Scale. Studies that analyzed differences in patient’s tumor-related and molecular characteristics associated with any differences in growth rate (GR), overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS), were considered eligible. RESULTS: Nineteen studies comprising a total of 5105 patients were analyzed. Patient-specific factors such as age and cardiovascular index, which demonstrated a predominant impact on OS, exhibited a high degree of consistency across the analyzed studies. Less concordance was found when exploring GR, with the main predictors being ethnicity, age, sex, comorbidity, symptoms, and eGFR. The analysis of tumor-related characteristics, such as tumor size, nephrometry score, and mass histology, among others, yielded contradictory outcomes concerning their impact on GR and CSS. CONCLUSION: Age, cardiovascular index, and chronic kidney disease have shown to be reliable predictors of OS. Nonetheless, significant debates persist regarding tumor characteristics or molecular markers that may influence survival and GR. Further research is awaited to shed light on the potential to identify prognostic factors. This would aid in pinpointing the subgroup of patients who could experience additional benefits from AS, potentially leading to a reduced risk of progression. It is imperative to standardize approaches to AS and reporting of results, as this will be pivotal for future quantitative analyses.","PeriodicalId":508303,"journal":{"name":"Kidney Cancer","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141002594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Papillary renal cell carcinoma (pRCC) comprises 15-20% of all patients with renal cell carcinoma (RCC). Although in the localized setting where pRCC appears to have better outcomes than clear cell RCC (ccRCC), patients with metastatic pRCC have significantly worse outcomes than patients with metastatic ccRCC. Because of the overall rarity of pRCC, there have been less research and clinical trials devoted to this subtype. Therefore, treatment of pRCC has generally been extrapolated from approved therapies for ccRCC. Recent data shows promise with newer tyrosine kinase inhibitors, and there is emerging evidence on their combination with immune checkpoint inhibitors. However, more dedicated clinical trials to pRCC are urgently needed, as response rates and outcomes still lag behind ccRCC. This review summarizes the pathophysiology, genetic features, the evolution of treatment approaches since the systemic cytokine era, and current challenges of managing pRCC.
{"title":"Papillary Renal Cell Carcinoma: Current Evidence and Future Directions","authors":"Albert Jang, Charbel Hobeika, Shilpa Gupta","doi":"10.3233/kca-230027","DOIUrl":"https://doi.org/10.3233/kca-230027","url":null,"abstract":"Papillary renal cell carcinoma (pRCC) comprises 15-20% of all patients with renal cell carcinoma (RCC). Although in the localized setting where pRCC appears to have better outcomes than clear cell RCC (ccRCC), patients with metastatic pRCC have significantly worse outcomes than patients with metastatic ccRCC. Because of the overall rarity of pRCC, there have been less research and clinical trials devoted to this subtype. Therefore, treatment of pRCC has generally been extrapolated from approved therapies for ccRCC. Recent data shows promise with newer tyrosine kinase inhibitors, and there is emerging evidence on their combination with immune checkpoint inhibitors. However, more dedicated clinical trials to pRCC are urgently needed, as response rates and outcomes still lag behind ccRCC. This review summarizes the pathophysiology, genetic features, the evolution of treatment approaches since the systemic cytokine era, and current challenges of managing pRCC.","PeriodicalId":508303,"journal":{"name":"Kidney Cancer","volume":"74 s318","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141002488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Belzutifan versus Everolimus in Advanced Kidney Cancer: A Commentary on LITESPARK-005 Trial from ESMO 2023","authors":"Shuchi Gulati, Primo Nery Lara","doi":"10.3233/kca-230024","DOIUrl":"https://doi.org/10.3233/kca-230024","url":null,"abstract":"","PeriodicalId":508303,"journal":{"name":"Kidney Cancer","volume":"278 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139852748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Belzutifan versus Everolimus in Advanced Kidney Cancer: A Commentary on LITESPARK-005 Trial from ESMO 2023","authors":"Shuchi Gulati, Primo Nery Lara","doi":"10.3233/kca-230024","DOIUrl":"https://doi.org/10.3233/kca-230024","url":null,"abstract":"","PeriodicalId":508303,"journal":{"name":"Kidney Cancer","volume":" 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139792726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eric A Jonasch, C. Balijepalli, K. Yan, L. Gullapalli, Joyce Li, M. Sundaram
Background: A small proportion of renal cell carcinoma (RCC) are associated with hereditary syndromes such as von Hippel-Lindau disease (VHL) and are commonly treated with surgical interventions. More recently, systemic treatments for VHL-associated RCC have been assessed as an alternative to surgery. Methods: A systematic literature review was conducted by searching MEDLINE, EMBASE, and Cochrane Registry of Controlled Trials to collect and interpret published evidence on treatments for VHL-associated RCC patients to better understand the treatment landscape. Results: This review identified 32 primary studies, comprised of single-arm clinical trials and real-world studies assessing systemic, surgical, radiological, or image guided ablation interventions. In clinical trials, treatment with sunitinib and pazopanib showed an objective response in 33% and 52% of RCC lesions respectively. For patients treated with belzutifan, 64% of patients showed an objective response, of which 7% were complete response and 57% were partial responses with a 24-month PFS rate of 96%. In real-world studies, treatment with sunitinib, pazopanib, axitinib, and sorafenib showed an objective response in 40%, 0%, 33%, and 25% of RCC lesions respectively, and all the responses were partial. In the studies assessing surgical, radiological, or image guided ablation interventions primary failure/re-intervention rates ranged from 2% to 84%. Conclusion: Local procedures are still a mainstay in the management of patients with non-metastatic VHL-associated RCC although multiple procedures incur an increasing rate of complications. A limited number of clinical trials and real-world studies evaluated VEGF-TKIs for the treatment of VHL-RCC, while responses were observed, long term treatment was limited by toxicities.
{"title":"Efficacy, Effectiveness, and Safety of Interventions for Von Hippel-Lindau Associated Renal Cell Carcinoma: A Systematic Literature Review","authors":"Eric A Jonasch, C. Balijepalli, K. Yan, L. Gullapalli, Joyce Li, M. Sundaram","doi":"10.3233/kca-230021","DOIUrl":"https://doi.org/10.3233/kca-230021","url":null,"abstract":"Background: A small proportion of renal cell carcinoma (RCC) are associated with hereditary syndromes such as von Hippel-Lindau disease (VHL) and are commonly treated with surgical interventions. More recently, systemic treatments for VHL-associated RCC have been assessed as an alternative to surgery. Methods: A systematic literature review was conducted by searching MEDLINE, EMBASE, and Cochrane Registry of Controlled Trials to collect and interpret published evidence on treatments for VHL-associated RCC patients to better understand the treatment landscape. Results: This review identified 32 primary studies, comprised of single-arm clinical trials and real-world studies assessing systemic, surgical, radiological, or image guided ablation interventions. In clinical trials, treatment with sunitinib and pazopanib showed an objective response in 33% and 52% of RCC lesions respectively. For patients treated with belzutifan, 64% of patients showed an objective response, of which 7% were complete response and 57% were partial responses with a 24-month PFS rate of 96%. In real-world studies, treatment with sunitinib, pazopanib, axitinib, and sorafenib showed an objective response in 40%, 0%, 33%, and 25% of RCC lesions respectively, and all the responses were partial. In the studies assessing surgical, radiological, or image guided ablation interventions primary failure/re-intervention rates ranged from 2% to 84%. Conclusion: Local procedures are still a mainstay in the management of patients with non-metastatic VHL-associated RCC although multiple procedures incur an increasing rate of complications. A limited number of clinical trials and real-world studies evaluated VEGF-TKIs for the treatment of VHL-RCC, while responses were observed, long term treatment was limited by toxicities.","PeriodicalId":508303,"journal":{"name":"Kidney Cancer","volume":"91 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139606139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Jackson-Spence, Matthew Young, A. Jovaišaitė, Bernadett Szabados, Thomas Powles
A number of adjuvant trials have attempted to improve outcomes for patients following nephrectomy for renal cell carcinoma (RCC). This was initially with cytokines and then Vascular Endothelial Growth Factor (VEGF) targeted therapies. More recently, a series of adjuvant immune checkpoint inhibitor (ICI) studies have been published. To date, only the KEYNOTE— 564 study using adjuvant pembrolizumab has positive Disease-Free Survival (DFS) data with an acceptable toxicity profile. There are many negative ICI and anti-VEGF adjuvant trials, which raises uncertainty. Further randomised trials may be required but importantly biomarker studies are needed to identify those individuals who may benefit from adjuvant therapy.
{"title":"Adjuvant Therapy in Renal Cell Cancer","authors":"F. Jackson-Spence, Matthew Young, A. Jovaišaitė, Bernadett Szabados, Thomas Powles","doi":"10.3233/kca-230013","DOIUrl":"https://doi.org/10.3233/kca-230013","url":null,"abstract":"A number of adjuvant trials have attempted to improve outcomes for patients following nephrectomy for renal cell carcinoma (RCC). This was initially with cytokines and then Vascular Endothelial Growth Factor (VEGF) targeted therapies. More recently, a series of adjuvant immune checkpoint inhibitor (ICI) studies have been published. To date, only the KEYNOTE— 564 study using adjuvant pembrolizumab has positive Disease-Free Survival (DFS) data with an acceptable toxicity profile. There are many negative ICI and anti-VEGF adjuvant trials, which raises uncertainty. Further randomised trials may be required but importantly biomarker studies are needed to identify those individuals who may benefit from adjuvant therapy.","PeriodicalId":508303,"journal":{"name":"Kidney Cancer","volume":"24 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139609031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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