A scan that makes cancer cells glow halved the need for prostate biopsies in a 660-patient trial

Half the biopsies. No missed cancers. Those are the headline numbers from PRIMARY2, a phase III clinical trial that tested whether a PSMA PET/CT scan could safely reduce the number of prostate biopsies performed on men with inconclusive or normal MRI results. The findings, presented at the European Association of Urology Congress in London, suggest the answer is yes.

The biopsy burden

Men with suspected prostate cancer typically undergo an MRI scan first. If the MRI shows something suspicious, they get a biopsy - a procedure that takes small tissue samples from the prostate and examines them for cancer cells. It is routine but invasive, sometimes uncomfortable, occasionally anxiety-inducing, and associated with side effects including infection and bleeding.

The problem intensifies for men whose MRI results are normal or ambiguous. These patients, particularly those at higher risk due to factors like strong family history, often proceed to biopsy anyway - because the MRI may have missed something. Many of these biopsies find nothing, or find cancers so low-risk they would never cause harm. The biopsies were unnecessary, but there was no reliable way to know that in advance.

Making cancer cells light up

PSMA PET/CT (prostate-specific membrane antigen positron emission tomography/computed tomography) works by injecting a molecule that binds preferentially to prostate cancer cells. More aggressive cancer cells express more PSMA on their surfaces, so they bind more of the tracer molecule and appear as bright spots on the scan. Low-risk cancers and healthy tissue glow less or not at all.

The PRIMARY2 trial recruited 660 men at higher risk of prostate cancer who had received normal results on their MRI. They were randomly assigned to either a standard biopsy or a PSMA PET/CT scan. Men with positive PSMA results received a targeted biopsy; those with negative results were spared the procedure entirely.

The results

The PSMA PET/CT approach halved the number of biopsies performed. Men with negative scans did not undergo biopsy and did not have any clinically significant cancers detected through the follow-up period. Men with positive scans received biopsies targeted to the suspicious areas identified by the scan, improving accuracy and potentially reducing complications.

Critically, the scan did not miss harmful cancers. The reduction in biopsies came entirely from eliminating unnecessary procedures - either in men without cancer or in men whose cancers were so low-risk they would likely never require treatment.

This addresses one of prostate cancer's central dilemmas: overdiagnosis. Many prostate cancers grow so slowly they will never threaten a man's life. But once diagnosed, the psychological burden and pressure to treat are substantial. Avoiding that diagnosis in the first place, when the cancer is genuinely harmless, may be the best outcome for the patient.

Availability and cost

PSMA PET/CT scanning is widely available in Australia, where the trial was conducted, and is becoming increasingly accessible in Europe and the United Kingdom. However, cost and availability remain significant barriers to widespread adoption. The scan requires specialized equipment, radioactive tracers, and nuclear medicine expertise that are not available at every hospital.

Whether the approach saves money overall depends on the cost-benefit calculation: fewer biopsies and fewer low-risk cancer diagnoses on one side, the cost of the scan itself on the other. Health economic analyses will likely follow the clinical data.

What remains to be seen

These are the first results from PRIMARY2. The trial will follow its 660 participants for two years, which will provide important data on whether any cancers were missed by the initial scan and whether the approach holds up over time. The trial was led from Peter MacCallum Cancer Centre in Melbourne and St Vincent's Hospital in Sydney - both institutions with deep expertise in PSMA imaging.

The study population was specifically men with normal or low-suspicion MRI results (PI-RADS 2 or 3), not men with highly suspicious scans. The approach is designed to complement MRI, not replace it - a second layer of evaluation for men who fall into the diagnostic grey zone.

If the two-year follow-up confirms these early findings, PSMA PET/CT could fundamentally change the diagnostic pathway for prostate cancer, sparing thousands of men annually from unnecessary biopsies while maintaining cancer detection for those who need it. The scan makes the dangerous cancers visible and lets the harmless ones stay invisible. For prostate cancer diagnosis, that distinction may be exactly what has been missing.