This is a prospective, multi-centre, single-arm Phase II trial conducted at Queen Mary Hospital and Princess Margaret Hospital, Hong Kong. The study adheres to the Declaration of Helsinki and ICH-GCP guidelines, with ethics approval obtained prior to initiation. Eligible patients are men aged ≥50 years, life expectancy >10 years, with histologically confirmed localized prostate cancer (ISUP Grade Group 2 or 3), at least one csPCa focus identified on systematic biopsy that is MRI-invisible (PI-RADS v2.1 score 1-2 in the corresponding region), total of 1-2 discrete cancer foci, PSA <20 ng/mL, and organ-confined disease. Exclusion criteria include prior prostate cancer treatment, pelvic radiotherapy, contraindications to MRI or PSMA PET-CT, and uncorrectable coagulopathy.
Enrolled patients undergo a dedicated pelvis-only ¹⁸F-PSMA-1007 PET-CT within 4 weeks of enrolment. No fasting is required; activity is weight-based. After a 90-minute uptake period, low-dose non-contrast CT and PET imaging of the pelvis are acquired. Iterative reconstruction optimised for small lesion detection is applied. A PRIMARY-adapted five-point PET-score system (1 to 5) is used; focal uptake scoring 3, 4, or 5 defines a PET-positive lesion. Only patients with a PET-positive lesion anatomically correlated with the MRI-invisible biopsy-positive location proceed to focal therapy.
Focal therapy is performed under general or spinal anaesthesia. The ¹⁸F-PSMA-1007 PET-CT DICOM dataset is imported into the Koelis Trinity® platform and fused with real-time transrectal ultrasound using organ-based tracking (OBT). The urologist selects the ablative modality based on tumour location and constraints from the following: targeted microwave ablation (TMA) using the TATO3® needle; high-intensity focused ultrasound (HIFU) using the Sonablate® system; or irreversible electroporation (IRE) using the NanoKnife® or PoriNova® systems. Treatment is transperineal, with a 5-10 mm intraprostatic margin around the PET-avid and any concurrent MRI-visible lesions, while maintaining a ≥5 mm safety distance from sphincter, rectum, and neurovascular bundles.
Follow-up includes PSA, adverse events, and validated questionnaires (IPSS, IIEF-5, EPIC-26) at month 3 and month 6. At month 6, a repeat mpMRI and transperineal MRI/ultrasound fusion biopsy (3-4 cores per treated area plus a 12-core systematic template) are performed. Pathology is read by dedicated uropathologists with ISUP Grade Group reporting per core and per lesion. Primary outcome: per-patient absence of csPCa (≥ Grade Group 2) on targeted biopsy of all treated zones at 6 months. Secondary outcomes: any cancer in treated zones, out-of-field recurrence, PSA kinetics, functional score changes, adverse events (Clavien-Dindo), quality of life, PET positivity proportion among enrolled patients, and technical success of PET/US fusion.
Sample size uses A'Hern's single-stage phase II design. With an assumed true in-field success rate (p₁) of 0.88 and an unacceptable threshold (p₀) of 0.73, one-sided α=0.05, power=0.80, the critical value is 34 successes out of 40 treated patients. Accounting for a 10% loss to follow-up/biopsy, 45 treated patients are required. Estimating that 75% of enrolled MRI-invisible csPCa patients will have a PET-avid lesion, a total of 60 patients will be enrolled. Recruitment over 24 months is feasible across the two centres, each performing ~200 MRI-guided biopsies annually, with ~15% revealing MRI-invisible csPCa. The primary analysis will be performed on the protocol population; the proportion achieving the primary endpoint will be reported with an exact 95% confidence interval. Secondary endpoints will be analysed using paired t-tests or Wilcoxon signed-rank tests for continuous variables, and McNemar or chi-square tests for categorical variables, with p<0.05 considered significant. SPSS will be used.
Data will be handled in accordance with Hospital Authority policies. Personal data will be coded, stored in locked cabinets and password-protected servers with restricted access, and retained for 10 years post-completion before destruction. Patients who are PET-negative will be managed per institutional standard, with their data collected for secondary analyses. The study is funded by The University of Hong Kong, with consumables for IRE and TMA provided free of charge by Zhejiang CuraWay Medical Technology Co., Ltd. and Chindex Hong Kong Limited, respectively.
