Researchers have found that many cases of high-risk nonmetastatic hormone-sensitive prostate cancer may be more advanced than previously thought, according to a recent study published by Holzgreve et al in JAMA Network Open.
Background
Prostate-specific membrane antigen–positron-emission tomography (PSMA-PET) imaging uses small amounts of radiotracers that bind to prostate cancer cells, making them visible on PET scans. Unlike conventional imaging—which provides only anatomic details—PSMA-PET imaging offers functional imaging that reveals the cancer’s biological activity and can significantly improve the accuracy of disease staging.
The clinical adoption of PSMA-PET imaging has recently changed the landscape of prostate cancer imaging, yet treatment decisions often rely on clinical trials that did not incorporate this advanced imaging technique for patient selection.
Study Methods and Results
In the study, the researchers sought to better understand the advantages of PSMA-PET imaging over conventional imaging. They conducted a post hoc, retrospective cross-sectional study using data from 182 patients with high-risk recurrent prostate cancers who were thought to have disease limited to the prostate and were eligible for the EMBARK trial.
Previous research demonstrated that adding the hormone therapy enzalutamide to androgen-deprivation therapy improved metastasis-free survival. However, the trial relied on conventional imaging to classify patients, which may have underestimated the disease's extent in some cases.
The researchers discovered that 46% of the patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging had metastatic disease when evaluated with advanced PSMA-PET imaging. Based on PSMA-PET imaging, 24% of the patients showed five or more lesions that had been missed by conventional imaging.
“We anticipated that PSMA-PET [imaging] 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,” detailed lead study author Adrien Holzgreve, MD, Visiting Assistant Professor at the UCLA David Geffen School of Medicine.
Conclusions
The findings challenged the interpretation of previous studies and supported the inclusion of PSMA-PET imaging for patient selection in clinical and trial interventions in prostate cancer in future, major industry-sponsored clinical trials. It also highlighted the need to reevaluate treatment strategies and provide opportunities to administer potentially curative treatments in some patients, including targeted radiotherapy, while raising important questions about integrating new imaging technologies into standard care. The researchers indicated that advanced imaging technology could play a critical role in redefining how prostate cancer is staged.
“Our study demonstrates the critical role of PSMA-PET [imaging] in accurately staging prostate cancer, which can significantly impact treatment decisions and outcomes,” emphasized senior study author Jeremie Calais, MD, PhD, Associate Professor in the Department of Molecular and Medical Pharmacology and Director of the clinical research program of the Ahmanson Translational Theranostics Division at the University of California, Los Angeles David Geffen School of Medicine.
Although the current findings underscored the potential of PSMA-PET imaging, the researchers are continuing 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 best guide therapy. Researchers are further analyzing follow-up data from four UCLA trials to assess how PSMA-PET imaging findings influenced treatment decisions and patient outcomes. As part of an international consortium studying over 6,000 patients, the researchers are investigating the prognostic value of PSMA-PET imaging.
“We have good rationales to assume that it is helpful to primarily rely on PSMA-PET [imaging] findings,” underscored Dr. Holzgreve. “[M]ore high-quality prospective data would be needed to claim superiority of PSMA-PET [imaging] for treatment-guidance in terms of patient outcomes. However, we are confident PSMA-PET [imaging] will continue to advance prostate cancer staging and guide personalized therapies,” he concluded.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
