Background:
Circulating tumor DNA (ctDNA) is predictive of recurrence in resected stage III melanoma, yet its role in the neoadjuvant setting for clinical stage III (cSIII) is unclear.

Objective:
Assess the association between ctDNA and outcomes following neoadjuvant immunotherapy (IO)+targeted therapy (TT) in cSIII melanoma.

Design:
Patients in the NeoACTIVATE study were treated with neoadjuvant IO+TT, underwent lymphadenectomy, and received adjuvant immunotherapy.

Methods:
Patients with ctDNA testing performed at baseline, pre- and post-operation were analyzed. Baseline positron emission tomography–computed tomography volumetrics and surgical, major pathological responses (MPR) were assessed.

Results:
Thirteen patients had serial ctDNA, 10 (77%) were detectable at baseline, and 9/10 (90%) had ctDNA clearance. Seven (54%) achieved MPR, all with undetectable preoperative ctDNA, yet 3/7 (43%) had disease recurrence.

Conclusion:
ctDNA and MPR are poor predictors of recurrence following neoadjuvant IO+TT for cSIII melanoma patients. Further studies are warranted to define the role of ctDNA in this setting.

Source:

Stoff, R., Routman, D. M., Yalon, M., Bogan, A. W., Block, M. S., & Hieken, T. J. (2026). Biomarker analysis of circulating tumor DNA in clinical stage III melanoma patients treated with neoadjuvant immunotherapy combined with targeted therapy. Therapeutic Advances in Medical Oncology, 18. https://doi.org/10.1177/17588359251412729

https://journals.sagepub.com/doi/pdf/10.1177/17588359251412729