Renal cell carcinoma (RCC) is one of the 10 most commonly diagnosed solid tumors. Most RCCs are histologically defined as clear cell, comprising approximately 75% of diagnoses. However, the remaining RCC cases are composed of a heterogeneous combination of diverse histopathologic subtypes, each with unique pathogeneses and clinical features. Although the therapeutic approach to both localized and metastatic RCCs has dramatically changed, first with the advent of antiangiogenic targeted therapies and more recently with the approval of immune checkpoint inhibitor (ICI)-based combinations, these advances have primarily benefited the clear cell RCC patient population. As such, there remains critical gaps in the optimization of treatment regimens for patients with non-clear cell, or variant, RCC histologies. Herein, we detail recent advances in understanding the biology of RCC with variant histology and how such findings have guided novel clinical studies investigating precision oncology approaches for these rare subtypes. Among the most common variant histology RCCs are papillary RCC, comprising approximately 15%-20% of all diagnoses. Although a histopathologically diverse subset of tumors, papillary RCC is canonically associated with amplification of the MET protooncogene; recently completed and ongoing trials have investigated MET-directed therapies for this patient population. Finally, we discuss the unique biology of RCC with sarcomatoid dedifferentiation and the recent clinical findings detailing its paradoxical sensitivity to ICIs.
American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting. 2024 Jun [Epub]
Nicholas J Salgia, Zeynep B Zengin, Sumanta K Pal, Nazli Dizman
Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY., Department of Internal Medicine, Yale University School of Medicine, New Haven, CT., Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA., Department of Hematology and Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.