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)

Ashesh B. Jani; Gregory C. Ravizzini; Benjamin A. Gartrell; Barry A. Siegel; Przemyslaw Twardowski; Daniel Saltzstein; Mark T. Fleming; Albert Chau; Phillip Davis; Brian F. Chapin; David M. Schuster; Mohamad Allaf; Ryan J. Avery; Norbert Avril; Helen Barker; Laurence Belkoff; Peter Bostrom; Michael L. Cher; Diane Chisholm; Matthew F. Covington; Ian Cox; Giuseppe Esposito; Peter Gardiner; David Gauden; Brian Helfand; Rick Hermsen; David Josephson; Matthew Kay; Bridget F. Koontz; Lale Kostakoglu; Phillip Kuo; William Lavely; Ing Han Liem; Mary Lokuta; Benjamin Lowentritt; Jeff Michalski; Matthew P. Miller; Karen Mourtzikos; Russell Pachynski; Ross Penny; Morand Piert; Andrei Purysko; Soroush Rais-Bahrami; Bital Savir-Baruch; Rik Somford; Ashutosh Tewari; Edward Uchio; Don Yoo; Katherine Zukotynski

doi:10.1097/JU.0000000000003493

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)

Ashesh B. Jani^*, Gregory C. Ravizzini, Benjamin A. Gartrell, Barry A. Siegel, Przemyslaw Twardowski, Daniel Saltzstein, Mark T. Fleming, Albert Chau, Phillip Davis, Brian F. Chapin, David M. Schuster, Mohamad Allaf, Ryan J. Avery, Norbert Avril, Helen Barker, Laurence Belkoff, Peter Bostrom, Michael L. Cher, Diane Chisholm, Matthew F. CovingtonIan Cox, Giuseppe Esposito, Peter Gardiner, David Gauden, Brian Helfand, Rick Hermsen, David Josephson, Matthew Kay, Bridget F. Koontz, Lale Kostakoglu, Phillip Kuo, William Lavely, Ing Han Liem, Mary Lokuta, Benjamin Lowentritt, Jeff Michalski, Matthew P. Miller, Karen Mourtzikos, Russell Pachynski, Ross Penny, Morand Piert, Andrei Purysko, Soroush Rais-Bahrami, Bital Savir-Baruch, Rik Somford, Ashutosh Tewari, Edward Uchio, Don Yoo, Katherine Zukotynski

^*Corresponding author for this work

Radiology

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	299-311
Number of pages	13
Journal	Journal of Urology
Volume	210
Issue number	2
DOIs	https://doi.org/10.1097/JU.0000000000003493
State	Published - Aug 1 2023

Funding

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.

Keywords

molecular imaging
positron-emission tomography
prostatic neoplasms

ASJC Scopus subject areas

Urology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/JU.0000000000003493

Cite this

Jani, A. B., Ravizzini, G. C., Gartrell, B. A., Siegel, B. A., Twardowski, P., Saltzstein, D., Fleming, M. T., Chau, A., Davis, P., Chapin, B. F., Schuster, D. M., Allaf, M., Avery, R. J., Avril, N., Barker, H., Belkoff, L., Bostrom, P., Cher, M. L., Chisholm, D., ... Zukotynski, K. (2023). 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). Journal of Urology, 210(2), 299-311. https://doi.org/10.1097/JU.0000000000003493

@article{f0255aebb2664c4aa9dc5b9daa740b00,

title = "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)",

abstract = "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.",

keywords = "molecular imaging, positron-emission tomography, prostatic neoplasms",

author = "Jani, {Ashesh B.} and Ravizzini, {Gregory C.} and Gartrell, {Benjamin A.} and Siegel, {Barry A.} and Przemyslaw Twardowski and Daniel Saltzstein and Fleming, {Mark T.} and Albert Chau and Phillip Davis and Chapin, {Brian F.} and Schuster, {David M.} and Mohamad Allaf and Avery, {Ryan J.} and Norbert Avril and Helen Barker and Laurence Belkoff and Peter Bostrom and Cher, {Michael L.} and Diane Chisholm and Covington, {Matthew F.} and Ian Cox and Giuseppe Esposito and Peter Gardiner and David Gauden and Brian Helfand and Rick Hermsen and David Josephson and Matthew Kay and Koontz, {Bridget F.} and Lale Kostakoglu and Phillip Kuo and William Lavely and Liem, {Ing Han} and Mary Lokuta and Benjamin Lowentritt and Jeff Michalski and Miller, {Matthew P.} and Karen Mourtzikos and Russell Pachynski and Ross Penny and Morand Piert and Andrei Purysko and Soroush Rais-Bahrami and Bital Savir-Baruch and Rik Somford and Ashutosh Tewari and Edward Uchio and Don Yoo and Katherine Zukotynski",

year = "2023",

month = aug,

day = "1",

doi = "10.1097/JU.0000000000003493",

language = "English (US)",

volume = "210",

pages = "299--311",

journal = "Journal of Urology",

issn = "0022-5347",

publisher = "Wolters Kluwer Health",

number = "2",

}

Jani, AB, Ravizzini, GC, Gartrell, BA, Siegel, BA, Twardowski, P, Saltzstein, D, Fleming, MT, Chau, A, Davis, P, Chapin, BF, Schuster, DM, Allaf, M, Avery, RJ, Avril, N, Barker, H, Belkoff, L, Bostrom, P, Cher, ML, Chisholm, D, Covington, MF, Cox, I, Esposito, G, Gardiner, P, Gauden, D, Helfand, B, Hermsen, R, Josephson, D, Kay, M, Koontz, BF, Kostakoglu, L, Kuo, P, Lavely, W, Liem, IH, Lokuta, M, Lowentritt, B, Michalski, J, Miller, MP, Mourtzikos, K, Pachynski, R, Penny, R, Piert, M, Purysko, A, Rais-Bahrami, S, Savir-Baruch, B, Somford, R, Tewari, A, Uchio, E, Yoo, D & Zukotynski, K 2023, '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)', Journal of Urology, vol. 210, no. 2, pp. 299-311. https://doi.org/10.1097/JU.0000000000003493

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). / Jani, Ashesh B.; Ravizzini, Gregory C.; Gartrell, Benjamin A. et al.
In: Journal of Urology, Vol. 210, No. 2, 01.08.2023, p. 299-311.

Research output: Contribution to journal › Article › peer-review

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

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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UR - http://www.scopus.com/inward/citedby.url?scp=85164250442&partnerID=8YFLogxK

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 -