Risk Factors Associated With First and Second Primary Melanomas in a High-Incidence Population

TAKE-HOME MESSAGE

• This population-based prospective cohort study of Australian citizens aged 40 to 69 years investigated the risk factors that differed between patients who developed two or more primary melanomas and those who developed only one primary melanoma. Compared with first primary melanomas, second primary melanomas were more likely to be in situ and thinner, with the authors postulating that this finding was due to higher levels of surveillance after the diagnosis of a first melanoma.

• Although limited by a median follow-up time of 7.4 years, this study suggests that numerous nevi and high polygenic risk are associated with the development of multiple melanomas.

–  Ruth McTighe, MD

Written by

 

 

Danny Zakria MD, MBA 

Written by

 



Nicholas Brownstone MD 

Written by

 

 

Darrell S. RigelMD, MS

The incidence of primary cutaneous melanoma (CM) has been on the rise, and many studies have shown that patients diagnosed with a CM are at an increased risk of developing a second one.1,2 However, despite the increased risk, the majority of patients do not ultimately develop second CMs. It is, therefore, important to understand which people are at higher risk for additional CMs and require closer surveillance.

This paper by Olsen et al describes a population-based prospective cohort that follows men and women aged 40 to 69 years from 2011 to 2018 in Queensland, Australia. The goal of this study was to compare the clinical characteristics of first and second primary CMs and uncover differences between phenotypic and environmental risk factors for each one.

One of the key findings (similar to prior studies) was that second CMs are more likely to be in situ or thin invasive tumors (≤1mm) than first melanomas. This demonstrates the efficacy of increased surveillance to catch second melanomas at an earlier state leading to improved outcomes. Additionally, the risk factors that were more strongly associated with second than first primary CMs include large mole count at age 21 years, a high polygenic risk score, and history of multiple nonmelanoma skin cancer excisions. On the other hand, risk factors such as age, sex, hair color, tanning ability, burning tendency, cumulative sun exposure, and family history of melanoma had a similar impact on the development of first and second CMs.

Given that patients with an initial primary melanoma are at an overall increased risk for developing an additional primary, regular follow-up is important for this cohort. This study presents factors to identify patients at greatest risk for subsequent melanoma and can help the clinician provide even closer surveillance in this higher risk group to improve outcomes minimizing inefficient utilization of healthcare resources.

References

1. Goggins WB, Tsao H. A population-based analysis of risk factors for a second primary cutaneous melanoma among melanoma survivors. Cancer. 2003;97(1):639-643. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.11116 
2. DiFronzo LA, Wanek LA, Elashoff R, et al. Increased incidence of second primary melanoma in patients with a previous cutaneous melanoma. Ann Surg Oncol. 1999;6(7):705-711. https://link.springer.com/article/10.1007/s10434-999-0705-0 

Abstract

IMPORTANCE

An increasing number of people develop more than 1 primary melanoma, yet to date, no population-based prospective cohort studies have reported on risk factors for developing first vs second primary melanomas.

OBJECTIVE

To compare the clinical characteristics of first and second melanomas and then to estimate the relative risks of developing 1 vs multiple melanomas associated with demographic, phenotypic, sun exposure, and genetic factors.

DESIGN, SETTING, AND PARTICIPANTS

This population-based prospective cohort study included men and women aged 40 to 69 years recruited in 2011 and followed up until December 2018 in Queensland, Australia. Data analysis was performed from February to July 2022.

EXPOSURES

Self-reported information about demographic, phenotypic, and sun exposure measures captured using a survey completed at baseline, and polygenic risk score for melanoma.

MAIN OUTCOMES AND MEASURES

Incident first or second primary melanoma diagnosis, and histologic and clinical characteristics thereof. The Wei-Lin-Weissfeld model for recurrent events was used to estimate the association of each factor with the risks of first and second primary melanoma.

RESULTS

A total of 38 845 patients (mean [SD] age at baseline, 56.1 [8.2] years; 17 775 men and 21 070 women) were included in the study. During a median follow-up period of 7.4 years, 1212 (3.1%) participants had a single primary melanoma diagnosis, and 245 (0.6%) had a second primary melanoma diagnosis. Second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (ie, ≤1 mm) than first melanomas. Having many moles at age 21 years (self-reported using visual scoring tool) was more strongly associated with second (hazard ratio [HR], 6.36; 95% CI, 3.77-10.75) than first primary melanoma (HR, 3.46; 95% CI, 2.72-4.40) (P value for difference between the HRs = .01). A high genetic predisposition (ie, polygenic risk score in tertile 3) was also more strongly associated with second (HR, 3.28; 95% CI, 2.06-5.23) than first melanoma (HR, 2.06; 95% CI, 1.71-2.49; P = .03). Second melanomas were more strongly associated with a history of multiple skin cancer excisions (HR, 2.63; 95% CI, 1.80-3.83) than first melanomas (HR, 1.86; 95% CI, 1.61-2.16; P = .05). For all other phenotypic characteristics and sun exposure measures, similarly elevated associations with first vs second melanomas were observed.

CONCLUSIONS AND RELEVANCE

Findings of this cohort study suggest that within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanomas.

JAMA Dermatology

Risk Factors Associated With First and Second Primary Melanomas in a High-Incidence Population

JAMA Dermatol 2022 Nov 23;[EPub Ahead of Print], CM Olsen, N Pandeya, JC Dusingize, RE Neale, S MacGregor, MH Law, DC Whiteman 

Sent from my iPhone

Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

Please excuse the shortness of this message, as it has been sent from
a mobile device.