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 - Funding Information:
Conflict of Interest: AC and PD are employees/consultants of Blue Earth Diagnostics. BAS: Progenics Pharmaceuticals: clinical trial support, Washington University: clinical trial support, Curium Pharma: consulting, clinical trial support, Lantheus: Consulting, GE Healthcare: consulting, Siemens: lecture honoraria (spouse); GCR: Blue Earth Diagnostics: grant support for a research trial unrelated to the compound; DMS: Global Medical Solutions Taiwan: consultant, Progenics Pharmaceuticals Inc: consultant, Heidelberg University: consultant, DuChemBio Co Ltd: consultant, Research: participates through the Emory Office of Sponsored Projects in full compliance with Emory University sponsored research and conflict of interest regulations in sponsored grants including those funded or partially funded by Blue Earth Diagnostics Ltd, Nihon MediPhysics Co Ltd,; Telix Pharmaceuticals (US) Inc, Advanced Accelerator Applications, FUJIFILM Pharmaceuticals U.S.A. Inc, Amgen Inc, Educational: School of Breast Oncology, PrecisCa. The remaining Authors have no conflicts of interest to disclose.
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
AN - SCOPUS:85164250442
SN - 0022-5347
VL - 210
SP - 299
EP - 311
JO - Journal of Urology
JF - Journal of Urology
IS - 2
ER -
