Enhanced metastatic risk stratification for cutaneous squamous cell carcinoma by combining clinical guidelines with the Erasmus MC model: Results from 2 nationwide nested case-control studies - 09/06/25

Doi : 10.1016/j.jaad.2025.05.1390

Olivia F.M. Steijlen, MD ^a, Lara Pozza, MSc ^b, Joleen J.H. Traets, PhD ^b, Barbara Rentroia-Pacheco, MSc ^a, Celeste J. Eggermont, MD ^a, Domenico Bellomo, PhD ^b, Sheril Alex, PhD ^c, Vishal A. Patel, MD ^d, Antien L. Mooyaart, MD, PhD ^e, Loes M. Hollestein, PhD ^a,^f, Marlies Wakkee, MD, PhD ^a,^⁎
^a Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
^b Department of Biostatistics, SkylineDx B.V., Rotterdam, the Netherlands
^c Department of Scientific and Clinical Development, SkylineDx B.V., Rotterdam, the Netherlands
^d Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia
^e Department of Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands
^f Department of Research & Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands

^∗Correspondence to: Marlies Wakkee, MD, PhD, Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Dr. Molewaterplein 40, PO Box 2040, Rotterdam, 3000 CA, the Netherlands.Department of DermatologyErasmus MC Cancer InstituteUniversity Medical Center RotterdamDr. Molewaterplein 40PO Box 2040Rotterdam3000 CAthe Netherlands

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Abstract

Background

Reliably assessing metastatic risk in cutaneous squamous cell carcinoma remains clinically challenging despite established guidelines.

Objective

To assess whether a clinicopathologic risk prediction model (Erasmus MC model) can enhance the identification of high-risk metastatic patients within the current European and National Comprehensive Cancer Network guidelines for cutaneous squamous cell carcinoma.

Methods

A Dutch nested case-control cohort (n = 390 derived from N = 12,325), was first stratified by guideline-defined risk groups. Each high-risk group was further stratified using thresholds for the risk estimated by the Erasmus MC model. The performance was assessed in an independent English nested case-control cohort (n = 696, derived from N = 31,981).

Results

The European guideline-defined high-risk group had a 3-year metastatic risk of 3.8% (95% CI 2.4% to 5.2%). Within this group, 18.2% of the patients were identified with a higher 3-year risk of 10.1% (95% CI 6.7% to 13.5%). For the National Comprehensive Cancer Network-defined very high-risk group, the overall 3-year risk was 7.4% (95% CI 2.0% to 9.2%). Of these, 34.5% of the patients had an even greater risk of 14.0% (95% CI 8.3% to 19.6%).

Limitations

Routinely collected health care data often lacks detailed clinical information.

Conclusion

The Erasmus MC model improves metastatic risk stratification by identifying higher risk groups within the frameworks of current European and National Comprehensive Cancer Network cutaneous squamous cell carcinoma guidelines.

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Key words : cutaneous squamous cell carcinoma, guidelines, metastases, prognosis, risk prediction model, risk stratification, skin cancer

Abbreviations used : AJCC8, BWH, CI, CSCC, EMC Model, NCC, NCCN, NCR, NOTR, Palga

Plan

Application of guidelines

Strengths and limitations

Application of EMC model

Conclusion

	Funding sources: The project was co-funded by the PPP Allowance made available by Health Holland (Top Sector Life Sciences & Health), and an independent donation by Alphatron. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or the writing of the report.
	Patient consent: Not applicable.
	IRB approval status: The Dutch study was approved by the Medical Ethics Review Committee of the Erasmus Medical Center (MEC-2020-0147). Informed consent from all patients was not required. Use of the English cohort did not require ethical approval or informed consent, as per Section 251 of the National Health Service Act 2006.