A study using data from two major melanoma centers in the United States and Australia, reported in the Journal of Clinical Oncology by Haydu et al, has shown a 5-year cumulative incidence of central nervous system (CNS) metastasis of 15.8% among patients with American Joint Committee on Cancer (AJCC) 8th Edition stage III melanoma.
The study involved 1,918 patients from The University of Texas MD Anderson Cancer Center and Melanoma Institute Australia diagnosed from 1998 to 2014 who had negative baseline CNS imaging within 4 months of diagnosis.
Key Findings
At a median follow-up of 70.2 months, distant recurrence was observed in 711 patients (37.1%). The first site of distant metastasis was extracranial only for 31.4%, CNS only for 3.9%, and CNS and extracranial for 1.8%.
“Similar rates of CNS metastasis were observed in two large, geographically distinct cohorts of patients with stage III melanoma. The results highlight the importance of primary tumor mitotic rate.”— Haydu et al
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Overall, 16.7% of patients were diagnosed with CNS metastasis during follow-up. The cumulative incidence of CNS metastasis at 1, 2, and 5 years was 3.6%, 9.6%, and 15.8%, respectively. There was no difference in cumulative incidence between patients from Melanoma Institute Australia and those from MD Anderson (P = .303).
On multivariate analysis, risk of CNS metastasis was significantly increased for males vs females (hazard ratio [HR] = 1.53, P = .001), decreasing age at diagnosis (HR = 0.90 per 10-year increments, P = .004), increasing AJCC 8th Edition stage group (HRs = 2.07 for IIIB, 2.46 for IIIC, and 3.17 for IIID vs IIIA, overall P < .001), and increased primary tumor mitotic rate (HRs = 1.77 for 5–9 and 2.18 for > 9 vs 0–4 per mm2, P < .001 for both comparisons).
The investigators concluded, “Similar rates of CNS metastasis were observed in two large, geographically distinct cohorts of patients with stage III melanoma. The results highlight the importance of primary tumor mitotic rate. Furthermore, they provide a framework for developing evidence-based surveillance strategies and evaluating the impact of contemporary adjuvant therapies on the risk of CNS metastasis development.”
Lauren E. Haydu, PhD, MPH, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by philanthropic contributions to The University of Texas MD Anderson Cancer Center’s Melanoma Moon Shots program, the National Health and Medical Research Council of Australia, and others. For full disclosures of the study authors, visit ascopubs.org.
