Findings from a large study highlight the importance of the primary tumor mitotic rate, and provide a framework for evidence-based surveillance strategies that can be used to monitor central nervous system (CNS) metastasis in patients with stage III melanoma (J Clin Oncol. 2020 Jan 28. Epub ahead of print).

“Improved understanding of the incidence, risk factors, and timing of CNS metastasis is needed to inform surveillance strategies for patients with melanoma,” explained Lauren E. Haydu, PhD, MPH, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, and colleagues.

Using databases from 2 melanoma centers in the United States and Australia, Dr Haydu et al gathered clinical data for 1918 patients with stage III melanoma diagnosed between 1998 and 2014. All patients had disease diagnosed in accordance with the American Joint Committee on Cancer (AJCC) 8th edition and negative baseline CNS imaging within 4 months of diagnosis.

According to the investigators, cumulative CNS metastasis incidence was calculated in the presence of the competing risk for death, from stage III presentation and at 1-, 2-, and 5-years post-diagnosis.

Distant recurrence was reported in 711 (37.1%) patients as of a median follow-up of 70.2 months. Furthermore, while CNS was the first site of distant metastasis in only 3.9% of patients, CNS and extracranial was the first for 1.8%, and extracranial only for 31.4%.

Ultimately, follow-up yielded a 16.7% diagnosis rate of CNS metastasis. At 1, 2, and 5 years, the cumulative incidence of CNS metastasis was 3.6% (95% CI, 2.9%-4.6%), 9.6% (95% CI, 8.3%-11.0%), and 15.8% (95% CI, 14.1%-17.6%), respectively.

In multivariable and conditional analyses, factors including patient sex, age, AJCC stage, primary tumor site, and primary tumor mitotic rate significantly influenced the risk for CNS metastasis.

In addition, a high primary tumor mitotic rate was significantly tied to increased risk for CNS metastasis at diagnosis and all subsequent time points evaluated.

“Similar rates of CNS metastasis were observed in 2 large, geographically distinct cohorts of patients with stage III melanoma. The results highlight the importance of primary tumor mitotic rate,” Dr Haydu and colleagues concluded.

“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,” they added.—Hina Porcelli