CT Perfusion Blood Flow Provides an Early Response Marker for Progression-free Survival in a Prospective Randomized Clinical Trial of Metastatic Renal Cell Carcinoma

Introduction: There is currently no biomarker for progression-free survival (PFS) for patients undergoing treatment for metastatic renal cell carcinoma (RCC). The aim of our study was to evaluate computed tomography perfusion (CTp) blood flow as an early marker of PFS in patients with mRCC treated with targeted agents. Methods: Associations between CTp blood flow and PFS were evaluated from prospective randomized evidence using univariable and multivariable Cox proportional hazards regression models with Harrell’s concordance index (c-index) in patients with mRCC randomized to receive one of three targeted agents (everolimus, bevacizumab, or pazopanib). Analyses included baseline tumor CTp blood flow (BF₀) and changes in blood flow after 8 weeks of therapy (ΔBF). Demographic and clinical prognostic factors (International mRCC Database Consortium [IMDC] risk score and ECOG performance) were included in the models as covariates. Results: The median PFS of the 55-patient cohort was 0.80 years (95% CI: 0.76-1.38 years), with no significant difference among the targeted agents. ΔBF and BF₀ were significantly associated with PFS on univariable analysis (p=0.002 and p=0.013, respectively). Multivariable analyses incorporating all the above factors indicated that higher baseline BF₀ (>166 mL/min/100g) and reduced ΔBF (<2.8%) were significantly associated with longer PFS (p<0.02). Conclusion: CTp blood flow may have utility as independent prognostic and early surrogate markers of PFS in mRCC patients treated with targeted agents, surpassing clinical markers like IMDC risk classification. Higher baseline perfusion (BF₀) delineates tumors responsive to targeted therapy, while reductions in perfusion (ΔBF) just 8 weeks after starting treatment are associated with longer PFS. These findings arise from randomized evidence, warranting further evaluations.