Dr Drakaki on the Evolution of Non–Clear Cell RCC Subtype Classifications

Alexandra Drakaki, MD, PhD, associate professor, Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, discusses how the classification of non–clear cell renal cell carcinoma (RCC) subtypes has evolved in recent years.

Historically, kidney cancer was thought to comprise 5 primary subtypes, Drakaki begins. Clear cell RCC, characterized by VHL mutations, was considered the most common subtype, she notes. Other subtypes included papillary type 1, papillary type 2, chromophobe, and oncocytoma, she details. However, the classification of non-clear cell RCC has expanded to include additional subtypes, such as collecting duct carcinoma, kidney medullary carcinoma, unclassified tumors, translocation-associated tumors, and kidney cancers with sarcomatoid features, Drakaki details.

A new classification system for kidney cancer was introduced in 2022, and reflected advancements in the understanding of this disease, she expands. With next-generation sequencing providing an accurate tool for tumor analysis, investigators can now identify more molecularly-defined subtypes within RCC, Drakaki states. These include tumors characterized by fumarate hydratase or succinate dehydrogenase deficiencies, which indicate unique metabolic vulnerabilities. Additionally, oncologists are seeing an increase in tumors with ALK rearrangements and those deficient in SMARCB1. SMARCB1-deficient RCC is often associated with renal medullary carcinoma, a rare but aggressive form of kidney cancer, she explains.

This updated classification is crucial for guiding treatment decisions, as it allows for more precise diagnoses and potential targeting of therapies based on molecular characteristics, Drakaki continues. She adds that deeper understanding of kidney cancer continues will lead to further expansion of the classification system, which reinforces the importance of individualized treatment plans. Identification of specific RCC subtypes allows treatment approaches to be tailored to each patient's unique genetic and molecular profile, thereby enhancing long-term outcomes, Drakaki concludes.