A Risk Prediction Model for the Development of Subsequent Primary Melanoma in a Population-based Cohort

A.E. Cust; C. Badcock; J. Smith; N.E. Thomas; L.E. Haydu; B.K. Armstrong; M.H. Law; J.F. Thompson; P.A. Kanetsky; C.B. Begg; Y. Shi; A. Kricker; I. Orlow; A. Sharma; S. Yoo; S.F. Leong; M. Berwick; D.W. Ollila; S. Lo


The British Journal of Dermatology. 2020;182(5):1148-1157. 

In This Article

Abstract and Introduction


Background: Guidelines for follow-up of patients with melanoma are based on limited evidence.

Objectives: To guide skin surveillance, we developed a risk prediction model for subsequent primary melanomas, using demographic, phenotypical, histopathological, sun exposure and genomic risk factors.

Methods: Using Cox regression frailty models, we analysed data for 2613 primary melanomas from 1266 patients recruited to the population-based Genes, Environment and Melanoma study in New South Wales, Australia, with a median of 14 years' follow-up via the cancer registry. Discrimination and calibration were assessed.

Results: The median time to diagnosis of a subsequent primary melanoma decreased with each new primary melanoma. The final model included 12 risk factors. Harrell's C-statistic was 0·73 [95% confidence interval (CI) 0·68–0·77], 0·65 (95% CI 0·62–0·68) and 0·65 (95% CI 0·61–0·69) for predicting second, third and fourth primary melanomas, respectively. The risk of a subsequent primary melanoma was 4·75 times higher (95% CI 3·87–5·82) for the highest vs. the lowest quintile of the risk score. The mean absolute risk of a subsequent primary melanoma within 5 years was 8·0 ± SD 4.1% after the first primary melanoma, and 46·8 ± 15·0% after the second, but varied substantially by risk score.

Conclusions: The risk of developing a subsequent primary melanoma varies considerably between individuals and is particularly high for those with two or more primary melanomas. The risk prediction model and its associated nomograms enable estimation of the absolute risk of subsequent primary melanoma, on the basis of on an individual's risk factors, and can be used to tailor surveillance intensity, communicate risk and provide patient education.


People with a primary melanoma have a higher risk of developing a second primary invasive melanoma, compared with the general population.[1] Secondary prevention through routine surveillance is important to ensure that subsequent melanomas are detected and treated at an early stage, when prognosis is better.[2] However, skin surveillance protocols for patients with melanoma, including intervals between clinic visits and duration of follow-up, differ considerably by country because the clinical practice guidelines are underpinned by low levels of evidence.[3,4] In some countries, follow-up intervals are tailored to individual risk factors, particularly number of previous primary melanomas, dysplastic naevi, family history of melanoma and CDKN2A mutations.[1,4] However, there are currently no detailed risk prediction models that combine multiple risk factors to estimate an individual's absolute risk of developing a subsequent primary melanoma.

Compared with using a one-size-fits-all approach for skin surveillance, a tailored approach, whereby higher-risk individuals have more regular and/or more specialized skin surveillance than lower-risk individuals do, could improve patient outcomes through earlier detection of new melanomas, and have psychological benefits such as reduced anxiety in lower-risk individuals. It may also lead to more efficient use of healthcare resources.[3]

To facilitate implementation of individual patient risk assessment and tailored skin surveillance for patients with melanoma, a comprehensive prediction model for subsequent primary cutaneous melanoma was developed using data from a large population-based sample of patients with melanoma, with a median 14 years of follow-up. Demographic, phenotypical, histopathological, sun exposure and genomic risk factors were included, and nomograms were produced to facilitate clinical use.