Many patients with advanced cutaneous squamous cell carcinoma (CSCC) have a poor prognosis1-4

Staging guidelines for advanced CSCC

The presence of any one of the following features defines CSCC as advanced (AJCC stages III and IV)5:


  • Tumor size ≥4 cm


  • Perineural invasion
  • Minor bone erosion
  • Invasion beyond the subcutaneous fat
  • Gross cortical bone or marrow invasion


  • Nodal metastasis
  • Distant metastasis

Advanced CSCC is associated with high mortality3,6,7

In the US, approximately 7,000a patients die annually from CSCC8,9

Percent annual CSCC mortality


Estimated annual US incidence is approximately 700,000. Each figure represents 7,000 CSCC patients.

a Estimated annual mortality rate of 7,000 was calculated using estimated annual incidence of 700,000—as of 2012—from Rogers et al, 2015, and multiplying it by estimated annual mortality rate of 1% from Clayman et al, 2005.

More than
of disease-specific death was reported to be caused by locoregional disease that has not distantly metastasized (M0).10,11

Guidelines recommend multidisciplinary team (MDT) consultation in order to assess all available treatment options12-14

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Squamous Cell Skin Cancer* recommend multidisciplinary tumor board consultation in a variety of scenarios, including12:

  • Regional
  • Distant
  • Residual disease
    remaining after resection when
    further surgery is contraindicated

* NCCN Guidelines® use “squamous cell skin cancer” to refer to cutaneous squamous cell carcinoma, or CSCC. These terms are interchangeable.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Consultation between surgeons, radiation oncologists, medical oncologists, and dermatologists may support consideration of additional therapeutic modalities for patients with high‑risk or advanced disease.12

Download this patient fact sheet for information about advanced CSCC to share with your patients.

References: 1. Haisma MS, Plaat BEC, Bijl HP, et al. Multivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck. J Am Acad Dermatol. 2016;75(4):722-730. 2. Mullen JT, Feng L, Xing Y, et al. Invasive squamous cell carcinoma of the skin: defining a high-risk group. Ann Surg Oncol. 2006;13(7):902-909. 3. Brunner M, Veness MJ, Ch’ng S, Elliott M, Clark JR. Distant metastases from cutaneous squamous cell carcinoma—analysis of AJCC stage IV. Head Neck. 2013;35(1):72-75. 4. Skin cancer treatment (PDQ®). National Cancer Institute website. Updated February 1, 2018. Accessed February 13, 2018. 5. Califano JA, Lydiatt WM, Nehal KS, et al. Cutaneous squamous cell carcinoma of the head and neck. In: Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. Springer; 2017:171-181. 6. Burton KA, Ashack KA, Khachemoune A. Cutaneous squamous cell carcinoma: a review of high-risk and metastatic disease [published online June 29, 2016]. Am J Clin Dermatol. 2016;17(5):491-508. doi:10.1007/s40257-016-0207-3. 7. Oddone N, Morgan GJ, Palme CE, et al. Metastatic cutaneous squamous cell carcinoma of the head and neck. Cancer. 2009;115(9):1883-1891. 8. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol. 2015;151(10):1081-1086. 9. Clayman GL, Lee JJ, Holsinger FC, et al. Mortality risk from squamous cell skin cancer. J Clin Oncol. 2005;23(4):759-765. 10. Motaparthi K, Kapil JP, Velazquez EF. Cutaneous squamous cell carcinoma: review of the eighth edition of the American Joint Committee on Cancer staging guidelines, prognostic factors, and histopathologic variants. Adv Anat Pathol. 2017;24(4):171-194. 11. Schmults CD, Karia PS, Carter JB, Han J, Qureshi AA. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol. 2013;149(5):541-547. 12. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Squamous Cell Skin Cancer V.2.2018. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed March 8, 2018. To view the most recent and complete version of the guideline, go online to 13. Harwood C. Guidelines for the treatment and referral of squamous cell carcinoma (SCC) of the skin. London Cancer. Published August 2013. Updated August 2014. Accessed January 29, 2018. 14. Motley R, Kersey P, Lawrence C. Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma. Br J Plast Surg. 2003;56(2):85-91.