Could PSMA PET/CT provide a viable form of triage when prostate multiparametric MRI (mpMRI) offers equivocal or non-suspicious findings for men at high risk of prostate cancer (PCa)?
For the PRIMARY2 multicenter, phase 3 randomized controlled trial, recently published in Lancet Oncology, researchers reviewed data from 660 biopsy-naïve men with PI-RADS 2 or 3 MRI findings with at least one clinical risk factor for PCa. The cohort was evenly randomized with one group having (68Ga)Ga-PSMA-11 PET/CT and the control group having a systematic transperineal prostate biopsy, according to the study. For participants in the PET/CT cohort, those with a positive PRIMARY score (3–5) proceeded to PET-CT-targeted transperineal biopsy while participants with a negative result (PRIMARY score 1–2) avoided biopsy and entered PSA surveillance.
At six months, the study authors found that 49 percent of participants in the PET/CT cohort were able to avoid prostate biopsy.
Defining clinically significant prostate cancer (csPCa) as a Gleason score 3+4 (> 10 percent pattern 4) or higher, the researchers noted non-inferior detection of csPCa between participants in the PET/CT triage group and the control group (12 percent vs. 16 percent).
“The PRIMARY2 trial is the first (randomized) trial to our knowledge to show that the addition of [⁶⁸Ga]Ga-PSMA-11 PET-CT to MRI in these men halves the number of men requiring prostate biopsy without compromising the detection of clinically significant malignancy,” noted lead study author James P. Buteau, MD, FRACP, FRCPC, a nuclear medicine physician at the Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues.
The study authors also noted that triage use of PET/CT led to an 18 percent reduction in the detection of clinically insignificant PCa in comparison to the control group (14 percent vs. 32 percent).
"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," added Buteau and colleagues.
Three Key Takeaways
- PSMA PET/CT significantly reduces unnecessary biopsies. In biopsy-naïve men with equivocal MRI findings (PI-RADS 2–3), adding (⁶⁸Ga)Ga-PSMA-11 PET/CT to the diagnostic pathway allowed nearly half (49 percent) of patients to avoid prostate biopsy entirely, with those scoring negative on the PRIMARY scale entering PSA surveillance instead.
- Clinically significant cancer detection remains non-inferior. Despite bypassing biopsy in a substantial portion of patients, the PET/CT triage approach detected csPCa (Gleason score ≥3+4 with >10% pattern 4) at a rate non-inferior to systematic transperineal biopsy (12 percent vs. 16 percent), suggesting no meaningful compromise in identifying cancers that warrant treatment.
- Overdiagnosis of clinically insignificant cancer is meaningfully reduced. The PET/CT triage arm detected clinically insignificant prostate cancer at a markedly lower rate than the systematic biopsy control group (14 percent vs. 32 percent), an 18 percent reduction. This is a clinically relevant finding as over-detection of indolent disease can lead to patient anxiety, unnecessary treatment, and associated morbidity.
While noting the need for future studies to assess cost-effectiveness of the PET/CT triage approach and validate these findings with other PSMA PET/CT agents, the researchers noted the possibility of an earlier role for (68Ga)(Ga)-PSMA-11 PET/CT in the evaluation of patients with elevated clinical risks for PCa.
“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. Additionally, a longer follow-up and data maturity of the other secondary outcomes not reported here might further provide information on the use of [68Ga]Ga-PSMA-11 PET-CT, and how this pathway affects patients’ quality of life, anxiety, cancer worry, and decision regret,” posited Buteau and colleagues.
(Editor’s note: For related content, see “Comparative Study Shows Merits of PSMA PET/CT for Local Staging of Intermediate and High-Risk PCa,” “Should PSMA PET/CT Supplant MRI for Staging of Patients with High-Risk PCa?” and “Study: PSMA PET/CT Changed Treatment Plans for Over a Third of Men with Prostate Cancer.”)
In regard to study limitations, the authors acknowledged the lack of a consensus standard for defining csPCa and noted that a higher number of study participants withdrew without biopsy from the control cohort in comparison to the PSMA PET/CT cohort.
