12. Metastatic disease and systemic therapies

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Clinical practice guidelines for keratinocyte cancer > 12. Metastatic disease and systemic therapies


Metastatic keratinocyte cancers are uncommon but potentially lethal malignancies.

Basal cell carcinoma

Metastatic basal cell carcinoma (BCC) is rare.[1]

Targeted therapy directed against the hedgehog signalling pathway has been shown to achieve responses among patients with metastatic BCC.[2][3]

The role of immunotherapy in treating patients with BCC is also being investigated, following case reports of checkpoint immunotherapy and the observation of a high mutation burden in patients BCC. In some cases, systemic therapy may be appropriate for patients with locally advanced disease that is not amenable to further local treatment such as surgery or radiotherapy, or where these therapies may lead to significant morbidity. Review of such patients by an experienced multidisciplinary team is recommended.

Cutaneous squamous cell carcinoma

Conventional chemotherapy is used in the treatment of metastatic cutaneous squamous cell carcinoma (cSCC), based on limited evidence.[4][5][6][7][8]

More recently, evidence has emerged for the efficacy and durability of checkpoint inhibitor immunotherapy in the treatment of metastatic cSCC.[9]

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  1. Paver K, Poyzer K, Burry N, Deakin M. Letter: The incidence of basal cell carcinoma and their metastases in Australia and New Zealand. Australas J Dermatol 1973 Apr;14(1):53 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/4753676.
  2. Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012 Jun 7;366(23):2171-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22670903.
  3. Migden MR, Guminski A, Gutzmer R, Dirix L, Lewis KD, Combemale P, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol 2015 Jun;16(6):716-28 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25981810.
  4. Suzuki T, Inoue Y, Kuramochi A, Kiyohara Y, Ikeda S. [Squamous cell carcinoma and basal cell carcinoma]. Gan To Kagaku Ryoho 1997 Jan;24(1):16-22 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9020940.
  5. Merimsky O, Neudorfer M, Spitzer E, Chaitchik S. Salvage cisplatin and adriamycin for advanced or recurrent basal or squamous cell carcinoma of the face. Anticancer Drugs 1992 Oct;3(5):481-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1450442.
  6. Ikegawa S, Saida T, Obayashi H, Sasaki A, Esumi H, Ikeda S, et al. Cisplatin combination chemotherapy in squamous cell carcinoma and adenoid cystic carcinoma of the skin. J Dermatol 1989 Jun;16(3):227-30 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2551943.
  7. Guthrie TH Jr, McElveen LJ, Porubsky ES, Harmon JD. Cisplatin and doxorubicin. An effective chemotherapy combination in the treatment of advanced basal cell and squamous carcinoma of the skin. Cancer 1985 Apr 15;55(8):1629-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/4038911.
  8. Guthrie TH Jr, Porubsky ES, Luxenberg MN, Shah KJ, Wurtz KL, Watson PR. Cisplatin-based chemotherapy in advanced basal and squamous cell carcinomas of the skin: results in 28 patients including 13 patients receiving multimodality therapy. J Clin Oncol 1990 Feb;8(2):342-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2405109.
  9. Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med 2018 Jul 26;379(4):341-351 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/29863979.

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