KIM-1 and Circulating Tumor DNA Are Prognostic Markers for Oligometastatic Clear-cell Renal Cell Carcinoma: Development of a Multivariable Prognostic Model.

Better tools are needed for clinical decision-making in oligometastatic clear-cell renal cell carcinoma (ccRCC). Plasma KIM-1 concentrations and circulating tumor DNA (ctDNA) were measured in a clinical trial evaluating metastasis-directed therapy (MDT) for oligometastatic ccRCC (NCT03575611). Shorter systemic therapy-free survival (STFS) was associated with high KIM-1 at baseline (hazard ratio per log10 pg/ml [HR]: 2.45, 95% confidence interval [CI] 1.48-4.08; p < 0.001), the end of radiation therapy (HR 2.56, 95% CI 1.56-4.21; p < 0.001), and 3-mo follow-up (HR 3.22, 95% CI 1.91-5.43; p < 0.001). KIM-1 was also associated with progression-free survival and overall survival. In multivariable analysis, both KIM-1 and ctDNA molecular residual disease status were independently associated with STFS when measured at baseline (KIM-1: HR 1.91, 95% CI 1.03-3.55; p = 0.041; ctDNA: HR 2.47, 95% CI 1.08-5.64; p = 0.03) and 3-mo follow-up (KIM-1: HR 2.22, 95% CI 1.09-4.51; p = 0.03; ctDNA: HR 2.70, 95%CI 1.09-6.67; p = 0.03). After elastic net-informed selection, Weibull regression fitted with four clinical variables plus baseline KIM-1 and ctDNA yielded a prognostic model (K-COMPASS) for STFS that demonstrated favorable discrimination (C index 0.76) and calibration. In conclusion, plasma KIM-1 and ctDNA were independently associated with patient outcomes across time points, and their prognostic value further improved with the addition of clinical variables.