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

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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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 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.

Original languageEnglish
Pages (from-to)3397-3403
Number of pages7
JournalClinical Cancer Research
Volume27
Issue number12
DOIs
StatePublished - Jun 2021

Keywords

  • Carcinoma, Renal Cell/drug therapy
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Humans
  • Kidney Neoplasms/drug therapy
  • Nephrectomy/adverse effects
  • Prognosis
  • Sunitinib/therapeutic use

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