Baseline Nodal Status on 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Intermediate- to High-risk Prostate Cancer Is Prognostic for Treatment Failure: Follow-up of the proPSMA Trial

Michael S Hofman; Veeru Kasivisvanathan; Emma Link; James Buteau; Matthew J Roberts; Roslyn J Francis; Colin Tang; Ian Vela; Paul Thomas; Natalie Rutherford; Jarad M Martin; Mark Frydenberg; Ramdave Shakher; Lih-Ming Wong; Kim Taubman; Sze Ting Lee; Edward Hsiao; Paul Roach; Michelle Nottage; Ian Kirkwood; Dickon Hayne; Amir Iravani; Scott Williams; Jonathan O'Brien; Nathan Lawrentschuk; Declan G Murphy

doi:10.1016/j.euo.2024.11.006

Baseline Nodal Status on ⁶⁸Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Intermediate- to High-risk Prostate Cancer Is Prognostic for Treatment Failure: Follow-up of the proPSMA Trial

Eur Urol Oncol. 2024 Nov 28:S2588-9311(24)00251-7. doi: 10.1016/j.euo.2024.11.006. Online ahead of print.

Authors

Michael S Hofman¹, Veeru Kasivisvanathan², Emma Link³, James Buteau⁴, Matthew J Roberts⁵, Roslyn J Francis⁶, Colin Tang⁷, Ian Vela⁸, Paul Thomas⁹, Natalie Rutherford¹⁰, Jarad M Martin¹¹, Mark Frydenberg¹², Ramdave Shakher¹³, Lih-Ming Wong¹⁴, Kim Taubman¹⁵, Sze Ting Lee¹⁶, Edward Hsiao¹⁷, Paul Roach¹⁷, Michelle Nottage¹⁸, Ian Kirkwood¹⁹, Dickon Hayne²⁰, Amir Iravani⁴, Scott Williams²¹, Jonathan O'Brien²², Nathan Lawrentschuk²³, Declan G Murphy²⁴

Affiliations

¹ Molecular Imaging and Therapeutic Nuclear Medicine, Cancer Imaging, Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia. Electronic address: [email protected].
² Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; Division of Surgery and Interventional Science, University College London, London, UK. Electronic address: [email protected].
³ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia; Centre for Biostatistics and Clinical Trials (BaCT), Peter MacCallum Cancer Centre, Melbourne, Australia.
⁴ Molecular Imaging and Therapeutic Nuclear Medicine, Cancer Imaging, Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.
⁵ Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
⁶ Department of Nuclear Medicine, Faculty of Health and Medical Sciences, Sir Charles Gairdner Hospital and University of Western Australia, Perth, Australia.
⁷ Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Australia.
⁸ Department of Urology, Princess Alexandra Hospital, Australian Prostate Cancer Research Center - Queensland, Queensland University of Technology, Translational Research Institute, Brisbane, Australia.
⁹ Department of Nuclear Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
¹⁰ Department of Nuclear Medicine, Hunter New England Health, Newcastle, Australia.
¹¹ School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
¹² Department of Surgery, FMNHS, Monash University and Cabrini Institute, Cabrini Health, Melbourne, Australia.
¹³ Monash Health Imaging, Monash Health, Melbourne, Australia.
¹⁴ Department of Urology and Surgery, St Vincent's Health Melbourne, University of Melbourne, Melbourne, Australia.
¹⁵ Department of Medical Imaging, PET/CT and St Vincent's Private Radiology, St Vincent's Health, Melbourne, Australia.
¹⁶ Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Australia.
¹⁷ Department of Nuclear Medicine and PET, Royal North Shore Hospital, University of Sydney, Sydney, Australia.
¹⁸ Clinical and Research Imaging Centre, SAHMRI, Adelaide, Australia; Dr Jones and Partners Medical Imaging, Adelaide, Australia.
¹⁹ Department of Nuclear Medicine and PET, Royal Adelaide Hospital, Adelaide, Australia; Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia.
²⁰ UWA Medical School, University of Western Australia, Perth, WA, Australia.
²¹ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Australian and New Zealand Urogenital and Prostate Cancer Trials (ANZUP), Australia.
²² Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia.
²³ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia; Department of Surgery, Royal Melbourne Hospital, Melbourne, Australia.
²⁴ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia.

PMID: 39613566
DOI: 10.1016/j.euo.2024.11.006

Abstract

Background and objective: There is uncertainty regarding the clinical significance of ⁶⁸Ga-PSMA-11 positron emission tomography (PET) computed tomography (CT) findings in men with prostate cancer. In this prespecified objective of the proPSMA study, we report the prognostic value of PET-defined nodal involvement.

Methods: Men with intermediate- to high-risk prostate cancer (grade group 3-5, prostate-specific antigen [PSA] ≥20 ng/ml, or clinical stage ≥T3) underwent ⁶⁸Ga-PSMA-11 PET-CT or CT and bone scanning as first- or second-line imaging. Patients without distant metastatic disease (miM0) in either arm were stratified by prostate-specific membrane antigen (PSMA) PET-CT negative (miN0) or positive (miN1) regional nodal status and followed for up to 54 mo. Treatment failure was defined as biochemical failure, commencement of salvage therapy, or development of distant metastatic disease. Freedom from treatment failure (FFTF) was plotted on Kaplan-Meier curves for patients with miN0 and miN1 cancer based on PET-CT and CT/bone scan classification. Cox proportional hazards were used to derive a hazard ratio (HR) for FFTF.

Key findings and limitations: A total of 302 patients were randomised at ten sites. Of them, 294 underwent a PSMA PET-CT. In all, 251 patients with miM0 disease were included in this analysis. Patients were treated with curative-intent surgery or radiotherapy ± androgen deprivation. FFTF was greater in the PSMA PET-CT miN0M0 group than in the miN1M0 group (HR 2.1 [95% confidence interval {CI} 1.2-3.7], p = 0.01). CT/bone scan-defined N0M0 versus N1M0 was not prognostic for FFTF (HR 0.6, 95% CI 0.1-2.4, p = 0.45). In a multivariate analysis, PSMA PET-CT miN1M0 versus miN0M0 remained prognostic after adjusting for PSA, Gleason grade group, and age (HR 2.0, 95% CI 1.10-3.64, p = 0.007).

Conclusions and clinical implications: PSMA PET-CT regional nodal staging at baseline is prognostic for medium-term oncological outcomes, identifying patients at a higher risk of treatment failure.

Patient summary: Men with prostate cancer who have cancer in their nearby lymph nodes observed on a prostate-specific membrane antigen positron emission tomography scan have poorer outcomes than men who have no nearby lymph node involvement.

Keywords: Positron emission tomography; Prostate cancer; Prostate-specific membrane antigen; Staging; Theranostics.