Expert Discussion on Neoadjuvant Therapy in Resectable Stage III Melanoma
Presented by Prof Dr Georgina Long (Melanoma Institute Australia, Sydney) & Prof Dr Bart Neyns (UZ Brussels, Belgium)
At the 2025 EADO Congress, Prof Dr Georgina Long (Melanoma Institute Australia, Sydney) and Prof Dr Bart Neyns (UZ Brussels, Belgium) share perspectives on the evolving role of neoadjuvant immunotherapy in resectable stage III melanoma. While not yet officially approved or reimbursed in Belgium, neoadjuvant therapy is being considered in selected high-risk patients, particularly those with macroscopic nodal disease. Both experts emphasise its value in providing an early assessment of treatment response, helping to avoid unnecessary therapy in patients who achieve a major pathological response (MPR).
Two key trials were discussed:
- SWOG S1801: Compared neoadjuvant plus adjuvant pembrolizumab vs. adjuvant-only therapy, showing a 42% reduction in event risk (progression, recurrence, or death).
- NADINA (Phase III): Compared neoadjuvant nivolumab + low-dose ipilimumab to adjuvant nivolumab, showing a 68% risk reduction. Patients with MPR did not continue further treatment.
A critical point raised was the importance of accurate pathological assessment after neoadjuvant therapy, which guides whether adjuvant therapy is needed. Training and resources for pathologists are essential. New research suggests the pathological workload can be reduced by 50–70% without losing accuracy.
Both experts agreed that in the future, neoadjuvant and stage IV treatment will dominate melanoma care, with adjuvant therapy becoming less central. The need for biomarkers to personalise treatment is growing — to guide who needs PD-1 monotherapy, who benefits from combination therapy, and who can avoid or de-escalate surgery.
Also discussed was the failure of recent adjuvant trials with checkpoint inhibitor combinations, possibly due to a lack of sufficient disease burden to activate an effective immune response. Finally, early approaches using molecular profiling and single-dose PD-1 therapy before sentinel node biopsy are being explored, but both experts emphasise that such strategies should be part of clinical trials.
Overall, the discussion highlights a shift toward individualised, biology-driven melanoma management, centred around neoadjuvant therapy and guided by pathological and biomarker insights.
References:
