The addition of gallium-68-prostate-specific membrane antigen-11 PET-CT to non-suspicious MRI with high clinical risk or equivocal MRI halves the number of men requiring prostate biopsy without reducing the detection of clinically significant malignancy.
The results from the PRIMARY2 study, published in The Lancet Oncology [link here], suggest benefit in extending the use of PSMA-PET from staging for nodal or distant metastatic disease to a triaging tool for men with equivocal or non-suspicious MRI but at clinical risk of prostate cancer.
The Australian study comprised 660 eligible male participants with no previous prostate biopsy or prostate cancer diagnosis, and equivocal or non-suspicious MRI with at least one red flag for clinical risk.
Red flags included PSA density >0·1 ng/mL/mL, abnormal digital rectal examination, strong family history of prostate cancer, BRCA mutation, PSA >10 ng/mL, PSA doubling time <36 months, or PSA velocity >0·75 ng/mL per year.
Participants were randomly assigned to receive [⁶⁸Ga] Ga-PSMA-11 PET-CT or systematic transperineal prostate biopsy. Participants with a positive PET-CT underwent targeted prostate biopsy while those with a normal result did not undergo biopsy and underwent PSA surveillance instead.
The study found the co-primary endpoint of clinically significant prostate cancer in 16% of the biopsy-only control group versus 12% of the PET-CT experimental group (non-significant difference of 3.7%).
In the other co-primary endpoint, the proportion of participants in the PET-CT group who avoided biopsy was 49%.
In secondary endpoints, clinically insignificant prostate cancer was diagnosed in 32% of the control group versus 14% of the experimental group (p<0·0001). There was no cancer on biopsy in 42% of the control group versus 22% of the experimental group
“Reducing insignificant cancer detection in this study from 32% in the systematic biopsy group to 14% with the addition of [⁶⁸Ga] Ga-PSMA-11 PET-CT is a clinically meaningful outcome,” it said.
“Addressing the overtreatment of men with clinically insignificant cancer is still a major unmet need in prostate cancer, and even if they are safely on active surveillance, this can be a source of anxiety for men and require substantial resources over time.”
The study said future work should consider the cost-effectiveness of incorporating [⁶⁸Ga]Ga-PSMA-11 PET-CT into the prostate cancer diagnostic pathway.
“It is feasible that additional costs of the PSMA PET-CT could be offset by a reduction in the number of men requiring prostate biopsy,” it said.
Investigators on the study included nuclear medicine physicians Professor Michale Hofman from the Peter MacCallum Cancer Centre and Professor Louise Emmett from St Vincent’s Hospital, Sydney.
A comment article in the journal [link here] said a non-invasive diagnostic test that avoids the need for an invasive test is valuable.
However, it said while the early findings were promising and “moves the field forward”, PRIMARY2 had not yet proved the study’s objective that a negative PSMA PET-CT could safely rule out clinically significant disease.
“In the experimental group, men with negative PSMA PET-CT generally did not undergo biopsy, and those with positive scans underwent targeted biopsy rather than the same systematic reference biopsy used in the control group,” it said.
“Thus, the primary endpoint is not the true prevalence of clinically significant prostate cancer; rather it is the detection of clinically significant prostate cancer within two different diagnostic pathways.”
The comment, by Professor Daniel Spratt from the University Hospitals Seidman Cancer Center in Cleveland, Ohio, said fewer biopsies inevitably translates to less cancer found, especially less low-volume disease.
“Whether this represents a wise de-escalation or missed diagnosis depends on follow-up, which is not yet mature for PRIMARY2.”
He said the 2-year follow-up will be central to whether the strategy is safe.
“If funding is available, it would be even more reassuring if 5-year data could also be collected to truly understand the clinical utility of the tested PSMA PET-CT pathway.”