Squamous Cell Carcinoma (SCC) Landscape

High-Risk Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma is an emerging problem in the United States. Patients with one or more risk factors suffer the majority of SCC mortality, but these factors alone are often not specific enough to determine their risk-appropriate treatment and further management.

Because cancer treatment plans and their outcomes are guided by risk of metastasis, improved prognostic accuracy has direct implications for patient management. Utility of traditional clinicopathologic risk factors is limited by their low positive predictive value.

Prognostic Risk Factors for Cutaneous Squamous Cell Carcinoma

There are a number of approaches to determine risk for patients diagnosed with cutaneous squamous cell carcinoma. These approaches have low positive predictive value.


BWH Tumor Staging System

T1 (0 factors)

T2a (1 factor)

T2b (2-3 factors)

T3 (≥4 factors or bone invasion)

Factors include:

  • Tumor diameter ≥2 cm
  • Poorly differentiated tumor histology
  • Perineural invasion ≥0.1 mm
  • Tumor invasion beyond fat

Presence of Specific Risk Factors

Factors include:

  • Tumor diameter ≥2 cm
  • Specific tumor locations (for example, ear, lip, cheek, or temple)
  • Immunosuppression
  • Tumor invasion beyond fat
  • Poorly differentiated histology
  • Perineural invasion ≥0.1 mm

NCCN High-Risk

One or more of a large number of possible factors (broadest high-risk characterization)

Similar to Mohs Appropriate Use Criteria

Cutaneous Squamous Cell Carcinoma Metastasis and Survival

Managing SCC is a significant clinical issue as deaths from SCC are now estimated to exceed those from melanoma. Because cancer treatment plans and their outcomes are guided by risk for metastasis, prognostic accuracy has direct implications on patient management. Unlike melanoma, breast and other common cancers, SCC patient care has not been personalized with risk predicting genomic tests. 

SCC Disease Related Mortality Is on the Rise
  • 0%
Annual patient deaths from


  • 0%
Annual patient deaths from


Established management approaches (for primary treatment and follow up/surveillance) provide potential for reduced or earlier detection of metastasis as well as improved survival.

Challenge: Identify True Risk for Patients With One or More Risk Factors

Not all SCC patients who are identified as high risk based on the presence of one or more risk factors will truly be at high risk of metastasis. If we can improve identification of those at greatest risk, we can address metastatic risk while minimizing potential overtreatment for those who would not benefit. Conversely, the low predictive accuracy of current methods to identify high-risk patients can lead to undertreatment if patients with a truly high biologic risk are missed. Because these patients cannot currently be identified, they will miss the opportunity to receive the most aggressive of today’s therapeutic options.


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A Review of the DecisionDx-SCC Clinical Validation Study in Future Oncology

by Dr. Sherrif F. Ibrahim

Enhanced Metastatic Risk Assessment in Cutaneous Squamous Cell Carcinoma with the 40-Gene Expression Profile Test: An Interview with the Lead Author of DecisionDx-SCC’s Validation Study.

Speaker: Sherrif F. Ibrahim, MD, PhD., Assistant Professor, Department of Dermatology, University of Rochester Medical Center

Video Webinar

An Introduction to DecisionDx–SCC by Dr. Jason Newman, UPenn

AHNS DecisionDx–SCC Webinar: Identifying the Risk of Metastasis in cSCC and cSCC-HN Patients

Speaker: Dr. Jason Newman, Professor of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania

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