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HLRCC FH-deficient RCC — SCE Medical Oncology MCQ

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HardCancer GeneticsHLRCC FH-deficient RCCSCE Medical Oncology

A 50-year-old woman with hereditary leiomyomatosis and renal cell cancer (HLRCC, fumarate hydratase germline mutation) develops a type 2 papillary RCC. What is important about FH-deficient RCC?

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Correct answer: D — FH-deficient papillary RCC is aggressive, does not respond to VEGF-targeted monotherapy well, and patients should be offered combination ICI-based regimens and clinical trials — sunitinib monotherapy is inadequate

HLRCC (FH germline mutation) predisposes to aggressive type 2 papillary RCC (often unilateral, unlike other hereditary RCCs). FH-deficient RCC has distinct biology: HIF activation through pseudo-hypoxia (succinate accumulation), high-grade aggressive behaviour, and historically poor responses to single-agent VEGF-TKIs. ICI-based combination regimens (pembrolizumab + axitinib; nivolumab + cabozantinib; nivolumab + ipilimumab) are recommended. Erlotinib + bevacizumab showed activity in a phase II trial. Screening includes annual renal MRI from childhood.

Reference: ESMO 2024 RCC and Hereditary Cancer; NICE; Grubb et al Lancet Oncol 2007