Basal cell carcinoma (BCC) is at least three times more common than SCC in nonimmunocompromised patients. It usually occurs on sun-exposed areas of skin, and the nose is the most frequent site. Although there are many different clinical presentations for BCC, the most characteristic type is the asymptomatic nodular or nodular ulcerative lesion that is elevated from the surrounding skin, has a pearly quality, and contains telangiectatic vessels.
BCC has a tendency to be locally destructive. High-risk areas for tumor recurrence after initial treatment include the central face (e.g., periorbital region, eyelids, nasolabial fold, or nose-cheek angle), postauricular region, pinna, ear canal, forehead, and scalp. A specific subtype of BCC is the morpheaform type. This subtype typically appears as a scar-like, firm plaque. Because of indistinct clinical tumor margins, the morpheaform type is difficult to treat adequately with traditional treatments.
BCCs are composed of nonkeratinizing cells derived from the basal cell layer of the epidermis. They are slow growing and rarely metastasize. However, they can result in serious deforming damage locally if left untreated or if local recurrences cannot be completely excised. BCCs often have a characteristic mutation in the patched 1 tumor suppressor gene (PTCH1), although the mechanism of carcinogenesis is not clear.
Treatment for Basal Cell Carcinoma of the Skin
There is a wide range of treatment approaches, including excision, radiation therapy, cryosurgery, electrodesiccation and curettage, photodynamic or laser-beam light exposure, and topical therapies. Mohs micrographic surgery is a form of tumor excision that involves progressive radial sectioning and real-time examination of the resection margins until adequate uninvolved margins have been achieved, avoiding wider margins than needed. Each of these methods is useful in specific clinical situations. Depending on case selection, these methods have recurrence-free rates ranging from 85% to 95%.
A systematic review of 27 randomized controlled trials comparing various treatments for BCC has been published. Eighteen of the studies were published in full, and nine were published in abstract form only. Only 19 of the 27 trials were analyzed by intention-to-treat criteria. Because the case fatality rate of BCC is so low, the primary endpoint of most trials is complete response and/or recurrence rate after treatment. Most of the identified studies had short follow-up times (only one study had a follow-up as long as 4 years) and were not of high quality. Short follow-up periods will lead to overestimates of tumor control. A literature review of recurrence rates in case series with long-term follow-up after treatment of BCCs indicated that only 50% of recurrences occurred within the first 2 years, 66% after 3 years, and 18% after 5 years. A rule of thumb was that the 10-year recurrence rates were about double the 2-year recurrence rates.
1. Excision with margin evaluation.
2. Mohs micrographic surgery.
3. Radiation therapy.
4. Curettage and electrodesiccation.
6. Photodynamic therapy.
7. Topical fluorouracil (5-FU).
8. Imiquimod topical therapy.
9. Carbon dioxide laser.
1. Excision with margin evaluation
This traditional surgical treatment usually relies on surgical margins ranging from 3 mm to 10 mm, depending on the diameter of the tumor. Re-excision may be required if the surgical margin is found to be inadequate on permanent sectioning. For example, in one trial, 35 of 199 (18%) primary BCCs were incompletely excised by the initial surgery and underwent a re-excision. In addition, many laboratories examine only a small fraction of the total tumor margin pathologically. Therefore, the declaration of tumor-free margins can be subject to sampling error.
Excision has been compared in randomized trials to radiation therapy, Mohs micrographic surgery, photodynamic therapy (PDT), and cryosurgery.
2. Mohs micrographic surgery
Mohs micrographic surgery is a specialized technique used with the intent to achieve the narrowest margins necessary to avoid tumor recurrence, while maximally preserving cosmesis. It is best suited to management of tumors in cosmetically sensitive areas or for tumors that have recurred after initial excision (e.g., eyelid periorbital area, nasolabial fold, nose-cheek angle, posterior cheek sulcus, pinna, ear canal, forehead, scalp, fingers, and genitalia). It is also often used to treat tumors with poorly defined clinical borders.
Mohs micrographic surgery requires special training. The tumor is microscopically delineated, with serial radial resection, until it is completely removed as assessed with real-time frozen sections. Noncontrolled case series suggested that the disease control rates were superior to other treatment methods for BCC. However, as noted in the section on excision, the disease control rate was not clearly better when directly compared to surgical excision of facial BCCs in a randomized trial of primary BCCs.
3. Radiation therapy
Radiation therapy is particularly useful in the management of patients with primary lesions that would otherwise require difficult or extensive surgery (e.g., nose or ears). Radiation therapy eliminates the need for skin grafting when surgery would result in an extensive defect. Cosmetic results are generally good, with a small amount of hypopigmentation or telangiectasia in the treatment port. Radiation therapy can also be used for lesions that recur after a primary surgical approach. Radiation therapy is avoided in patients with conditions that predispose them to radiation-induced cancers, such as xeroderma pigmentosum or basal cell nevus syndrome.
Radiation therapy has been compared to excision in a randomized trial that showed better response and cosmesis associated with surgery.
4. Curettage and electrodesiccation
This procedure is also sometimes called electrosurgery. It is a widely employed method for removing primary BCCs, especially superficial lesions of the neck, trunk, and extremities that are considered to be at low risk for recurrence. A sharp curette is used to scrape away the tumor down to its base, followed by electrodesiccation of the lesion base. Although it is a quick method for destroying the tumor, the adequacy of treatment cannot be assessed immediately since the surgeon cannot visually detect the depth of microscopic tumor invasion.
A Cochrane Collaboration systematic review found no randomized trials comparing this treatment method with other approaches. In a large, single-center case series of 2,314 previously untreated BCCs managed at a major skin cancer unit, the 5-year recurrence rate of BCCs of the neck, trunk, and extremities was 3.3%. However, rates increased substantially for tumors larger than 6 mm in diameter at other anatomic sites.[Level of evidence 3iiiDii]
Cryosurgery may be considered for patients with small, clinically well-defined primary tumors. It is infrequently used for the management of BCC, but may be useful for patients with medical conditions that preclude other types of surgery.
Contraindications include abnormal cold tolerance, cryoglobulinemia, cryofibrinogenemia, Raynaud disease (in the case of lesions on hands and feet), and platelet deficiency disorders. Additional contraindications to cryosurgery include tumors of the scalp, ala nasi, nasolabial fold, tragus, postauricular sulcus, free eyelid margin, upper lip vermillion border, lower legs, and tumors near nerves. Caution should also be used before treating nodular ulcerative neoplasia more than 3 cm in diameter, carcinomas fixed to the underlying bone or cartilage, tumors situated on the lateral margins of the fingers and at the ulnar fossa of the elbow, or recurrent carcinomas following surgical excision.
6. Photodynamic therapy
Photodynamic therapy with photosensitizers is used in the management of a wide spectrum of superficial epithelial tumors. A topical photosensitizing agent such as 5-aminolevulinic acid or methyl aminolevulinate is applied to the tumor, followed by exposure to a specific wavelength of light (whether laser or broad band), depending upon the absorption characteristics of the photosensitizer. In the case of multiple BCCs, short-acting systemic (intravenous) photosensitizers such as verteporfin have been used investigationally. Upon light activation, the photosensitizer reacts with oxygen in the tissue to form singlet oxygen species, resulting in local cell destruction.
In case series, PDT has been associated with high initial CR rates. However, substantial regrowth rates of up to 50% have been reported with long-term follow-up. A randomized trial of PDT versus excision is summarized in the section on simple excision above. Two small trials, one reported in abstract form only, comparing PDT with cryosurgery are summarized in the cryosurgery section above, showing similar antitumor efficacy but better cosmesis with PDT.
7. Topical fluorouracil (5-FU)
Topical 5-FU, as a 5% cream, may be useful in specific limited circumstances. It is a Food and Drug Administration (FDA)-approved treatment for superficial BCCs in patients for whom conventional methods are impractical, such as individuals with multiple lesions or difficult treatment sites. Safety and efficacy in other indications have not been established. [Level of evidence: 3iiiDiv] Given the superficial nature of its effects, nonvisible dermal involvement may persist, giving a false impression of treatment success. In addition, the brisk accompanying inflammatory reaction may cause substantial skin toxicity and discomfort in a large proportion of patients.
8. Imiquimod topical therapy
Imiquimod is an agonist for the toll-like receptor 7 and/or 8, inducing a helper T-cell cytokine cascade and interferon production. It purportedly acts as an immunomodulator. It is available as a 5% cream and is used in schedules ranging from twice weekly to twice daily over 5 to 15 weeks. Most of the experience is limited to case series of BCCs that are less than 2 cm2 in area and that are not in high-risk locations (i.e., within 1 cm of the hairline, eyes, nose, mouth, ear; or in the anogenital, hand, or foot regions). Follow-up times have also been generally short. Reported CR rates vary widely, from about 40% to 100%. [Level of evidence 3iiiDiv]
There have been a number of randomized trials of imiquimod. However, the designs of all of them make interpretation of long-term efficacy impossible. Most were industry-sponsored dose-finding studies, with small numbers of patients on any given regimen; and patients were only followed for 6 to 12 weeks, with excision at that time to determine histologic response.[Level of evidence 1iDiv] Therefore, although imiquimod is an FDA-approved treatment for superficial BCCs, some investigators in the field do not recommend it for initial monotherapy for BCC; some reserve it for patients with small lesions in low-risk sites who cannot undergo treatment with more established therapies.
9. Carbon dioxide laser
This method is used very infrequently in the management of BCC because of the difficulty in controlling tumor margins. Few clinicians have extensive experience with the technique for BCC treatment. There are no randomized trials comparing it with other modalities.