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Xu W , Puligandla M , Halbert B , Haas NB , Flaherty KT , Uzzo RG , Dutcher JP , DiPaola RS , Sabbisetti V , Bhatt RS
Plasma KIM-1 Is Associated with Recurrence Risk after Nephrectomy for Localized Renal Cell Carcinoma: A Trial of the ECOG-ACRIN Research Group (E2805)
Clin Cancer Res. 2021 Apr 8;27(12) :3397-3403
PMID: 33832947 URL: https://www.ncbi.nlm.nih.gov/pubmed/33832947
AbstractPURPOSE: 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 after nephrectomy. Lognormal accelerated failure time 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% confidence interval (CI), 0.42-0.73; P < 0.001]. The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement (P (interaction) = 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models [Stage, Size, Grade, and Necrosis (SSIGN) concordance 0.57 vs. 0.43, P = 0.05; UCLA International Staging System (UISS) concordance 0.60 vs. 0.40, P = 0.0005]. Higher post-nephrectomy KIM-1 was also associated with worse 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.
Notes1557-3265 Xu, Wenxin Orcid: 0000-0002-8450-2037 Puligandla, Mäneka Halbert, Brian Orcid: 0000-0002-3515-6019 Haas, Naomi B Flaherty, Keith T Uzzo, Robert G Dutcher, Janice P Orcid: 0000-0002-2267-9187 DiPaola, Robert S Sabbisetti, Venkata Bhatt, Rupal S Journal Article United States Clin Cancer Res. 2021 Apr 8. doi: 10.1158/1078-0432.CCR-21-0025.