Home›Drug Pipeline› PSMA PET-CT Cuts Biopsies in High-Risk Prostate Cancer
PSMA PET-CT Cuts Biopsies in High-Risk Prostate CancerPET scan shows potential to skip prostate biopsy for some men
The Lancet. OncologyPublished September 18, 2026Study authors: Buteau James P, Moon Daniel, Fahey Michael T, Roberts Matthew J, Ayati Narjess, Papa Nathan, Murphy …PubMed ↗NCT05154162 ↗DOI ↗Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development
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Key Takeaway
PSMA PET-CT detected similar significant cancer and helped 49% of men avoid biopsy.
This multicentre phase 3 randomized controlled trial evaluated gallium-68-prostate-specific membrane antigen-11 (PSMA) PET-CT against systematic transperineal prostate biopsy in 660 biopsy-naive men with clinical suspicion of significant prostate cancer and equivocal (PI-RADS 3) or non-suspicious (PI-RADS 2) MRI but high clinical risk.
The primary outcome, detection of clinically significant prostate cancer, occurred in 12% of the PSMA PET-CT group versus 16% of the biopsy group (difference -3.7%, 95% CI -8.9% to 1.5%; p=0.0093 for non-inferiority). Among men randomized to PSMA PET-CT, 49% avoided biopsy within 6 months (95% CI 44% to 55%; p<0.0001).
Secondary outcomes included pain, haematuria, and haematospermia. Pain was reported by 21% in both groups. Haematuria occurred in 38% of the PSMA PET-CT group versus 43% of the biopsy group, and haematospermia in 48% versus 45%, respectively. Adverse events, serious adverse events, and discontinuations were not reported.
Limitations include that ethnicity data were not collected. The trial was funded by the Prostate Cancer Foundation, National Health and Medical Research Council, St Vincent's Curran Foundation, and Peter MacCallum Cancer Foundation.
These findings suggest that PSMA PET-CT has potential to improve the diagnostic pathway for patients with high clinical risk but non-suspicious or equivocal prostate MRI, though further research is needed to confirm clinical implementation.
How this fits prior evidence
This finding addresses a gap in the diagnostic pathway for high-risk prostate cancer. While prior coverage noted that PSA-based screening is associated with reduced prostate cancer-specific mortality, this study specifically evaluates the diagnostic accuracy of gallium-68-PSMA-11 PET-CT in patients with high clinical risk but non-suspicious MRI results. It provides a specific diagnostic alternative for the population identified as high-risk in other contexts.
When doctors suspect prostate cancer, the standard next step is often a biopsy. However, these procedures can be uncomfortable. A large study involving 660 men looked at whether a specific PET-CT scan could help identify cancer accurately enough to skip the needle. This was especially important for men whose initial MRIs were unclear or not suspicious, but who still had a high clinical risk of cancer.
The study compared the PET-CT scan to the traditional transperineal biopsy. The results showed that the scan was just as effective at finding significant cancer as the biopsy. In fact, nearly half of the men who received the PET-CT scan were able to avoid a biopsy entirely within six months.
While the scan showed similar results for finding cancer, it also tracked other factors like pain and bleeding. The study did not report any serious safety issues. While the results are promising for changing how doctors test for prostate cancer, more research is needed to see how this fits into everyday medical practice.
What this means for you:
A PET-CT scan can accurately find prostate cancer, potentially allowing some high-risk men to skip a biopsy.
Common questions
Can this scan accurately find prostate cancer?
Yes. The study found that the PET-CT scan was just as effective as a traditional biopsy at finding clinically significant prostate cancer. In the study, 12% of men in the scan group and 16% of men in the biopsy group were found to have significant cancer.
Can this scan help me avoid a biopsy?
The scan may help some men avoid the procedure. In the study, 49% of the men who received the PET-CT scan were able to skip the biopsy entirely within a six-month period.
Are there any side effects to the PET-CT scan?
The study did not report any serious adverse events or specific safety issues regarding the PET-CT scan. It also tracked symptoms like pain and bleeding, which were similar between the two groups.
BACKGROUND: MRI is recommended for men with clinical suspicion of significant prostate cancer. Those with high clinical risk but non-suspicious or equivocal MRI often undergo prostate biopsy, but have a low likelihood of clinically significant prostate cancer, and a high incidence of clinically insignificant prostate cancer. We aimed to investigate whether gallium-68 ([Ga]Ga)-prostate-specific membrane antigen (PSMA)-11 PET-CT could reduce the number of people requiring prostate biopsy and limit biopsy to targeted cores, without compromising clinically significant prostate cancer diagnosis.
METHODS: In this multicentre, non-inferiority, phase 3, randomised controlled trial, done at at seven Australian hospitals, we recruited biopsy-naive participants with clinical suspicion of significant prostate cancer, equivocal (Prostate Imaging-Reporting and Data System [PI-RADS] 3) or non-suspicious (PI-RADS 2) MRI but high clinical risk (eg, prostate-specific antigen [PSA] density of >0·1 ng/mL/mL, strong family history of prostate cancer, abnormal digital rectal examination, BRCA mutation, PSA >10 ng/mL, PSA doubling time <36 months, or PSA velocity >0·75 ng/mL per year), PSA of 20 ng/mL or less, and clinical T2 disease or less. Participants were randomly assigned (1:1) using a centralised web-based system to undergo [Ga]Ga-PSMA-11 PET-CT (experimental group) or systematic transperineal prostate biopsy (control group), using block sizes of two or four and stratification by study site. There was no masking for participants or investigators. Participants with positive [Ga]Ga-PSMA-11 PET-CT (PRIMARY score 3-5) underwent PSMA-PET-targeted transperineal prostate biopsies, whereas those with a negative result (PRIMARY score 1-2) avoided biopsy. The co-primary outcomes were the proportion of participants with clinically significant prostate cancer, defined as a Gleason score of 3 + 4 (≥10% pattern 4) or higher, and the proportion of participants in the [Ga]Ga-PSMA-11 PET-CT group who avoided biopsy within 6 months of random assignment. A two-sided 95% Wald CI based on a binomial model was used to estimate the risk difference in the proportion of participants with clinically significant prostate cancer (non-inferiority margin 10%) and to estimate the proportion of participants in the experimental group who had avoided biopsy 6 months after random assignment (20% threshold), analysed based on intention to treat. This trial is registered with ClinicalTrials.gov, NCT05154162, and participant follow-up is ongoing.
FINDINGS: Between March 2, 2022, and Aug 24, 2025, 660 eligible male participants were enrolled and had a median age of 61 years (IQR 56-66), a median PSA of 5·2 ng/mL (4·0-7·0), and a median PSA density of 0·13 ng/mL/mL (0·09-0·17). There were PI-RADS 2 in 335 (51%) participants and PI-RADS 3 in 325 (49%) participants. Ethnicity data were not collected. 329 (50%) were assigned to the control group with systematic transperineal prostate biopsy, and 331 (50%) were assigned to the experimental group with [Ga]Ga-PSMA-11 PET-CT. The proportion of participants with clinically significant prostate cancer in the experimental group (39 [12%] of 331) was non-inferior to the control (51 [16%] of 329; difference -3·7% [95% CI -8·9 to 1·5%]; p=0·0093). Use of [Ga]Ga-PSMA-11 PET-CT avoided biopsy in 163 (49%) of 331 participants (95% CI 44 to 55%; p <0·0001). After prostate biopsy, participants reported similar proportions of pain (33 [21%] in the experimental group vs 62 [21%] in the control group), haematuria (60 [38%] vs 126 [43%]), and haematospermia (77 [48%] vs 133 [45%]).
INTERPRETATION: [Ga]Ga-PSMA-11 PET-CT could have the potential to improve the diagnostic pathway of patients with a high clinical risk but non-suspicious or equivocal prostate MRI. Further research, including health-economic analyses and validation with other PSMA radiopharmaceuticals, are needed to confirm the clinical implementation and generalisability of this approach.
FUNDING: Prostate Cancer Foundation, National Health and Medical Research Council, St Vincent's Curran Foundation, and Peter MacCallum Cancer Foundation.
