Vascular endothelial growth factor (VEGF) inhibitors such as sunitinib and tivozanib have been shown to improve progression-free survival in patients with advanced renal-cell carcinoma (RCC). However, some patients may not respond to VEGF inhibition, and the cost and adverse events associated with VEGF inhibition can negatively impact patient quality of life. Therefore, determining which patients will respond to these therapies early in treatment would be clinically beneficial. Dynamic contrast-enhanced computed tomography (DCE-CT) is a functional imaging technique that can measure blood flow and has shown promise for predicting response to tyrosine kinase inhibitor (TKI) therapy.1
In this prospective study, 82 patients with advanced RCC and an indication for antiangiogenic therapy were enrolled between September 2011 and April 2015. DCE-CT was performed at baseline and between 8 and 10 weeks after initiation of a TKI to obtain tumor perfusion images. Traditional computed tomography was also used to determine response to therapy through December 2020.1
Of the 82 enrolled patients, 71 patients were included in the final analysis. At baseline, mean age was 64 years, and most patients had favorable (N = 38) or intermediate (N = 30) prognostic scores. TKIs administered included sunitinib (N = 46), pazopanib (N = 19), sorafenib (N = 2), cabozantinib (N = 2), axitinib (N = 1), and tivozanib (N = 1).1
DCE-CT–measured blood flow reduction to target lesions by ≥50% at first follow-up was considered treatment response, whereas increased blood flow or reduction <50% was considered nonresponse. A total of 42 patients met the criteria for response, with a mean blood flow reduction from baseline of 79.37%. Among the nonresponders, the mean blood flow reduction was 27.7% in 21 patients, whereas blood flow increased by 8% in the remaining 8 patients. Changes in blood volume measured by DCE-CT were similar to measures of blood flow.1
Over a median follow-up of 27 months, progression-free survival was 15 months for responders (95% confidence interval [CI], 10.9-19.0), 4 months for nonresponders with decreasing blood flow (95% CI, 2.0-5.9), and 2 months for nonresponders with increasing blood flow (95% CI, 1.3-2.7). Median overall survival was 34 months (95% CI, 13.9-54.1), 12 months (95% CI, 5.6-18.4), and 7 months (95% CI, 2.8-11.2), respectively.1
DCE-CT–based response assessment was shown to accurately classify RECIST-based responders as well. All patients with partial response according to RECIST version 1.1 criteria were classified as responders by blood flow, whereas all patients with progressive disease were classified as nonresponders by blood flow. Of the 31 patients with stable disease, 14 were considered responders, and 17 were considered nonresponders by blood flow change. However, there was a significant difference in survival for the patients with RECIST-based stable disease classified as responders versus nonresponders.1
The authors concluded that DCE-CT–based measures of blood flow are independent predictors of survival in patients with advanced RCC who are receiving TKIs.1
- Spek A, Graser A, Casuscelli J, et al. Dynamic contrast-enhanced CT-derived blood flow measurements enable early prediction of long term outcome in metastatic renal cell cancer patients on antiangiogenic treatment. Urol Oncol. 2021;40:13.e1-13.e8.