Overview of Non–Clear Cell Renal Cell Carcinoma
Panelists discuss first-line therapy for non–clear cell renal cell carcinoma, emphasizing its diverse histologies, the challenges posed by limited clinical trial data, and the importance of molecular diagnostics and multidisciplinary strategies to guide personalized treatment.
This Cancer Network Training Academy session focuses on first-line therapy for non–clear cell renal cell carcinoma (nccRCC), a diverse group of rare kidney cancer variants. A panel of medical oncologists from leading institutions convenes to discuss the current standards of care, recent clinical trial data, and best practices for managing nccRCC. Unlike clear cell renal cell carcinoma (ccRCC), which comprises about 75% of cases, nccRCC represents the remaining 25%, encompassing a heterogeneous mix of histologies such as papillary, chromophobe, unclassified RCC, and molecularly defined subtypes like FH- and SDH-deficient tumors.
The discussion opens with an overview of these non–clear cell variants, emphasizing their rarity and biological complexity. Papillary RCC accounts for 10% to 15% of RCC diagnoses, while chromophobe and unclassified RCC each make up around 5%. Because these subtypes differ significantly in terms of molecular drivers and clinical behavior, they require tailored diagnostic and therapeutic approaches. The panel highlights the limitations of existing clinical trial data, as nccRCC patients are often underrepresented or grouped together, making it difficult to generate specific treatment guidance for each subtype.
The experts stress the importance of detailed pathological and molecular assessment at diagnosis, including the use of next-generation sequencing and, where appropriate, germline genetic testing. These tools help guide both treatment decisions and potential clinical trial eligibility. Imaging strategies may also differ from those used in ccRCC, with PET scans occasionally offering added value in aggressive or poorly differentiated subtypes. Ultimately, the panel emphasizes a multidisciplinary approach, often involving tumor boards, surgical teams, radiologists, and geneticists, to navigate the complexities of nccRCC and deliver optimal, personalized care.
