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

Source: https://onco.cc/ideas/idea-adjuvant-selection-rcc/  
OnCo record `idea-adjuvant-selection-rcc` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- 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.
- Proposed test: Biomarker-stratified adjuvant trial with a surveillance arm for low-risk-signature patients; CAIX PET substudy.
- Maturity: early-clinical

## Sources

- ClinicalTrials.gov NCT03142334: KEYNOTE-564: https://clinicaltrials.gov/study/NCT03142334
- ClinicalTrials.gov NCT05239728: LITESPARK-022: https://clinicaltrials.gov/study/NCT05239728

## Connected records

- cancers: [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- technologies: [CAIX PET (89Zr-girentuximab)](https://onco.cc/technologies/caix-pet/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Belzutifan](https://onco.cc/drugs/belzutifan/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- trials: [IMvigor011](https://onco.cc/trials/imvigor011/), [KEYNOTE-564](https://onco.cc/trials/keynote-564/), [LITESPARK-022](https://onco.cc/trials/litespark-022/)
- key papers: [KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery](https://onco.cc/key-papers/paper-keynote-564-nejm-2021/)

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