Conventional imaging may understage prostate cancer, new data suggest

Prostate-specific membrane antigen (PSMA)-PET/CT was able to detect metastases in 46% of patients who were classified with high-risk non-metastatic hormone-sensitive prostate cancer (nmHSPC) on conventional imaging, suggesting that conventional scans may routinely understage patients with prostate cancer.¹

Distant metastasis was detected in 46% of patients overall.

Data from the post-hoc, retrospective study were published in JAMA Network Open.

“Our study demonstrates the critical role of PSMA-PET in accurately staging prostate cancer, which can significantly impact treatment decisions and outcomes,” said senior author Jeremie Calais, MD, PhD, in a news release on the findings.² Calais is the director of the Ahmanson Translational Theranostics Division’s clinical research program and associate professor at the department of molecular and medical pharmacology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA).

In total, the study included 182 patients who were enrolled in 4 prospective studies conducted from September 2016 to September 2021. All patients met the eligibility criteria for the EMBARK trial (NCT02319837) and experienced recurrence of prostate cancer following treatment with radical prostatectomy (n = 91), definitive radiotherapy (n = 39), or salvage radiotherapy (n = 52). The median age of participants at PET/CT scan was 69 years (IQR, 64-73 years).

Data showed that PSMA-PET scans were positive in 84% of patients overall. This included in 80% of patients following radical prostatectomy, 92% of patients following definitive radiotherapy, and 84% of patients following radical prostatectomy and salvage radiotherapy.

Further, distant metastasis was detected in 46% of patients overall. 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).

Pelvic nodal disease was found by PSMA-PET in 29% of patients overall, including in 40% of patients following radical prostatectomy, 13% of patients following definitive radiotherapy, and 23% of patients following radical prostatectomy and salvage radiotherapy.

PSMA-PET scans also found polymetastatic disease (5 or more lesions) in 24% of patients overall. This consisted of 19% of patients after radical prostatectomy, 36% of patients after definitive radiotherapy, and 23% of patients after radical prostatectomy and salvage radiotherapy.

“We anticipated that PSMA-PET would detect more suspicious findings compared to conventional imaging,” explained lead author Adrien Holzgreve, MD, MHA, a visiting assistant professor at the David Geffen School of Medicine at UCLA, in the news release.² “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.”

According to the authors, these findings challenge the interpretation of previous studies such as EMBARK, which relied on conventional imaging in their assessments, and support the use of PSMA-PET. However, the authors also note that prospective data is still warranted to determine the utility of PSMA-PET for patient selection in clinical practice and trial interventions.

The authors concluded, “PSMA-PET provides novel additional risk stratification for patients with high-risk nmHSPC without distant metastasis based on conventional imaging. Further studies are needed to assess its potential independent prognostic value and its use for treatment guidance. Integration of PSMA-PET in major industry-sponsored clinical trials for secondary end points analyses is warranted.”

References

1. Holzgreve A, Armstrong WR, Clark KJ, et al. PSMA-PET/CT findings in patients with high-risk biochemically recurrent prostate cancer with no metastatic disease by conventional imaging. JAMA Netw Open. 2025;8(1):e2452971. doi:10.1001/jamanetworkopen.2024.52971

2. Advanced imaging uncovers hidden metastases in high-risk prostate cancer cases. News release. University of California, Los Angeles (UCLA), Health Sciences. January 2, 2025. Accessed January 3, 2025. https://www.newswise.com/articles/advanced-imaging-uncovers-hidden-metastases-in-high-risk-prostate-cancer-cases