Integrating translational research and clinical practice to refine risk stratification in renal cell carcinoma: the value of DNA methylation markers

Renal Cell Carcinoma (RCC) is the most common form of kidney cancer, accounting for over 90% of kidney tumors and 2–3% of the global cancer burden. The most frequent subtype, clear cell RCC (ccRCC). In the last decades, there has been a rising incidence in recent decades due to improved diagnostic techniques. Survival rates have also improved, especially for early-stage diagnoses. RCC is more prevalent in males and linked to risk factors such as smoking and obesity. Patients with non-metastatic ccRCC are often treated with (partial) nephrectomy. However, approximately 30% of these patients develop metastases during follow-up, and ~10% die of disease progression within five years post-surgery. Identifying high-risk patients at diagnosis remains challenging despite existing clinical prognostic models.
This thesis identified DNA methylation markers and developed a prognostic risk model combining these markers with clinical characteristics, showing added value for localized ccRCC patients. Additionally, RCC cases from the Netherlands Cohort Study (NLCS), one of the largest population-based series, were re-evaluated using updated WHO classifications. A systematic review conducted in this thesis identified new prognostic DNA methylation markers requiring further validation and discussed obstacles preventing their clinical implementation.