Validation of the 2022 National Comprehensive Cancer Network Risk Stratification for Cutaneous Squamous Cell Carcinoma

Abstract

ImportanceThe 2022 National Comprehensive Cancer Network (NCCN) reclassified cutaneous squamous cell carcinoma (CSCC) into low-, high-, and very high-risk groups to better risk stratify tumors. Mohs micrographic surgery (Mohs) or peripheral and deep en face margin assessment (PDEMA) became preferred surgical modalities for high- and very high-risk tumors. This new risk stratification and the recommendation for Mohs or PDEMA in high- and very high-risk groups have not been validated.ObjectiveTo compare outcomes in very high-, high-, and low-risk NCCN groups of CSCCs and in CSCCs treated with Mohs or PDEMA compared with wide local excision (WLE).Design, Setting, and ParticipantsThis retrospective cohort study of CSCCs was performed in 2 tertiary care academic medical centers. Patients 18 years or older and diagnosed between January 1, 1996, and December 31, 2019, at Brigham and Women’s Hospital and Cleveland Clinic Foundation were included. Data were analyzed from October 20, 2021, to March 29, 2023.ExposuresNCCN risk group, Mohs or PDEMA, and WLE.Main Outcomes and MeasuresLocal recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD).ResultsA total of 10 196 tumors from 8727 patients were stratified by NCCN guidelines into low-, high-, and very high-risk groups (6003 [59.0%] men; mean [SD] age, 72.4 [11.8] years). Compared with the low-risk group, the high- and very high-risk groups demonstrated a greater risk of LR (high-risk subhazard ratio [SHR], 1.99 [95% CI, 1.21-3.27; P = .007]; very high-risk SHR, 12.66 [95% CI, 7.86-20.39; P < .001]), NM (high-risk SHR, 4.26 [95% CI, 1.28-14.23; P = .02]; very high-risk SHR, 62.98 [95% CI, 19.24-206.17; P < .001]), DM (high-risk SHR, 2.2 × 107 [95% CI, 4.7 × 103-1.1 × 1011; P < .001]; very high-risk SHR, 6.3 × 108 [95% CI, 1.4 × 105-2.9 × 1012; P < .001]), and DSD (high-risk SHR, 4.02 [95% CI, 1.18-13.71; P = .03]; very high-risk SHR, 93.87 [95% CI, 29.19-301.85; P < .001]). Adjusted 5-year cumulative incidence was significantly higher in very high- vs high- and low-risk groups for LR (9.4% [95% CI, 9.2%-14.0%] vs 1.5% [95% CI, 1.4%-2.1%] and 0.8% [95% CI, 0.5%-1.2%], respectively), NM (7.3% [95% CI, 6.8%-10.9%] vs 0.5% [95% CI, 0.4%-0.8%] and 0.1% [95% CI, 0.03%-0.3%], respectively), DM (3.9% [95% CI, 2.6%-5.6%] vs 0.1% [95% CI, 0.04%-0.2%] and 0.01% [95% CI, not applicable], respectively), and DSD (10.5% [95% CI, 10.3%-15.4%] vs 0.5% [95% CI, 0.4%-0.8%] and 0.1% [95% CI, 0.04%-0.3%], respectively). Compared with CSCCs treated with WLE, those treated with Mohs or PDEMA had lower risk of LR (SHR, 0.65 [95% CI, 0.46-0.90]; P = .009), DM (SHR, 0.38 [95% CI, 0.18-0.83]; P = .02), and DSD (SHR, 0.55 [95% CI, 0.36-0.84]; P = .006).Conclusions and RelevanceThe findings of this cohort study suggest that the NCCN high- and very high-risk groups identify CSCCs at greatest risk for developing poor outcomes. Further, Mohs or PDEMA resulted in lower LR, DM, and DSD compared with WLE.

Extensive Perineural Invasion vs Nerve Caliber to Assess Cutaneous Squamous Cell Carcinoma Prognosis

“…First, this study contributes a plausible definition of what constitutes ePNI to the CSCC literature. Second, given the high overall rate of poor outcomes and the independent association with both local recurrence and disease-specific death, ePNI may merit inclusion alongside deep PNI and lcPNI in the very high-risk CSCC entity recently delineated by the NCCN and validated in a large multi-institutional cohort study . In our cohort, the 36.8% overall poor outcome rate for tumors with ePNI was more than twice the rate of those with lcPNI (14.9%) and more than 3 times the rate of patients with deep PNI (10.7%).…”

Slow Mohs - A Surgical Option for Treatment of Skin Cancer in Head and Neck Surgery

“…Micrographic techniques are considered the gold standard in the treatment of highrisk skin cancer as they evaluate 100% of the margins and not just a sample of 3 to 5% of the margins as in the traditional "bread loaf" analysis technique (3). The PDEMA/Slow Mohs technique is a viable, safe and easy-toperform option for those who do not have classic Mohs surgery in their service.…”

“…Due to the high risk of recurrence and the delicate location, they require different treatment. (1)(2)(3). One of the proposed forms of treatment is the concept of "Peripheral and Deep en Face Margin Assessment (PDEMA)".…”

Molecular and Histopathological Characterization of Metastatic Cutaneous Squamous Cell Carcinomas: A Case–Control Study

“…In particular, solid organ transplant recipients seem to be particularly at risk of developing cSCC [ 7 , 8 ]. Depending on the extent of the disease, cSCC is classified into primary and advanced cSCC [ 9 , 10 , 11 , 12 ]. A large variety of tumor-intrinsic and tumor-extrinsic factors contribute to the definition of high-risk cSCCs, including, among other factors, tumor diameter and thickness, differentiation, anatomical location, and immune suppression [ 13 ].…”

“…A large variety of tumor-intrinsic and tumor-extrinsic factors contribute to the definition of high-risk cSCCs, including, among other factors, tumor diameter and thickness, differentiation, anatomical location, and immune suppression [ 13 ]. However, high-risk primary SCCs—as defined by different guidelines [ 9 , 10 , 11 , 12 ]—are amenable to curative surgery or radiotherapy [ 14 ]. On the contrary, advanced SCCs (either locally advanced or metastatic) cannot be radically treated with surgery and/or radiation therapy, but require systemic treatment [ 15 ].…”