Incorporation of the 40-Gene Expression Profile (40-GEP) Test to Improve Treatment Decisions in High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients: Case Series and Algorithm

Abstract

Cutaneous squamous cell carcinoma (cSCC) has become a significant public health issue due to its rapidly rising incidence and an estimated 1.8 million newly diagnosed cases annually. As with other cancers, treatment decisions for patients with cSCC are based primarily on a patient's risk for poor outcomes. There has been improvement in clinicopathologic factor-based risk assessment approaches, either through informal methods or ever evolving staging approaches. However, these approaches misidentify patients who will eventually have disease progression as low-risk and conversely, over classify patients as high-risk who do not experience relapse. To improve the accuracy of risk assessment for patients with cSCC, the 40-gene expression profile (40-GEP) test has been validated to show statistically significant stratification of a high-risk cSCC patient's risk of nodal or distant metastasis, independent of currently available risk-assessment methods. The 40-GEP test allows for a more accurate classification of metastatic risk for high-risk cSCC patients, with the aim to influence appropriate allocation of clinician time and therapeutic resources to those patients who will most benefit. The objective of this article is to present a treatment algorithm in which clinicians can easily integrate the results of the 40-GEP test into their current treatment approaches to tailor patient care based on individual tumor biology. The following modalities were considered: surveillance imaging, sentinel lymph node biopsy (SLNB), adjuvant radiation therapy (ART), and clinical follow-up. The authors have contributed their own cases for discussion as to how they have seen the beneficial impact of 40-GEP test results in their own practice. Overall, clinicians can identify risk-aligned treatment pathway improvements with the use of the 40-GEP test for challenging to manage, high-risk cSCC patients.

Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically Relevant Subgroups of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients

“…Different treatment pathways may be considered as the study results suggest that the Class 2B patients would benefit from ART [ 27 ] and the Class 1 patients have a low likelihood of developing metastatic disease [ 14 ]. These results are consistent with previous studies and have led to the development of physician-derived NCCN-aligned patient management pathways that integrate the 40-GEP test with clinicopathologic features [ 11 , 20 , 21 ].…”

“…Robust validation of the 40-GEP has led to clinical use of the test [ 19 , 20 ] to improve precision risk stratification, resulting in reduction of potential overtreatment of biologically low-risk patients and undertreatment of patients with aggressive tumor biology. Algorithms have been developed that detail integration of test results into current treatment approaches [ 21 ].…”

“…Current areas of use include clinical decision-making for nodal assessment (primarily use of imaging), adjuvant radiation therapy (ART) and surgical or therapeutic intervention. These clinical usage management decisions demonstrate a risk-aligned reduction or de-escalation for low-risk, Class 1 patients and increased or escalation in higher-risk Class 2A and 2B patients [ 21 , 23 ].…”

40-Gene Expression Profile Representative of Metastatic Risk of Squamous Cell Carcinoma in a Mohs Surgical Patient

“…Metastasis can be difficult to detect, but early metastasis detection can improve patient survival due to the early implication of suitable treatment [4]. The current staging systems are not fully adequate in predicting the metastatic risk profile in cutaneous SCC patients [5][6]. This results in misidentifying high-risk vs low-risk patients [5][6].…”

“…The current staging systems are not fully adequate in predicting the metastatic risk profile in cutaneous SCC patients [5][6]. This results in misidentifying high-risk vs low-risk patients [5][6]. To better quantify the metastatic potential of SCCs, a 40-gene expression profile (40-GEP) was developed to better capture metastasis and metastatic risk as an independent predictor [4].…”