Related Experiment Video
Updated: Mar 25, 2026
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Unclear territory: navigating metastatic nonclear cell renal cell carcinoma
Taylor Goodstein1, Vivian Wong2, Gabriela Bravo Montenegro3
1Department of Urology, Emory University, Atlanta, Georgia.
Purpose Of Review:
To summarize recent updates in the classification, clinical trial evidence, and evolving treatment strategies for nonclear cell renal cell carcinoma (nccRCC).
Recent Findings:
The 2022 WHO classification eliminated the type 1/2 papillary paradigm, refined molecularly defined tumors such as fumarate hydratase (FH)-deficient and anaplastic lymphoma kinase-rearranged RCC, while acknowledging indolent tumors like clear cell papillary renal cell tumors. Prospective and retrospective data increasingly support the use of immune checkpoint inhibitor (ICI)-based regimens, particularly ICI/ tyrosine kinase inhibitor (TKI) combinations. KEYNOTE-B61 and ARON-1 demonstrated consistent activity of pembrolizumab + lenvatinib across nccRCC subtypes, while the randomized SUNNIFORECAST trial validated ipilimumab + nivolumab as a first-line option with overall survival (OS) benefit over standard therapy. Subtype-specific approaches are also emerging: bevacizumab + erlotinib and sintilimab + axitinib showed high response rates in FH-deficient RCC, and prognostic tools such as VENUSS remain valuable for papillary RCC risk stratification. Despite progress, many studies remain limited by histologic heterogeneity and small sample sizes. Multiple ongoing trials, including ICONIC, SAMETA, and PAPMET2, are expected to further clarify optimal management strategies in 2026.
Summary:
Therapeutic advances are reshaping the management of nccRCC, with IO/TKI regimens and histology-specific therapies showing promise. Continued integration of molecular classification, rare subtype-specific trials, and international collaboration will be essential to establish evidence-based treatment standards for this diverse and understudied population.
Insights
Recent advances in nonclear cell renal cell carcinoma (nccRCC) include updated classifications and promising immune checkpoint inhibitor (ICI)/tyrosine kinase inhibitor (TKI) combination therapies. Further research and subtype-specific trials are crucial for establishing optimal treatment standards.
Area of Science:
- Oncology
- Genitourinary Pathology
- Clinical Trials
Background:
- Nonclear cell renal cell carcinoma (nccRCC) comprises a heterogeneous group of kidney cancers.
- Accurate classification and understanding of nccRCC subtypes are essential for effective treatment.
Purpose of the Study:
- To review recent updates in nccRCC classification.
- To summarize clinical trial evidence for novel treatment strategies.
- To discuss evolving therapeutic approaches for nccRCC.
Main Methods:
- Review of recent literature on nccRCC classification and treatment.
- Analysis of data from prospective and retrospective clinical trials.
- Evaluation of emerging therapeutic regimens and prognostic tools.
Main Results:
- The 2022 WHO classification refined nccRCC subtypes, including molecularly defined tumors.
- Immune checkpoint inhibitor (ICI)/tyrosine kinase inhibitor (TKI) combinations show significant activity across nccRCC subtypes.
- Subtype-specific therapies and prognostic tools like VENUSS are emerging.
Conclusions:
- Therapeutic advances, including IO/TKI regimens and histology-specific therapies, are transforming nccRCC management.
- Integrating molecular classification and conducting rare subtype-specific trials are vital.
- International collaboration is needed to establish evidence-based treatment standards for nccRCC.
