Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma: A trial of the ECOG-ACRIN Research Group (E2805).

PURPOSE No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. EXPERIMENTAL DESIGN The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 levels were measured from banked plasma at trial enrollment 4-12 weeks post-nephrectomy. Lognormal accelerated failure time (AFT) models were used to test for association between KIM-1 and disease-free survival (DFS) as well as overall survival (OS). RESULTS Plasma from 418 patients was analyzed. Higher post-nephrectomy KIM-1 was associated with worse DFS across all study arms after adjustment for Fuhrman grade, T-stage, N-stage, and tumor histology (survival time ratio 0.56 for 75th vs 25th percentile of KIM-1, 95% CI 0.42-0.73, p < 0.001). The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement (p-value for interaction 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models (SSIGN concordance 0.57 vs 0.43, p = 0.05; UISS concordance 0.60 vs 0.40, p = 0.0005). Higher post-nephrectomy KIM-1 was also associated with worse overall survival (OS) after multivariable adjustment (survival time ratio 0.71 for 75th vs 25th percentile of KIM-1, 95% CI 0.56-0.91, p < 0.001). CONCLUSIONS Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.