¹⁸ F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing first line tyrosine kinase or checkpoint inhibitor therapy.

Abstract

455 Background: Evaluating the effectiveness of systemic therapy in patients with metastatic renal cell carcinoma (mRCC) is crucial for timely treatment adjustments. In an earlier preliminary study on a subset of mRCC patients, we compared responses to systemic therapy using [¹⁸F]PSMA-1007 PET and conventional imaging methods. In this research, our aim was to compare response assessments using PSMA PET versus CT scans in a larger cohort of mRCC patients undergoing systemic therapy. Additionally, we investigated the potential of using PSMA-PET-derived responses to predict outcomes. Methods: We performed a retrospective single-center analysis of patients with mRCC who underwent [¹⁸F]PSMA-1007 PET/CT in the context of tyrosine kinase or checkpoint inhibition and had at least one PET avid metastatic RCC lesion at baseline. All patients were treated with IO combination therapy either in combination with a TKI or ICI. Early treatment response at a mean of 9.5 weeks after the start of systemic therapy was compared to baseline scans. PET responses and measurements were correlated with CT results, progression-free (PFS) and overall survival (OS). Survival data were analyzed using log rank testing and Kaplan-Meier analysis. Results: 25 patients with mRCC were enrolled. Median age was 65.2 years (range 24-87). Median PFS was 16.6 months (range 1.38 -58.69) and median OS 28.8 months (range 3.6 - 65.16). Median SUV, TTV, CT or PET response were not correlated with PFS or OS. Patients with a 10% reduction in SUVmax had a significant longer PFS with 23.1 months (95% CI 13.8-32.3) vs 3.6 (95% CI 1.4 – 5.9) months and OS of 36.2 months (95% CI 17.5 – 70.6) vs 11.1 months (95% CI 5.604 – 16.8) than patients without SUVmax response. SUVmax response was independent of administration of tyrosine kinase inhibitors or checkpoint inhibitors. Conclusions: Reduction of PSMA uptake on PET scans may be an independent biomarker beyond CT findings and warrants further investigation in mRCC. PSMA PET could be used for a better understanding of drug efficacy. Changes in PSMA PET are independent of the mechanism of action of systemic therapy in early prediction of therapy response and therefore might be considered a clinical biomarker.