Predictive value of De Ritis ratio in metastatic renal cell carcinoma treated with tyrosine-kinase inhibitors

World J Urol. 2021 Aug;39(8):2977-2985. doi: 10.1007/s00345-021-03628-2. Epub 2021 Mar 1.

Abstract

Background: Predictive markers can help tailor treatment to the individual in metastatic renal cell carcinoma (mRCC). De Ritis ratio (DRR) is associated with oncologic outcomes in various solid tumors.

Objective: To assess the value of DRR in prognosticating survival in mRCC patients treated with tyrosine-kinase inhibitors (TKI).

Methods: Overall, 220 mRCC patients treated with TKI first-line therapy were analyzed. An optimal cut-off point for DRR was determined with Youden's J. We used multiple strata for DRR, performed descriptive, Kaplan-Meier and multivariable Cox-regression analyses to assess associations of DRR with progression-free (PFS) and overall survival (OS).

Results: Patients above the optimal cut-off point for DRR of ≥ 1.58 had fewer liver metastases (p = 0.01). There was no difference in PFS (p > 0.05) between DRR groups. DRR above the median of 1.08 (HR 1.42; p = 0.03), DRR ≥ 1.1(HR 1.44; p = 0.02), ≥ 1.8 (HR 1.56; p = 0.03), ≥ 1.9 (HR 1.59; p = 0.02) and ≥ 2.0 (HR 1.63; p = 0.047) were associated with worse OS. These associations did not remain after multivariable adjustment. In the intermediate MSKCC group, DRR was associated with inferior OS at cut-offs ≥ 1.0 (HR 1.78; p = 0.02), ≥ 1.1 (HR 1.81; p = 0.01) and above median (HR 1.88; p = 0.007) in multivariable analyses. In patients with clear-cell histology, DRR above median (HR 1.54; p = 0.029) and DRR ≥ 1.1 (HR 1.53; p = 0.029) were associated with OS in multivariable analyses.

Conclusion: There was no independent association between DRR and survival of mRCC patients treated with TKI in the entire cohort. However, OS of patients with intermediate risk and clear-cell histology were affected by DRR. DRR could be used for tailored decision-making in these subgroups.

Keywords: De ritis ratio; Metastatic renal cell carcinoma; Prognostic marker; Tumor markers; Tyrosine-kinase inhibitors.

MeSH terms

  • Alanine Transaminase / analysis
  • Alanine Transaminase / blood*
  • Aspartate Aminotransferases / analysis
  • Aspartate Aminotransferases / blood*
  • Carcinoma, Renal Cell* / blood
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / pathology
  • Carcinoma, Renal Cell* / surgery
  • Cytoreduction Surgical Procedures / methods
  • Female
  • Humans
  • Indazoles* / administration & dosage
  • Indazoles* / adverse effects
  • Karnofsky Performance Status
  • Kidney Neoplasms* / blood
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / pathology
  • Kidney Neoplasms* / surgery
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Nephrectomy / methods*
  • Predictive Value of Tests
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines* / administration & dosage
  • Pyrimidines* / adverse effects
  • Sorafenib / administration & dosage
  • Sorafenib / adverse effects
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / adverse effects
  • Sunitinib* / administration & dosage
  • Sunitinib* / adverse effects
  • Survival Analysis

Substances

  • Indazoles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • pazopanib
  • Sorafenib
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Sunitinib