A study led by UCLA Health Jonsson Comprehensive Cancer Center, published in JAMA Network Open, shows that nearly half of the patients classified as nonmetastatic by conventional imaging were found to have metastatic disease when evaluated with advanced PSMA-PET (prostate-specific membrane antigen–positron emission tomography) imaging. This highlights the limitations of traditional imaging in accurately assessing cancer spread.
PSMA-PET/CT images of an 85-year-old patient with hormone-sensitive prostate cancer. The whole-body PET image (see right) shows two areas of focally increased PSMA tracer uptake in the pelvis, suspicious for metastatic disease (see arrows). While CT images show unremarkable pelvic lymph nodes (see bottom left, lymph node size: 1.1 cm × 0.7 cm), intense focal tracer uptake on PSMA-PET (see top left, SUVmax 7.1) indicates the presence of lymph node metastases (see arrows). Image Credit: Dr. Adrien Holzgreve
The study revealed that high-risk nonmetastatic hormone-sensitive prostate cancer may often be more advanced than previously believed.
Our study demonstrates the critical role of PSMA-PET in accurately staging prostate cancer, which can significantly impact treatment decisions and outcomes.
Dr. Jeremie Calais, Study Senior Author and Associate Professor, David Geffen School of Medicine, University of California Los Angeles
Calais is also the Study Director of the Ahmanson Translational Theranostics Division’s clinical research program.
The way prostate cancer is staged is being redefined in large part by this cutting-edge imaging technology. Tiny quantities of radioactive “tracers,” or radiotracers, are used in PSMA-PET imaging.
These tracers attach to prostate cancer cells and make them visible on PET scans. PSMA-PET offers functional imaging, which shows the biological activity of the cancer, in contrast to conventional imaging, which only provides anatomical details. This can greatly increase the precision of disease staging.
Although PSMA-PET's clinical adoption has transformed prostate cancer imaging, clinical trials that did not use this cutting-edge imaging method for patient selection are frequently used to inform treatment choices.
Researchers used data from 182 patients with high-risk recurrent prostate cancers who were considered to have prostate-limited disease and were eligible for the EMBARK trial to perform a post hoc, retrospective cross-sectional study to better understand the benefits of PSMA-PET over traditional imaging.
This clinical trial previously showed that metastasis-free survival is significantly increased when androgen deprivation therapy is combined with enzalutamide, a type of hormone therapy. However, the trial classified patients using traditional imaging, which may have understated the severity of the disease in certain instances, according to researchers.
Even though traditional imaging had indicated no evidence of cancer spread, the researchers discovered that PSMA-PET identified cancer metastases in 46% of the patient cohort. According to PSMA-PET, five or more lesions that were missed by traditional imaging were even visible in 24% of the patients.
We anticipated that PSMA-PET would detect more suspicious findings compared to conventional imaging. However, it was informative to uncover such a high number of metastatic findings in a well-defined cohort of patients resembling the EMBARK trial population that was supposed to only include those without metastases.
Dr. Adrien Holzgreve, Visiting Assistant Professor and Study First Author, David Geffen School of Medicine, University of California Los Angeles
These findings challenge the conclusions of previous studies, such as the EMBARK trial, and advocate for the incorporation of PSMA-PET in patient selection for future major industry-sponsored clinical trials and interventions in prostate cancer.
Along with bringing up significant issues regarding the incorporation of new imaging technologies into routine care, it also emphasizes the necessity of reevaluating treatment approaches and provides some patients with potentially curative options, such as targeted radiotherapy.
Even though the present results highlight the potential of PSMA-PET, more research is being done to examine its wider uses. Calais pointed out that more study is required to fully comprehend its influence on long-term patient outcomes and how it can most effectively direct therapy.
We have good rationales to assume that it is helpful to primarily rely on PSMA-PET findings. But more high-quality prospective data would be needed to claim the superiority of PSMA-PET for treatment guidance in terms of patient outcome. However, we are confident PSMA-PET will continue to advance prostate cancer staging and guide personalized therapies.
Dr. Adrien Holzgreve, Visiting Assistant Professor and Study First Author, David Geffen School of Medicine, University of California Los Angeles
UCLA researchers are currently analyzing follow-up data from four UCLA trials to evaluate how PSMA-PET findings impacted treatment decisions and patient outcomes. As part of an international consortium studying over 6,000 patients, the team is exploring the prognostic significance of PSMA-PET.
Journal Reference:
Holzgreve, A., et al. (2025) PSMA-PET/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging. JAMA Network Open. doi.org/10.1001/jamanetworkopen.2024.52971.