Biomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)

Adjuvant pembrolizumab in KEYNOTE-564, and pembrolizumab with belzutifan in LITESPARK-022, are given to everyone at high pathological risk after nephrectomy, although most would never relapse. This idea proposes selecting patients with a biomarker instead: because renal cell carcinoma sheds little ctDNA, candidates include CAIX PET with 89Zr-girentuximab, kidney-specific ctDNA or methylation assays, and transcriptomic signatures such as ClearCode34. The rationale is that the number needed to treat is high, a year of PD-1 blockade plus HIF-2alpha inhibition carries real toxicity, and IMvigor011 set a precedent in bladder cancer. The proposed test is a biomarker-stratified adjuvant trial with a surveillance arm and a CAIX PET substudy, at an early clinical stage.