Dra. Maria José Passos

Oncologist

Melanoma

Inform to prevent

HPA Magazine 20

What is melanoma?
Cutaneous melanoma is a malignant tumour of the melanocytes, which are the cells responsible for skin pigmentation. 
Despite being a relatively rare tumour, it represents about 5 to 10% of cutaneous malignancies and is the most lethal, responsible for about 80% of all skin cancer deaths.  
It can appear as a brown or black “spot”, although rare, it can be pink or white (amelanotic melanoma).
It can affect any age group and is relatively common in young adults (<30 years) but rare in children.  The risk of developing melanoma is the same for both sexes, with differences between countries. It appears more frequently in Caucasian individuals, but it can also appear in the black race.

What are the symptoms and warning signs?
Early on in the disease, there are usually no symptoms; some suspicious morphological alterations may occur in spots (nevi), such as an increase in size, colour change, asymmetry of the borders, ulceration or bleeding (ABCDE criteria). 
Pruritus (itching), bleeding, ulceration over a pre-existing lesion can also be suspected of being a malignant lesion and should mean a visit to the doctor.
Everyone should know and be aware of the warning signs. Melanoma can appear anywhere on the body, even in areas not exposed to the sun, such as the palms of the hands and soles of the feet, as is the case with the black race.
Do not forget that people with fair skin, blue or green eyes, blonde or red hair, with multiple atypical nevi are more sensitive to the sun and should be observed regularly by a dermatologist. All lesions should be photographed. If any of these spots undergo changes in their morphology, they must be removed. It is essential for everyone to know that it is important to periodically monitor the morphological alterations of spots as well as the appearance of new skin lesions, by consulting your doctor.
All risky behaviour should be avoided and the advice of the Portuguese League against cancer should be followed. As far as prevention is concerned, what should be done and which are the risk groups?
Despite the huge therapeutic advances that have taken place this last decade, prevention and an early diagnosis remain the best weapons in the fight against melanoma. 
Obviously, it is better to prevent a melanoma, or if this is not possible, to diagnose it in the early stages. We know that the survival rate of a naive with a thickness less than, or equal to 1mm, at the end of 5 years is 95% for stage I, but it drops to 62% when there is regional lymph node involvement, and to 20% in advanced tumours (stage IV). This illustrates the importance of an early diagnosis.
The main risk factors are well established. People with fair skin, freckles, red or blond hair (photo-types I and II), with light coloured eyes, atypical nevi, with a history of intense and intermittent sun exposure (sunburn), especially in childhood, have a higher risk of developing melanoma. 
It is also important to highlight the importance of a personal and family history of melanoma and immunosuppression, which also represents a risk factor for developing melanoma.
What is the current prevalence of melanoma?
Melanoma is the type of cancer with the highest incidence among Caucasians, with an annual incidence increase of 3 to 7% in the US and doubling the number of cases and mortality rate every 10-20 years.
The number of cases of skin cancer continues to increase worldwide, particularly in the US, Australia and Northern Europe. According to 2020 data from Globocan, it is estimated that in Portugal, in 5 years the prevalence will be 3488 cases (rate of 34.2%) an incidence of 1071 with a mortality of 289 per year. We believe that these figures are underestimated, mainly due to the pandemic.
We know that in 2020, there was a reduction in the number of melanomas diagnosed and those that were detected were in an advanced stage. This reality was transversal to several countries, including Portugal. In the future we will have more robust figures for this period and certainly more informed conclusions.
The causes for this increase in the number of cases is due to several factors: genetic, environmental and are mainly related to risky behaviour which should be avoided. 
Excessive, chronic or intermittent sun exposure (“sunburn”) between midday and 4pm, when ultraviolet radiation is most dangerous; solariums should be avoided as well as intense sun exposure, especially during childhood.
For many years, Portuguese dermatologists have been provided excellent work in the area of prevention and early diagnosis of melanoma, but unfortunately, we still see many cases of melanoma diagnosed at an advanced stage and neglected for years.
It is necessary to continue working to develop new prevention strategies and to invest in education/training in Oncodermatology by society and health professionals, with emphasis on General Practitioners and family doctors.

On a therapeutic level, what treatment is currently available for melanoma? Are there more innovative therapies, such as biopharmaceuticals?
Surgery remains the treatment of choice for early-stage melanoma (stages I) with a cure rate of over 90%. However, patients with high-risk melanoma in stages IIB and CIII, when diagnosed and metastatic melanoma (stage IV) have a different and more complex therapeutic approach.
In these cases, the prognosis is not so favourable, although in the last decade there have been significant advances in the medical treatment of high-risk and advanced melanoma, with the use of immunotherapy with check-point inhibitors and targeted therapies in melanomas with BRAF mutation.
Since 2011 new drugs have emerged, with different action mechanisms, which have resulted in an increase in patient’s survival rate, first with advanced melanoma and, currently, also in its earlier stages. 
This is the case with immunotherapy (CTLA-4 and PD1 checkpoint inhibitors) and targeted therapy for patients with a mutation in the BRAF gene. 
Unlike antineoplastic chemotherapy, immunotherapy acts on the host and not directly on the tumour, modulating the body's immune responses, so that it can fight melanoma effectively. 
The mechanism of action of the different immunological agents determine the clinical response and the secondary effects of an autoimmune cause. As a rule, these effects are manageable when recognized and treated early with corticosteroids.
Immunotherapy and targeted therapies, now used in the treatment of this disease, have led to an overall survival rate increase and long-lasting response, often transforming an aggressive disease into a chronic disease with few symptoms.
Currently in our hospitals, patients with melanoma are treated with these new agents (immunotherapy in combination and/or monotherapy) and BRAF inhibitors + MEK inhibitors, in advanced stages of the disease and more recently also as an aid in stages III, which has represented another important advance in the treatment of Portuguese people with high-risk and metastatic melanoma.
What expectations await us in the near future?  
We hope that the year 2023 will be a year of progress and recovery in the activity of our institutions, not neglecting primary prevention and early diagnosis of cancer, namely melanoma, but also other skin cancers.
I wish to end with a message of hope and optimism to all of our melanoma patients. Immunotherapy with checkpoint inhibitors and targeted anti-BRAF/MEK therapies have radically changed the natural history of melanoma, definitively dethroning antineoplastic chemotherapy and demonstrating incomparable efficacy, in a metastatic context and now also adjuvant.
We still have many challenges ahead, but the revolution continues...