The following article features coverage from the NCCN 2022 Annual Conference. Click here to read more of Cancer Therapy Advisor’s conference coverage.

A new study supports the reclassification of cutaneous squamous cell carcinoma (CSCC) into low, high, and very high risk groups, according to researchers.

The study showed that patients in the very high risk group had a significantly higher risk of recurrence, metastasis, and death, when compared with patients in the low and high risk groups.

“Very high risk tumors had about a 7 to 20 times higher risk of poor outcomes, including for local recurrence, nodal metastasis, distant metastasis, and disease-specific death,” said Jacqueline Suzanne Stevens, MD, PhD, of Harvard University in Boston.

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Dr Stevens and colleagues presented these results in a poster at the NCCN 2022 Annual Conference.

The researchers noted that the 2021 NCCN guidelines reclassified CSCC patients into low, high, and very high risk groups, and Mohs micrographic surgery (MMS) or peripheral and deep margin assessment became the preferred surgical modalities for very high risk tumors. However, neither of these recommendations had been validated.

With that in mind, Dr Stevens and colleagues evaluated data from adults with primary CSCC tumors diagnosed between November 15, 1996, and October 1, 2020. The team examined 11,269 tumors that were classified as low or high risk and 1365 tumors classified as very high risk.   

In a multivariate analysis, the risk of local recurrence was significantly higher in the very high risk group than in the low/high risk group (subhazard ratio [SHR], 7.17; P <.001). Patients in the very high risk group also had a significantly higher risk of nodal metastasis (SHR, 17.6; P <.001), distant metastasis (SHR, 20.0; P <.001), and disease-specific death (SHR, 22.7; P <.001).

The researchers also found that, for patients in the very high risk group, MMS resulted in a lower risk of local recurrence, when compared with wide local excision (SHR, 0.72; P =.023). However, there was no significant difference between the MMS and wide local excision groups when it came to nodal metastasis (P =.975), distant metastasis (P =.074), or disease-specific death (P =.367).

“This study is important because it validates the recent NCCN risk stratification of cutaneous SCC tumors and the recommendation that very high risk tumors should undergo Mohs micrographic surgery or the equivalent procedure with local margin assessment,” Dr Stevens said. “Validation of these guidelines will help providers to make informed recommendations for patients.”

Read more of Cancer Therapy Advisor’s coverage of NCCN 2022 by visiting the conference page.


Stevens JS, Murad F, Smile TD, et al. A dual-center retrospective cohort validation of the 2021 NCCN risk stratification for cutaneous squamous cell carcinoma. Presented at NCCN 2022 Annual Conference; March 31 – April 2, 2022. Abstract CLO22-085.