TY - JOUR
T1 - Diagnostic Performance and Safety of 18F-rhPSMA-7.3 Positron Emission Tomography in Men With Suspected Prostate Cancer Recurrence
T2 - Results From a Phase 3, Prospective, Multicenter Study (SPOTLIGHT)
AU - Jani, Ashesh B.
AU - Ravizzini, Gregory C.
AU - Gartrell, Benjamin A.
AU - Siegel, Barry A.
AU - Twardowski, Przemyslaw
AU - Saltzstein, Daniel
AU - Fleming, Mark T.
AU - Chau, Albert
AU - Davis, Phillip
AU - Chapin, Brian F.
AU - Schuster, David M.
AU - Allaf, Mohamad
AU - Avery, Ryan J.
AU - Avril, Norbert
AU - Barker, Helen
AU - Belkoff, Laurence
AU - Bostrom, Peter
AU - Cher, Michael L.
AU - Chisholm, Diane
AU - Covington, Matthew F.
AU - Cox, Ian
AU - Esposito, Giuseppe
AU - Gardiner, Peter
AU - Gauden, David
AU - Helfand, Brian
AU - Hermsen, Rick
AU - Josephson, David
AU - Kay, Matthew
AU - Koontz, Bridget F.
AU - Kostakoglu, Lale
AU - Kuo, Phillip
AU - Lavely, William
AU - Liem, Ing Han
AU - Lokuta, Mary
AU - Lowentritt, Benjamin
AU - Michalski, Jeff
AU - Miller, Matthew P.
AU - Mourtzikos, Karen
AU - Pachynski, Russell
AU - Penny, Ross
AU - Piert, Morand
AU - Purysko, Andrei
AU - Rais-Bahrami, Soroush
AU - Savir-Baruch, Bital
AU - Somford, Rik
AU - Tewari, Ashutosh
AU - Uchio, Edward
AU - Yoo, Don
AU - Zukotynski, Katherine
N1 - Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Purpose:SPOTLIGHT (NCT04186845) evaluated diagnostic performance and safety of radiohybrid 18F-rhPSMA-7.3, a novel high-affinity positron emission tomography radiopharmaceutical.Materials and Methods:Men with prostate cancer recurrence underwent positron emission tomography/CT 50-70 minutes after intravenous administration of 296±20% MBq 18F-rhPSMA-7.3. To assess the coprimary end points (verified detection rate and combined region-level positive predictive value), 3 blinded, independent central readers evaluated the scans. Verified detection rate is equivalent to the overall detection rate × positive predictive value. Standard of truth was established for each patient using histopathology or confirmatory imaging. Statistical thresholds (lower bounds of the confidence intervals) of 36.5% and 62.5% were prespecified for verified detection rate and combined region-level positive predictive value, respectively. Additional end points included detection rate, verified detection rate, and combined region-level positive predictive value in patients with histopathology standard of truth, and safety.Results:The overall 18F-rhPSMA-7.3 detection rate among all 389 patients with an evaluable scan was 83% (majority read). Among the 366 patients (median prostate-specific antigen 1.27 ng/mL) for whom a standard of truth (histopathology [n=69]/confirmatory imaging only [n=297]) was available, verified detection rate ranged from 51% (95% CI 46.1-56.6) to 54% (95% CI 48.8-59.3), exceeding the prespecified statistical threshold. Combined region-level positive predictive value ranged from 46% (95% CI 42.0-50.3) to 60% (95% CI 55.1-65.5) across the readers, not meeting the threshold. In the subset of patients with histopathology standard of truth, the verified detection rate and combined region-level positive predictive value were both above the prespecified thresholds (majority read, 81% [95% CI 69.9-89.6] and 72% [95% CI 62.5-80.7], respectively). No significant safety concerns were identified.Conclusions:18F-rhPSMA-7.3 offers a clinically meaningful verified detection rate for localization of recurrent prostate cancer. Despite missing the coprimary end point of combined region-level positive predictive value, the totality of the data support the potential clinical utility of 18F-rhPSMA-7.3.
AB - Purpose:SPOTLIGHT (NCT04186845) evaluated diagnostic performance and safety of radiohybrid 18F-rhPSMA-7.3, a novel high-affinity positron emission tomography radiopharmaceutical.Materials and Methods:Men with prostate cancer recurrence underwent positron emission tomography/CT 50-70 minutes after intravenous administration of 296±20% MBq 18F-rhPSMA-7.3. To assess the coprimary end points (verified detection rate and combined region-level positive predictive value), 3 blinded, independent central readers evaluated the scans. Verified detection rate is equivalent to the overall detection rate × positive predictive value. Standard of truth was established for each patient using histopathology or confirmatory imaging. Statistical thresholds (lower bounds of the confidence intervals) of 36.5% and 62.5% were prespecified for verified detection rate and combined region-level positive predictive value, respectively. Additional end points included detection rate, verified detection rate, and combined region-level positive predictive value in patients with histopathology standard of truth, and safety.Results:The overall 18F-rhPSMA-7.3 detection rate among all 389 patients with an evaluable scan was 83% (majority read). Among the 366 patients (median prostate-specific antigen 1.27 ng/mL) for whom a standard of truth (histopathology [n=69]/confirmatory imaging only [n=297]) was available, verified detection rate ranged from 51% (95% CI 46.1-56.6) to 54% (95% CI 48.8-59.3), exceeding the prespecified statistical threshold. Combined region-level positive predictive value ranged from 46% (95% CI 42.0-50.3) to 60% (95% CI 55.1-65.5) across the readers, not meeting the threshold. In the subset of patients with histopathology standard of truth, the verified detection rate and combined region-level positive predictive value were both above the prespecified thresholds (majority read, 81% [95% CI 69.9-89.6] and 72% [95% CI 62.5-80.7], respectively). No significant safety concerns were identified.Conclusions:18F-rhPSMA-7.3 offers a clinically meaningful verified detection rate for localization of recurrent prostate cancer. Despite missing the coprimary end point of combined region-level positive predictive value, the totality of the data support the potential clinical utility of 18F-rhPSMA-7.3.
KW - molecular imaging
KW - positron-emission tomography
KW - prostatic neoplasms
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U2 - 10.1097/JU.0000000000003493
DO - 10.1097/JU.0000000000003493
M3 - Article
C2 - 37126069
SN - 0022-5347
VL - 210
SP - 299
EP - 311
JO - Journal of Urology
JF - Journal of Urology
IS - 2
ER -