A dynamic recurrence risk prediction tool for adjuvant therapy in stage III melanoma

Background: Prognosis for AJCC stage III melanoma varies significantly. Adjuvant therapies, including pembrolizumab, nivolumab, and dabrafenib/trametinib, have markedly reduced recurrence risk, as shown in pivotal trials (Keynote-054, CheckMate-238, and Combi-AD). Despite these advancements, clinicians lack tools to dynamically assess recurrence risk across the patient journey.

Patients and methods: Using pooled individual patient data (IPD) from Kaplan-Meier curves of these trials, we developed a tool to dynamically estimate relapse-free survival (RFS) and distant metastasis-free survival (DMFS) over time. Conditional survival analyses incorporated AJCC-8 substages, treatment regimens, and recurrence data.

Results: The analysis included 2206 patients (IIIA: 174, IIIB: 768, IIIC: 1169, IIID: 95). Of these, 861 received adjuvant anti-PD-1 therapy (pembrolizumab or nivolumab), 434 were treated with dabrafenib/trametinib, and 911 were in the observation group. Median follow-up ranged from 61 to 74 months. The dynamic calculator, hosted at the MIA website (Risk Prediction Tools: www.melanomarisk.org.au), allows input of time since treatment initiation, AJCC-8 stage, and therapy type, providing dynamic RFS and DMFS estimates up to 60 months. Case examples illustrate both baseline and conditional risks, facilitating tailored clinical discussions.

Conclusions: This tool enhances accessibility to individualized, dynamic, time-specific risk estimates for patients with stage III melanoma. It serves as a practical resource for clinicians to support personalized follow-up plans, empowering informed decision-making. Updates will incorporate emerging data to maintain clinical relevance.