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

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.

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.

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.

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.