Diagnostic Performance of PIFLUFOLASTAT (18F) PSMA PET/CT for Detecting Recurrence in Favourable Intermediate‑Risk Localized Prostate Cancer After Focal HIFU: A Pilot Study

The primary objective is to assess the diagnostic accuracy of PSMA PET/CT for identifying recurrence of prostate cancer at the one‑year post‑treatment visit in patients with favourable intermediate‑risk disease who have undergone high‑intensity focused ultrasound (HIFU) as first‑line curative therapy, with 12‑month biopsy serving as the reference standard. Secondary objectives are to: – describe the diagnostic performance of multiparametric prostate MRI (mpMRI) for the same recurrence endpoint, using biopsy as the gold standard; – estimate the false‑negative rate of PSMA PET at initial diagnosis (pre‑HIFU); and – evaluate the diagnostic utility of the PRIMARY score derived from PSMA PET for detecting one‑year recurrence.

The trial enrolled adult males with prostate cancer meeting predefined clinical and pathological criteria; participants were required to be at least 70 years of age, have a life expectancy greater than five years, and present with clinical stage T1c–T2a disease, PSA < 20 ng/mL, and a single prostate lesion classified as PIRADS 3–5 with prostate volume under 150 mL. Biopsy findings had to show unilateral ISUP 2 involvement in no more than two contiguous sextants, with or without additional ISUP 1 foci, and patients needed to be affiliated with a social security scheme and provide informed consent. The sponsor did not provide information on the total number of participants, and no specific lifestyle factors such as diet or physical activity were reported for the selected population. Selection was based on the outlined inclusion parameters, and no additional exclusion criteria were detailed in the available data.

The pilot study is a prospective, single‑arm diagnostic trial evaluating the performance of PSMA PET/CT for detecting clinically significant prostate cancer recurrence one year after focal HIFU therapy in patients with favourable intermediate‑risk disease. Eligible participants (age ≥ 70 years, PSA < 20 ng/mL, clinical stage T1c–T2a, unilateral ISUP 2 lesion, prostate volume < 150 mL, and meeting biopsy and imaging criteria) undergo an initial screening visit to confirm eligibility and obtain informed consent. Baseline assessments include standard laboratory tests, multiparametric MRI, and the HIFU procedure. Follow‑up visits are scheduled at 12 months post‑treatment for PSMA PET/CT imaging, concurrent multiparametric MRI, and targeted prostate biopsies, which serve as the reference standard for recurrence. An end‑of‑study visit occurs shortly after the 12‑month assessments to collect final safety and outcome data. Participant involvement spans approximately 13 months, encompassing screening, treatment, and the one‑year follow‑up. Early termination may occur if a participant withdraws consent, experiences a serious adverse event, is lost to follow‑up, or is unable to complete the required imaging or biopsy procedures.

The investigational radiopharmaceutical PIFLUFOLASTAT (18F) is supplied in the pharmaceutical form identified as PHF00231MIG and is administered by intravenous injection or infusion. Each participant receives a single dose of 360 MBq (megabecquerel) of the tracer, delivered as a one‑time intravenous administration prior to the scheduled PSMA PET/CT scan. No repeated dosing or chronic administration is required during the study.

All participants undergo focal high‑intensity focused ultrasound (HIFU) as the standard‑of‑care curative therapy for favourable intermediate‑risk localized prostate cancer. This non‑experimental treatment is performed before study enrollment and serves as the reference therapeutic modality against which imaging outcomes are evaluated.

Following the intravenous administration of the radiotracer, participants are monitored for adherence to the imaging protocol, including timing of PET/CT acquisition at the appropriate post‑injection interval. Compliance with the single‑dose schedule is documented in the case report form, and any deviations from the planned administration route or timing are recorded for safety and data integrity purposes.

The efficacy assessment will be based on the detection of prostate cancer recurrence at the 1‑year follow‑up visit. The primary endpoint is the presence of recurrence identified by PSMA PET/CT and confirmed by biopsy, with the sensitivity, specificity, and positive predictive values of the imaging modality estimated. Secondary endpoints include the detection of recurrence by multiparametric MRI confirmed by biopsy, the false negative rate of the PET imaging at diagnosis, and the estimation of the diagnostic performance of the primary score.

At the 12‑month assessment, participants will undergo a PET/CT scan using the investigational radiotracer, followed by targeted biopsy of any suspected lesions to serve as the reference standard. Multiparametric MRI will be performed in parallel for comparative analysis. Data from the imaging studies will be compared with histopathology results to calculate sensitivity, specificity, predictive values, and false‑negative rates. All analyses will be conducted using predefined statistical methods appropriate for diagnostic performance evaluation.