Validation of Four Cutaneous Squamous Cell Carcinoma Staging Systems Using Nationwide Data

Zoe Claire Venables; Selin Tokez; Loes M. Hollestein; Antien L. Mooyaart; Renate Ruthvan den Bos; Brian Rous; Irene M. Leigh; Tamar Nijsten; Marlies Wakkee


The British Journal of Dermatology. 2022;186(5):835-842. 

In This Article

Abstract and Introduction


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.


Cutaneous squamous cell carcinoma (cSCC) is the second commonest cancer worldwide.[1–3] While the majority has an excellent post-surgical prognosis, a small subset (2–5%) of tumours metastasizes.[4–8] A low-risk cSCC may require no clinical follow-up or further investigations whereas a high-risk cSCC may be considered for intense surveillance, imaging, sentinel lymph node biopsy or even adjuvant therapy. With the development of targeted immunotherapies, accurate identification of high-risk patients becomes even more important for treatment, clinical trials and healthcare planning.[9]

The most widely used staging system is the American Joint Committee on Cancer 8th edition (AJCC8).[10] Due to the suboptimal performance of its previous 7th edition,[11] the Brigham and Women's Hospital (BWH)[12] and Tübingen University[13] (i.e. Breuninger) staging systems were developed. Comparative studies on their predictive performances have mostly been limited to single academic centre data.[14,15] Only one study has validated AJCC8, BWH and Tübingen staging systems using population-based data but the number of metastatic cSCCs were relatively small (n = 103).[16] Recently, aimed at further refining the AJCC8 T3 stage to reduce prognostic heterogeneity, the Salamanca T3 classification was developed.[17] In the present study, we aimed to validate the predictive performances of the AJCC8, BWH, Tübingen and Salamanca staging systems in nationwide cancer registry data from England, comprising the largest sample of metastatic cSCC so far.