Can early ⁶⁸Ga-PSMA-11 PET/CT predict 6-month disease control in patients receiving first-line systemic therapy for metastatic clear-cell renal cell carcinoma? Protocol for the multicentre prospective phase II PSMA-RENAL study in Belgium.

Abstract

The introduction of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors has improved outcomes in metastatic clear cell renal cell carcinoma (ccRCC). However, conventional imaging modalities often lack efficacy for response evaluation, facing challenges such as pseudo-progression, mixed responses or delayed responses. Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of ccRCC, suggesting that PSMA-targeted positron emission tomography (PET) imaging may serve as an early biomarker of treatment efficacy. PSMA-RENAL is a prospective, multicentre, phase II trial enrolling patients with histologically confirmed metastatic ccRCC and PSMA-positive lesions. Patients will undergo 68Ga-PSMA-11 PET/CT imaging at baseline and 6 weeks after initiation of ICI-based systemic therapy. Conventional imaging (CT or MRI with bone scan) will continue every 12 weeks. The primary outcome is the association between the percentage change in Standardized Uptake Value (SUV)max on ⁶⁸Ga-PSMA-11 PET/CT from baseline to week 6 and disease control rate (DCR) at 6 months. Disease control is defined as complete response, partial response or stable disease on conventional imaging. Secondary outcomes are the association between early change in PSMA-PET uptake and objective response rate, the association between baseline PSMA-PET uptake and DCR, and the association between early change in PSMA-PET uptake and progression-free survival. A total of 75 patients will be recruited, accounting for a 10% drop-out rate and assuming a 90% PSMA-positivity rate. The study has 80% power to detect a clinically meaningful difference in the area under the receiver operating characteristic curve. This study is the first to evaluate whether early changes in PSMA-PET imaging can predict outcomes in patients with metastatic ccRCC receiving systemic therapy. Early identification of responders may allow timely therapeutic adjustments, potentially enhancing patient outcomes and optimising healthcare resource allocation. The protocol has received ethical approval. All participants will provide written informed consent. Trial Registration: EU reference number (CTIS): 2024-517098-26-00.Protocol code: PSMA-RENAL.Trial Phase: Therapeutic exploratory (Phase II).Date of registration: March 2025. Currently recruiting.