Researchers at UCLA Health’s Jonsson Comprehensive Cancer Center have made a significant breakthrough in the understanding of high-risk nonmetastatic hormone-sensitive prostate cancer, challenging conventional perspectives on how the disease is staged and treated. Their study, published in JAMA Network Open, revealed that nearly half of prostate cancer patients previously categorized as nonmetastatic using standard imaging techniques actually exhibit metastatic disease when evaluated using advanced prostate-specific membrane antigen–positron emission tomography (PSMA-PET) imaging. This discovery underscores the limitations of traditional imaging methods and highlights the need for a paradigm shift in prostate cancer staging and treatment.
Prostate cancer is one of the most common malignancies affecting men worldwide, with early detection and accurate staging being pivotal in determining the best course of treatment. The current staging system often relies on conventional imaging techniques such as CT scans, MRI, and bone scans, which primarily focus on anatomical structures to assess the spread of the disease. However, these imaging methods are not without flaws and may fail to capture the true extent of cancer progression in a significant subset of patients.
The UCLA-led study demonstrates the transformative role of PSMA-PET imaging in addressing these shortcomings. PSMA-PET works by using radiotracers that bind specifically to prostate cancer cells, enabling precise visualization of their presence and activity throughout the body. Unlike traditional imaging, PSMA-PET provides a combination of anatomical and functional insights, significantly enhancing the accuracy of disease staging.
Dr. Jeremie Calais, the study’s senior author and director of the Ahmanson Translational Theranostics Division’s clinical research program, emphasized the clinical implications of these findings. “Our study demonstrates the critical role of PSMA-PET in accurately staging prostate cancer, which can significantly impact treatment decisions and outcomes,” he stated.
To assess the utility of PSMA-PET compared to conventional imaging, the researchers conducted a retrospective study involving 182 patients with high-risk recurrent prostate cancer who were previously classified as nonmetastatic using traditional techniques. These patients were part of the EMBARK trial, which examined the benefits of adding enzalutamide, a form of hormone therapy, to androgen deprivation therapy. The EMBARK trial relied on conventional imaging for patient selection, which may have underestimated the spread of disease in some cases.
The findings were eye-opening. PSMA-PET identified metastatic disease in 46% of patients who had no apparent metastases on standard imaging. Moreover, 24% of the participants showed five or more metastatic lesions that had been entirely missed by conventional imaging methods. This stark contrast underscores the limitations of standard imaging in capturing the full extent of prostate cancer spread, particularly in high-risk cases.
Dr. Adrien Holzgreve, the first author of the study and a visiting assistant professor at UCLA, noted the significant implications of these results. “We anticipated that PSMA-PET would detect more suspicious findings compared to conventional imaging,” he said. “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.”
These findings call into question the conclusions of previous studies like the EMBARK trial, which relied on less sensitive imaging techniques. Incorporating PSMA-PET into clinical practice and clinical trials could lead to more accurate patient selection and improve outcomes by ensuring that treatment strategies are tailored to the true extent of disease progression.
One of the most exciting aspects of PSMA-PET is its potential to open up new treatment avenues for prostate cancer patients. By providing a more accurate picture of metastases, clinicians can consider targeted radiotherapy or other aggressive interventions that might have been deemed unsuitable based on traditional imaging findings. These curative treatment options could significantly improve the prognosis for patients who were previously thought to have localized disease.
While the benefits of PSMA-PET are clear, researchers caution that further studies are needed to fully understand its impact on long-term patient outcomes. Dr. Calais noted the importance of gathering more data to validate the superiority of PSMA-PET in guiding treatment decisions. “We have good rationales to assume that it is helpful to primarily rely on PSMA-PET findings,” he said. “But more high-quality prospective data would be needed to claim superiority of PSMA-PET for treatment guidance in terms of patient outcome.”
The UCLA team is actively pursuing additional research to address these questions. This includes analyzing follow-up data from four UCLA clinical trials to examine how PSMA-PET findings influenced treatment decisions and patient outcomes. The researchers are also participating in an international consortium involving more than 6,000 patients, which aims to assess the prognostic value of PSMA-PET and its potential to redefine prostate cancer care on a global scale.
The study also raises important questions about how new imaging technologies should be integrated into standard care practices. Despite the proven benefits of PSMA-PET, its adoption in routine clinical settings faces challenges, including cost, availability, and the need for specialized expertise. Nevertheless, as the body of evidence supporting its use continues to grow, there is a compelling case for making PSMA-PET more widely accessible to patients with high-risk prostate cancer.
From a broader perspective, this research reflects a larger trend in oncology: the shift toward personalized medicine. Advanced imaging techniques like PSMA-PET exemplify the power of combining biological insights with cutting-edge technology to tailor treatment strategies to individual patients’ needs. By providing a clearer picture of disease progression, PSMA-PET enables clinicians to make more informed decisions and potentially improve outcomes for patients with challenging diagnoses.
The UCLA study represents a pivotal step in this direction, shedding light on the hidden complexities of high-risk prostate cancer and paving the way for more accurate staging and treatment. With ongoing research and collaboration, it is likely that PSMA-PET will become a cornerstone of prostate cancer care, helping to bridge the gap between traditional imaging methods and the demands of modern oncology. As we continue to refine and expand our understanding of prostate cancer, advanced imaging technologies like PSMA-PET will undoubtedly play a central role in shaping the future of cancer diagnosis and treatment.
Reference: JAMA Network Open (2025). DOI: 10.1001/jamanetworkopen.2024.52971