Divergent paths of metastatic renal cell carcinoma in two young adults shaped by precision therapy and financial barriers: two case reports

Abstract Background Renal cell carcinoma (RCC) is uncommon in young adults and, in this age group, may reflect hereditary predisposition and aggressive tumour biology. Fumarate hydratase (FH)-deficient RCC is an aggressive non–clear cell subtype with limited evidence to guide management. We report two young patients with metastatic RCC whose contrasting courses illustrate the influence of tumour biology and access to therapy on outcome. Case presentation: A 20-year-old woman presented with abdominal pain, vomiting, and a 7 kg weight loss over two months. Computed tomography showed a 14.5 cm right renal mass with nodal, hepatic, and pulmonary metastases, and biopsy confirmed clear cell RCC. Although immune checkpoint inhibitor-based combinations were recommended, financial constraints led her to choose tyrosine kinase inhibitor (TKI) monotherapy, and germline evaluation was advised. A 39-year-old man presented after a fall with a haemorrhagic left renal mass and underwent laparoscopic radical nephrectomy with lymph node excision, which revealed pT3aN1 papillary RCC (ISUP grade 3); genetic testing identified an FH exon 8 mutation. Following nodal, supraclavicular, and hepatic progression, he received nivolumab plus cabozantinib and achieved a complete metabolic response by August 2022. After 47 cycles of nivolumab and continued maintenance cabozantinib, he remained free of metabolically active disease three years later, apart from a minimally FDG-avid femoral lesion under surveillance. Immune-related hypothyroidism and inflammatory arthritis were managed without interrupting treatment. Conclusions Metastatic RCC in young adults warrants a high index of suspicion, histological and molecular characterisation, and germline evaluation. Nivolumab plus cabozantinib can induce durable responses even in FH-mutated papillary RCC, but such outcomes depend on access to therapy, which remains a major barrier in resource-limited settings.