Radioactive Counts From PSMA PET/CT-Targeted Biopsy Specimens for Real-time Diagnosis of Prostate Cancer: A Prospective Study

This is a single-center, prospective, observational proof-of-concept study designed to validate the diagnostic value of radioactive counts (CPM) from prostate biopsy cores in intraoperative real-time differentiation between cancer-containing and non-cancer-containing tissue, using histopathology as the gold standard.

All enrolled patients will undergo PSMA PET/CT imaging, followed by prostate biopsy within 3 hours after image acquisition. Biopsy procedures will be performed by a designated urological ultrasonographer using a combined targeted and systematic approach: targeted biopsy (up to 3 cores per suspicious lesion identified on PET/CT) will be performed for each detectable lesion, supplemented by systematic biopsy. The biopsy procedure itself does not deviate from the current standard clinical protocol.

The distinctive procedural addition lies in specimen handling: immediately after each core is obtained, it will be placed into a pre-labeled EP tube. Within 30 minutes following completion of the biopsy procedure, each core will be measured for counts per minute (CPM) using a calibrated gamma spectrometer. All CPM measurements will be recorded independently without knowledge of the corresponding pathological results and will subsequently be compared with final histopathological diagnoses on a core-by-core basis in a blinded manner. To minimize the impact of counting overflow or statistical fluctuation, each core will be measured for a duration of 60 seconds, with the measurement repeated twice and the mean value taken as the final CPM. For cores containing multiple tissue fragments, the total radioactivity of all fragments will be measured without separation.

In the post-processing phase, receiver operating characteristic (ROC) analysis will be used to determine the optimal CPM diagnostic cutoff value. Further quantitative analyses will be performed to evaluate the correlations between CPM values and ISUP grade, tumor length, and immunohistochemical PSMA expression levels. Additionally, this study will preliminarily explore the feasibility of using a CPM threshold as a reference range for safely omitting biopsy, specifically by investigating whether there exists a lower CPM limit below which the probability of clinically significant prostate cancer (csPCa) detected in the corresponding core falls below a pre-specified safety threshold.

The CPM data obtained in this study will be jointly analyzed with patients' baseline clinical information (e.g., PSA levels), multiparametric MRI features (PI-RADS score, ADC value), and PET/CT quantitative parameters (SUVmax, SUVmean), in order to assess whether CPM provides additional diagnostic information independent of existing imaging parameters. All pathological diagnoses will be rendered independently by two experienced uropathologists, with consensus reached through discussion in cases of disagreement.

This study adds only the radioactive measurement procedure to the biopsy cores, without altering the routine clinical diagnostic and treatment pathway or the biopsy protocol, and does not subject patients to additional invasive procedures or radiation exposure beyond standard care. The study has been approved by the Institutional Review Board of Peking University First Hospital, and written informed consent will be obtained from all enrolled participants.

Inclusion criteria

• Age 18-80 years;
• Meeting clinical indications for prostate biopsy (serum PSA persistently >4 ng/mL, and at least one lesion with PI-RADS ≥ 3 on magnetic resonance imaging [MRI]);
• At least one suspicious lesion detected on PSMA PET/CT;
• No prior prostate biopsy

Exclusion criteria

• Prior chemotherapy, pelvic radiotherapy, or androgen deprivation therapy (ADT) for prostate cancer;
• Prior prostate surgery (transurethral resection of the prostate, etc.);
• Any contraindications to prostate biopsy, such as active urinary tract infection or indwelling urinary catheter;
• Biopsy core data with failed gamma spectrometer measurement due to technical reasons.