# ctDNA-guided adjuvant therapy in stage II-III melanoma

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

## TL;DR

Most stage II patients never relapse, yet all are offered a year of immunotherapy. Use a blood test to treat only those with detectable residual disease.

## Summary

The idea is to reserve adjuvant PD-1 therapy in stage II to III melanoma for patients with detectable residual disease on a tumour-informed ctDNA assay, or to start it when ctDNA appears, instead of treating everyone. KEYNOTE-716 and CheckMate 76K treat all stage IIB and IIC patients for a modest absolute benefit although most never relapse, so over-treatment and immune toxicity are substantial. Melanoma sheds ctDNA in proportion to burden, and IMvigor011 proved the concept of ctDNA-triggered adjuvant immunotherapy in bladder cancer. The hypothesis is equivalent distant metastasis-free survival with far fewer patients treated; the test is the UK DETECTION design of ctDNA-triggered versus standard adjuvant pembrolizumab, addressing the dormancy bottleneck.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- Hypothesis: Reserving adjuvant PD-1 for ctDNA-positive patients (or starting at ctDNA conversion) achieves equivalent distant metastasis-free survival with far fewer patients treated.
- Rationale: Melanoma sheds ctDNA proportional to burden; IMvigor011 proved the concept in bladder cancer; over-treatment and immune toxicity in stage II are substantial.
- Proposed test: Randomised trial of ctDNA-triggered versus standard adjuvant pembrolizumab in stage IIB-IIIA with DMFS endpoint (the DETECTION design).
- Maturity: early-clinical

## Sources

- ClinicalTrials.gov NCT03553836: KEYNOTE-716: https://clinicaltrials.gov/study/NCT03553836
- ClinicalTrials.gov NCT04660344: IMvigor011: https://clinicaltrials.gov/study/NCT04660344

## Connected records

- cancers: [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [Melanoma](https://onco.cc/cancers/melanoma/), [Stage IIB and IIC melanoma](https://onco.cc/cancers/stage-ii-melanoma/), [Stage III melanoma (after surgery)](https://onco.cc/cancers/stage-iii-melanoma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- terms: [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- trials: [IMvigor011](https://onco.cc/trials/imvigor011/), [KEYNOTE-716](https://onco.cc/trials/keynote-716/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)

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