The management of early and late stage melanoma in the modern era

Early detection of melanoma is vital for improving survival. Personalized surveillance in high-risk individuals, such as those with multiple (atypical) naevi or a CDKN2A germline mutation, can aid in earlier diagnosis. In our study, most melanomas developed from pre-existing naevi, supporting the use of total body photography (TBP) and sequential dermoscopy. Surgical removal of naevi in CDKN2A mutation carriers may help prevent melanoma. The introduction of immune checkpoint inhibitors has significantly improved survival in stage III/IV melanoma in both adjuvant and systemic settings. However, severe adverse events can occur. We found that the presence of comorbidities and reduced ECOG performance status were associated with a higher risk of toxicity. In the neoadjuvant setting, immunotherapy has shown superior outcomes compared to adjuvant therapy alone and may become the preferred treatment for high-risk stage III melanoma. For advanced melanoma, factors such as age, LDH levels, brain metastases, and histologic subtype influence therapy response. Nodular melanoma showed worse overall survival than superficial spreading melanoma, despite similar treatment responses. Lastly, we observed heterogeneous immune responses (e.g., mixed response, pseudoprogression) not well captured by RECIST 1.1. Continued imaging and therapy may still lead to benefit in such cases, highlighting the need for better response assessment tools.