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Observational Study
. 2023 Nov 1;159(11):1213-1222.
doi: 10.1001/jamadermatol.2023.3256.

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

Neel M Helvind  1 , Marie Brinch-Møller Weitemeyer  1 , Annette H Chakera  1 , Helle W Hendel  2 , Eva Ellebæk  3   4 , Inge Marie Svane  3   4 , Mette W Kjærskov  5 , Sophie Bojesen  6 , Helle Skyum  7 , Søren K Petersen  8 , Lars Bastholt  8 , Christoffer Johansen  9 , Pernille E Bidstrup  10 , Lisbet R Hölmich  1
Affiliations
Observational Study

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

Neel M Helvind et al. JAMA Dermatol. .

Abstract

Importance: To ensure optimal treatment and surveillance of patients with melanoma, knowledge of the clinical stage-specific risk of recurrence, mortality, and recurrence patterns across the American Joint Committee on Cancer Eighth Edition (AJCC8) substages is needed.

Objective: To estimate stage-specific recurrence and melanoma-specific mortality rates, assess absolute stage-specific risks of recurrence and mortality, and describe stage-specific recurrence patterns, including conditional rates.

Design: Retrospective cohort study of prospectively collected nationwide population-based registry data.

Setting: Nationwide, population-based cohort study.

Participants: The 25 720 Danish patients, 18 years or older, diagnosed with first-time stage IA to IV cutaneous melanoma between January 1, 2008, and December 31, 2019, were included and followed up from time of primary treatment until December 31, 2021.

Exposures: First diagnosis of stage IA to IV cutaneous melanoma.

Main outcomes: Stage-specific cumulative incidence of recurrence and melanoma-specific mortality, melanoma-specific recurrence-free survival, and assessed absolute stage-specific risks of recurrence and melanoma-specific mortality. Secondary outcomes were stage-specific recurrence patterns, including conditional rates, and melanoma-specific survival.

Results: We followed up 25 720 patients for a median of 5.9 years (95% CI, 58.9-59.3 years). Mean age was 59.1 years (95% CI, 58.9-59.3 years). Patients with stage IIB to IIC melanoma were older, had more comorbidities at diagnosis, and had the lowest rate of pathologic staging by sentinel node biopsy (81.6%-87.4%). A total of 10.6% of patients developed recurrence; first recurrence included distant recurrence, alone or with synchronous locoregional recurrence, in 56.6% of patients. We found a comparable risk of recurrence in stages IIIA and IIB (29.7% vs 33.2%) and in stages IIIB and IIC (35.9% vs 36.8%), respectively. Melanoma-specific mortality was comparable between stages IIIA and IIA (13.0% vs 13.6%) and between stages IIIB and IIB (18.4% vs 22.0%), respectively. These risk patterns persisted in cause-specific hazards models.

Conclusions and relevance: This nationwide, population-based cohort study found that the increasing stages of the current AJCC8 staging system do not accurately reflect an increasing risk of recurrence and mortality in melanoma. The high proportion of distant recurrences suggests that hematogenous spread is a more common metastatic pathway than previously assumed, and surveillance with routine functional/cross-sectional imaging should be considered for stages IIB to IV. Future efforts should be put toward developing new tools for risk stratification and determining the survival effect of routine imaging in surveillance.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Helvind reported receiving grants from the Danish Cancer Society, the Danish Cancer Research Foundation, and the Herlev Gentofte Hospital Research Foundation during the conduct of the study and personal fees from MSD Denmark (speaker’s honoraria) and meeting expenses from AIM at Melanoma outside the submitted work. Dr Brinch-Møller Weitemeyer reported receiving a personal research salary from SkylineDX to conduct a validation study on their risk prediction test, the Merlin test, on a Danish retrospective cohort, grants from MSD Denmark to conduct a descriptive report of the incidence and survival of stage II and III melanoma in Denmark, and personal fees from MSD Denmark (participation on advisory board) outside the submitted work. Dr Chakera reported receiving grants for melanoma research from the Danish Cancer Society and the Innovation Fund Denmark outside the submitted work. Dr Ellebæk reported receiving personal fees from Pierre Fabre (invited speaker), MSD (invited speaker), BMS (invited speaker), Novartis (invited speaker and consulting fees), and Pfizer (invited speaker) and nonfinancial support from Pierre Fabre (travel and conference expenses) and MSD (travel and conference expenses) outside the submitted work. Dr Svane reported receiving personal fees from Novartis (consulting fees, invited speaker), MSD (consulting fees, invited speaker, travel and conference expenses), Pierre Fabre (consulting fees, invited speaker), Sanofi Aventis (invited speaker), and TILT Biotherapeutics (consulting fees), Novo Nordisk (invited speaker), Takeda (invited speaker), BMS (invited speaker, clinical trial material [drugs]); nonpersonal research grants from Evaxion Biotech, Adaptimmune, IO Biotech, Lytix Biopharma, TILT Biotherapeutics, Enara Bio and Asgard Biotech; and owning stock or stock options in IO Biotech. Dr Johansen reported receiving personal fees from Pfizer, Janssen, and Astellas as an invited speaker and owning stock or stock options in yMabs, Janssen, and Zealand Pharma. Dr Hölmich reported receiving grants from the Danish Cancer Society during the conduct of the study and grants from Skyline DX and MSD outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Incidence of Recurrence per American Joint Committee on Cancer Eighth Edition Stage
Data are from 25 310 Danish patients with stage IA to IIID melanoma.
Figure 2.
Figure 2.. Melanoma-Specific Recurrence-Free Survival per American Joint Committee on Cancer Eighth Edition Stage
Data are from 25 310 Danish patients with stage IA to IIID melanoma.
Figure 3.
Figure 3.. Cumulative Incidence of Death From Melanoma per American Joint Committee on Cancer Eighth Edition Stage
Data are from 25 720 Danish patients with stage IA to IV melanoma.
See this image and copyright information in PMC

References

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