2026-06-18

Prostate

Diagnostic-pathway data: PSMA-PET as a biopsy-avoidance gate in biopsy-naive high-risk men with equivocal MRI.

PRIMARY2 NCT05154162

ForBiopsy-naive, high clinical risk, PI-RADS 2-3 MRI, PSA ≤20 ng/mL

TL;DRPSMA-PET avoided biopsy in 49% while staying non-inferior for csPCa detection (12% vs 16%) vs systematic biopsy in high-risk equivocal-MRI men.

vs leading data

Phase 3 confirmation of the PRIMARY (Emmett et al) PSMA-PET PRIMARY-score pathway for csPCa detection

Phase 3 RCT Challenges SOC

8 details 3 trials watching

Methods

🔍 Phase 3 non-inferiority RCT, 7 Australian sites, N=660, randomised 1:1 PSMA-PET-CT vs systematic transperineal biopsy, no masking
🔍 Biopsy-naive, high clinical risk, PI-RADS 2 (51%) or 3 (49%) MRI, PSA ≤20 (median 5·2), ≤cT2
🔍 PRIMARY score 3-5 on PSMA-PET → targeted biopsy; score 1-2 → biopsy avoided

CONSORT flow

Assessed / enrolled 660

↓

Randomized 660

↓

PSMA-PET-CT

allocated 331

analyzed 331

Systematic biopsy

allocated 329

analyzed 329

Results

📊 Co-primary endpoints, PSMA-PET vs systematic biopsy

Endpoint PSMA-PET Control Effect

csPCa detected 39/331 (12%) 51/329 (16%) diff −3·7% (95% CI −8·9 to 1·5), p=0·0093
Biopsy avoided ≤6mo 163/331 (49%) n/a 95% CI 44-55%, p<0·0001
📊 Post-biopsy morbidity by arm (among biopsied)

Symptom PSMA-PET arm Control

Pain 33 (21%) 62 (21%)
Haematuria 60 (38%) 126 (43%)
Haematospermia 77 (48%) 133 (45%)

Endpoint	PSMA-PET	Control	Effect
csPCa detected	39/331 (12%)	51/329 (16%)	diff −3·7% (95% CI −8·9 to 1·5), p=0·0093
Biopsy avoided ≤6mo	163/331 (49%)	n/a	95% CI 44-55%, p<0·0001

Symptom	PSMA-PET arm	Control
Pain	33 (21%)	62 (21%)
Haematuria	60 (38%)	126 (43%)
Haematospermia	77 (48%)	133 (45%)

Critique

⚠️ Non-inferiority design with a wide 10% margin; csPCa detection point estimate favoured control, raising missed-cancer vs avoided-overdiagnosis question
⚠️ Follow-up ongoing; whether biopsy-avoided men later develop csPCa is not yet established
⚠️ Open-label, single-country, Ga-PSMA-11 only; generalisability to F-18 PSMA tracers and other settings unproven

Open questions

Do biopsy-avoided men later develop clinically significant prostate cancer?

recruiting Evaluation of Prostate Specific Membrane Antigen Positron Emission Tomography-Computed Tomography in Active Surveillance for Prostate CancEr Phase NA

n=200 · primary completion 2028-12 · PSMA-PET to rule out csPCa in active surveillance
Generalisability to other PSMA radiopharmaceuticals (F-18 tracers) and non-Australian settings

recruiting POSLUMA® (18F-rhPSMA-7.3) PET-CT for PIRADS 2/3 Lesions Phase 2

n=30 · primary completion 2030-07 · F-18 rhPSMA-7.3 detection in PIRADS 2/3 MRI

recruiting Comparing a New PSMA Imaging Agent to MRI for Detecting Prostate Cancer, BEACON Trial Phase Early 1

n=30 · primary completion 2036-01 · F-18 flotufolastat to guide targeted biopsy
Cost-effectiveness vs systematic biopsy

Sourced from Buteau, James P et al.

📚 Sources · 📄 1 paper

📄 PAPER Buteau, James P; Moon, Daniel; Fahey, Michael T et al. · The Lancet Oncology (2026-06)

Effect of [68Ga]Ga-PSMA-11 PET-CT in the diagnosis of prostate cancer in men with equivocal or clinically high-risk non-suspicious findings on multiparametric MRI (PRIMARY2): a multicentre, non-inferiority, phase 3, randomised controlled trial

doi

🌰 Prostate

PRIMARY2 NCT05154162

Prostate