Neel M. Helvind, MD, PhD

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High numbers of distant recurrences of cutaneous melanoma indicate a more common hematogenous metastatic pathway than previously thought, according to recent findings, suggesting the need for routine functional/cross-sectional imaging for stages IIB to IV.¹

These new findings resulted from a nationwide study on recurrence and death rates of patients with cutaneous melanoma in the country of Denmark, with the investigators using data drawn from patients registered in the Danish Melanoma Database (DMD).²

The team’s research was led by Neel M. Helvind, MD, PhD, from Copenhagen University Hospital’s Department of Plastic Surgery.

“The aims of this study were to assess the stage-specific rates of recurrence and death from melanoma and melanoma-specific (MS) recurrence-free survival (RFS) and to assess the absolute stage-specific risk of recurrence and death from melanoma at 1, 3, 5, and 10 years after initial treatment,” Helvind and colleagues wrote.

Background and Findings

The investigators used a nationwide retrospective cohort design in which clinical and pathologic data was drawn from 5 national databases: the Danish Pathology Register (DPR), the DMD, the Danish Civil Registration System, the Danish National Patient Register (NPR), and the Danish Cause of Death Registry.

The research team recruited participants aged 18 and up that had a first-time diagnosis of invasive cutaneous melanoma—stage IA to IV—between January 2008 and December 2019. The study participants were categorized by pathologic or clinical stage.

The investigators’ follow-up was carried out up until emigration, until an event took place, until the end of follow-ups in December 2021, or until diagnosis of a higher-stage subsequent primary melanoma. Guidelines as well as treatment practices, such as surgical margins and assessments of lymph nodes, evolved at the time of the study.

The team gathered information regarding participant, tumor, and treatment characteristics from the DMD as well as their sources. Both recurrence and metastasis data were taken from several of the registries and then categorized into distinct types.

Statistical analyses, including cumulative incidence rates, recurrence-free survival estimates, proportional hazards models, and stage-specific risks, were conducted using R statistical software. The research team sought to provide insights into the recurrence as well as the risks of mortality linked with various melanoma stages based upon these comprehensive data sources and rigorous statistical analysis.

The investigators followed-up with a cohort of 25,720 participants over a median time period of 5.9 years (95% CI, 58.9 - 59.3 years). They reported that the mean age of these individuals was 59.1 years (95% CI, 58.9 - 59.3 years).

Overall, those included who had diagnoses of stage IIB - IIC melanoma were shown to generally skew older and to have greater comorbidity prevalence during their diagnoses. The team also pointed out that these individuals exhibited the lowest rate of pathologic staging through sentinel node biopsy, with the range being from 81.6% - 87.4%.

The investigators noted that 10.6% of participants reported a recurrence across the follow-up’s span. They added that the majority of initial recurrences reported by participants in 56.6% of the cases had been described as being by distant recurrence, with either the recurrence being on its own or concurrent with locoregional recurrence.

Notably, the investigators found that there were comparable recurrence risks in between the stages of IIIA and IIB—with 29.7% compared to 33.2%, respectively—and between stages IIIB and IIC—35.9% compared to 36.8%, respectively.

Additionally, the investigators noted that melanoma-specific rates of death were shown to be similar between stages IIIA and IIA—with 13.0% compared to 13.6%, respectively—as well as between stages IIIB and IIB—with 18.4% compared to 22.0%, respectively. Such trends were shown to have persisted even when the team analyzed while using cause-specific hazard models.

“The high proportion of distant recurrences suggests a larger role of hematogenous dissemination in the metastatic pathways than previously assumed,” they wrote. “Future efforts should be put toward refining risk stratification and determining the survival effect of routine imaging in surveillance.”

References

1. ^{Helvind NM, Brinch-Møller Weitemeyer M, Chakera AH, et al. Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021: A National Observational Cohort Study of 25 720 Patients With Stage IA to IV Melanoma. JAMA Dermatol. Published online August 31, 2023. doi:10.1001/jamadermatol.2023.3256.}
2. ^{Hölmich LR, Klausen S, Spaun E, et al. The Danish Melanoma Database. Clin Epidemiol. 2016;8:543-548. doi:10.2147/CLEP.S99484.}