Prognosis Comparison Between Synchronous and Metachronous Metastasis of Renal Cell Carcinoma: A Meta-Analysis and Systematic Review.

Abstract

Renal cell carcinoma (RCC), a common urologic malignancy, is associated with a poor prognosis in metastatic settings. Nevertheless, the prognostic significance of metastatic timing remains inadequately characterized. A comprehensive systematic search was conducted across the PubMed, Embase, Web of Science, and Cochrane Library databases through October 2025 to identify relevant studies. Data extraction focused on evaluating the prognostic impact of metastatic timing on overall survival (OS), progression-free survival (PFS), and time to treatment failure (TTF). Individual patient-level OS data were reconstructed where necessary. Meta-analysis was performed using Stata 18, with reconstructed patient-level data analyzed in R 4.4.2. Nine studies showed superior OS in metachronous metastasis (relative risk [RR], 1.18; 95% confidence interval [CI], 1.05-1.31; p < 0.05). The re-analyzed data still indicated that patients with metachronous metastasis have a better OS (HR, 1.959; 95% CI, 1.581-2.428; p < 0.001). This survival advantage persisted in both targeted-therapy (RR, 1.14; 95% CI, 1.11-1.18; p < 0.05) and immunotherapy (RR, 1.91; 95% CI, 1.53-2.39; p < 0.05) cohorts. However, no significant difference in OS was observed in the brain metastasis (BM) subgroup. The post-reconstruction analysis remained consistent with the original result. Additionally, there was no statistically significant difference in PFS and TTF between the two groups. Synchronous metastasis independently predicts poorer OS for patients with metastatic RCC (mRCC), particularly those under targeted therapy or immunotherapy. Although metastatic timing emerges as a clinically significant prognostic biomarker in mRCC, these findings require additional validation.