Squamous cell carcinoma of the skin medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2], Raviteja Guddeti, M.B.B.S. [3]
Overview
Medical therapy for squamous cell carcinoma includes chemotherapy with cisplatin, topical fluorouracil, capecitabine, methotrexate, cetuximab, bleomycin and doxorubicin. Other treatment modalities include cryotherapy, radiation therapy and photodynamic therapy.
Medical Therapy
Once the diagnosis of cutaneous squamous cell carcinoma (SCC) has been established by skin biopsy and histopathologic examination, the assessment of the risk of locoregional recurrence and regional or distant metastasis is the most important step to determine the treatment approach.
Characteristics that impact the risk for recurrence and metastasis include:[1]
- Location of tumor
- Tumor depth ( > 2mm) and size
- Immunosuppressed patients
- Site of previous radiotherapy
- Chronic inflammation
- Rapidly growing tumor
- Neurologic symptoms
- Poorly differentiated tumor
- Acantholytic (adenoid), adenosquamous, desmoplastic, or metaplastic (carcinosarcomatous) subtypes
- Lymph node involvement
According to the 2018 NCCN guidelines and in order to determine the approach to treatment, low risk and high risk cutaneous squamous cell carcinoma can be categorized as follows:[1]
| Low risk of cutaneous SCC | High risk of cutaneous SCC |
|---|---|
| Well-defined, primary lesions <20 mm located on trunk or extremities (excluding pretibia, hands, feet, nail units, and ankles) | Lesions ≥20 mm located on trunk or extremities (excluding pretibia, hands, feet, nail units, and ankles) |
| Well-defined, primary lesions <10 mm located on cheeks, forehead, scalp, neck, and pretibia | Lesions ≥10 mm located on cheeks, forehead, scalp, neck, and pretibia |
| Primary tumor | Lesions of any size located in the "mask area" (ie, central face, eyelids, eyebrows, periorbital, temple, nose, lips, chin, mandible, pre- and postauricular), genitalia, hands, and feet |
| Histopathologically well or moderately differentiated tumor, <2 mm in thickness, without perineural, lymphatic, or vascular invasion | Histopathologically poorly differentiated tumor, ≥2 mm in thickness, with perineural, lymphatic, or vascular invasion |
Medical care of squamous cell carcinoma of the skin includes cryosurgery, electrosurgery, radiation therapy and topical treatment for cutaneous lesions, and chemotherapy for systemic disease.
- Chemotherapy
- Used for patients with locally advanced squamous cell carcinoma of the skin that cannot be adequately managed with surgical excision or radiation therapy or in patients with metastatic squamous cell carcinoma.
- Chemotherapeutic agents used:
- Cisplatin and carboplatin have been used as chemosensitizing agents in conjunction with radiation therapy for patients with squamous cell carcinoma of the skin arising in noncutaneous sites. However, an additional benefit with these agents has not been demonstrated in patients with high-risk cutaneous squamous cell carcinoma.
- Cryotherapy[2]
- Destroys malignant cells by freezing them and then allowing them to thaw.
- Useful for small, well-defined, low-risk invasive cutaneous squamous cell carcinoma, and for Bowen's disease
- Liquid nitrogen is applied to the tumor and a surrounding rim of normal-appearing skin (usually ≥3 mm).
- Tumor cell death is due to the formation of intracellular and extracellular ice crystals, hypertonicity, disruption of the phospholipid membrane, and vascular stasis.
- Quick procedure and cost-effective
- Not indicated for large recurrent lesions, deeply invasive lesions, and other high risk cutaneous squamous cell carcinoma
- Topical 5-fluorouracil (5-FU)[3]
- Is approved by the Food and Drug Administration (FDA) for the treatment of actinic keratoses.
- Although topical 5-FU is not approved for the treatment of cutaneous squamous cell carcinoma in situ, it is widely used for this indication when other treatment modalities are impractical and for patients who refuse surgical treatment.
- It is especially valuable for situations in which postoperative healing is compromised, such as in lesions that involve the lower extremity in elderly patients or those with venous stasis disease.
- Topical 5-FU is also useful to treat the widespread cutaneous squamous cell carcinoma in situ lesions that may occur in arsenical dermatitis or xeroderma pigmentosum (XP).[4]
- Topical 5-FU is available in 0.5%, 1% and 5% concentrations.
- 1% and 0.5% are used for actinic keratosis.
- 5% cream is used twice daily for 4 - 8 weeks in the treatment of cutaneous squamous cell carcinoma in situ.
- 1% and 0.5% are used for actinic keratosis.
- Cure rates of up to 85% were achieved in one study with this type of treatment. For recurrent disease, courses are repeated.
- 5-FU gives favorable cosmetic results, but is contraindicated in invasive lesions.
- Radiation therapy
- In high-risk cSCC, radiation therapy is not routinely utilized as monotherapy given the higher rate of local recurrence (15 to 20 percent or greater) compared with surgery with or without postoperative radiation therapy.[5]
- Is an excellent choice for the management of initial small well defined lesions, especially primary SCCs in older individuals and those who are not candidates for surgical procedures. This form of treatment is administered in a fractionated form requiring nearly 30 treatments.[6]
- For low risk lesions the cure rate approaches nearly 90%. The main advantage of this kind of treatment is sparing of the surrounding normal healthy skin, thus providing superior cosmetic benefits. Radiotherapy is contraindicated in:[7]
- Tumors located on the trunk, extremities, ear and nose.
- Patients younger than 40-50 years.
- Recurrent SCCs that have previously been irradiated.
- Cancers with large and poorly defined lesions, and other high risk SCCs.
- Photodynamic therapy
- Based upon the ability of porphyrins to produce cytotoxicity in the presence of oxygen after stimulation by light of an appropriate wavelength
- Not recommended for the treatment of invasive cutaneous squamous cell carcinoma, due to high recurrence rates associated with photodynamic therapy
References
- ↑ 1.0 1.1 Skulsky SL, O'Sullivan B, McArdle O, Leader M, Roche M, Conlon PJ; et al. (2017). "Review of high-risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committee on Cancer and NCCN Clinical Practice Guidelines In Oncology". Head Neck. 39 (3): 578–594. doi:10.1002/hed.24580. PMID 27882625.
- ↑ Holt PJ (1988). "Cryotherapy for skin cancer: results over a 5-year period using liquid nitrogen spray cryosurgery". Br J Dermatol. 119 (2): 231–40. PMID 3166941.
- ↑ Hamouda B, Jamila Z, Najet R, Slim T, Rafiaa N, Noureddine B; et al. (2001). "Topical 5-fluorouracil to treat multiple or unresectable facial squamous cell carcinomas in xeroderma pigmentosum". J Am Acad Dermatol. 44 (6): 1054. PMID 11369927.
- ↑ Mackenzie-Wood A, Kossard S, de Launey J, Wilkinson B, Owens ML (2001). "Imiquimod 5% cream in the treatment of Bowen's disease". J Am Acad Dermatol. 44 (3): 462–70. doi:10.1067/mjd.2001.111335. PMID 11209116.
- ↑ Miller SJ, Alam M, Andersen J, Berg D, Bichakjian CK, Bowen G; et al. (2010). "Basal cell and squamous cell skin cancers". J Natl Compr Canc Netw. 8 (8): 836–64. PMID 20870631.
- ↑ Lovett RD, Perez CA, Shapiro SJ, Garcia DM (1990). "External irradiation of epithelial skin cancer". Int J Radiat Oncol Biol Phys. 19 (2): 235–42. PMID 2394605.
- ↑ Kwan W, Wilson D, Moravan V (2004). "Radiotherapy for locally advanced basal cell and squamous cell carcinomas of the skin". Int J Radiat Oncol Biol Phys. 60 (2): 406–11. doi:10.1016/j.ijrobp.2004.03.006. PMID 15380573.