(UroToday.com) The 2022 GU ASCO Annual meeting included a session discussing the evolution of multidisciplinary management across the spectrum of prostate cancer and a presentation by Dr. David Schuster and colleagues discussing results of SPOTLIGHT, a phase 3, prospective, multicenter study assessing the detection rate of 18F-rhPSMA-7.3 PET in patients with suspected prostate cancer recurrence. 18F-labeled PSMA PET ligands offer a longer half-life and improved spatial resolution compared with 68Ga-PSMA. At the GU ASCO 2022 meeting, Dr. Schuster reported on the detection rate of 18F-rhPSMA-7.3, a novel high affinity theranostic PET ligand with potential for low bladder activity.
SPOTLIGHT (NCT04186845) included men with prior curative intent treatment of localized prostate adenocarcinoma, with elevated PSA suspicious for biochemical recurrence, who were potentially eligible for salvage therapy with curative intent. Imaging included 296 MBq of 18F-rhPSMA-7.3, followed by PET/CT 50-70 minutes post-injection. The co-primary endpoints for this trial included patient level correct detection rate (percentage of all patients scanned with ≥1 true positive lesion) and region level positive predictive value (all PET positive regions combined) of 18F-rhPSMA-7.3 using histopathology and/or conventional imaging as a composite Standard of Truth. These metrics were also evaluated in a subset of patients with a histopathology-only Standard of Truth. Prespecified statistical thresholds of at least 36.5% and 62.5% were set for correct detection rate and positive predictive value, respectively. Overall detection rate stratified by PSA was also documented. Image guided biopsies of PET lesions took place ≤60 days post-PET and any confirmatory imaging took place ≤90 days. Three blinded central readers evaluated the scans with majority read accepted as final interpretation. A separate truth panel established Standard of Truth for each patient.
The overall detection rate in the 389 men (who had a median PSA of 1.10 [range: 0.03-134.6] ng/mL) who had an evaluable 18F-rhPSMA-7.3 scan was 83% by majority read:
In the 366 men (who had a median PSA of 1.27 [range: 0.03-134.6] ng/mL) with a composite Standard of Truth, the patient level correct detection rate was 56.8% (95% CI, 51.6-62.0), meeting the prespecified threshold. However, the region level positive predictive value was 59.7% (54.7-64.7), not meeting the prespecified threshold. In the subset of patients with a histopathology-only Standard of Truth, the patient level correct detection rate and region level positive predictive value were higher at 81.2% (69.9-89.6) and 71.6% (62.5-80.7), respectively, which would have exceeded the prespecified threshold:
The most frequently reported adverse events were (i) hypertension (1.8%), (ii) diarrhea (1.0%), injection site reaction (0.5%), and headache (0.5%). There were 16 (4.1%) patients that had at least one treatment-emergent adverse event that was considered possibly related to 18F-rhPSMA-7.3, however there were no serious adverse events attributable to 18F-rhPSMA-7.3.
Dr. Schuster concluded his presentation of the SPOTLIGHT phase 3 trial assessing detection rate of 18F-rhPSMA-7.3 PET in patients with suspected prostate cancer recurrence with the following take home messages:
- Overall detection rates were high for 18F-rhPSMA-7.3 even at low PSA values
- 18F-rhPSMA-7.3 has a clinically meaningful correct detection rate that meets the prespecified threshold
- While the region level positive predictive value does not meet the prespecified threshold, the data in patients with a composite Standard of Truth are limited by the high proportion of prostate/bed scans (92%) that relied on conventional imaging, a suboptimal Standard of Truth
- For the subset of patients with the more robust histopathology Standard of Truth for at least one region per patient, a high positive predictive value is seen and the lower bound of the 95% CI would have exceeded the prespecified threshold
- There were no significant safety signals identified
- Together, these data support the clinical utility of 18F-rhPSMA-7.3 PET in men with recurrent prostate cancer across a wide PSA range
Presented by: David M. Schuster, MD, Division of Nuclear Medicine and Molecular Imaging, Emory University, Winship Cancer Institute, Atlanta, GA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022