Radiological response heterogeneity is of prognostic significance in metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy

Hall, P. E. et al. (2020) Radiological response heterogeneity is of prognostic significance in metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. European Urology Focus, 6(5), pp. 999-1005. (doi: 10.1016/j.euf.2019.01.010) (PMID:30738795)

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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.

Item Type:Articles
Keywords:Heterogeneity, prognostic factor, radiological response, renal cell carcinoma, vascular endothelial growth factor.
Glasgow Author(s) Enlighten ID:Jones, Professor Robert
Authors: Hall, P. E., Shepherd, S. T.C., Brown, J., Larkin, J., Jones, R., Ralph, C., Hawkins, R., Chowdhury, S., Boleti, E., Bahl, A., Fife, K., Webb, A., Crabb, S. J., Geldart, T., Hill, R., Dunlop, J., McLaren, D., Ackerman, C., Wimalasingham, A., Beltran, L., Nathan, P., and Powles, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:European Urology Focus
ISSN (Online):2405-4569
Published Online:06 February 2019
Copyright Holders:Copyright © 2019 Elsevier B.V. on behalf of European Association of Urology
First Published:First published in European Urology Focus 6(5): 999-1005
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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