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CAP Just Oliveres
L’Hospitalet de Llobregat
Basal cell carcinoma (BCC) is the most frequent malignant tumour in the Caucasian human population, and its incidence is increasing worldwide. BCC is a slow-growing, locally invasive malignant epidermal skin tumour. If left untreated, it can cause extensive destruction of tissue, but metastatic potential is negligible. The tumour may occur at any age, but the incidence of BCC increases markedly after the age of 50. Risk factors are fair skin, chronic exposure to ultraviolet radiation (sun, sun beds or phototherapy), exposure to ionising radiation, immunosuppression and genetic predisposition. BCC most commonly occurs on the face and trunk. The clinical appearances are diverse, including superficial, nodular, ulcerated, morphoeic, cystic, keratotic and pigmented variants. The superficial and nodular histological subtypes of BCCs are considered nonagressive. The morphoeic, infiltrative and micronodular histological subtypes are more agressive, due to clinically invisible root-like extensions into the underlying tissue. Factors affecting the prognosis of BCC are tumour size, tumour site, histological subtype, failure of previous treatment and immunosuppression. BCC can be divided into low- and high-risk categories by considering the previously mentioned prognostic factors. Low-risk BCCs are small, well-defined, primary lesions at noncritical sites with nonaggressive histology. High-risk BCCs are large (>2cm), poorly defined, recurrent, at the H part of the face (eyes, ears, lips, nose and nasolabial folds), with aggressive histological subtype or perineural spread. Table 1 summarises all treatments currently available.
The choice of therapy requires consideration of the prognostic factors of the BCC, and a desire for a high cure rate without causing loss of form, function or cosmesis. The treatments currently available can be divided into two categories: surgical and nonsurgical (see Table 1). Surgical modalities have been the treatment of choice because they result in the fewest recurrence rate, and the cosmetic outcome is satisfactory in most cases.(1) Surgical techniques include curettage and cautery, cryosurgery, CO(2) laser, surgical excision and Mohs micrographic surgery.
Curettage and cautery
The surface of BCC is scraped away with a curette and the wound is cauterised. This cycle is usually performed three times. The procedure is quick and simple, but recurrence rates can be high. This is the usual choice for low-risk lesions.(2) Thorough curettage immediately prior to cryosurgery or CO2 laser may help increase cure rate.
The tumour is destroyed by freezing. Individual techniques can vary considerably, using the open or closed spray techniques and single, double or triple freeze cycles. Drawbacks are pain and residual hypopigmentation. This treatment is widely used to treat low-risk BCCs, but a careful selection of appropriate lesions is important in order to achieve high cure rates.(3)
Laser surgery is not a widely used form of treatment and there is currently little follow-up data available.(4) Laser is only recommended for low-risk lesions.
Surgical excision is generally the first-line treatment of most low- and high-risk BCC. The cure rates are high and there is tissue available for confirmation of the margins of excision. The cosmetic outcome is highly dependent on the surgeon’s skill at excision, and reconstructive surgery with flaps or grafts may be performed. Thick scarring is the most common side-effect.
Mohs micrographic surgery
Thin layers of tissue are examined histologically during the procedure, and surgery is complete when all areas of tissue are tumour-free. This procedure requires considerable skill. It is also more time-consuming and, therefore, more expensive than surgical excision. Mohs’ surgery results in the highest cure rate for primary BCC, and is the preferred treatment for high-risk BCC at the H part of the face.(5)
The need for nonsurgical treatments arises when patients present with multiple BCC, cannot undergo surgical techniques or refuse surgical techniques to avoid scarring. In fact, there is a growing tendency among younger patients to request nonsurgical treatments because they are generally noninvasive, nonablative and less aggressive than surgery. These techniques are safe and effective for the treatment of BCC, with excellent cosmetic outcome, but may result in higher recurrence rates than surgery. Nonsurgical modalities include 5-fluorouracil, systemic retinoids, radiotherapy, photodynamic therapy, intralesional interferon and imiquimod.
The cream is applied on the BCC by the patient at home, with local irritation and ulceration being common reactions. This therapy can be particularly helpful in the management of multiple low-risk BCCs on the trunk. It is not used routinely because the recurrence rate is high.(6)
Systemic retinoids have been demonstrated to prevent or delay the development of new BCCs in patients with nevoid BCC (Gorlin’s) syndrome, but in otherwise healthy patients with BCC, retinoid therapy does not work well. Unfortunately, the relatively high doses necessary mean that compliance may be poor, and relapse occurs following the discontinuation of treatment.(7)
Radiotherapy includes a range of treatments using different types of equipment, each with its own specific indications. Modern fractionated dose therapy has many advantages but requires multiple visits to a specialist centre. Dyspigmentations, telangiectasia, radiodystrophy and alopecia are the most common side-effects. Radiotherapy is an extremely useful form of treatment and can be used to treat many types of BCC, even those overlying bone and cartilage. Careful patient selection can result in very high cure rates.(8)
Photodynamic therapy (PDT) is a nonionising radiation therapy that involves two steps: topical application of 5-aminolevulinic acid on the BCC, followed by activation of the photosensitiser by a specific light source. Advantages of PDT include selective destruction of the tumour, lack of toxicity, possibility to treat multiple lesions at the same time or to repeat therapy without side-effects, and excellent cosmetic outcome. Treatment of thicker lesions with PDT leads to limited results, because the photosensitizer or the light cannot penetrate deeply enough into the thicker tumour volume. Recent studies evaluate the efficacy of intralesional administration of 5-aminolevulinic acid. Topical PDT is most suitable for elderly patients with large and multiple low-risk BCC.(9)
Intralesional interferon has been demonstrated to be effective in BCC, but it is very expensive and time-consuming. In addition, it has the disadvantage of requiring injections three times a week for three weeks. Most patients experience pain at the injection site and flu-like symptoms. This treatment is unlikely to prove useful in high-risk tumours.(10)
Imiquimod is a synthetic imidazoquinolinamine of 240.3Da that binds Toll-like receptors 7 of dendritic cells and monocytes. Imiquimod is a potent cytokine inducer, mainly of interferon-a, with immunomodulating properties on the innate and acquired immune systems. Imiquimod induces an antitumoural immune response against the BCC and increases the apoptosis signalling pathway of BCC cells, leading to tumour regression. Imiquimod 5% cream was initially approved for the treatment of external anogenital warts, but several randomised clinical trials have proven its efficacy in patients with superficial and nodular BCC. Imiquimod is applied on the BCC by the patient at home, five nights per week for six weeks. Erosion, ulceration and crusting at the treatment site are common reactions that are well tolerated by patients. Imiquimod is highly effective for the treatment of superficial and nodular BCCs and offers a real alternative to surgery for patients with multiple low-risk BCC (see Figure 1).(11)
Future directions and conclusion
Future directions in the treatment of BCCs include combining both nonsurgical and surgical treatments in order to achieve higher efficacy rates and minimal scar. Nonsurgical treatments may be applied in extensive BCCs to reduce the size of the tumour prior to surgery (eg, imiquimod or PDT as adjuvant treatment of Mohs micrographic surgery), or be used after a surgical procedure (eg, imiquimod adjunct to curettage and cautery).
In conclusion, the first-line treatment of BCC is often surgical excision, but BCCs are a very heterogeneous group of tumours and factors such as tumour site, size and histological subtype, patients’ preferences and general health and physician experience are important to determine optimum treatment in each individual case.