Prostate-specific membrane antigen (PSMA)-PET is already a standard imaging tool in prostate cancer treatment. Now, a phase 3 clinical trial suggests the imaging modality may also help determine which men can safely avoid prostate biopsy during the diagnostic workup.

The study, published this month in The Lancet Oncology, found that using gallium-68 PSMA-11-PET-CT in men at high clinical risk for significant prostate cancer but with non-suspicious or equivocal MRI findings allowed nearly half of patients to avoid a biopsy, while achieving a statistically noninferior detection rate for clinically significant prostate cancer. PSMA-PET also reduced the diagnosis of clinically insignificant cancers.

“This is a landmark study and one of the more encouraging developments in prostate cancer diagnosis,” said Wayne Brisbane, MD, of the University of California, Los Angeles, who studies image-guided diagnosis and treatment of prostate cancer, but was not involved in the new work. “It’s an elegant use of imaging to spare men a procedure many of them never needed.”

In an accompanying editorial, Daniel Spratt, MD, called the findings “promising” but cautioned that they “do not yet prove” a negative PSMA-PET can safely rule out clinically significant disease. Spratt, of Case Comprehensive Cancer Center in Cleveland, argued that follow-up of patients who avoided biopsy “should be viewed not as a secondary embellishment but as central to whether the strategy is safe.”

The noninferiority study was conducted at seven hospitals in Australia. Researchers randomly assigned 660 men with a median PSA of 5.2 ng/mL to receive either systematic transperineal prostate biopsy (the control group) or [⁶⁸Ga]Ga-PSMA-11 PET-CT (the experimental group). The scans were interpreted based on the five-point PRIMARY score by independent reviewers masked to MRI and clinical information. Scores of 1 or 2 were considered negative, and scores of 3, 4, or 5 were considered positive.

Men with a positive result underwent targeted transperineal prostate biopsy based on PSMA-PET-CT and MRI targets within 3 months after random assignment. Those with negative scans avoided biopsy and remained under PSA surveillance, with 2-year follow-up ongoing.

Overall, 49% of patients assigned to PSMA-PET-CT avoided biopsy. Clinically significant prostate cancer was detected in 12% of the experimental group (39 of 331 patients) and nearly 16% of the control group (51 of 329), meeting the prespecified 10% noninferiority margin (difference, -3.7%; 95% CI, -8.9% to 1.5%; P = .0093). Clinically insignificant cancer was diagnosed less frequently in the PSMA-PET-CT group (14% vs 32%; P < .0001).

Among all randomized patients, no cancer was identified in 42% of men in the control arm and 22% in the experimental arm, suggesting that the PSMA-PET strategy directed biopsy toward men more likely to harbor cancer.

Brisbane described PSMA-PET-CT as “a smart filter” that allowed many men to skip biopsy and “roughly halved the diagnosis of slow-growing, harmless cancers that often lead to unnecessary treatment” while maintaining a noninferior detection rate for clinically significant disease.

But he said the scan wasn’t ready for prime time “just yet,” with more mature data needed “to confirm that the men who skipped biopsy stay safe over time.” In addition, the “trial used one specific tracer (Ga-PSMA-11) at expert centers in a single country, and many practices now use other PSMA tracers — we shouldn’t assume the results transfer automatically.”

Brisbane concluded that “if these findings hold up with other PSMA tracers and longer follow-up, this approach could reshape the front end of prostate cancer diagnosis and spare a lot of men a biopsy they never needed.”

The study had no commercial funding. Brisbane reported being a consultant for Blue Earth Diagnostics and Telix, both of which make PSMA tracers. Spratt reported receiving personal fees from several drugmakers.