Predictive value of [F]FDG PET/CT and index lymph node response following neoadjuvant pembrolizumab in resectable stage 3 melanoma: Real world data from the largest melanoma centres in the Netherlands.

[BACKGROUND] Neoadjuvant immunotherapy is increasingly used in resectable stage III melanoma, with major pathological response (MPR) closely linked to improved outcomes. Predictive biomarkers are needed to identify responders and potentially allow surgical de-escalation. [¹⁸F]FDG-PET/CT is a non-invasive method to assess metabolic response, and the index lymph node (ILN) may reflect response of the entire nodal bain.

[METHODS] This retrospective analysis of largely prospectively collected data included patients with resectable stage III melanoma treated with two cycles of neoadjuvant pembrolizumab at two Dutch melanoma centres. [¹⁸F]FDG-PET/CT was performed before and after treatment, with metabolic response classified using EORTC criteria. Volumetric PET parameters, metabolic tumour volume (MTV) and total lesion glycolysis (TLG), were analysed retrospectively. Pathological response was assessed according to INMC criteria. In patients undergoing therapeutic lymph node dissection, ILN response was compared with the entire nodal basin.

[RESULTS] Forty-seven patients initiated neoadjuvant pembrolizumab, and 39 underwent surgery. Twenty-four patients had evaluable PET/CT scans: complete metabolic response (CMR) in 12.5%, partial metabolic response (PMR) in 37.5%, stable disease in 16.7%, and progressive metabolic disease (PMD) in 33%. Overall, 59% achieved MPR. All patients with CMR achieved MPR; 64% with PMR achieved MPR, compared with only 12.5% with PMD. All patients with pathological complete or near-complete response showed reductions in both ΔTLG and ΔMTV. ILN response was fully concordant with total nodal basin response in all evaluable cases. Three patients who declined surgery after CMR remained recurrence-free during follow-up.

[CONCLUSION] Metabolic response on [¹⁸F]FDG-PET/CT, particularly CMR, strongly correlates with pathological response after neoadjuvant pembrolizumab. ILN response accurately reflects total nodal basin response, supporting response-adapted surgical strategies.