Risk Factors and Metastasis Prediction in Small (≤4 cm) Clear Cell Renal Cell Carcinoma: A Nested Case-Control Study

Purpose To investigate the clinicopathological factors affecting the metastasis and prognosis in small clear cell renal carcinoma (ccRCC) (≤ 4 cm), so as to guide clinical management and follow-up. Methods This study retrospectively analyzed the clinical and pathological data, as well as the follow-up data of 1,054 small ccRCC patients undergoing surgery at the Third Hospital of Peking University between 2012 and 2024. Following the identification of 50 small ccRCC patients with metastasis (the case group), a nested case-control study was further carried out with the matching of 281 small ccRCC patients without metastasis during the same period (the control group), according to a ratio of 1:6. Furthermore, risk factors affecting the metastasis of small ccRCC were investigated by using univariate and multivariate logistic regression analyses. Results Of the 1,054 small ccRCC patients, metastasis (synchronous metastasis, 1.8%; and metachronous metastasis, 2.9%) occurred in 4.7% of small ccRCC patients. The 5-year overall survival rates were 99.1% and 75.8% for patients with non-metastatic and metastatic small ccRCC, respectively. Multivariate logistic regression analysis revealed that the presence of clinical symptoms, R.E.N.A.L. score (moderate complexity group and high complexity group), pT3 and pathological grade III and IV were independent risk factors for metastasis in small ccRCC patients. Conclusion Patients with small ccRCC may experience a metastatic rate of 4.7%. Clinical symptoms, higher R.E.N.A.L. score, pT3 stage, and higher pathological grading may be risk factors for metastasis of small ccRCC.