Metastatic risk in clear cell renal cell carcinoma: a tool incorporating sex, size, and grade

To identify predictors of metastases, estimate the proportion of metastatic clear cell renal cell carcinoma (ccRCC) cases according to these predictors, and subsequently create a risk table showing the absolute difference in metastasis proportion for each 10 mm increase in tumour size.

Patients diagnosed with histopathological confirmed ccRCC in 2010-2018 in Denmark identified in the nationwide Danish Multidisciplinary Renal Cancer Group (DaRenCa) Study-3. Association between diagnostic variables and metastases were assessed with logistic regression analyses. Proportion of cases with metastases were assess based on tumour sizes using a logistic regression model.

The study included 2109 cases with non-metastatic ccRCC at diagnosis and 450 cases with metastatic ccRCC. Multivariable logistic regression analyses found sex, tumour size and grade were associated with metastatic ccRCC, whereas age was not. The proportion of cases with metastasis increased with larger tumours sizes and higher grade. As an example, the proportion of metastases in female cases with tumour size of 40 mm was 2.9% (95% confidence interval [CI] 1.7-4.8%) in Grade 1 and 16% (95% CI 12-22%) in cases with Grade 4. Comparable numbers in cases with a tumour size of 70 mm were 6.6% (95% CI 4.0-11%) and 31% (95% CI 25-38). The absolute increase in the proportion of cases with metastases with a 10 mm increase in size was <2% for tumours <40 mm and Grade 1-2. In contrast, cases with tumour sizes >50 mm and/or Grade 3-4 had a moderate (2-<4%) to high (≥4%) absolute increase in the proportion of cases with metastases with each 10 mm increase.

The risk table presented offers a valuable tool for discussing the risk of progression to metastases in patients under expected management for ccRCC, enabling clinicians to make more informed, evidence-based decisions.