Malignant epithelial tumors: Part II. Therapy and prevention

Authors

  • Ioannis Manousaridis,

    1. Department of Dermatology, Venereology and Allergology of the Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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  • Martin Leverkus

    1. Department of Dermatology, Venereology and Allergology of the Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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  • Conflict of interest I.M. declares no conflict of interest. M.L. has received financial support in the form of honoraria for lectures and travel expenses from the companies Roche and Galderma.

  • Section Editor Prof. Dr. Jan C. Simon, Leipzig

  • As in about 10 % of patients with SCC in situ (KIN) progression to an invasive SCC occurs, there is consensus in Germany that KIN should be treated.

  • Cryosurgery (cryotherapy) is perhaps the most frequently employed method for the treatment of KIN of the free skin.

  • PDT shows good results in the treatment of KIN and is an important form of therapy for field cancerization and for complicated anatomic sites (e.g. ears).

  • Imiquimod 5 % cream (3 times weekly over 8 hours each time over 4 weeks) is licensed for the treatment of KIN.

  • Diclofenac is available as a 3 % hyaluronic acid gel for the treatment of KIN (twice daily over 90 days).

  • Therapy success should be assessed after 6–12 months.

  • Ingenol mebutate leads to direct necrosis of neoplastic keratinocytes with subsequent neutrophilic antibody-dependent cellular toxicity of tumor cells.

  • Small lesions of cheilitis can first be treated with a topical method or, alternatively, with cryosurgery according to the principles for KIN of the free skin.

  • If there is no healing within 6 months, ablative techniques, for example CO2 laser therapy, should be employed, that lead to complete remission in almost 100 % of cases.

  • The risk of invasive SCC of the skin should be assessed on the basis of tumor size (>2 cm diameter), tumor penetration depth (<2 mm, no risk; >2 mm, moderate risk, >6 mm, high risk) and the histological classification after complete excision (desmoplasia, dedifferentiation).

  • Therapy of choice of an invasive SCC is excision with histological control of margins.

  • To date no consensus exists on the use of sentinel lymph node biopsy in the treatment of high-risk SCC of the skin.

  • Radiotherapy is a suitable alternative therapeutic procedure for multi-morbid patients with a high surgical risk.

  • Due to the success of radiotherapy in combination with EGFR inhibitors in SCC of the oropharynx/ larynx (head and neck SCC [HNSCC]), combination therapy can also be considered.

  • In the event that SCC metastasizes, the metastases develop in most cases within the first two years after diagnosis.

  • To date larger studies comparing therapeutic approaches to metastatic SCC are lacking.

  • More aggressive polychemotherapy often can not be performed for treatment of metastatic SCC of the skin due to the therapy-associated toxicity.

  • Successful combination therapy with cetuximab and COX 2 inhibitors or radiotherapy has been reported.

  • The treatment of choice for BCC is surgery.

  • In the event of incomplete excision, all possibilities of surgical re-excision should be utilized first.

  • BCC with a high risk of recurrence should be removed with MCS.

  • BCC on the face with a diameter <1 cm or tumors on the rest of the body with a diameter <2 cm are considered low-risk tumors.

  • In low-risk BCC, particularly superficial BCC, along with topical drug therapy, other less time-consuming and more economical destructive procedures are employed.

  • If drug therapy is chosen, dermatologic follow-up in 3–6-month intervals is of utmost importance.

  • Topical treatment with imiquimod (5 times weekly over 6 weeks) has proven useful particularly for multiple superficial BCC.

  • Radiotherapy should be preferred in primarily inoperable BCC or in patients with comorbidities that make surgery a risk. Basal cell nevus syndrome (BCNS) is an absolute contraindication for radiotherapy.

  • Since the end or the 20th century – as a result of the knowledge on the molecular pathogenesis of BCC – various small molecule inhibitors of the sonic hedgehog signaling pathway have been identified.

  • The most common side effects of treatment with vismodegib are alopecia, dysgeusia and muscle cramps.

  • When the histological diagnosis of KA is definitive and secure or when the tumor is already in the stage of involution, close follow-up for spontaneous healing is justifiable. As alternatives to surgical or ìwait-and-seeî therapy, intralesional therapy with MTX, 5-FU, bleomycin or interferon-α can be considered.

  • For larger, rapidly proliferating KA, a surgical approach is recommended.

  • A great clinical problem is the development of further, independent tumors in high-risk patients.

  • A modification of immunosuppressive medication (switching to mTOR inhibitors such as everolimus in patients with organ transplants) should be discussed.

  • Consistent use of sunscreens can significantly reduce the development of new KIN in immunocompetent [38, 39] and chronically immunosuppressed patients [40].

  • While topical application of retinoids is without effect, systemic retinoids have been effective in several studies on long-term chemoprevention of KIN in patients with a moderate risk (>10 KIN and maximally 2 invasive SCC).

  • No larger controlled studies on topical drug therapy with 5-FU, imiquimod, diclofenac or ingenol mebutate for proactive therapy of field cancerization in high-risk patients exist as of yet.

  • In the high-risk collective of homosexual men, HPV immunization can likewise reduce the development of HPV-related anal intraepithelial neoplasia (AIN).

Univ.-Prof. Dr. Martin Leverkus, Department of Dermatology, Venereology and Allergology, University Hospital Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68167 Mannheim, Germany E-mail: Martin.Leverkus@medma.uni-heidelberg.de

Summary

A multitude of surgical and non-surgical therapies are available to treat malignant epithelial tumors of the skin. The article summarizes the current treatment options for basal cell carcinoma, squamous cell carcinoma and keratoacanthoma. Moreover, the possibilities of primary and secondary prevention for high-risk patients are reviewed. The decision about the best therapeutic option depends on location, age, and general health of the patient as well as the risk of tumor recurrence.

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