Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is becoming more prevalent in the use of staging for clinically significant prostate cancer. The PRIMARY score standardises interpretation of intraprostatic PSMA uptake patterns to aid in identifying clinically significant disease. This study aimed to characterise the histopathological features of patients with no discernible PSMA uptake pattern (PRIMARY score 1) and compare the prevalence of intraductal carcinoma of the prostate (IDC-P) to patients with uptake patterns (PRIMARY score ≥2).

We conducted a two-centre retrospective cohort study of patients who underwent [68Ga]Ga-PSMA-11 or [18F]DCFPyL PET prior to radical prostatectomy between January 2020 and August 2023. All PSMA PET scans were centrally reviewed by blinded nuclear medicine physicians and assigned PRIMARY scores. Whole-mount prostatectomy histopathology was reviewed for IDC-P and other tumour characteristics. Statistical analysis compared IDC-P prevalence and pathological features between PRIMARY score groups.

Among 178 patients included, 30 (17%) had no uptake pattern (PRIMARY score 1). IDC-P was more frequent in this group compared to those with PRIMARY score ≥2 (40% vs 21%, p=0.026). Within PRIMARY score 1 patients, those with IDC-P had significantly higher rates of pathological grade group ≥3 disease (100% vs 33%) and more advanced pathological stage (pT3/4 in 75% vs 33%). IDC-P-positive patients showed similar rates of high-grade and high-stage disease regardless of PSMA uptake pattern.

A lack of intraprostatic PSMA uptake on PET (PRIMARY score 1) does not exclude aggressive prostate cancer. IDC-P is over-represented in this subset and is associated with higher-grade disease. PSMA PET may not reliably detect all clinically significant prostate cancer variants, and multimodal imaging approaches, including MRI, remain essential in diagnosis and risk stratification.