Impact of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography on Prostate Cancer Salvage Radiotherapy Management: Results from a Prospective Multicenter Randomized Phase 3 Trial (PSMA-SRT NCT03582774).

Biochemical recurrence Positron emission tomography/computed tomography Prostate cancer Prostate-specific membrane antigen Salvage radiotherapy

Journal

European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719

Informations de publication

Date de publication:
29 Jan 2024
Historique:
received: 18 07 2023
revised: 12 12 2023
accepted: 10 01 2024
medline: 31 1 2024
pubmed: 31 1 2024
entrez: 30 1 2024
Statut: aheadofprint

Résumé

Both imaging and several prognostic factors inform the planning of salvage radiotherapy (SRT). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can localize disease unseen by other imaging modalities. To evaluate the impact of PSMA-PET on biochemical recurrence-free survival rate after SRT. This prospective randomized, controlled, phase 3 clinical trial randomized 193 patients with biochemical recurrence of prostate cancer after radical prostatectomy to proceed with SRT (control arm, n = 90) or undergo a PSMA-PET/computed tomography (CT) scan prior to SRT planning (investigational arm, n = 103) from June 2018 to August 2020. Any other approved imaging modalities were allowed in both arms (including fluciclovine-PET). This is a secondary endpoint analysis: impact of PSMA-PET on SRT planning. Case-report forms were sent to referring radiation oncologists to collect the management plans before randomization and after completion of SRT. The relative frequency (%) of management changes within each arm were compared using chi-square and Fisher's exact tests. The delivered SRT plan was available in 178/193 patients (92.2%; 76/90 control [84.4%] and 102/103 PSMA-PET [99%]). Median prostate-specific antigen levels at enrollment was 0.30 ng/ml (interquartile range [IQR] 0.19-0.91) in the control arm and 0.23 ng/ml (IQR 0.15-0.54) in the PSMA-PET arm. Fluciclovine-PET was used in 33/76 (43%) in the control arm. PSMA-PET localized recurrence(s) in 38/102 (37%): nine of 102 (9%) outside of the pelvis (M1), 16/102 (16%) in the pelvic LNs (N1, with or without local recurrence), and 13/102 (13%) in the prostate fossa only. There was a 23% difference (95% confidence interval [CI] 9-35%, p = 0.002) of frequency of major changes between the control arm (22% [17/76]) and the PSMA-PET intervention arm (45% [46/102]). Of the major changes in the intervention group, 33/46 (72%) were deemed related to PSMA-PET. There was a 17.6% difference (95% CI 5.4-28.5%, p = 0.005) of treatment escalation frequency between the control arm (nine of 76 [12%]) and the intervention arm (30/102 [29%]). Treatment de-escalation occurred in the control and intervention arms in eight of 76 (10.5%) and 12/102 (11.8%) patients, and mixed changes in zero of 76 (0%) and four of 102 (3.9%) patients, respectively. In this prospective randomized phase 3 study, PSMA-PET findings provided information that initiated major management changes to SRT planning in 33/102 (33%) patients. The final readout of the primary endpoint planned in 2025 may provide evidence on whether these changes result in improved outcomes. Prostate-specific membrane antigen positron emission tomography leads to management changes in one-third of patients receiving salvage radiotherapy for post-radical prostatectomy biochemical recurrence of prostate cancer.

Sections du résumé

BACKGROUND BACKGROUND
Both imaging and several prognostic factors inform the planning of salvage radiotherapy (SRT). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can localize disease unseen by other imaging modalities.
OBJECTIVE OBJECTIVE
To evaluate the impact of PSMA-PET on biochemical recurrence-free survival rate after SRT.
DESIGN, SETTING, AND PARTICIPANTS METHODS
This prospective randomized, controlled, phase 3 clinical trial randomized 193 patients with biochemical recurrence of prostate cancer after radical prostatectomy to proceed with SRT (control arm, n = 90) or undergo a PSMA-PET/computed tomography (CT) scan prior to SRT planning (investigational arm, n = 103) from June 2018 to August 2020. Any other approved imaging modalities were allowed in both arms (including fluciclovine-PET).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS METHODS
This is a secondary endpoint analysis: impact of PSMA-PET on SRT planning. Case-report forms were sent to referring radiation oncologists to collect the management plans before randomization and after completion of SRT. The relative frequency (%) of management changes within each arm were compared using chi-square and Fisher's exact tests.
RESULTS AND LIMITATIONS CONCLUSIONS
The delivered SRT plan was available in 178/193 patients (92.2%; 76/90 control [84.4%] and 102/103 PSMA-PET [99%]). Median prostate-specific antigen levels at enrollment was 0.30 ng/ml (interquartile range [IQR] 0.19-0.91) in the control arm and 0.23 ng/ml (IQR 0.15-0.54) in the PSMA-PET arm. Fluciclovine-PET was used in 33/76 (43%) in the control arm. PSMA-PET localized recurrence(s) in 38/102 (37%): nine of 102 (9%) outside of the pelvis (M1), 16/102 (16%) in the pelvic LNs (N1, with or without local recurrence), and 13/102 (13%) in the prostate fossa only. There was a 23% difference (95% confidence interval [CI] 9-35%, p = 0.002) of frequency of major changes between the control arm (22% [17/76]) and the PSMA-PET intervention arm (45% [46/102]). Of the major changes in the intervention group, 33/46 (72%) were deemed related to PSMA-PET. There was a 17.6% difference (95% CI 5.4-28.5%, p = 0.005) of treatment escalation frequency between the control arm (nine of 76 [12%]) and the intervention arm (30/102 [29%]). Treatment de-escalation occurred in the control and intervention arms in eight of 76 (10.5%) and 12/102 (11.8%) patients, and mixed changes in zero of 76 (0%) and four of 102 (3.9%) patients, respectively.
CONCLUSIONS CONCLUSIONS
In this prospective randomized phase 3 study, PSMA-PET findings provided information that initiated major management changes to SRT planning in 33/102 (33%) patients. The final readout of the primary endpoint planned in 2025 may provide evidence on whether these changes result in improved outcomes.
PATIENT SUMMARY RESULTS
Prostate-specific membrane antigen positron emission tomography leads to management changes in one-third of patients receiving salvage radiotherapy for post-radical prostatectomy biochemical recurrence of prostate cancer.

Identifiants

DOI: 10.1016/j.eururo.2024.01.012 PMID: 38290964
pubmed: 38290964
pii: S0302-2838(24)00013-7
doi: 10.1016/j.eururo.2024.01.012
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Auteurs

Wesley R Armstrong (WR)

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; UCLA-Caltech Medical Scientist Training Program, David Geffen School of Medicine, Los Angeles, CA, USA.

Amar U Kishan (AU)

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.

Kiara M Booker (KM)

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Tristan R Grogan (TR)

Department of Medicine Statistics Core (DOMStat), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

David Elashoff (D)

Department of Medicine Statistics Core (DOMStat), David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Ethan C Lam (EC)

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Kevyn J Clark (KJ)

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Michael L Steinberg (ML)

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.

Wolfgang P Fendler (WP)

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK) - University Hospital Essen, Essen, Germany.

Thomas A Hope (TA)

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.

Nicholas G Nickols (NG)

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; Department of Radiation Oncology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

Johannes Czernin (J)

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.

Jeremie Calais (J)

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: jcalais@mednet.ucla.edu.

Classifications MeSH