INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

Centre for Cancer Genomics and Computational Biology Barts Cancer Institute Queen Mary University of London London United Kingdom; Centre for Cancer Biology and Therapy School of Applied Sciences London South Bank University London United Kingdom

Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands

Department of Dermatology Brigham and Women's Hospital Boston Massachusetts

Department of Dermatology Edouard Herriot Hospital Lyon France

Department of Dermatology Faculty of Medicine Baskent University Ankara Turkey

Department of Dermatology Hospital de Santa Maria and Faculdade de Medicina da Universidade de Lisboa Lisbon Portugal

Department of Dermatology Hospital Universitari Vall d'Hebron Barcelona Spain

Department of Dermatology Leiden University Medical Center Leiden The Netherlands

Department of Dermatology Leiden University Medical Center Leiden The Netherlands; Department of Dermatology Netherlands Cancer Institute Amsterdam The Netherlands

Department of Dermatology Medical University of Vienna Vienna Austria

Department of Dermatology NHS Greater Glasgow and Clyde Glasgow United Kingdom

Department of Dermatology Oxford University Hospitals NHS Foundation Trust Oxford United Kingdom

Department of Dermatology Royal London Hospital Barts Health NHS Trust London United Kingdom

Department of Dermatology University Hospital of Zürich University of Zürich Zürich Switzerland

Department of Dermatology University Hospitals Leuven Leuven Belgium

Department of Dermatology University Medical Centre Groningen University of Groningen Groningen The Netherlands

Department of Dermatology University of São Paulo Sao Paulo Brazil

Department of Dermatology Waikato Clinical Campus University of Auckland Hamilton New Zealand

Department of Dermatovenereology Charles University Hospital Pilsen Czech Republic

Department of Nephrology Transplantology and Internal Medicine Faculty of Medicine Medical University of Gdansk Gdansk Poland

Dermatology Unit Departments of Translational Medicine and Health Science University of Eastern Piedmont Novara Italy

Division of Experimental Surgery Department of Surgery University Hospital Regensburg Regensburg Germany

Molecular and Clinical Medicine School of Medicine University of Dundee Dundee United Kingdom

N Dermatology and STD Outpatient Clinic Copernicus Medical Centre Gdansk Poland

Population Health Department QIMR Berghofer Medical Research Institute Brisbane Australia

Unit of Dermatology Department of Medicine University of Padua Padua Italy

Unit of Dermatology Department of Medicine University of Padua Padua Italy; Soft Tissue Peritoneum and Melanoma Surgical Oncology Unit IOV IRCSS Padua Italy