Renal cell carcinoma (RCC) is a heterogeneous disease that represents the most common type of kidney cancer. The classification of RCC is primarily based on distinct morphological and molecular characteristics, with two broad categories: clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC). Clear cell RCC is the predominant subtype, representing about 70-80% of all RCC cases, while non-clear cell subtypes collectively make up the remaining 20-30%. Non-clear cell RCC encompasses many histopathological variants, each with unique biological and clinical characteristics. Additionally, any RCC subtype can undergo sarcomatoid dedifferentiation, which is associated with poor prognosis and rapid disease progression. Recent advances in molecular profiling have also led to the identification of molecularly defined variants, further highlighting the complexity of this disease. While immunotherapy has shown efficacy in some RCC variants and subpopulations, significant gaps remain in the treatment of rare subtypes. This review explores the outcomes of immunotherapy across RCC subtypes, including rare variants, and highlights opportunities for improving care through novel therapies, biomarker-driven approaches, and inclusive clinical trial designs.
Cancers. 2025 Jan 20*** epublish ***
Justin W Miller, Jeffrey S Johnson, Christopher Guske, Gowtam Mannam, Firas Hatoum, Michelle Nassar, Marine Potez, Adnan Fazili, Philippe E Spiess, Jad Chahoud
USF Health Morsani College of Medicine, Tampa, FL 33602, USA., Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA., University of South Florida, Tampa, FL 33602, USA., Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.