经皮鳞状细胞癌（cSCC）是一种常见的皮肤癌，每年影响全球200万人以上，其中2-5%的患者出现转移。然而，目前的临床分期系统无法提供转移风险的绝对估计，因此错失了为患者提供个性化治疗建议的机会。我们的目标是开发一个临床病理模型，用于预测cSCC患者的转移风险。使用来自以下全国范围的队列：（1）2007-2008年在荷兰出现初次原发性cSCC的所有患者和（2）2013-2015年在英国出现cSCC的所有患者，以得到嵌套病例对照队列。鉴定了产生局部或远处转移的原发性cSCC的病理记录，并将这些cSCC与无转移的病例对照的原发性cSCC进行匹配（1:1比例）。该模型是在荷兰队列（n=390）上使用带有向后选择的加权Cox回归模型进行开发，并在英国队列（n=696）上进行验证。采用加权版本的C指数、校准度量和决策曲线分析评估模型的性能，并与Brigham and Women's Hospital（BWH）和美国联合委员会（AJCC）分期系统进行比较。对多学科皮肤癌结果（SCOUT）联盟成员进行调查，以在临床环境中解释转移风险的截断值选择。其中选择了11个临床病理变量中的8个。该模型表现出良好的判别能力，在开发队列中乐观修正后的C指数为0.80（95%置信区间（CI）0.75-0.85），在验证队列中C指数为0.84（95% CI 0.81-0.87）。模型的预测具有良好的校准性：在验证队列中的校准斜率为0.96（95% CI 0.76-1.16）。决策曲线分析显示相对于当前分期系统，模型提供了改进的净利益，尤其适用于关于随访和辅助治疗决策的阈值。该模型可作为一个在线基于网页的计算器使用（https://emc-dermatology.shinyapps.io/cscc-abs-met-risk/）。该经验证模型使用常规报告的组织学和患者特异性风险因素为cSCC患者分配个性化的转移风险预测。该模型可以帮助临床医生和医疗系统识别高危cSCC患者，并提供个性化的照护/治疗和随访。需要进一步研究该模型在不同患者人群中的临床决策制定中的应用。PPP津贴由荷兰健康部门提供，旨在促进公私合作伙伴关系。 © 2023 作者。

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, affecting more than 2 million people worldwide yearly and metastasising in 2-5% of patients. However, current clinical staging systems do not provide estimates of absolute metastatic risk, hence missing the opportunity for more personalised treatment advice. We aimed to develop a clinico-pathological model that predicts the probability of metastasis in patients with cSCC.Nationwide cohorts from (1) all patients with a first primary cSCC in The Netherlands in 2007-2008 and (2) all patients with a cSCC in 2013-2015 in England were used to derive nested case-control cohorts. Pathology records of primary cSCCs that originated a loco-regional or distant metastasis were identified, and these cSCCs were matched to primary cSCCs of controls without metastasis (1:1 ratio). The model was developed on the Dutch cohort (n = 390) using a weighted Cox regression model with backward selection and validated on the English cohort (n = 696). Model performance was assessed using weighted versions of the C-index, calibration metrics, and decision curve analysis; and compared to the Brigham and Women's Hospital (BWH) and the American Joint Committee on Cancer (AJCC) staging systems. Members of the multidisciplinary Skin Cancer Outcomes (SCOUT) consortium were surveyed to interpret metastatic risk cutoffs in a clinical context.Eight out of eleven clinico-pathological variables were selected. The model showed good discriminative ability, with an optimism-corrected C-index of 0.80 (95% Confidence interval (CI) 0.75-0.85) in the development cohort and a C-index of 0.84 (95% CI 0.81-0.87) in the validation cohort. Model predictions were well-calibrated: the calibration slope was 0.96 (95% CI 0.76-1.16) in the validation cohort. Decision curve analysis showed improved net benefit compared to current staging systems, particularly for thresholds relevant for decisions on follow-up and adjuvant treatment. The model is available as an online web-based calculator (https://emc-dermatology.shinyapps.io/cscc-abs-met-risk/).This validated model assigns personalised metastatic risk predictions to patients with cSCC, using routinely reported histological and patient-specific risk factors. The model can empower clinicians and healthcare systems in identifying patients with high-risk cSCC and offering personalised care/treatment and follow-up. Use of the model for clinical decision-making in different patient populations must be further investigated.PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships.© 2023 The Author(s).