Squamous Cell Carcinoma of the Skin Treatment
Localized squamous cell carcinoma (SCC) of the skin is a highly curable disease. There are a variety of treatment approaches to localized SCC, including excision, radiation therapy, cryosurgery, and electrodesiccation and curettage. 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.
There is little or no good-quality evidence that allows direct comparison of outcomes for patients with sporadic, clinically localized SCCs treated with local therapies. A systematic literature review found only one randomized controlled trial in the management of such patients, and that trial compared adjuvant therapy to observation after initial local therapy rather than different local therapies. In that small single-center trial, 66 patients with high-risk, clinically localized SCC were assigned randomly, after surgical excision of the primary tumor (with or without radiation, depending on clinical judgment), to receive either combined 13-cis-retinoic acid (1 mg/kg orally per day) plus interferon-alpha (3 × 106 U subcutaneously 3 times/week) for 6 months or to observation. In the 65 evaluable patients after a median follow-up of 21.5 months, there was no difference in the combined (primary) endpoint of SCC recurrence or second primary tumor (45% vs. 38%; hazard ratio = 1.13; 95% confidence interval [CI], 0.53–2.41), nor in either of the individual components of the primary endpoint.[Level of evidence 1iiDii]
Absent high-quality evidence from controlled clinical trials, the management of clinically localized cutaneous SCC is based upon case series and consensus statements from experts. The commonly used treatments are listed below.
Treatment for Squamous Cell Carcinoma of the Skin
Treatment options include the following:
Surgical excision with margin evaluation
Excision is probably the most common therapy for SCC. This traditional surgical treatment usually relies on surgical margins ranging from 4 mm to 10 mm, depending on the diameter of the tumor and degree of differentiation. In a prospective case series of 141 SCCs, a 4-mm margin was adequate to encompass all subclinical microscopic tumor extension in more than 95% of well-differentiated tumors up to 19 mm in diameter. Wider margins of 6 mm to 10 mm were needed for larger or less-differentiated tumors or tumors in high-risk locations (e.g., scalp, ears, eyelids, nose, and lips). Re-excision may be required if the surgical margin is found to be inadequate on permanent sectioning.
Mohs micrographic surgery
Mohs micrographic surgery is a specialized technique used to achieve the narrowest margins necessary to avoid tumor recurrence, while maximally preserving cosmesis. In case series, it has been associated with a lower local recurrence rate than the other local modalities, but there are no randomized trials allowing direct comparison. This surgery is best suited to the 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).[7,8]
Mohs micrographic surgery is also often used to treat high-risk tumors with poorly defined clinical borders or with perineural invasion. The method requires special training. The tumor is microscopically delineated, with serial radial resection, until it is completely removed as assessed with real-time frozen sections. Nevertheless, since the technique removes tumor growing in contiguity and may miss noncontiguous in-transit cutaneous micrometastases, some practitioners remove an additional margin of skin in high-risk lesions even after the Mohs surgical procedure confirms uninvolved margins.[Level of evidence: 3iiiDiv]
Radiation therapy is a logical treatment choice, particularly for patients with primary lesions requiring difficult or extensive surgery (e.g., nose, lip, or ears).[4,9] 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.
Although radiation therapy, with or without excision of the primary tumor, is used for histologically proven clinical lymph node metastases and has been associated with favorable disease-free survival rates, the retrospective nature of these case series makes it difficult to know the impact of nodal radiation on survival.[11,12][Level of evidence 3iiiDii]
Curettage and electrodesiccation
This procedure is also sometimes called electrosurgery. A sharp curette is used to scrape 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. Its use is limited to small (<1 cm), well-defined, and well-differentiated tumors.[Level of evidence: 3iiiDii]
Cryosurgery may be considered for patients with small, clinically well-defined primary tumors. It 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.
Edema is common following treatment, especially around the periorbital region, temple, and forehead. Treated tumors usually exude necrotic material after which an eschar forms and persists for about 4 weeks. Permanent pigment loss at the treatment site is unavoidable, so the treatment is not well suited to dark-skinned patients. Atrophy and hypertrophic scarring have been reported as well as instances of motor and sensory neuropathy.
The management of SCC in situ (Bowen disease) is similar to good-risk SCC. However, since it is noninvasive, surgical excision, including Mohs micrographic surgery, is usually not necessary. In addition, high complete response (CR) rates are achievable with photodynamic therapy (PDT). In a multicenter trial, 229 patients (209 evaluated in the per-protocol/per-lesion analysis) were randomly assigned to receive PDT (methyl aminolevulinate + 570–670 nm red light; n = 91), placebo cream with red light (n = 15); or treatment by physician choice (cryotherapy, n = 77; topical 5-fluorouracil, n = 26). The sustained complete clinical response rates at 12 months were 80%, 67%, and 69% in the three respective active therapy groups (P = .04 for the comparison between PDT and the two combined physician-choice groups).[Level of evidence 1iiDii] The cosmetic results were best in the PDT group. (For comparison, the CR rates at 3 months for PDT and placebo/PDT were 93% and 21%, respectively.)
Treatment for Recurrent Squamous Cell Carcinoma of the Skin
SCCs have definite metastatic potential, and patients should be followed regularly after initial treatment. Overall, local recurrence rates after treatment of primary SCCs ranged from about 3% to 23%, depending upon anatomic site. About 58% of local recurrences manifest within 1 year, 83% within 3 years, and 95% within 5 years. The metastatic rate for primary tumors of sun-exposed skin is 5%; for tumors of the external ear, 9%; and for tumors of the lip, 14%. Metastases occur at an even higher rate for primary SCCs in scar carcinomas or in nonexposed areas of skin (about 38%). About 69% of metastases are diagnosed within 1 year, 91% within 3 years, and 96% within 5 years. Tumors that are 2 cm or larger in diameter, 4 mm or greater in depth, or poorly differentiated have a relatively bad prognosis  and even higher local recurrence and metastasis rates than those listed. Reported rates also vary by treatment modality, with the lowest rates associated with Mohs micrographic surgery, but at least some of the variation may be the result of patient selection factors; no randomized trials directly compare the various local treatment modalities.
Recurrent nonmetastatic SCCs are considered high risk and are generally treated with excision, often using Mohs micrographic surgery. Radiation therapy is used for lesions that cannot be completely resected.
As is the case with BCC, patients who develop a primary SCC are also at increased risk of subsequent primary skin cancers because the susceptibility of their sun-damaged skin to additional cancers persists.[15,16]
Treatment for Metastatic Squamous Cell Carcinoma (or Advanced Disease Untreatable by Local Modalities)
As is the case with BCC, metastatic and far-advanced SCC is unusual, and reports of systemic therapy are limited to case reports and very small case series with tumor response as the endpoint.[Level of evidence 3iiiDiv] Cisplatin-based regimens appear to be associated with high initial tumor response rates.[17,18] High response rates have also been reported with the use of 13-cis-retinoic acid plus interferon-alpha-2a. Since there is no standard therapy, clinical trials are appropriate if available. Information about ongoing clinical trials is available from the NCI Web site.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with squamous cell carcinoma of the skin. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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