Validating 4 Staging Systems for Cutaneous Squamous Cell Carcinoma Using Population-Based Data

Abstract

IMPORTANCE Cutaneous squamous cell carcinoma (cSCC) has metastatic potential, but the prognostic value of current staging systems in nonselected patients is uncertain. OBJECTIVE To assess the effect of risk factors for metastasis and to evaluate validity and usefulness of 4 staging systems for cSCC using population-based data. DESIGN, SETTING, AND PARTICIPANTS This was a nationwide, population-based, nested case-control study. The Cancer Registry of Norway, which receives compulsory data on all cancers in the Norwegian population of approximately 5.2 million inhabitants. All patients diagnosed as having a primary invasive cSCC in the period 2000 to 2004 (n = 6721) were identified. Of these, 112 patients were diagnosed with metastasis within 5 years. As control patients, 112 patients with cSCC without metastases, matched for sex and age at diagnosis, were identified by random. Clinical data and biopsy specimens of primary cSCC were collected for all 224 patients. The biopsies were reexamined histologically by an experienced pathologist using well-established criteria for cSCC, yielding 103 patients with metastasis (cases) and 81 cSCC without metastasis (controls). Variables necessary for accurate staging were not assessable in 26 patients (14.1%); multiple imputation was therefore performed. MAIN OUTCOMES AND MEASURES The ability of 4 cSCC staging systems (ie, the American Joint Committee on Cancer, 7th edition [AJCC 7] staging system, the staging system used by Breuninger et al, the Brigham and Women's Hospital [BWH] staging system, and the AJCC, 8th edition [AJCC 8] staging systems) to identify patients who developed metastasis with 5 years of follow-up. External validation was performed by logistic regression, discrimination (sensitivity, specificity, proportion correctly classified, concordance index), and calibration (R 2 , Hosmer-Lemeshow test, plots) statistics. RESULTS Of 6721 patients; 3674 (54.7%) were men, and 3047 (45.3%) were women, with a mean age at diagnosis of 78 years. Of the 103 patients with cSCC diagnosed with metastasis within 5 years, 60 [58.3%] were men, and mean [SD] age 72.7 [13.5] years. Of the 81 patients with cSCC without metastasis, 51 [63.0%] were men, and mean [SD] age 74.6 [11.7] 15 years. The staging systems distinguished poorly to moderately between patients who developed metastasis and those who did not. The ability to cluster patients with similar outcomes within the same staging category was low, particularly when using the AJCC 7 system. Using the AJCC 7 system, the risk of metastasis for T2 patientswasmorethan5-fold,comparedwithT1patients(OR,5.55;95%CI,2.24-13.75).Inthesystem usedbyBreuningeretal,high-riskcategoriesfordiameterandtumorthicknessandtheBWHsystem's T2b category collected relatively homogeneous groups. In the systems used by Breuninger et al and Brigham-Women's Hospital, risk of metastasis was significantly elevated with increasing stage or risk category. Using the system by Breuninger et al, the risk of metastasis was 3-fold for tumors in the high co-risk factor ...

European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention

“…Staging systems (AJCC 7th and 8th version, BWH and Breuninger) were compared in a population-based cohort study where the BWH and Breuninger systems performed best in identifying cSCC patients at high risk of metastases [115]. However it was commented that staging systems were still not optimal [116].…”

“…However it was commented that staging systems were still not optimal [116]. Among the 103 patients with metastasis, 37.9% fell in the BWH T2a and 39.8% in BWH T2b category, while with AJCC8 more than 60% fell in the T3 category [115]. AJCC8 was compared with the BWH classification system in the retrospective study of Ruiz et al in 680 primary CSCC of the head and neck.…”

AXIN2 and SNAIL expression predict the risk of recurrence in cutaneous squamous cell carcinoma after Mohs micrographic surgery

“…The clinical risk factors for cSCC recurrence include tumor invasion depth, size, differentiation status, presence of perineural invasion and location (6). In addition, certain molecular biomarkers, including tumor protein 53, cyclin-dependent kinase inhibitor 2A, telomerase reverse transcriptase gene (TERT) and programmed cell death ligand 1 (PD-L1) have been considered as potential factors involved in cSCC progression.…”

“…In particular, TERT promoter mutations and increased PD-L1 expression have been considered as molecular risk factors for cSCC recurrence (7)(8)(9). However, these predictive risk factors are inadequate to properly assess the recurrence risk of cSCC with high reproducibility and reliability (5,6).…”

High-Risk Nonmelanoma Skin Cancers: Identification, Management, and Reconstruction

“…6 Roscher et al directly compared multiple staging systems (AJCC 7, AJCC 8, BWH, Breuninger) for cSCC using a population-based, nested case-control study and showed AJCC 8 and BWH systems performed better than AJCC 7. 9 A formal staging system for BCC does not exist. Historically, it has been grouped together with other cutaneous malignancies, including cSCC, in the AJCC.…”