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

Figures & data

Table 1. Characteristics of the NCCN high-risk cSCC cohort (n = 300).

Feature of modeling cohort	Cases (% of cohort)
Age: median years (range)	70 (34–95)
Sex: male	219 (73%)
Immune deficient	76 (25%)
Located on H&N	201 (67%)
Tumor diameter^a: mean cm (≥2 cm)	1.85 (36%)
Tumor thickness^b: mean mm (>6 mm)	3.90 (16%)
Poorly differentiated	36 (12%)
Clark level IV/V	62 (21%)
PNI present	36 (12%)
Subcutaneous fat invasion	43 (14%)
40-GEP result
Class 1	189 (63%)
Class 2A	87 (29%)
Class 2B	24 (8%)

^a275 cases had tumor diameter reported; ^b109 cases had thickness reported.

Abbreviations. NCCN, National Comprehensive Cancer Network; H&N, head and neck; PNI, perineural invasion; GEP, gene expression profile.

Notes. NCCN high-risk criteria include tumor size ≥2 cm; tumor depth >6 mm or invasion beyond subcutaneous fat; poorly differentiated; perineural invasion; bone invasion; on ear or lip; on mask area of the face; on genitalia, hands, or feet; on forehead, scalp, cheek, or neck (size ≥10 mm); rapid growth; immunosuppression; site of prior radiation therapy or chronic inflammatory process; recurrent tumor; neurologic symptoms; high-risk subtypes (acantholytic, adenosquamous, or desmoplastic).

Figure 1. Application of 40-GEP test results to NCCN-defined high-risk status and T stage for improving risk-appropriate management of cSCC. (A) Using a cohort (n = 300) of clinicopathologically-defined cSCC patients meeting study criteria and who were NCCN-defined high risk, the 40-GEP test stratified the patients into three groups depending on risk for metastasis at 3 years post-diagnosis: low (Class 1, n = 189), high (Class 2A, n = 87), or highest (Class 2B, n = 24). Patients stratified as Class 1, 2A, and 2B had a 9%, 21%, and 63% risk for metastasis, respectively, per the 40-GEP test alone. Corresponding AJCC8 and BWH T stages and metastasis rates were analyzed. (B) Incorporation of 40-GEP Class plus AJCC8 and BWH T stages into three metastasis risk bins (<10%, 10–49%, and ≥50% risk) resulted in low, moderate, and high intensity management strategies. The 40-GEP integration demonstrates low management intensity for 53.0% (AJCC8) or 57.7% (BWH), high intensity management for 8.0%, and moderate intensity management for the remainder (39.0%, AJCC8; 34.3%, BWH) of the 300-patient cohort. (C) Metastasis-free survival (MFS) rates of patients from the cohort risk-aligned with low, moderate, or high intensity management per 40-GEP Class and AJCC8 or BWH T stage. Kaplan–Meier analysis revealed 3-year MFS rates of 92.5% for patients in the low intensity management category (both AJCC8 and BWH), 82.1% and 80.6% for those in the moderate intensity category (AJCC8 and BWH, respectively), and 41.7% for patients in the high intensity category (both AJCC8 and BWH). Statistically significant differences were found for these MFS curves for both 40-GEP Class plus AJCC8 and 40-GEP Class plus BWH T stage (p ≤ .001, log-rank).

Figure 2. Recommended risk-aligned cSCC patient management plans within the NCCN guidelines framework for prognostic groups based on 40-GEP Class and T stage. Risk for regional/distant metastasis is reported for 40-GEP Class and BWH T stage. *Adjustment of clinical follow-up should be based on risk per the NCCN guidelines. **Imaging, nodal biopsy, and/or neck dissection should be considered (moderate intensity management) or recommended (high intensity management) when warranted per the NCCN, American Academy of Dermatology, and Que et al.⁴¹.

Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: management of advanced and high-stage tumors. J Am Acad Dermatol. 2018;78(2):249–261.

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