Circulating tumor DNA predicts survival in patients with resected high risk stage II/III melanoma

Abstract

Background

Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma.

Patients and methods

We performed droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial.

Results

Mutant BRAF or NRAS ctDNA was detected (≥1 copy of mutant ctDNA) in 15/132 (11%) BRAF mutant patient samples and 4/29 (14%) NRAS mutant patient samples. Patients with detectable ctDNA had a decreased disease-free interval (DFI; hazard ratio [HR] 3.12; 95% confidence interval [CI] 1.79-5.47; P<0.0001) and distant metastasis-free interval (DMFI; HR 3.22; 95% CI 1.80-5.79; P<0.0001) versus those with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for performance status (PS) and disease stage (DFI HR 3.26, 95% CI 1.83-5.83, P<0.0001; DMFI HR = 3.45, 95% CI 1.88-6.34, P<0.0001). Five year overall survival (OS) rate for patients with detectable ctDNA was 33% (95% CI 14-55%) versus 65% (95% CI 56-72%) for those with undetectable ctDNA. OS was significantly worse for patients with detectable ctDNA (HR 2.63; 95% CI 1.40-4.96); P=0.003) and remained significant after adjustment for PS (HR 2.50, 95% CI 1.32-4.74, P=0.005).

Conclusion

CtDNA predicts for relapse and survival in high-risk resected melanoma and could aid selection of patients for adjuvant therapy.

Clinical trial number

ISRCTN 81261306