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 0Á73 [95% confidence interval (CI) 0Á68-0Á77], 0Á65 (95% CI 0Á62-0Á68) and 0Á65 (95% CI 0Á61-0Á69) for predicting second, third and fourth primary melanomas, respectively. The risk of a subsequent primary melanoma was 4Á75 times higher (95% CI 3Á87-5Á82) for the highest vs. the lowest quintile of the risk score. The mean absolute risk of a subsequent primary melanoma within 5 years was 8Á0 AE SD 4.1% after the first primary melanoma, and 46Á8 AE 15Á0% 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.What's already known about this topic?• Current guidelines for the frequency and length of follow-up to detect new primary melanomas in patients with one or more previous primary melanomas are based on limited evidence. A risk prediction model for subsequent primary melanomas, A.E. Cust et al. 1149 A risk prediction model for subsequent primary melanomas, A.E. Cust et al. 1153 A risk prediction model for subsequent primary melanomas, A.E. Cust et al. 1155

IMPORTANCEA previous single-center study observed fewer excisions, lower health care costs, thinner melanomas, and better quality of life when surveillance of high-risk patients was conducted in a melanoma dermatology clinic with a structured surveillance protocol involving full-body examinations every 6 months aided by total-body photography (TBP) and sequential digital dermoscopy imaging (SDDI).OBJECTIVE To examine longer-term sustainability and expansion of the surveillance program to numerous practices, including a primary care skin cancer clinic setting. DESIGN, SETTING, AND PARTICIPANTSThis prospective cohort study recruited 593 participants assessed from 2012 to 2018 as having very high risk of melanoma, with a median of 2.9 years of follow-up (interquartile range, 1.9-3.3 years), from 4 melanoma high-risk clinics (3 dermatology clinics and 1 primary care skin cancer clinic) in New South Wales, Australia. Data analyses were conducted from February to September 2020.EXPOSURES Six-month full-body examination with the aid of TBP and SDDI. For equivocal lesions, the clinician performed SDDI at 3 or 6 months. MAIN OUTCOMES AND MEASURESAll suspect monitored or excised lesions were recorded, and pathology reports obtained. Outcomes included the incidence and characteristics of new lesions and the association of diagnostic aids with rates of new melanoma detection. RESULTS Among 593 participants, 340 (57.3%) were men, and the median age at baseline was 58 years (interquartile range, 47-66 years). There were 1513 lesions excised during follow-up, including 171 primary melanomas. The overall benign to malignant excision ratio, including keratinocyte carcinomas, was 0.8:1.0; the benign melanocytic to melanoma excision ratio was 2.4:1.0; and the melanoma in situ to invasive melanoma ratio was 2.2:1.0. The excision ratios were similar across the 4 centers. The risk of developing a new melanoma was 9.0% annually in the first 2 years and increased with time, particularly for those with multiple primary melanomas. The thicker melanomas (>1-mm Breslow thickness; 7 of 171 melanomas [4.1%]) were mostly desmoplastic or nodular (4 of 7), self-detected (2 of 7), or clinician detected without the aid of TBP (3 of 7). Overall, new melanomas were most likely to be detected by a clinician with the aid of TBP (54 of 171 [31.6%]) followed by digital dermoscopy monitoring (50 of 171 [29.2%]). CONCLUSIONS AND RELEVANCEThe structured surveillance program for high-risk patients may be implemented at a larger scale given the present cohort study findings suggesting the sustainability and replication of results in numerous settings, including a primary care skin cancer clinic.

Communicating personalized genomic risk results for common diseases to the general population as a form of tailored prevention is novel and may require alternative genetic counseling service delivery models. We describe the development and evaluation of a communication protocol for disclosing melanoma genomic risk information to the asymptomatic general population and assess participants' satisfaction and acceptability. Participants (n = 117) were aged 22-69 years, living in New South Wales, Australia and unselected for family history. They provided a saliva sample and had genomic testing for melanoma for low to moderate penetrant melanoma susceptibility variants in 21 genes. Participants could choose to receive their results from a genetic counselor via telephone, followed by a mailed booklet or to receive their risk result via mailed booklet only with a follow-up call for those at high risk. A follow-up questionnaire was completed by 85% of participants 3-months later. Most participants (80%) elected to receive their result via telephone. Participants were highly satisfied with the delivery of results (mean 3.4 out of 4, standard deviation 0.5), and this did not differ by delivery mode, risk category, age or sex. On follow-up, 75% accurately recalled their risk category, 6% indicated a preference for a different delivery mode, either electronic or face-to-face. The process of disclosing genomic risk results to the general population over the telephone with accompanying written material was feasible and acceptable, and may be useful for communicating polygenic risk for common diseases in the context of increasing demands for genomic testing.