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

Peter E. Hall, Scott T.C. Shepherd, Janet Brown, James Larkin, Robert Jones, Christy Ralph, Robert Hawkins, Simon Chowdhury, Ekaterini Boleti, Amit Bahl, Kate Fife, Andrew Webb, Simon J. Crabb, Thomas Geldart, Robert Hill, Joanna Dunlop, Duncan McLaren, Charlotte Ackerman, Akhila Wimalasingham, Luis BeltranPaul Nathan, Thomas Powles

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalEuropean Urology Focus
Early online date6 Feb 2019
Publication statusPublished - 2019


  • Heterogeneity
  • Prognostic factor
  • Radiological response
  • Renal cell carcinoma
  • Vascular endothelial growth factor

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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