The PSMA-RENAL study addresses a key limitation in response assessment for metastatic clear cell renal cell carcinoma (ccRCC) treated with modern first-line systemic regimens combining immune checkpoint inhibitors and tyrosine kinase inhibitors. Conventional imaging modalities can be unreliable for early response evaluation due to phenomena such as pseudo-progression, mixed responses or delayed radiological change.
Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of ccRCC, which provides a biologic rationale for using PSMA-targeted positron emission tomography to image tumor-associated vasculature activity. The trial tests whether early changes on 68Ga-PSMA-11 PET/CT can serve as an early biomarker of therapeutic efficacy and predict medium-term disease control.
PSMA-RENAL is a prospective, multicentre, phase II clinical trial. Eligible participants are adults with histologically confirmed metastatic ccRCC and at least one PSMA-positive lesion on imaging. The study enrolls patients initiating first-line systemic therapy that includes ICI-based regimens.
All participants must provide written informed consent. The protocol has received ethical approval. The trial is registered with the EU reference number (CTIS): 2024-517098-26-00 under the protocol code PSMA-RENAL. Date of registration is March 2025. The study is described as currently recruiting.
Participants undergo 68Ga-PSMA-11 PET/CT at two scheduled timepoints: at baseline (prior to initiation of systemic therapy) and at 6 weeks after starting treatment. Conventional imaging—CT or MRI with bone scan—continues on a standard schedule every 12 weeks to monitor radiographic response per routine clinical practice.
The PET/CT analysis focuses on semiquantitative uptake metrics, principally the Standardized Uptake Value maximum (SUVmax) of target lesions. The primary imaging measure is the percentage change in SUVmax from baseline to week 6.
Primary outcome:
Secondary outcomes:
These endpoints are designed to evaluate both early predictive value (week 6 PET/CT) and baseline prognostic value of PSMA-PET measures in the context of systemic therapy for metastatic ccRCC.
The protocol plans to recruit a total of 75 patients, which includes an allowance for a 10% drop-out rate. This recruitment target assumes an underlying PSMA-positivity rate of 90% among screened patients. The study is powered at 80% to detect a clinically meaningful difference in the area under the receiver operating characteristic (ROC) curve for the primary analysis associating early PET change with 6-month DCR.
Statistical analysis will focus on the relationship between percentage change in SUVmax and binary disease control status at 6 months, with ROC curve methods used to quantify discriminatory performance. Details of covariate adjustment, handling of missing data, and prespecified subgroup analyses were not reported in the source summary.
Ethical approval for the trial has been obtained, and participants will provide written informed consent before enrollment. Trial registration information: EU reference number (CTIS): 2024-517098-26-00; Protocol code: PSMA-RENAL; Trial Phase: Therapeutic exploratory (Phase II); Date of registration: March 2025. The source reports the study as currently recruiting.
This is the first prospective study specifically designed to evaluate whether early changes on 68Ga-PSMA-11 PET/CT can predict outcomes for patients with metastatic ccRCC receiving systemic therapy. If early PSMA-PET changes correlate with 6-month disease control or with progression-free survival, clinicians may be able to identify responders or non-responders earlier than with conventional imaging alone. Early identification of non-responders could enable timely therapeutic adjustments, potentially improving individual patient outcomes and optimising use of healthcare resources.
However, the source article is a protocol summary and does not report results. Details on analytic thresholds, exact PET quantification methodology, or planned secondary statistical models were not reported in the available summary and will require consultation of the full protocol or subsequent study reports for comprehensive methodological specifics.