¹⁸F-PSMA-1007 PET-CT-Directed Focal Therapy for MRI-Invisible Prostate Cancer

Multiparametric magnetic resonance imaging (mpMRI) is the standard imaging modality for prostate cancer diagnosis and focal therapy planning. However, 10-20% of clinically significant prostate cancers (csPCa) are not visible on mpMRI (PI-RADS 1-2). These MRI-invisible lesions, typically identified only on systematic biopsy, are currently not targetable by MRI-guided focal therapy, leaving patients with the choice between whole-gland radical treatment or active surveillance. This prospective, multi-centre, single-arm phase II trial investigates whether pelvis-only ¹⁸F-PSMA-1007 positron emission tomography-computed tomography (PET-CT) can identify MRI-invisible csPCa and serve as the therapeutic navigation tool for focal ablation. Men aged ≥50 years with localized, intermediate-risk prostate cancer (ISUP Grade Group 2-3) and at least one MRI-invisible csPCa focus undergo a PET-CT. If a PET-avid lesion corresponds anatomically to the MRI-invisible biopsy-positive site, the patient receives focal therapy using an energy modality (targeted microwave ablation, high-intensity focused ultrasound, or irreversible electroporation) selected based on tumour anatomy, guided by organ-based tracking. The primary endpoint is the absence of csPCa (Grade Group ≥2) on 6-month targeted biopsy of all treated zones. Secondary endpoints include out-of-field recurrence, functional outcomes, and safety. The study requires 45 treated patients (total enrolment \~60) across two Hong Kong centres and will be completed within 3 years.

Sex

Male

Minimum age

50 Years

Inclusion Criteria:

1. Men aged ≥50 years
2. Life expectancy \>10 years
3. Histologically confirmed localized prostate cancer, ISUP Grade Group 2 or 3
4. At least one clinically significant cancer focus (≥1 systematic biopsy core with Grade Group 2-3) that is MRI-invisible, defined as:

   \- The corresponding sextant/region on mpMRI (performed within 6 months) shows PI-RADS v2.1 score 1 or 2, or no identifiable lesion that could account for the positive biopsy
5. Total of 1-2 discrete cancer foci (MRI-visible + PET-detected MRI-invisible) on study entry, with each MRI-visible focus having maximum diameter ≤15 mm on mpMRI
6. Organ-confined disease on mpMRI and no evidence of seminal vesicle invasion or lymph node/distant metastasis
7. Serum PSA \<20 ng/mL
8. Able to provide informed consent

Exclusion Criteria:

1. Previous treatment for prostate cancer (radiotherapy, surgery, focal therapy, androgen deprivation)
2. Prior pelvic radiotherapy for any cause
3. Contraindication to MRI or gadolinium contrast
4. Contraindication to PSMA PET-CT (e.g. severe claustrophobia, inability to lie flat)
5. Contraindication to general or spinal anaesthesia
6. Uncorrectable coagulopathy (INR \>1.5, platelet \<50×10⁹/L) or anticoagulant/antiplatelet therapy that cannot be stopped (low-dose aspirin 80-100 mg is permitted)
7. Active urinary tract infection or acute prostatitis
8. MRI-invisible focus located in a region where focal therapy would likely cause sphincter or rectal injury, as determined by biopsy mapping and anatomical constraints
9. Bladder pathology (bladder stone, bladder cancer) or known urethral stricture

• BACKGROUNDTosoian JJ, Mamawala M, Epstein JI, Landis P, Macura KJ, Simopoulos DN, Carter HB, Gorin MA. Active Surveillance of Grade Group 1 Prostate Cancer: Long-term Outcomes from a Large Prospective Cohort. Eur Urol. 2020 Jun;77(6):675-682. doi: 10.1016/j.eururo.2019.12.017. Epub 2020 Jan 7. PMID 31918957
• BACKGROUNDGeorge AK, Miocinovic R, Patel AR, Lomas DJ, Correa AF, Chen DYT, Rastinehad AR, Schwartz MJ, Sidana A, Stensland KD, Helfand BT, Gahan JC, Meng X, Yu A, Brisbane WG, Vourganti S, Barqawi AB, Uchio EM, Wysock JS, Polascik TJ, McClure TD, Fainberg J, Coleman JA. Irreversible Electroporation for Prostate Tissue Ablation in Patients with Intermediate-risk Prostate Cancer: Results from the PRESERVE Trial. Eur Urol. 2026 Jan;89(1):57-68. doi: 10.1016/j.eururo.2025.06.003. Epub 2025 Jul 19. PMID 40685282
• BACKGROUNDTurkbey B, Rosenkrantz AB, Haider MA, Padhani AR, Villeirs G, Macura KJ, Tempany CM, Choyke PL, Cornud F, Margolis DJ, Thoeny HC, Verma S, Barentsz J, Weinreb JC. Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2. Eur Urol. 2019 Sep;76(3):340-351. doi: 10.1016/j.eururo.2019.02.033. Epub 2019 Mar 18. PMID 30898406
• BACKGROUNDDelongchamps NB, Peltier A, Potiron E, Bladou F, Diamand R, Messas A, Roche JB, Robert G, Hoepffner JL, Piechaud T, Anract J, Velthoven RV. Targeted microwave ablation of localised prostate cancer (VIOLETTE trial): a prospective multicentre study. BJU Int. 2026 Jun;137(6):1032-1039. doi: 10.1111/bju.70220. Epub 2026 Mar 11. PMID 41810596
• BACKGROUNDvan den Bos W, Scheltema MJ, Siriwardana AR, Kalsbeek AMF, Thompson JE, Ting F, Bohm M, Haynes AM, Shnier R, Delprado W, Stricker PD. Focal irreversible electroporation as primary treatment for localized prostate cancer. BJU Int. 2018 May;121(5):716-724. doi: 10.1111/bju.13983. Epub 2017 Sep 4. PMID 28796935
• BACKGROUNDShah TT, Peters M, Eldred-Evans D, Miah S, Yap T, Faure-Walker NA, Hosking-Jervis F, Thomas B, Dudderidge T, Hindley RG, McCracken S, Greene D, Nigam R, Valerio M, Minhas S, Winkler M, Arya M, Ahmed HU. Early-Medium-Term Outcomes of Primary Focal Cryotherapy to Treat Nonmetastatic Clinically Significant Prostate Cancer from a Prospective Multicentre Registry. Eur Urol. 2019 Jul;76(1):98-105. doi: 10.1016/j.eururo.2018.12.030. Epub 2019 Jan 9.