JU INSIGHT Diagnostic 18F-rhPSMA-7.3 Positron Emission Tomography in Men With Suspected Prostate Cancer Recurrence

By: Ashesh B. Jani, MD, Winship Cancer Institute of Emory University, Atlanta, Georgia; Gregory C. Ravizzini, MD, The University of Texas MD Anderson Cancer Center, Houston; Benjamin A. Gartrell, MD, Montefiore Medical Center, Bronx, New York; Barry A. Siegel, MD, Mallinckrodt Institute of Radiology and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri; Przemyslaw Twardowski, MD, John Wayne Cancer Institute, Santa Monica, California; Daniel Saltzstein, MD, Urology San Antonio, Texas; Mark T. Fleming, MD, Virginia Oncology Associates, US Oncology Research, Norfolk; Albert Chau, MSc, CStat, Blue Earth Diagnostics Ltd, Oxford, United Kingdom; Phillip Davis, MD, Blue Earth Diagnostics Inc, Monroe Township, New Jersey; Brian F. Chapin, MD, The University of Texas MD Anderson Cancer Center, Houston; David M. Schuster, MD, Emory University, Atlanta, Georgia On behalf of the SPOTLIGHT Study Group | Posted on: 30 Aug 2023

Jani AB, Ravizzini GC, Gartrell BA, et al. Diagnostic performance and safety of ¹⁸F-rhPSMA-7.3 positron emission tomography in men with suspected prostate cancer recurrence: results from a phase 3, prospective, multicenter study (SPOTLIGHT). J Urol. 2023;210(2):299-311.

Study Need and Importance

Radiohybrid (rh) ¹⁸F-rhPSMA-7.3 is a novel high-affinity prostate-specific membrane antigen—targeted positron emission tomography (PET) radiopharmaceutical in development for diagnostic imaging of prostate cancer. ¹⁸F-rhPSMA-7.3 has lower than average urinary excretion reported for the existing prostate-specific membrane antigen ligands, which may enhance visualization of the prostate region. This phase 3, multicenter, open-label study was conducted to evaluate the diagnostic performance of ¹⁸F-rhPSMA-7.3-PET for localization of recurrent prostate cancer as read by 3 blinded central readers.

What We Found

¹⁸F-rhPSMA-7.3 was well tolerated and provided a high overall detection rate (83%) among 389 patients with biochemically recurrent prostate cancer. A standard of truth (SoT; histopathology or confirmatory imaging) verified detection rate (VDR) of 51%-54% across readers was determined, exceeding the prespecified statistical threshold for this coprimary end point. A second coprimary end point, combined region-level positive predictive value, ranged from 46%-60% across readers, not exceeding the threshold. Notably, both VDR and combined region-level positive predictive value exceeded the statistical thresholds when evaluating a subset of patients with histopathology rather than conventional imaging SoT.

Limitations

The data are limited by a low frequency of histopathology SoT. SPOTLIGHT employed a rigorous binary imputation method for the primary end points, whereby a PET-positive region not confirmed on imaging or histopathology was categorized as false-positive by default. The predominance of CT, MRI, and bone scans as the SoT likely led to a proportion of PET-positive lesions being categorized as false-positive that would have been categorized true-positive by a more sensitive SoT.

Interpretation for Patient Care

¹⁸F-rhPSMA-7.3 has a favorable safety profile and a clinically meaningful VDR. ¹⁸F-rhPSMA-7.3-PET provides another diagnostic option that can be used to correctly restage patients with recurrent prostate cancer.