What question did this study set out to answer?

This review aims to summarize differences in melanoma characteristics and treatment responses between adolescents and young adults (AYAs) and non-AYAs.

April 23, 2026EJC Skin Cancer0 citationsOpen Access

De-escalation of targeted therapy in melanoma: A literature review

ECE. ChatziioannouUniversity Children's Hospital Tübingen KLK. LallasAristotle University of Thessaloniki ULU. LeiterUniversity Children's Hospital Tübingen

Key Points

This review aims to summarize differences in melanoma characteristics and treatment responses between adolescents and young adults (AYAs) and non-AYAs.
Literature review of melanoma cases focusing on age-related differences.
Kaplan-Meier analysis and Cox regression models applied to patient outcomes.
Comparison of tumor characteristics and treatment responses between AYAs and non-AYAs.
AYAs exhibited a lower mean Breslow thickness and higher rates of stage I melanomas.
Superior 5-year progression-free survival (96.5% in AYAs vs. 92.4% in non-AYAs) was observed.
BRAF mutations were more prevalent in AYAs, while NRAS mutations were more commonly found in non-AYAs.

Abstract

were assessed using Kaplan-Meier analysis and Cox regression models.Results: Of the 1,653 patients with CM, 290 (17.5%) were classified as AYA while 1,363 (82.5%) were non-AYA patients.AYAs were more frequently female (58.6% vs. 47.0%,p < 0.001) and showed more favorable tumor characteristics, including a lower mean Breslow thickness (0.7 mm vs. 1.1 mm, p = 0.01), a lower prevalence of ulceration (6.2% vs. 13.4%,p = 0.001), and earlier disease stage at diagnosis, with a higher proportion of stage I melanomas (55.8% vs. 48.9%,p = 0.014).Superficial spreading melanoma was the most common histologic subtype in both groups but occurred significantly more often among AYAs (88.0% vs. 80.3%, p = 0.007).Familial melanoma was also reported more frequently in AYAs (13.1% vs. 6.9%,p < 0.001).Among patients who underwent mutational testing (33 AYA and 165 non-AYA), BRAF V600 mutations were more prevalent in AYAs (63.6% vs. 45.5%,p = 0.075), whereas NRAS mutations predominated in older adults (27.3% vs. 3.3%, p = 0.022).Among patients receiving firstline systemic therapy with immune checkpoint inhibitors (ICIs) or BRAF/MEK targeted therapy, AYAs more often received targeted therapy (9/17, 52.9%), whereas non-AYAs mainly received ICIs (112/161, 69.6%) (p = 0.085).Treatment was mainly administered in the adjuvant setting in AYAs (15/17, 88.2%), and in the metastatic setting in non-AYAs (71/161, 44.1%) (p = 0.01).AYAs exhibited significantly superior 5-year PFS compared with non-AYAs (96.5% vs. 92.4%,log-rank p = 0.041), remaining significant after multivariable adjustment (adjusted HR = 0.51, 95% CI 0.27-0.95,p = 0.034) Conclusions: Within our cohort, CM in AYA was characterized by female predominance, thinner primary tumors, a higher prevalence of familial melanoma, and a superior 5-year PFS.These findings highlight age-related differences in melanoma presentation and outcomes, suggesting distinct biological features in AYAs and underscoring the need for further studies to refine risk stratification and to develop age-adapted management strategies.

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