Urol Oncol. 2026 Sep 12:S1078-1439(26)00703-9. doi: 10.1016/j.urolonc.2026.07.035. Online ahead of print.
ABSTRACT
PURPOSE: Rare renal cell carcinoma (RCC) subtypes present unique challenges for clinical trial design and drug development. This consensus initiative aimed to provide actionable expert guidance on advancing preclinical and clinical development of rational therapeutic strategies for non-clear cell RCC variants, including papillary, chromophobe, MiT family/translocation, collecting duct, renal medullary carcinoma, and fumarate hydratase-deficient RCC.
METHODS: A modified Delphi method was employed to develop consensus statements among a multidisciplinary panel of 46 experts in urologic oncology, medical oncology, radiation oncology, molecular biology, genetics, and biostatistics, with representatives from pharmaceutical industry, regulatory affairs, and patient advocacy. Over multiple rounds, including an in-person meeting on November 13, 2025, 20 initial statements were proposed, evaluated, refined, and voted on. Consensus was defined a priori as a median Likert score ≥8 out of 10.
RESULTS: Twenty final consensus statements were endorsed across 5 thematic domains: (1) Trial Design and Endpoints; (2) Perioperative Trials; (3) Operations and Accrual; (4) Biology-driven and Histology/molecular Strategy Trials; and (5) Preclinical Efforts, Target Identification, and Early Signal Testing. Key recommendations include prioritizing histology-specific trial designs over pooled “non-clear cell” approaches, adopting innovative single-arm and adaptive designs for ultra-rare subtypes, leveraging patient advocacy collaborations and natural history registries, and pursuing mechanism-informed therapeutic development.
CONCLUSIONS: These recommendations provide a framework to guide researchers, cooperative groups, regulatory bodies, and pharmaceutical industry partners in advancing evidence generation and therapeutic development for patients with rare kidney cancer variants.
PMID:42731937 | DOI:10.1016/j.urolonc.2026.07.035
