Dr Galsky on the Importance of Improved Disease Classification Within Non–Clear Cell RCC

Matthew Galsky, MD, professor of medicine, hematology and medical oncology, professor of urology, director of Genitourinary Medical Oncology, codirector, the Center of Excellence for Bladder Cancer, and associate director, Translational Research at the Tisch Cancer Institute, Mount Sinai, discusses the importance of developing specific disease classifications within non–clear cell renal cell carcinoma (nccRCC).

nccRCC is considered a heterogeneous group of several rare kidney cancers that are subclassified by their distinct clinical behavior, histology, genetics, pathogenesis, and natural history, Galsky begins. Subtypes within this group include papillary RCC, chromophobe RCC, collecting duct RCC, renal medullary RCC, and translocation RCC This subset is often characterized by poor patient prognosis, and has few standard-of-care treatments available. Moreover, subgroups of nccRCC are often underrepresented in prospective clinical trials, Galsky says. The heterogeneity and rarity of nccRCC subtypes often requires investigators to pool distinct nccRCC entities into a single study population when compared with clear cell RCC (ccRCC).

Notably, the use of next-generation sequencing has provided new genomic insights and could help histologically-specific investigations in nccRCC evolve, but the intricacies of disease characterization are not well understood. Accordingly, treatment choices for nccRCC are primarily based on findings extrapolated from trials in ccRCC, retrospective data, and case studies. Improving the understanding and molecular characterization of nccRCC subtypes would decrease the need for this approach, and address the gap in their clinical management, Galsky states.

Some mechanistic research has already been done to elucidate the molecular pathogenesis for several nccRCC entities, and genomic research has identified several relevant molecular alterations associated with each subtype. However, this knowledge has not significantly influenced the development of agents to target these markers yet, Galsky notes. Therefore, ongoing efforts to define molecular subtypes in RCC are vital for the future creation of collaborative clinical trials that are rationale-directed at these patient subgroups, Galsky concludes.

Disclosures: Dr Galsky reported serving as a consultant or in an advisory role for Aileron Therapeutics, Astellas Pharma, AstraZeneca, Basilea, BioMotiv, Bristol Myers Squibb, Dendreon, Dracen, Dragonfly Therapeutics, EMD Serono, Genentech, Gilead Sciences, GlaxoSmithKline, Incyte, Infinity Pharmaceuticals, Inovio Pharmaceuticals, Janssen, Lilly, Merck, Novartis, NuMab, Pfizer, Seattle Genetics, Silverback Therapeutics, Urogen pharma; he reports receiving research funding from AstraZeneca, Bristol Myers Squibb, Dendreon, Genentech/Roche, Janssen Oncology, Merck, and Novartis; he has ownership interests in Rappta Therapeutics.