Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management

Abstract

Objective: To integrate gene expression profiling into the management of high-risk cutaneous squamous cell carcinoma (cSCC) within the National Comprehensive Cancer Network (NCCN) guidelines to improve risk-aligned management recommendations.

Methods: A cohort of 300 NCCN-defined high-risk cSCC patients, along with the American Joint Committee on Cancer (AJCC) T stage, Brigham and Women’s Hospital (BWH) T stage, and known patient outcomes were analyzed. Risk classifications using a validated 40-gene expression profile (40-GEP) test and T stage were applied to NCCN patient management guidelines. Risk-directed patient management recommendations within the NCCN guidelines framework were aligned based on risk for metastasis.

Results: Of the 300 NCCN high-risk cSCC patients, 159 (53.0%) were 40-GEP Class 1 and AJCC T1-T2, and 173 (57.7%) were Class 1 and BWH T1-2a, indicating low risk for metastasis and, thereby, suggesting low management intensity. The 40-GEP integration suggested high intensity management for only 24 (8.0%) patients (all Class 2B), and moderate intensity management for the remainder of the cohort.

Conclusions: The 40-GEP test can be integrated within existing NCCN guideline recommendations for managing cSCC patients to help refine risk-directed management decisions. Integration of the 40-GEP test would allow >50% of this NCCN-defined high-risk cohort to be managed with the lowest intensity recommendations within the broad NCCN guidelines. High intensity management was deemed risk-appropriate for a small subpopulation (8.0%). This study demonstrates that the 40-GEP test, in combination with T stage, has clinical utility to impact patient management decisions in NCCN high-risk cSCC for improving risk-aligned management within the NCCN guidelines framework.

Keywords:

• Cutaneous squamous cell carcinoma
• metastasis risk
• gene expression profile
• tumor biology
• patient management

This article is related to:

Impact of a prognostic 40-gene expression profiling test on clinical management decisions for high-risk cutaneous squamous cell carcinoma

Transparency

Declaration of funding

Research for this study and writing of this manuscript were supported by Castle Biosciences, Inc.

Declaration of financial/other relationships

ASF and SMD serve as members on the advisory board for Castle Biosciences, Inc. MAH, KRC, SJK, and RWC are employees and also hold stock options at Castle Biosciences, Inc. A peer reviewer on this manuscript discloses cooperation with Castle Biosciences in research works on cutaneous squamous cell carcinoma, but they have not been implicated in this particular paper. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no other relevant financial relationships to disclose.

Author contributions

ASF, RWC, SJK, KRC, and SMD were involved in the conception and design, as well as analysis and interpretation of data. MAH, SJK, and RWC drafted the manuscript. ASF, MAH, LD, SJK, RWC, and SMD were involved with revising it critically for intellectual content. All authors approved the final version of the manuscript submitted and agree to be accountable for all aspects of the work.

Acknowledgements

The authors thank Federico Monzon, MD for his expert advice and intellectual guidance while writing and revising this manuscript, as well as Alison Fitzgerald, PhD for her intellectual contributions (both employees at Castle Biosciences, Inc.).

Previous presentations

Data from this study were submitted for poster presentation at the 2020 Winter Clinical Dermatology Conference, January 17–22, 2020, and the Maui Derm for Dermatologists 2020 meeting, January 25–29, 2020.