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

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.

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).

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).

Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Apr 08 [Epub ahead of print]

Wenxin Xu, Maneka Puligandla, Brian Halbert, Naomi B Haas, Keith T Flaherty, Robert G Uzzo, Janice P Dutcher, Robert S DiPaola, Venkata Sabbisetti, Rupal S Bhatt

Medical Oncology, Dana-Farber Cancer Institute., Department of Biostatistical Sciences, Dana-Farber Cancer Institute., Division of Hematology-Oncology, Beth Israel Deaconess Medical Center., Medical Oncology, Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania., Developmental Therapeutics, Massachusetts General Hospital Cancer Center., Division of Urologic Oncology, Department of Surgical Oncology, Fox Chase Cancer Center., Hematology/Oncology, Cancer Research Foundation of New York, Inc., Medical Oncology, University of Kentucky College of Medicine., Medicine, Brigham and Women's Hospital., Division of Hematology-Oncology, Beth Israel Deaconess Medical Center .

email news signup