FDG-PET associations with pathological response and survival with neoadjuvant immunotherapy for melanoma.

Background: Neoadjuvant immunotherapy has become the new standard of care for stage III melanoma. This study sought to describe the metabolic changes seen with fludeoxyglucose-18-positron emission tomography (FDG-PET) following neoadjuvant immunotherapy in patients with melanoma and explore associations with pathological response and recurrence-free survival (RFS).

Methods: Data from patients with macroscopic stage III nodal melanoma treated with neoadjuvant checkpoint inhibitor therapy were pooled from five melanoma centers. All patients underwent baseline and preoperative FDG-PET and CT assessments, and all had surgery. Pathological response was determined using the International Neoadjuvant Melanoma Consortium criteria, radiological response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and FDG-PET response using European Organization for Research and Treatment of Cancer (EORTC) criteria. The primary endpoint was to explore the associations of metabolic and radiological responses with pathological response; secondary endpoints were RFS outcomes stratified by each response category.

Results: 115 patients were included, 69% male, median age 59 years (27-92), 43% BRAF mutant, and median follow-up was 22.2 months (95% CI 13.7 to 26.4). 40 patients received anti-PD-1 monotherapy, 20 patients received pembrolizumab combined with lenvatinib, and 55 patients received ipilimumab and nivolumab. The major pathological response (MPR) rate was 62%, and the pathological complete response rate was 51%. RECIST response underestimated pathological response; patients achieving RECIST stable disease (38%) had a 50% chance of achieving MPR. The FDG-PET metabolic response rate was 73%, with most achieving an MPR (80%), especially in patients with a complete metabolic response (CMR, 96% MPR). A small proportion of patients (10%) had stable metabolic disease on FDG-PET, and all these patients were non-MPR. Patients with progressive metabolic disease were also in the majority non-MPR (79%). Patients with MPR, complete response/partial response on CT, and CMR/partial metabolic response on FDG-PET had a favorable 24-month RFS (95.6%, 97.3%, and 93.7%, respectively), with FDG-PET able to identify a greater proportion of patients with favorable progression-free survival (PFS) than pathology or CT (73%, 62%, and 43%, respectively).

Conclusion: Neoadjuvant immunotherapy has high FDG-PET response rates in melanoma. FDG-PET response associates with pathological response and confers impressive RFS, suggesting this could be an important clinical tool.