Validation of four cutaneous squamous cell carcinoma staging systems using nationwide data*

Zoe Claire Venables, Selin Tokez, Loes M. Hollestein, Antien L. Mooyaart, Renate Ruth van den Bos, Brian Rous, Irene M. Leigh, Tamar Nijsten, Marlies Wakkee*

*Corresponding author for this work

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    Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer worldwide with relatively low metastatic potential (2–5%). Developments in therapeutic options have highlighted the need to better identify high-risk patients who could benefit from closer surveillance, adjuvant therapies and baseline/follow-up imaging, while at the same time safely omitting low-risk patients from further follow-up. Controversy remains regarding the predictive performance of current cSCC staging systems and which methodology to adopt. 

    Objectives: To validate the performance of four cSCC staging systems [American Joint Committee on Cancer 8th edition (AJCC8), Brigham and Women’s Hospital (BWH), Tübingen and Salamanca T3 refinement] in predicting metastasis using a nationwide cohort. 

    Methods: A nested case–control study using data from the National Disease Registration Service, England, 2013–2015 was conducted. Metastatic cSCC cases were identified using an algorithm to identify all potential cases for manual review. These were 1 : 1 matched on follow-up time to nonmetastatic controls randomly selected from 2013. Staging systems were analysed for distinctiveness, homogeneity, monotonicity, specificity, positive predictive value (PPV), negative predictive value (NPV) and c-index. 

    Results: We included 887 metastatic cSCC cases and 887 nonmetastatic cSCC controls. The BWH system showed the highest specificity [92.8%, 95% confidence interval (CI) 90.8–94.3%, PPV (13.2%, 95% CI 10.6–16.2) and c-index (0.84, 95% CI 0.82–0.86). The AJCC8 showed superior NPV (99.2%, 95% CI 99.2–99.3), homogeneity and monotonicity compared with the BWH and Tübingen diameter and thickness classifications (P < 0.001). Salamanca refinement did not show any improvement in AJCC8 T3 cSCC staging. 

    Conclusions: We validated four cSCC staging systems using the largest nationwide dataset of metastatic cSCC so far. Although the BWH system showed the highest overall discriminative ability, PPV was low for all staging systems, which shows the need for further improvement and refining of current cSCC staging systems.

    Original languageEnglish
    Pages (from-to)835-842
    Number of pages8
    JournalBritish Journal of Dermatology
    Issue number5
    Early online date3 Dec 2021
    Publication statusPublished - 2 May 2022

    Bibliographical note

    Funding Information: No external funding.

    Open Access: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

    Publisher Copyright: © 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

    Citation: Venables, Z.C., Tokez, S., Hollestein, L.M., Mooyaart, A.L., van den Bos, R.R., Rous, B., Leigh, I.M., Nijsten, T. and Wakkee, M. (2022), Validation of four cutaneous squamous cell carcinoma staging systems using nationwide data*. Br J Dermatol, 186: 835-842.



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