{"entity":{"id":"idea-adjuvant-selection-rcc","kind":"idea","name":"Biomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)","aka":[],"tldr":"Adjuvant immunotherapy after kidney cancer surgery is given to everyone at high pathological risk although most would never relapse, so a year of toxicity is spread across the whole group to help a minority. A biomarker such as CAIX PET or kidney-specific tumour DNA could pick out the few who need it.","summary":"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.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03142334: KEYNOTE-564","url":"https://clinicaltrials.gov/study/NCT03142334"},{"label":"ClinicalTrials.gov NCT05239728: LITESPARK-022","url":"https://clinicaltrials.gov/study/NCT05239728"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":["caix-pet","mrd-testing"],"targets":[],"drugs":["pembrolizumab","belzutifan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-564","litespark-022","imvigor011"],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-564-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A post-nephrectomy residual-disease or high-risk signature can identify a subgroup with ≥30% two-year relapse risk in whom adjuvant pembrolizumab ± belzutifan gives an absolute DFS gain of ≥15%, while sparing low-signature patients.","rationale":"Number needed to treat in KEYNOTE-564 is high; toxicity of a year of IO plus HIF-2α inhibition is not trivial; precedent in IMvigor011 for ctDNA-guided adjuvant IO in bladder cancer.","test":"Biomarker-stratified adjuvant trial with a surveillance arm for low-risk-signature patients; CAIX PET substudy.","maturity":"early-clinical"},"route":"/ideas/idea-adjuvant-selection-rcc/","neighbours":{"cancer":[{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"caix-pet","kind":"technology","name":"CAIX PET (89Zr-girentuximab)","route":"/technologies/caix-pet/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"belzutifan","kind":"drug","name":"Belzutifan","route":"/drugs/belzutifan/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"trial":[{"id":"imvigor011","kind":"trial","name":"IMvigor011","route":"/trials/imvigor011/"},{"id":"keynote-564","kind":"trial","name":"KEYNOTE-564","route":"/trials/keynote-564/"},{"id":"litespark-022","kind":"trial","name":"LITESPARK-022","route":"/trials/litespark-022/"}],"paper":[{"id":"paper-keynote-564-nejm-2021","kind":"paper","name":"KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery","route":"/key-papers/paper-keynote-564-nejm-2021/"}]}}