The novel approach used in the phase 3 trial makes cancer cells glow, especially the more aggressive lesions.
A new imaging approach could significantly reduce the need for prostate biopsies while maintaining detection of clinically significant cancer, according to early results from the PRIMARY2 trial presented at the European Association of Urology Congress 2026.
Multiparametric MRI is currently recommended for men with suspected significant prostate cancer (sPCa), but those with PI-RADS 2 or 3 lesions often still proceed to biopsy due to ongoing clinical concern. These patients have a relatively low likelihood of sPCa and a higher chance of being diagnosed with insignificant PCa.
The trial, sponsored by the Peter MacCallum Cancer Centre and co-led with St Vincent’s Hospital, Sydney, investigated whether adding prostate-specific membrane antigen (PSMA) PET/CT imaging before biopsy could reduce the need for biopsy without compromising detection efficacy. The technique uses a radiotracer that binds to prostate cancer cells, causing more aggressive lesions to light up in imaging.
Between March 2022 and August 2025, 660 participants with a median age of 61 years and a median PSA of 5.2ng/mL were enrolled. Participants had PI-RADS 2 (51%) or PI-RADS 3 (49%) findings on MRI. In the control arm, where patients proceeded to standard biopsy, clinically significant prostate cancer was diagnosed in 16% (51/329).
In contrast, the PSMA PET/CT-guided approach allowed nearly half of patients (163/331) to avoid biopsy altogether. Despite this reduction, detection of sPCa remained comparable at 12% (39/331), meeting criteria for non-inferiority (difference –3.7%). At the same time, the PSMA-guided strategy substantially reduced the diagnosis of insignificant PCa, from 32% in the control group to 14%, a difference of -18%.
Biopsy avoidance was assessed at six months following randomisation. For patients who did require biopsy, PSMA PET/CT enabled more targeted sampling of suspicious areas, potentially improving diagnostic accuracy while reducing complications.
“PSMA PET/CT scanning makes prostate cancer cells light up in a remarkable way, particularly in more aggressive cancers,” Dr James Buteau, a nuclear medicine physician at Peter MacCallum Cancer Centre, told media.
“It’s rare to see such strong imaging that could be so powerful in the clinic. Incorporating this testing into clinical care could help to address the major challenge of prostate cancer overdiagnosis, which leads to at best unnecessary and at worst harmful treatment for cancers that would never cause any harm.”
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Prostate biopsy remains a routine, but invasive, procedure associated with discomfort, anxiety and potential side effects. By better distinguishing between aggressive and low-risk disease, PSMA PET/CT may help avoid unnecessary procedures and reduce overdiagnosis.
The study focused on individuals at higher risk of prostate cancer, including those with strong family histories, who would typically proceed to biopsy despite non-suspicious or inconclusive MRI findings. The results suggested that PSMA PET/CT could safely identify patients who either did not have cancer or had disease unlikely to cause harm, allowing them to avoid biopsy without missing clinically significant cases.
“PSMA PET/CT safely halved the number of biopsies, enabled targeted biopsies without compromising sPCa diagnosis and reduced the diagnosis of insignificant prostate cancer,” said Dr Buteau.
“PSMA PET/CT should be incorporated in the diagnostic pathway of patients with a PI-RADS 3 or high clinical suspicion PI-RADS 2 MRI.”
PSMA PET/CT is already widely available in Australia and is increasingly used in Europe and the UK, although cost and access remain barriers in some settings.
These initial trial results have not yet been peer-reviewed. Participants will be followed up for a further two years.
