Pierro Michael J, Gallan Alexander, Kilari Deepak
Division of Hematology and Oncology, Department of Internal Medicine, Froedtert & the Medical College of Wisconsin, Milwaukee, WI, USA.
Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.
Transl Cancer Res. 2024 Nov 30;13(11):6403-6412. doi: 10.21037/tcr-24-737. Epub 2024 Nov 12.
Advances in non-clear cell renal cell carcinoma (RCC) have lagged behind clear cell RCC due to the heterogeneity and relative rarity of the disease. However, more advanced molecular and genetic testing has allowed us to gain a more detailed and nuanced appreciation of these malignancies. This has laid the foundation for the identification of the distinct mutational and molecular patterns such as succinate dehydrogenase (SDH)-deficient RCC, fumarate hydratase (FH)-deficient RCC, and translocation RCC, so that clinicians can create a more personalized approach to their clinical management. Particularly for the rare non-papillary RCC variant histologies, clinical trial representation is lacking. In the discussed studies, no histology enrolled more than 29 patients of any particular RCC aside from Papillary. As such, evidence-based management decisions can be challenging to make for this patient population.
We have collected the most up-to-date available evidence to describe the pathophysiology, molecular, and pathologic characteristics of the more commonly seen non-clear cell RCC variants, including papillary, chromophobe, translocation, FH-deficient, as well as a group of "unclassified" RCCs. Additionally, we provide an overview of the available evidence from recent clinical trials for non-clear cell RCC and current treatment paradigms.
The diagnostic approach for renal malignancies is rapidly changing, favoring a more molecular and genetically based approach. These techniques will allow for a more detailed understanding of the clinical behavior of these cancers. Most data for non-clear cell RCC are from single-arm phase 2 clinical trials. The clinical response to vascular endothelial growth factor (VEGF)-tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) varies greatly by histology.
Molecularly targeted therapy as monotherapy or when combined with immunotherapy have efficacy in non-clear cell RCC, though there are differences in treatment response by histology.
非透明细胞肾细胞癌（RCC）的进展因疾病的异质性和相对罕见性而落后于透明细胞RCC。然而，更先进的分子和基因检测使我们能够对这些恶性肿瘤有更详细和细致入微的认识。这为识别不同的突变和分子模式奠定了基础，如琥珀酸脱氢酶（SDH）缺陷型RCC、富马酸水合酶（FH）缺陷型RCC和易位型RCC，从而使临床医生能够为其临床管理制定更个性化的方法。特别是对于罕见的非乳头状RCC变异组织学类型，临床试验代表性不足。在讨论的研究中，除乳头状RCC外，没有任何一种组织学类型纳入超过29例特定RCC患者。因此，为该患者群体做出基于证据的管理决策可能具有挑战性。
我们收集了最新的可用证据，以描述更常见的非透明细胞RCC变异体的病理生理学、分子和病理特征，包括乳头状、嫌色细胞、易位型、FH缺陷型以及一组“未分类”RCC。此外，我们概述了非透明细胞RCC近期临床试验的现有证据和当前的治疗模式。
肾恶性肿瘤的诊断方法正在迅速变化，倾向于采用更基于分子和基因的方法。这些技术将使人们对这些癌症的临床行为有更详细的了解。非透明细胞RCC的大多数数据来自单臂2期临床试验。血管内皮生长因子（VEGF）-酪氨酸激酶抑制剂（TKIs）和免疫检查点抑制剂（ICIs）的临床反应因组织学类型而异。
分子靶向治疗作为单一疗法或与免疫疗法联合使用在非透明细胞RCC中具有疗效，尽管不同组织学类型的治疗反应存在差异。
