Longitudinal data on advanced cutaneous squamous cell carcinoma from the Dutch Keratinocyte Cancer Collaborative (DKCC): a nationwide real-world database study

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Background: While Cutaneous Squamous Cell Carcinoma (CSCC) is one of the most common cancers, epidemiological data is scarce. Therefore, the aim of this study was to collect high quality epidemiological data, which is needed to identify differences in outcomes and improve patient care. To achieve this aim, we designed the Dutch Keratinocyte Cancer Collaborative (DKCC), which is a nationwide database, including longitudinal data on locally advanced, recurrent, and metastatic CSCC (advanced CSCC). Methods: Advanced CSCCs were identified from the Dutch nationwide Pathology Databank (Palga) using a validated algorithm. Manual registration of a selection of 500 patients with advanced CSCC per year (all metastatic, all recurrences and a random selection of locally advanced CSCCs) was performed by the Netherlands Cancer Registry to obtain data on tumour characteristics, diagnostics, disease progression and treatment. Data was linked to the Netherland Organ Transplant Registry to obtain information about immunosuppressed patients and to the municipal records for vital status. Findings: We estimated that 8.0% (1846/23,065 CSCC, 95% confidence interval: 7.4-8.6) of all diagnosed CSCC in 2021 were locally advanced CSCC. In 2021-2022, 920 patients with advanced CSCC were registered in the DKCC. A quarter of metastatic patients had recurrent CSCC before developing metastasis (i.e., 13/51 patients with skin metastasis, 63/296 patients with regional lymph node metastasis, 20/72 patients with distant metastasis). The median time to recurrence or metastasis after an American Joint Committee on Cancer (AJCC) T3/T4 primary CSCC was 11 months (Interquartile range [IQR] 6-19) and 9 months (IQR 6-17), respectively. In 6% (4/67, skin metastasis only) to 20% (17/83, distant metastasis) of episodes with metastasis, no treatment was provided. Interpretation: The DKCC is the first nationwide longitudinal data source on advanced CSCC. Its methodology can serve as an example for designing efficient registries for advanced CSCC in other countries or even for other rare cancer outcomes. The high number of locally advanced CSCC puts a large burden on the health care system, as these patients need more extensive work-up and treatment. Data from the DKCC provides essential information to improve clinical guidelines for optimal CSCC patient care. Funding: Funded by Sanofi Genzyme/Regeneron.

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