Presurgical 68Ga-PSMA-11 Positron Emission Tomography for Biochemical Recurrence Risk Assessment: A Follow-up Analysis of a Multicenter Prospective Phase 3 Imaging Trial

Loïc Djaïleb; Wesley R Armstrong; Daniel Thompson; Andrei Gafita; Andrea Farolfi; Abhejit Rajagopal; Tristan R Grogan; Kathleen Nguyen; Matthias R Benz; Masatoshi Hotta; Francesco Barbato; Francesco Ceci; Sarah M Schwarzenböck; Marcus Unterrainer; Helle D Zacho; Roxanna Juarez; Matthew Cooperberg; Peter Carroll; Samuel Washington; Robert E Reiter; Matthias Eiber; Ken Herrmann; Wolfgang P Fendler; Johannes Czernin; Thomas A Hope; Jeremie Calais

doi:10.1016/j.eururo.2023.06.022

Presurgical ⁶⁸Ga-PSMA-11 Positron Emission Tomography for Biochemical Recurrence Risk Assessment: A Follow-up Analysis of a Multicenter Prospective Phase 3 Imaging Trial

Eur Urol. 2023 Dec;84(6):588-596. doi: 10.1016/j.eururo.2023.06.022. Epub 2023 Jul 21.

Authors

Loïc Djaïleb¹, Wesley R Armstrong², Daniel Thompson³, Andrei Gafita⁴, Andrea Farolfi⁵, Abhejit Rajagopal³, Tristan R Grogan⁶, Kathleen Nguyen⁴, Matthias R Benz⁷, Masatoshi Hotta⁴, Francesco Barbato⁸, Francesco Ceci⁹, Sarah M Schwarzenböck¹⁰, Marcus Unterrainer¹¹, Helle D Zacho¹², Roxanna Juarez³, Matthew Cooperberg¹³, Peter Carroll¹⁴, Samuel Washington¹³, Robert E Reiter¹⁵, Matthias Eiber⁸, Ken Herrmann¹⁶, Wolfgang P Fendler¹⁶, Johannes Czernin¹⁷, Thomas A Hope¹⁸, Jeremie Calais¹⁷

Affiliations

¹ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: ldjaileb@chu-grenoble.fr.
² Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; ULCA-Caltech Medical Scientist Training Program, David Geffen School of Medicine, Los Angeles, CA, USA.
³ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
⁴ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁶ Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, CA, USA.
⁷ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Department of Radiological Sciences, University of California Los Angeles, Los Angeles, CA, USA.
⁸ Department of Nuclear Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany.
⁹ Division of Nuclear Medicine, IEO European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milan, Milan, Italy.
¹⁰ Department of Nuclear Medicine, University Medical Centre, Rostock, Germany.
¹¹ Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
¹² Department of Nuclear Medicine and Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark.
¹³ Department of Urology, University of California San Francisco, San Francisco, CA, USA.
¹⁴ Department of Urology, University of California San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
¹⁵ Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.
¹⁶ Department of Nuclear Medicine, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.
¹⁷ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Institute of Urologic Oncology, University of California Los Angeles, Los Angeles, CA, USA.
¹⁸ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.

PMID: 37482512
DOI: 10.1016/j.eururo.2023.06.022

Abstract

Background: In the initial staging of patients with high-risk prostate cancer (PCa), prostate-specific membrane antigen positron emission tomography (PSMA-PET) has been established as a front-line imaging modality. The increasing number of PSMA-PET scans performed in the primary staging setting might be associated with decreases in biochemical recurrence (BCR)-free survival (BCR-FS).

Objective: To assess the added prognostic value of presurgical PSMA-PET for BCR-FS compared with the presurgical Cancer of the Prostate Risk Assessment (CAPRA) and postsurgical CAPRA-Surgery (CAPRA-S) scores in patients with intermediate- to high-risk PCa treated with radical prostatectomy (RP) and pelvic lymph node dissection.

Design, setting, and participants: This is a follow-up study of the surgical cohort evaluated in the multicenter prospective phase 3 imaging trial (n = 277; NCT03368547, NCT02611882, and NCT02919111).

Outcome measurements and statistical analysis: Each ⁶⁸Ga-PSMA-11-PET scan was read by three blinded independent readers. PSMA-PET prostate uptake (low vs high), PSMA-PET extraprostatic disease (N1/M1), and CAPRA and CAPRA-S scores were used to assess the risk of BCR. Patients were followed after RP by local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level increasing to ≥0.2 ng/ml after RP or initiation of PCa-specific secondary treatment (>6 mo after surgery). Univariate and multivariable Cox models, and c-statistic index were performed to assess the prognostic value of PSMA-PET and for a comparison with the CAPRA and CAPRA-S scores.

Results and limitations: From December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median follow-up after surgery was 32.4 (interquartile range 23.3-42.9) mo. Of 240 BCR events, 91 (38%) were observed. PSMA-PET N1/M1 was found in 41/240 (17%) patients. PSMA-PET prostate uptake, PSMA-PET N1/M1, and CAPRA and CAPRA-S scores were significant univariate predictors of BCR. The addition of PSMA-PET N1/M1 status to the presurgical CAPRA score improved the risk assessment for BCR significantly in comparison with the presurgical CAPRA score alone (c-statistic 0.70 [0.64-0.75] vs 0.63 [0.57-0.69]; p < 0.001). The C-index of the postsurgical model utilizing the postsurgical CAPRA-S score alone was not significantly different from the presurgical model combining the presurgical CAPRA score and PSMA-PET N1/M1 status (p = 0.19).

Conclusions: Presurgical PSMA-PET was a strong prognostic biomarker improving BCR-FS risk assessment. Its implementation in the presurgical risk assessment with the CAPRA score improved the performance and reduced the difference with the reference standard (postsurgical CAPRA-S score).

Patient summary: The use prostate-specific membrane antigen positron emission tomography improved the assessment of biochemical recurrence risk in patients with intermediate- and high-risk prostate cancer who were treated with radical prostatectomy and pelvic lymph node dissection.

Keywords: Cancer of the Prostate Risk Assessment score; Cancer of the Prostate Risk Assessment—Surgery score; Pelvic lymph node dissection; Prognostic value; Prostate-specific membrane antigen positron emission tomography; Radical prostatectomy.

Publication types

Clinical Trial, Phase III
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Follow-Up Studies
Gallium Radioisotopes
Humans
Male
Positron Emission Tomography Computed Tomography / methods
Positron-Emission Tomography
Prospective Studies
Prostatectomy / methods
Prostatic Neoplasms* / diagnostic imaging
Prostatic Neoplasms* / surgery

Presurgical ⁶⁸Ga-PSMA-11 Positron Emission Tomography for Biochemical Recurrence Risk Assessment: A Follow-up Analysis of a Multicenter Prospective Phase 3 Imaging Trial

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