Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; European Association of Urology (EAU) Young Academic Urologists (YAU) Renal Cancer Working Group.
Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Addenbrookes Hospital, Cambridge, UK.
Eur Urol Oncol. 2021 Feb;4(1):22-41. doi: 10.1016/j.euo.2020.12.011. Epub 2021 Jan 3.
The epidemiological signature of renal cell carcinoma (RCC) during the past decades is explained by overdetection and overtreatment of indolent cancers; furthermore, a non-negligible proportion of patients undergoing surgery for suspected RCC harbour benign renal tumours. As the gold standard for RCC diagnosis remains histopathological analysis of surgical or biopsy specimens, implementation of noninvasive diagnostic strategies to discriminate between benign and malignant renal masses is an urgent unmet need.
To systematically review novel liquid biomarkers and imaging modalities for RCC diagnosis.
A systematic review of the recent English-language literature was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42020190773) using the MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov databases. Risk-of-bias assessment was performed according to the QUADAS 2 tool.
Overall, 15 studies (six on biomarkers and nine on imaging) and eight clinical trials were included. None of the biomarkers or imaging modalities has been validated or shown to have a distinct clinical value for RCC. Specific combinations of urinary cell-free and exosomal miRNAs, urinary miR-15a, and specific panels of urinary metabolites assessed by metabolomics appear promising. In addition, machine/deep learning algorithms and radiomics applied to cross-sectional images may have potential to improve RCC diagnosis. Most studies are limited by the retrospective design, size, and lack of external validation.
Liquid biomarkers or imaging modalities are not ready for integration in the clinic and further well-designed studies must validate preliminary findings and explore utility in clinical decision-making.
We provide a comprehensive overview of the currently available biomarkers (measured in blood or urine) and novel imaging tests (other than conventional imaging) to discriminate kidney cancer from benign renal masses in a noninvasive fashion. None of the biomarkers or imaging modalities studied was validated or added clinical value; therefore, none of them can be implemented in the clinic. However, these approaches appear to be promising for improving the diagnosis of kidney cancer in the future.
过去几十年来，肾细胞癌（RCC）的流行病学特征可以用惰性癌症的过度检测和过度治疗来解释；此外，相当一部分接受疑似 RCC 手术的患者患有良性肾肿瘤。由于 RCC 的金标准仍然是手术或活检标本的组织病理学分析，因此实施非侵入性诊断策略来区分良性和恶性肾肿块是一种迫切需要满足的需求。
系统综述用于 RCC 诊断的新型液体生物标志物和影像学方法。
根据欧洲泌尿外科学会指南和 PRISMA 声明建议（PROSPERO ID：CRD42020190773），使用 MEDLINE、Cochrane 中央对照试验注册库、Web of Science 和 ClinicalTrials.gov 数据库进行了系统的文献回顾。根据 QUADAS 2 工具进行了偏倚风险评估。
总共纳入了 15 项研究（6 项关于生物标志物，9 项关于影像学）和 8 项临床试验。没有一种生物标志物或影像学方法已得到验证或显示出对 RCC 具有独特的临床价值。尿液无细胞和外泌体 miRNAs、尿液 miR-15a 的特定组合以及代谢组学评估的特定尿液代谢物组合似乎很有前途。此外，应用于横截面图像的机器学习/深度学习算法和放射组学可能有潜力改善 RCC 的诊断。大多数研究受到回顾性设计、规模和缺乏外部验证的限制。
液体生物标志物或影像学方法尚未准备好整合到临床实践中，必须进行进一步的精心设计研究来验证初步发现并探索其在临床决策中的应用。
我们提供了目前可用的生物标志物（在血液或尿液中测量）和新型影像学检查（常规影像学以外）的综合概述，以无创方式区分肾癌和良性肾肿块。研究中没有一种生物标志物或影像学方法得到验证或增加了临床价值；因此，都不能在临床上实施。然而，这些方法似乎很有前途，可以提高未来肾癌的诊断。
