Elsevier

The Lancet

Volume 392, Issue 10151, 15–21 September 2018, Pages 971-984
The Lancet

Seminar
Melanoma

https://doi.org/10.1016/S0140-6736(18)31559-9Get rights and content

Summary

Cutaneous melanoma causes 55 500 deaths annually. The incidence and mortality rates of the disease differ widely across the globe depending on access to early detection and primary care. Once melanoma has spread, this type of cancer rapidly becomes life-threatening. For more than 40 years, few treatment options were available, and clinical trials during that time were all unsuccessful. Over the past 10 years, increased biological understanding and access to innovative therapeutic substances have transformed advanced melanoma into a new oncological model for treating solid cancers. Treatments that target B-Raf proto-oncogene serine/threonine-kinase (BRAF)V600 (Val600) mutations using selected BRAF inhibitors combined with mitogen-activated protein kinase inhibitors have significantly improved response and overall survival. Furthermore, advanced cutaneous melanoma has developed into a prototype for testing checkpoint-modulating agents, which has increased hope for long-term tumour containment and a potential cure. These expectations have been sustained by clinical success with targeted agents and antibodies that block programmed cell-death protein 1 in locoregional disease, which induces prolongation of relapse-free, distant-metastasis-free, and overall survival times.

Section snippets

Incidence, mortality, and survival

Worldwide, about 232 100 (1·7%) cases of all newly diagnosed primary malignant cancers (excluding non-melanoma skin cancer) are cases of cutaneous melanoma, and about 55 500 cancer deaths (0·7% of all cancer deaths) are due to cutaneous melanoma annually. The incidence and mortality rates of cutaneous melanoma differ widely by country. In 2012, the age-standardised (world standard population) incidence of cutaneous melanoma ranged from 0·2 per 100 000 person-years in southeast Asia to 7·7 per

Mechanisms and pathophysiology

The malignant transformation of melanocytes into metastatic melanoma is the result of a process that requires a complex interaction between exogenous and endogenous triggers as well as tumour-intrinsic and immune-related factors. Although melanocytes only rarely divide (less than twice per year),16 the proliferative index steadily increases as melanocytic neoplasms sequentially evolve, a process accompanied by a constant increase of point mutations and copy-number alterations.17 Cross-cancer

Histopathological classification

Melanoma is diagnosed histopathologically, with subsequent treatment decisions being based on histological classification and risk calculation. Classification is established with tumour thickness (T stage; Breslow staging),28 lymph node involvement (N stage), and presence of metastasis (M stage). The majority of melanomas are diagnosed before lymph node or distant metastases occur (N0 and M0 stage).29, 30 According to Breslow,28 the most crucial criterion for assessing prognosis and further

Screening and melanoma surveillance

People at an increased risk for melanoma (ie, those who have a fair skin type, multiple atypical moles, or a family history of melanoma) should be screened at regular intervals. The screening populations and methods differ between countries, and often no exact guidelines exist. Generally, screening for melanoma includes a total body skin examination supported by dermoscopy or other imaging techniques, with both examinations performed by an experienced physician. Screening is usually not

Primary tumour: surgical excision and lymph node biopsy

The primary treatment of localised disease (primary tumours) consists of wide local excision with different safety margins, depending on the Breslow22 thickness of the melanoma. Usually, 0·5 cm margins are recommended for in-situ melanomas, 1 cm margins for tumours with a thickness of up to 2 mm, and 2 cm margins for tumours thicker than 2 mm. Several studies analysed narrow versus wide margins, and although they found a reduction in local recurrences for wide margins, they did not show any

Conclusion

Prevention, early detection, and the arrival of effective adjuvant treatment strategies in stage-3 melanoma will increase overall survival and cure rates for patients with melanoma. Using PD-1-based treatment algorithms and targeted agents in BRAFv600-mutant melanoma, 5-year overall survival rates for metastatic melanoma have increased substantially from less than 10% to up to 40–50% today in countries that have access to these innovations.145 Patients with high tumour burden, brain metastasis,

Search strategy and selection criteria

We searched MEDLINE between Dec 1, 2017, and Dec 19, 2017, with no language restrictions. We used the search terms “melanoma” in combination with specific terms covering the different steps of diagnosis and treatment as appropriate. We largely selected publications in the past 5 years, but did not exclude commonly referenced and highly regarded older publications. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Review

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