Baseline serum folic acid as a prognostic biomarker in metastatic renal cell carcinoma treated with targeted therapy

BACKGROUND: Serum folic acid (SFA) is a key component of one-carbon metabolism. Its prognostic significance in metastatic renal cell carcinoma (mRCC) has not been established. Thus, this study investigated the association between SFA levels and survival outcomes in patients with mRCC receiving targeted therapy. METHODS: This retrospective dual-center cohort included 220 mRCC patients. Baseline SFA levels measured within three months before treatment initiation were recorded. Receiver operating characteristic analysis determined an optimal SFA cutoff of 5.5 ng/mL for overall survival (OS), categorizing patients into high (> 5.5 ng/mL) and low (≤ 5.5 ng/mL) SFA groups. Survival outcomes were estimated using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazards models identified independent prognostic factors. RESULTS: The median follow-up was 34.4 months. The median progression-free survival (PFS) and OS for the entire cohort were 10 and 24.0 months, respectively. Patients with high SFA had longer PFS (11.1 vs. 9.8 months; p = 0.034) and OS (31.3 vs. 20.8 months; p < 0.001) compared to those with low SFA. In multivariate analysis, SFA was not an independent predictor of PFS. However, low SFA independently predicted inferior OS (hazard ratio [HR]: 2.04, 95% confidence interval [CI] 1.40–2.99; p < 0.001), along with IMDC intermediate- (HR: 2.19, 95% CI 1.11–4.30, p = 0.023) and poor-risk categories (HR: 5.96, 95% CI 2.90-12.25, p < 0.001 ) and presence of brain metastasis (HR 1.93, 95% CI 1.10–3.37; p = 0.020). CONCLUSIONS: Baseline SFA was independently associated with OS and may serve as a readily available host-related prognostic marker; further studies are warranted to validate these findings and to determine whether SFA adds prognostic value beyond established risk models.