Skin cancer: An overview

Damien O’Brien MPSI provides a clinical overview of the various forms of skin cancer and their possible presentations

Introduction

Skin cancer occurs when skin cells grow uncontrollably and form malignant tumours. It is the most common form of cancer. The primary cause of skin cancer is prolonged exposure to ultraviolet (UV) radiation, either from the sun or tanning devices. Skin cancers are often located on sun-exposed areas of the head and neck. Epidemiologic studies have illustrated a rising incidence of skin cancer in recent years. The increasing incidence of skin cancer may be due to factors such as sun exposure, lifestyle changes and ageing populations. Pharmacists are accessible healthcare professionals and can play an important role in patient education, prevention, detection and management of skin cancer.¹

Overview

Skin cancer is classified into two categories: Non-melanoma, and melanoma. Melanoma is a cancer that originates from melanocytes, which are the cells that produce pigment in the skin. Melanoma is much less common than non-melanoma, but it is generally more dangerous. This is due to the fact that it can metastasize to other organs if not detected early, leading to a higher mortality rate than non-melanoma skin cancers.^1,2

Non-melanoma skin cancers can be further classified into basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC is the most common skin cancer. It usually develops on sun-damaged skin, originating in cells lining the bottom of the epidermis. It is generally a slow-growing form of cancer and metastases are rare. BCC is rarely fatal, but it can destroy and disfigure local tissue if treatment is delayed or inadequate.³ SCC is the second-most common skin cancer, originating in the cells lining the top of the epidermis. SCC is also related to UV exposure and can occur in various parts of the body. SCC is more likely to metastasize than BCC.⁴

Actinic keratosis is a precancerous area of thick and scaly skin. It is associated with chronic UV radiation exposure. Individuals with actinic keratosis may present with irregular scaly plaques on sun-exposed regions of the body.⁵

Symptoms

The most common symptoms of skin cancer include new moles, changes in existing moles, ulceration, bleeding, itching and pain. Melanoma generally presents as a new mole or a change in an existing mole, usually on an area of the body that has been exposed to UV radiation. The moles usually correspond to the mnemonic ABCDE:²

• Asymmetry: Asymmetrical with an irregular shape.
• Borders: An uneven, irregular border.
• Colour: A variation of colours.
• Diameter: Usually larger than 6mm.
• Evolving: Changes over time.¹

The first symptoms of non-melanoma skin cancer are usually persistent sores or scaly patches that do not resolve and progress over months or years. These usually develop on skin that has been exposed to UV radiation. BCC may present as a small and shiny papule with a waxy appearance. It often grows and may bleed or develop into an ulcer. SCC often presents as a firm pink papule with some surface scale. The papule is usually tender, may bleed and develop into an ulcer.^3,4

Aetiology

UV radiation is the primary etiologic factor in the development of skin cancers. The risk of developing BCC and SCC is correlated with cumulative lifetime UV exposure. Meanwhile, the risk of developing melanoma is correlated with UV exposure during adolescence. UV exposure causes carcinogenesis in two main ways: Generating DNA damage that leads to the formation of mutations, and reducing the ability of the immune system to eliminate malignant cells. Other risk factors associated with the development of skin cancers include family history, chemical exposure, human papillomavirus and immunosuppressed status.¹

Prevention of skin cancer

Preventive strategies can be effective in reducing the risk of skin cancer. Sun protection is one of the most important aspects of prevention of skin cancers. Individuals should be encouraged to wear protective clothing when outdoors and avoid sun exposure during peak UV radiation times (approximately 10am to 4pm). They should also use broad-spectrum sunscreens with an appropriate SPF and avoid tanning beds, which greatly increase the risk of skin cancer. Finally, patients should undergo regular self-examinations, as well as regular dermatologic evaluations, particularly for high-risk patients.⁶

Diagnosis

Early detection of skin cancer is critical for initiating appropriate treatment and improving clinical outcomes. The diagnosis is generally carried out by a dermatologist and usually starts with a visual examination of suspicious moles or lesions. A skin biopsy is the gold standard for clinical confirmation of skin cancer, where a portion of the sample undergoes histopathological examination. Dermoscopy is a specialised imaging technique used to evaluate skin lesions and may be useful in diagnosing skin cancer. Imaging techniques such as computed tomography (CT) scan, magnetic resonance imaging (MRI) or positron emission tomography (PET) scans may be used to determine if the cancer has metastasised.^1,3

Treatment

Treatment of skin cancers should be individualised and tailored to each case to achieve the best clinical outcome. The choice of therapy may depend on the patient’s age, gender and the site, size and type of tumour. Management of skin cancer may involve a combination of pharmacological and non-pharmacological methods. The main objectives of treatment are to completely remove the tumour to prevent recurrence or metastasis, correct functional impairment from the tumour and provide the best cosmetic result.

Pharmacological treatment

Topical therapy

Topical therapy is a potential treatment option for actinic keratosis, BCC and SCC. Topical 5-fluorouracil and topical imiquimod are used to treat superficial skin cancers. They are good treatment options for patients with multiple superficial lesions and for those who are poor candidates for surgery. Reactions at the site of application are common adverse effects and can include pain, erythema, pruritus, hypopigmentation, hyperpigmentation, crusting and bleeding. These topical treatment options also have the disadvantage of lacking histologic confirmation of complete tumour elimination.^3,4

Imiquimod works by stimulating the innate immune system to secrete cytokines, including interferon-? (IFN-?), interleukin-6 (IL-6) and tumour necrosis factor-? (TNF-?), which attack cancerous cells. Imiquimod cream for the treatment of BCC is generally applied five times per week for six weeks. The treatment area should be washed with mild soap and water before drying. Sufficient cream should be applied to the treatment area and one centimetre of skin surrounding the tumour. The cream should be rubbed in, left on for approximately eight hours and then removed with mild soap and water. The response to treatment should be assessed 12 weeks after the end of treatment.⁷

5-fluorouracil works by inhibiting DNA synthesis in rapidly-dividing cells, particularly as a thymidylate synthase inhibitor. It should be applied once or twice daily to malignant tumours, under an occlusive dressing where applicable. The usual treatment course is initially for three-to-four weeks, but this may be prolonged if there isn’t a marked inflammatory response from the treatment area. A topical corticosteroid may be used to alleviate discomfort. The cream should not come into contact with the eyes or mucous membranes.⁸

Systemic therapy

There are several systemic treatment options that can be effective in treating skin cancer. Targeted therapies have improved survival rates for advanced skin cancers. Hedgehog pathway inhibitors are used to treat advanced or metastatic BCC, where conventional treatment options are not suitable. Vismodegib has many adverse effects, including nausea, diarrhoea, dysgeusia, muscle spasms, alopecia, weight loss and fatigue, which can lead to discontinuation in many patients.²

BRAF is a gene involved in the regulation of cell growth and is often mutated in skin cancers. Dabrafenib acts as an inhibitor of BRAF and is indicated in the treatment of metastatic melanoma. The most common adverse effects of dabrafenib include papilloma, headache, nausea, vomiting, alopecia and fatigue.³

Later-stage skin cancer may have a poor prognosis and may require adjuvant chemotherapy, radiation therapy or immunotherapy. Chemotherapy is not commonly used in skin cancer but may be used in advanced cases of melanoma or SCC that have metastasised. Pembrolizumab and nivolumab are immune checkpoint inhibitors that are used as immunotherapy to treat advanced melanoma.^1,3

Non-pharmacological treatment

Non-pharmacological treatment options, particularly surgical and radiation therapies, are often used and are effective in managing skin cancer. Isolated precancerous actinic keratoses may be treated with a lesion-directed treatment option, such as cryotherapy. This involves the use of liquid nitrogen to freeze and destroy superficial skin cancers or precancerous lesions.

Patients with numerous lesions may require field-directed therapy instead of treating each individual lesion. Photodynamic therapy can be used in this case, after the skin is sensitised with a topical agent. Photodynamic therapy uses light-activated drugs to destroy cancer cells and is often used for actinic keratosis and superficial BCC.

Photodynamic therapy has two main steps. Firstly, the patient will receive a photosensitising drug. After 24-to-72 hours, most of the drug will be eliminated from healthy cells but remains in the cancerous or precancerous cells. Secondly, the skin cancer will be exposed to the light source. Photodynamic therapy has the advantage of being generally well tolerated, with limited damage to healthy cells. However, it is only effective for superficial cancerous or precancerous lesions. Adverse effects may include scarring and burns at the treatment site.^1,9

Surgical interventions are often the preferred treatment option for many skin cancers. Surgical excision is a common treatment option for BCC and SCC. Melanomas may require a more extensive procedure, known as a wide local excision technique. Mohs micrographic surgery (MMS) is preferred in cases that meet the appropriate use criteria. This includes lesions with a diameter greater than 2cm, cosmetically sensitive areas and high-risk areas. MMS involves removing the skin cancer layer-by-layer and examining using a microscope to ensure complete removal.

Surgery can be associated with complications, including infection, bleeding, nerve damage and scarring. Radiation therapy may be used as the primary treatment option if surgery is not possible, or as an adjunct to treatment for high-risk or recurrent skin cancer cases. Potential complications of radiotherapy include skin irritation, fatigue, risk of secondary malignancies and lymphedema.^1,3,4

Role of the pharmacist

Pharmacists play an important role in the prevention and management of skin cancer. They can educate patients on practical measures that can reduce the risk of developing skin cancer. Furthermore, they can recognise suspicious skin lesions and refer patients if necessary.

Pharmacists are ideally placed to counsel patients on their treatment regimens, including the management of adverse effects and the importance of medication adherence. Pharmacists possess the expert knowledge and communication skills to help reduce the incidence of skin cancer and improve clinical outcomes for patients diagnosed with it.