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Updated: Nov 5, 2025
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Non-clear cell renal carcinomas: Review of new molecular insights and recent clinical data
Philippe Barthélémy1, Nathalie Rioux-Leclercq2, Constance Thibault3
1Medical Oncology Department, Institut de cancérologie Strasbourg Europe, Strasbourg University Hospital, Strasbourg, France.
Abstract:
Non-clear cell renal cell carcinomas (nccRCC) represent a highly heterogeneous group of kidney tumors, consisting of the following subtypes: papillary carcinomas, chromophobe renal cell carcinoma, so-called unclassified carcinomas or aggressive uncommon carcinomas such as Bellini carcinoma, renal cell carcinoma (RCC) with ALK rearrangement or fumarate hydratase-deficient RCC. Although non-clear cell cancers account for only 15 to 30% of renal tumors, they are often misclassified and accurate diagnosis continues to be an issue in clinical practice. Current therapeutic strategy of metastatic nccRCC is based primarily on guidelines established for clear cell tumors, the most common subtype, however this approach remains poorly defined. To date, published clinical trials for all histological nccRCC subtypes have been collectively characterized into one group, in contrast to clear cell RCC, and given the small numbers of cases, the interpretation of study results continues to be challenging. This review summarizes the available literature for each nccRCC subtype and highlights the lack of supportive evidence from prospective clinical trials and retrospective studies. Future trials should evaluate treatment approaches which focus on a specific histological subtype and progress in treating nccRCC will be contingent on understanding the unique biology of their individual histologies.
Insights
Non-clear cell renal cell carcinomas (nccRCC) are diverse kidney tumors often misdiagnosed. Current treatments, based on clear cell types, lack specific evidence for nccRCC subtypes, hindering progress.
Area of Science:
- Oncology
- Nephrology
- Pathology
Background:
- Non-clear cell renal cell carcinomas (nccRCC) comprise a heterogeneous group of kidney tumors, including papillary, chromophobe, and rare aggressive subtypes.
- Accurate diagnosis of nccRCC remains challenging, contributing to their misclassification in clinical practice.
- nccRCC constitute 15-30% of renal tumors, yet are often managed using treatment strategies developed for clear cell RCC.
Purpose of the Study:
- To review the current literature on the various subtypes of nccRCC.
- To highlight the limitations in clinical trial data and retrospective studies for nccRCC.
- To emphasize the need for subtype-specific treatment strategies in nccRCC.
Main Methods:
- Comprehensive literature review of published clinical trials and retrospective studies.
- Analysis of data pertaining to distinct nccRCC histological subtypes.
- Synthesis of evidence regarding therapeutic approaches for metastatic nccRCC.
Main Results:
- Published clinical trials often group all nccRCC subtypes together, complicating result interpretation due to small case numbers.
- There is a significant lack of robust evidence from prospective clinical trials and retrospective studies for specific nccRCC subtypes.
- Current therapeutic strategies for metastatic nccRCC are poorly defined and often extrapolated from clear cell RCC guidelines.
Conclusions:
- Effective treatment of nccRCC requires a move away from a one-size-fits-all approach.
- Future clinical trials must focus on evaluating treatments tailored to specific histological subtypes of nccRCC.
- Advancements in nccRCC treatment are dependent on a deeper understanding of the unique biology of each subtype.
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