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

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).

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.

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).

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.

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).

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).

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.

European urology. 2023 Jul 21 [Epub ahead of print]

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

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: ., 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., Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA., Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA., 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., Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, CA, USA., 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., Department of Nuclear Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany., Division of Nuclear Medicine, IEO European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milan, Milan, Italy., Department of Nuclear Medicine, University Medical Centre, Rostock, Germany., Department of Radiology, University Hospital, LMU Munich, Munich, Germany., Department of Nuclear Medicine and Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark., Department of Urology, University of California San Francisco, San Francisco, CA, USA., 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., 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., Department of Nuclear Medicine, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany., 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., 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.