A recent UCLA Health study indicates that prostate-specific membrane antigen positron emission tomography (PSMA-PET) imaging may reveal metastatic disease in individuals with high-risk nonmetastatic hormone-sensitive prostate cancer, which was not detected by conventional imaging methods. This suggests that current methods may be understaging the disease in many patients.
The study, published in JAMA Network Open, highlights the potential of PSMA-PET to improve the accuracy of prostate cancer staging. PSMA-PET uses radiotracers that bind to prostate cancer cells, making them visible on PET scans and providing functional imaging that reveals the biological activity of the cancer. This functional imaging can significantly enhance the accuracy of disease staging compared to traditional anatomical imaging.
Study Details and Findings
Researchers conducted a retrospective study using data from 182 subjects with high-risk recurrent prostate cancers who were eligible for the EMBARK trial, which used conventional imaging for classification. The EMBARK trial previously demonstrated that adding enzalutamide to androgen deprivation therapy improves metastasis-free survival. However, the UCLA study suggests that the trial's reliance on conventional imaging may have underestimated the disease's extent.
The UCLA study found that PSMA-PET detected cancer metastases in 46% of subjects, with 24% having five or more lesions missed by conventional imaging. Patients who underwent radical prostatectomy were significantly less likely to have distant metastasis compared with those in the other treatment arms. Specifically, M1 status was detected in 34% of patients in the radical prostatectomy arm vs 56% of patients in the definitive radiotherapy arm and 60% of patients in the radical prostatectomy and salvage radiotherapy arm (P = .005).
Implications for Treatment and Clinical Trials
The findings challenge earlier studies' interpretations and advocate for the inclusion of PSMA-PET in subject selection for future clinical trials. The study also suggests a need to reevaluate treatment strategies, potentially offering curative options like targeted radiotherapy for some individuals.
Dr. Jeremie Calais, associate professor at the David Geffen School of Medicine at UCLA, stated, "Our study demonstrates the critical role of PSMA-PET in accurately staging prostate cancer, which can significantly impact treatment decisions and outcomes."
Ongoing Research
Further research is ongoing to understand the impact of PSMA-PET on long-term outcomes and its role in guiding therapy. UCLA is analyzing follow-up data from four trials to evaluate treatment decisions and results influenced by PSMA-PET. In addition, an international consortium is studying the prognostic value of PSMA-PET in more than 6,000 subjects.
PSMA-PET Impact on Treatment Decisions
Another study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium indicated that PSMA staging was associated with higher rates of androgen deprivation therapy (ADT) and androgen receptor pathway inhibitor (ARPI) utilization compared to conventional imaging. The adjusted hazard ratio (aHR) was 1.26 (95% CI, 1.19-1.44) for ADT usage and 1.52 (95% CI, 1.33-1.78) for ARPI use. PSMA staging also correlated with lower prostatectomy usage (aHR: 0.69; 95% CI, 0.56-0.83).
