According to the World Health Organization there are between 2 and 3 million cases of skin cancer reported yearly, of which melanoma is the most serious.
Melanoma is a malignant tumour that develops in the skin’s melanocytes. This very aggressive tumour that frequently metastasizes, is extremely resistant to chemotherapy and radiotherapy, and has a median survival rate of one year at the metastatic stage. Every year, 130,000 persons throughout the world are diagnosed with melanoma, which causes over 37,000 deaths per year.
It is the second most common cancer in the 15-34 year-old age group. The incidence rates of melanoma doubles every 10 to 20 years among Caucasian populations. It remains rare in people who are not white-skinned. In the United States the incidence rate is 6.5 out of 100,000 people with an annual death rate, over the last 20 years, of 9000 people. New Zealand and Australia have the highest incidence rates in the world with 30 to 40 cases reported out of 100,000. The associated treatment costs are estimated at 1,5 million dollars per year.
In Europe, the incidence rate is 11,3 out of 100,000 people and varies according to region, with the highest rate in northern and western European countries. Melanoma is responsible for 14,000 deaths per year.
In France, over 100,000 cases of skin cancer are reported every year, the majority of which are basal cell carcinomas (a type of skin cancer which responds very well to treatment).
In France, 9000 new cases of melanoma are diagnosed every year, with a death rate of 20 to 30% after five years (1600 deaths per year). The incidence rate of melanoma has increased faster than any other type of cancer. In almost twenty years, the incidence has multiplied by three in men and 2,4 in women. Melanoma is also increasingly on the rise among young people.
According to the French National Authority for Health, the diagnosis and treatment of patients every year result in about 500,000 excisions (surgical ablations) of superficial skin lesions, 12,000 hospitalizations, as many chemotherapy sessions, and about 40,000 patients are registered with chronic long-term illness. This has a total cost in care management of 236 million euros of medical procedures reimbursed by health insurance (PMSI data2008, and health insurance reimbursements, 2008 tariffs).
People at the highest risk of cutaneous melanoma meet the following criteria:
Cutaneous phototype I or II, fair skin, red or blond hair, light-coloured eyes, freckles, many moles (more than 40), irregular nævi, giant congenital naevi (birthmarks – with a diameter of >20).
A history of sunburn, irrespective of age when it occurred, or sunbed sessions and exposure to artificial UV rays particularly before the age of 35
Actinic damage (linked to UV rays), personal or family history of cutaneous melanoma
Out of all the risk factors for cutaneous melanoma, intervention is only possible in the cases of overexposure to the sun or artificial UV. One cannot act on the other factors as they are associated with phenotypic characteristics or genetic factors.
Early management of skin cancer can be greatly improved by making use of newly developed predisposition tests (such as Melapred), which can point the way to screening for people most at risk.
Skin cancer risk factors can be classified into three groups:
Clinical risk factors:
The number of moles (beauty spots)
The phototype (tanning capacity)
The individual’s physical pigmentation characteristics (fairness of skin, eye and hair colouring)
The presence of freckles
The presence of giant congenital naevi
A family history of melanoma
Behavioural risk factors:
Exposure to ultraviolet rays is an important factor – notably childhood sunburn and exposure to artificial UV rays in tanning salons.
Genetic risk factors:
Some people who are not at risk, a priori because of their phototype and their physical characteristics, can, nevertheless present a high risk of developing skin cancer. In this situation, only genetic testing will be able to detect a predisposition to the disease.
There are two types of genetic disposition:
Familial predisposition concerns about 10% of patients who have melanoma. We talk about major predisposition genes of which the best known are CDKN2A and CDK4. There are mutations of these two genes in 10 to 20% of familial types of melanoma, and probably other major predisposition to melanoma genes exist that have not yet been identified.
The multifactorial predisposition concerns 90% of melanomas. It is based on the combination of minor predisposition genes, such as pigmentation (MC1R, MATP/SLC45A2 or ASIP), or other genes such as TERT-CLPTL1 and CASP8. The variants of these genes are alleles with low penetrance susceptibility (the proportion of individuals with a specific genotype that express the corresponding phenotype). The MC1-R has been studied the most. It codes for the melanocortin receptor type 1, and presents numerous variants (over 65 identified). Their frequency varies from 5% (black African populations) to 50% (Caucasian Irish and British populations).
Nowadays, early melanoma diagnosis is carried out with the involvement of different actors: the patient, the general practitioner, the dermatologist and eventually, the pathologist. The appearance of a suspect lesion, will lead the patient to consult their doctor, who will refer them to a dermatologist, who in turn will be able to diagnose a suspected cancer and if there is the smallest doubt, will recommend a biopsy or a resection (surgical ablation) of the lesion. Finally, the pathologist’s examination will confirm the diagnosis and will measure the thickness of the melanoma (Breslow’s Depth). The dermatologist will also keep an eye on patients at risk and will show them how to make self-examinations.
Surgery (or surgical ablation) is the standard treatment for melanoma. The operation is carried out under local or general anaesthetic depending on the location of the lesion.
Decisions about treatment are made collectively and summarized in a personalized care programme. Surgery is the first option in the treatment envisaged. If the melanoma has spread beyond the first primary tumour, one or more treatments may be suggested: surgical removal or locoregional radiotherapy on the lymph nodes in case of local lymph node damage; surgery and/or radiotherapy, and/or chemotherapy, in the case of metastatic development.
In the last few years, new molecules have emerged in the treatment of metastatic melanoma, which basically, fall into two categories: those that seek to increase the host’s immune response (anti-CTLA4, anti-PD1), and the inhibitors that target the MAP kinase pathway (BRAF or MEK inhibitors).
Whatever the case, early management of cutaneous skin cancer is a key factor in treatment success!