Advanced imaging technology detects undiagnosed metastases in high-risk prostate cancer

A new study led by UCLA Health Jonsson Comprehensive Cancer Center researchers found that many high-risk cases of non-metastatic hormone-sensitive prostate cancer may be more advanced than previously thought.

The study, published in JAMA Network Openfound that nearly half of high-risk prostate cancer patients previously classified as nonmetastatic by conventional imaging actually have metastatic disease when evaluated with advanced prostate-specific antigen-positron emission tomography (PSMA-PET), which suggests that traditional imaging may underestimate how far the cancer has spread in many cases.

“Our study demonstrates the critical role of PSMA-PET in the accurate staging of prostate cancer, which can significantly influence treatment decisions and outcomes,” said senior study author Dr. Jeremie Calais, clinical research program director of the Ahmanson Translational Theranostics Division and partner. professor in the department of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA.

This advanced imaging technology is playing a critical role in redefining how prostate cancer is staged. PSMA-PET imaging uses tiny amounts of radioactive “tracers,” called radiotracers, that bind to prostate cancer cells, making them visible on PET scans. Unlike conventional imaging, which only provides anatomical details, PSMA-PET offers functional imaging that reveals the biological activity of cancer, which can significantly improve the accuracy of disease staging.

The clinical adoption of PSMA-PET has changed the landscape of prostate cancer imaging, yet treatment decisions are often based on clinical trials that did not incorporate this advanced imaging technique for patient selection.

To better understand the advantages of PSMA-PET over conventional imaging, researchers conducted a retrospective, cross-sectional study using data from 182 patients with high-risk, recurrent prostate cancers who were thought to have disease confined to the prostate and were eligible for the EMBARK trial.

This clinical trial previously showed that adding enzalutamide, a type of hormone therapy, to androgen deprivation therapy significantly improves metastasis-free survival. However, the trial relied on conventional imaging to classify patients, which researchers believe may have underestimated the extent of disease in some cases.

In the patient cohort, the researchers found that PSMA-PET detected cancer metastases in 46% of patients, even though traditional imaging had shown no evidence of cancer spread. Based on PSMA-PET, 24% of patients even showed 5 or more lesions missed by conventional imaging.

We expected that PSMA-PET would detect more suspicious findings compared with conventional imaging. However, it was informative to reveal such a high number of metastatic findings in a well-defined cohort of patients that resembled the EMBARK trial population that was supposed to include only those without metastases.”

Dr. Adrien Holzgreve, visiting assistant professor at the David Geffen School of Medicine and first author of the study

These results challenge the interpretation of previous studies, such as the EMBARK trial, and support the inclusion of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer in future large industry-sponsored clinical trials. It also highlights the need to reassess treatment strategies and opens the door to potential treatment options for some patients, such as targeted radiation therapy, while raising important questions about the integration of new imaging technologies into standard care.

While the current findings highlight the potential of PSMA-PET, researchers continue to explore its broader applications through additional studies. More research is needed to understand its impact on long-term patient outcomes and how it can better guide treatment, Calais noted.

“We have good reason to believe that it is useful to rely primarily on PSMA-PET findings,” said Holzgreve. “But more prospective high-quality data will be needed to claim the superiority of PSMA-PET for treatment guidance in terms of patient outcome. However, we are confident that PSMA-PET will continue to advance prostate cancer staging and guide personalized treatments.”

Ongoing efforts at UCLA include analyzing follow-up data from four UCLA trials to assess how PSMA-PET findings influenced treatment decisions and patient outcomes. Additionally, as part of an international consortium studying over 6,000 patients, the team is investigating the prognostic value of PSMA-PET.