Second PSMA PET Identifies Disease in More Than Half of Negative Cases

Biochemical recurrence of prostate cancer after prostatectomy or radiation can be difficult to localize when imaging is negative. Uncertain disease sites may delay salvage therapy and expose patients to ineffective treatment. Although prostate-specific membrane antigen (PSMA) positron emission tomography has improved detection, about 30% of patients still show no visible disease on an initial scan despite rising prostate-specific antigen levels. Investigators evaluated whether a second PSMA PET scan can uncover disease and guide treatment decisions.

Researchers from the University of Toronto and the Joint Department of Medical Imaging at Princess Margaret Cancer Centre assessed the clinical value of repeating imaging in men with suspected recurrence. The approach focused on PSMA PET and PSMA PET/CT performed after an initial negative result. The analysis, reported in the July issue of The Journal of Nuclear Medicine, examined whether new findings would prompt management changes.

The prospective multicenter registry study drew 210 patients from the Registry for Recurrent Prostate Cancer in Ontario whose first PSMA PET was negative. Investigators compared second-scan positivity, serum prostate-specific antigen (PSA), PSA doubling time, and subsequent management changes with baseline data. Disease distribution on repeat imaging was categorized as local recurrence, locoregional spread, oligometastatic involvement defined as fewer than five sites, or extensive metastatic disease defined as more than five sites.

A second PSMA PET scan identified disease in 56% of these patients, spanning local and distant sites. The new information led to management changes in nearly 50% of cases, with the highest impact seen in oligometastatic disease. Detection on repeat imaging was more likely in patients with higher PSA levels and a PSA doubling time under 12 months.

These findings support selective repeat PSMA imaging when biochemical relapse persists after a negative initial study. By clarifying disease extent, repeat PSMA PET can refine decisions on focal, systemic, or surveillance strategies in recurrent prostate cancer. The study was published in the July 2026 issue of The Journal of Nuclear Medicine.

"There is little information on the utility of repeating a PSMA PET after an initial negative scan. In our study, my colleagues and I sought to determine the benefit of a second PSMA PET scan, as well as to assess predictors for positive PSMA PET scans," said Ur Metser, BSc, MD, FRCPC, professor of radiology at the University of Toronto and head of the Division of Molecular Imaging at the Joint Department of Medical Imaging at Princess Margaret Cancer Centre in Toronto.

"The findings in this study further strengthen the pivotal role of PSMA PET in the management of men with recurrence of prostate cancer after first-line therapy. Understanding the extent of disease in patients who have initial negative PSMA PET scans provides valuable information for physicians as they create treatment plans," stated Metser.

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