ASO Author Reflections: Effects of the Updated AJCC Classification for Patients with Stage III Melanoma

Abstract

PASTThe incidence of cutaneous melanoma is steadily increasing in most countries with fair-skin populations. According to the American Joint Committee on Cancer (AJCC) staging manual, patients with satellite/in-transit metastasis and/or regional lymph node disease are classified as stage III melanoma, which is further divided into subgroups according to prognosis. The AJCC 7th edition was recently replaced with the updated AJCC 8th edition, and the number of subgroups in stage III were revised from three (A-C) to four (A-D) groups. 1 The subgroup classification now depends on both T and N status, and the previous low-risk group (stage IIIA) has an even better prognosis, while patients with the highest risk are now classified as stage IIID. This substage migration can have an impact on the clinical management of patients with stage III melanoma. PRESENTCurrently, there is a paradigm shift with the introduction of new effective systemic treatments for patients with both stage III and IV disease. Three immune checkpoint inhibitors have been approved for use in advanced melanoma, i.e. the CTLA-4 inhibitor ipilimumab and the PD-1 inhibitors nivolumab and pembrolizumab. In addition, targeted therapies (BRAF/MEK inhibitors) are also available as a treatment for patients with BRAF-mutated melanomas. Adjuvant trials have recently shown a relapse-free survival (RFS) benefit of systemic treatment in stage III melanoma, leading to a change in therapeutic approach for stage III patients after radical surgery; 2 however, all these adjuvant trials were performed using the former AJCC 7th edition for stage classification. A recent publication using a prospective population-based registry including all Swedish patients with melanoma showed an improved 5-and 10-year melanoma-specific survival (MSS) for substages IIIA, IIIB, and IIIC when patients were reclassified according to the updated AJCC 8th edition, while the new substage IIID had the worst prognosis. 3 FUTUREA recent update from one of the adjuvant trials (the EORTC1325/KEYNOTE-054 trial) showed that only 8% of patients would be classified as stage IIIA according to the AJCC 8th edition, compared with 15% according to the AJCC 7th edition used in the trial. Moreover, this analysis showed that when reclassifying patients according to the AJCC 8th edition, the 1-year recurrence-free survival in the stage IIIA subgroup was 92.7% versus 92.5% in the placebo arm. 4 These differences based on substage migration ASO Author Reflections is a brief invited commentary on the article ''A Population-Based Comparison of the AJCC 7th and AJCC 8th Editions for Patients Diagnosed with Stage III Cutaneous Malignant