Radiological Response Heterogeneity Is of Prognostic Significance in Metastatic Renal Cell Carcinoma Treated with Vascular Endothelial Growth Factor-targeted Therapy

Eur Urol Focus. 2020 Sep 15;6(5):999-1005. doi: 10.1016/j.euf.2019.01.010. Epub 2019 Feb 6.

Abstract

Background: Response evaluation criteria in solid tumours (RECIST) is widely used to assess tumour response but is limited by not considering disease site or radiological heterogeneity (RH).

Objective: To determine whether RH or disease site has prognostic significance in patients with metastatic clear-cell renal cell carcinoma (ccRCC).

Design, setting, and participants: A retrospective analysis was conducted of a second-line phase II study in patients with metastatic ccRCC (NCT00942877), evaluating 138 patients with 458 baseline lesions.

Intervention: The phase II trial assessed vascular endothelial growth factor-targeted therapy±Src inhibition.

Outcome measurements and statistical analysis: RH at week 8 was assessed within individual patients with two or more lesions to predict overall survival (OS) using Kaplan-Meier method and Cox regression model. We defined a high heterogeneous response as occurring when one or more lesion underwent a ≥10% reduction and one or more lesion underwent a ≥10% increase in size. Disease progression was defined by RECIST 1.1 criteria.

Results and limitations: In patients with a complete/partial response or stable disease by RECIST 1.1 and two or more lesions at week 8, those with a high heterogeneous response had a shorter OS compared to those with a homogeneous response (hazard ratio [HR] 2.01; 95% confidence interval [CI]: 1.39-2.92; p<0.001). Response by disease site at week 8 did not affect OS. At disease progression, one or more new lesion was associated with worse survival compared with >20% increase in sum of target lesion diameters only (HR 2.12; 95% CI: 1.43-3.14; p<0.001). Limitations include retrospective study design.

Conclusions: RH and the development of new lesions may predict survival in metastatic ccRCC. Further prospective studies are required.

Patient summary: We looked at individual metastases in patients with kidney cancer and showed that a variable response to treatment and the appearance of new metastases may be associated with worse survival. Further studies are required to confirm these findings.

Keywords: Heterogeneity; Prognostic factor; Radiological response; Renal cell carcinoma; Vascular endothelial growth factor.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzodioxoles / therapeutic use*
  • Carcinoma, Renal Cell / diagnostic imaging*
  • Carcinoma, Renal Cell / drug therapy*
  • Double-Blind Method
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Humans
  • Kidney Neoplasms / diagnostic imaging*
  • Kidney Neoplasms / drug therapy*
  • Male
  • Prognosis
  • Quinazolines / therapeutic use*
  • Retrospective Studies
  • Tomography, X-Ray Computed*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • Benzodioxoles
  • Enzyme Inhibitors
  • Quinazolines
  • Vascular Endothelial Growth Factor A
  • saracatinib
  • cediranib

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma

Associated data

  • ClinicalTrials.gov/NCT00942877