The Role of 18F-PSMA PET in Prostate Cancer Diagnosis in Equivocal MRI

Official title

The Role of 18F-PSMA PET in Prostate Cancer Diagnosis in Equivocal MRI: a Multi-center Randomised Controlled Trial

Overview

This study is a multi-center RCT to compare the clinically significant prostate cancer (csPCa) detection and/or change in clinical management in MRI guided (MRI arm) biopsy and MRI+18F-PSMA guided (Combined arm) biopsies in men with equivocal MRI prostate scans. If additional clinical value is shown by adding 18F-PSMA PET to equivocal MRI, then this should be the new standard of care.

Detailed description

The investigators propose to conduct a phase III multi-center randomised controlled trial to evaluate the detection of clinically significant prostate cancer (csPCa) by MRI-guided biopsy approach (MRI arm) versus MRI+PSMA approach (COMBINED arm). Clinically significant prostate cancer (csPCa) is defined as prostate cancer classified as ISUP (International Society of Urogenital Pathology) Grade group 2 or higher. Patients with clinical suspicion of prostate cancer on MRI with PI-RADS (Prostate Imaging-Reporting and Data System, version 2.1) score 2 with red flag (PSA density \>0.2 OR Prostate health index, PHI\>35), PI-RADS 3, or PI-RADS 4 (and PSAd \<0.1 OR PHI\<35) will be randomised in a 1:1 manner to MRI arm or COMBINED arm. The detection rates of csPCa will be compared between arms. The study hypothesis is that COMBINED arm is superior to MRI arm in detecting csPCa and changing clinical management.

Interventions

• Procedure MRI+PSMA-guided approach
  MRI+PSMA-guided approach prostate biopsy
• Procedure MRI-guided approach
  MRI-guided approach prostate biopsy

Primary outcome measures

• Proportion of men with clinically significant Prostate cancer (csPCa) [Time frame: When histology results available, at an expected average of 30 days post-biopsy]
• Proportion of men with additional csPCa detected only in PET targets which will affect clinical management [Time frame: When histology results available, at an expected average of 30 days post-biopsy]

Secondary outcome measures (6)

• Proportion of men with csPCa detected in targeted and systematic biopsy [Time frame: When histology results available, at an expected average of 30 days post-biopsy]
• Proportion of men with diagnosis of clinically insignificant prostate cancer [Time frame: When histology results available, at an expected average of 30 days post-biopsy]
• Proportion of men in combined arm with negative PET who could avoid a biopsy [Time frame: When PET results available, at an expected average of 7 days post-scan]
• Correlation Between PET SUVmax of Targeted Lesion and Histologically Confirmed Clinically Significant Prostate Cancer (csPCa) [Time frame: When histology results available, at an expected average of 30 days post-biopsy]
• Proportion of men with post-biopsy adverse events within 30 days after biopsy [Time frame: 30 days post biopsy]
• Health-related Quality of life scores [Time frame: Assessed at baseline and at 30 days after intervention]

Eligibility criteria

Inclusion criteria

• Men ≥18 years of age
• Serum Prostate-specific antigen (PSA) 4-15 ng/mL, repeated at least once
• Prostate mpMRI done within 6 months
• MRI prostate with PI-RADS (11) scores of:

• PI-RADS score 2 with red flag (PSA density >0.2 OR Prostate health index, PHI>35),
• PI-RADS 3, OR
• PI-RADS 4 with lower csPCa risks (PSAd <0.1 OR PHI<35)
• Normal Digital rectal examination
• Patient agrees for targeted and systematic prostate biopsy

Exclusion criteria

• Prostate biopsy within past 5 years
• Past or current history of prostate cancer
• Contraindicated to undergo PSMA PET-CT scan
• Contraindicated to prostate biopsy: active urinary tract infection, fail insertion of transrectal ultrasound probe into rectum (abdominal perineal resection, anal stenosis), fail to be placed in lithotomy position, uncorrectable coagulopathy, antiplatelet or anticoagulant which cannot be stopped (keep aspirin before and after biopsy is permitted)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Hong Kong · 1 center

• Prince of Wales Hospital — Hong Kong

Publications

• Chiu PK, Teoh JY, Chan SY, Chu PS, Man CW, Hou SM, Ng CF. Role of PSA density in diagnosis of prostate cancer in obese men. Int Urol Nephrol. 2014 Dec;46(12):2251-4. doi: 10.1007/s11255-014-0826-7. Epub 2014 Sep 9. PMID 25201460
• Chiu PK, Teoh JY, Lee WM, Yee CH, Chan ES, Hou SM, Ng CF. Extended use of Prostate Health Index and percentage of [-2]pro-prostate-specific antigen in Chinese men with prostate specific antigen 10-20 ng/mL and normal digital rectal examination. Investig Clin Urol. 2016 Sep;57(5):336-42. doi: 10.4111/icu.2016.57.5.336. Epub 2016 Aug 31. PMID 27617315
• Chiu PK, Roobol MJ, Teoh JY, Lee WM, Yip SY, Hou SM, Bangma CH, Ng CF. Prostate health index (PHI) and prostate-specific antigen (PSA) predictive models for prostate cancer in the Chinese population and the role of digital rectal examination-estimated prostate volume. Int Urol Nephrol. 2016 Oct;48(10):1631-7. doi: 10.1007/s11255-016-1350-8. Epub 2016 Jun 27. PMID 27349564
• Gudmundsson J, Sulem P, Gudbjartsson DF, Masson G, Agnarsson BA, Benediktsdottir KR, Sigurdsson A, Magnusson OT, Gudjonsson SA, Magnusdottir DN, Johannsdottir H, Helgadottir HT, Stacey SN, Jonasdottir A, Olafsdottir SB, Thorleifsson G, Jonasson JG, Tryggvadottir L, Navarrete S, Fuertes F, Helfand BT, Hu Q, Csiki IE, Mates IN, Jinga V, Aben KK, van Oort IM, Vermeulen SH, Donovan JL, Hamdy FC, Ng CF PMID 23104005
• Chiu PK, Leow JJ, Chiang CH, Mok A, Zhang K, Hsieh PF, Zhu Y, Lam W, Tsang WC, Fan YH, Lin TP, Chan TY, Leung CH, Teoh JY, Chu PS, Zhu G, Ye DW, Wu HC, Tan TW, Tsu JH, Ng CF, Chiong E, Huang CY. Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter PMID 37036248
• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae. PMID 15273542
• Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA; Grading Committee. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System. Am J Surg Pathol. 2016 Feb;40(2):244-52. doi: 10.1097/PAS.0000000000000530. PMID 26492179
• Luo L, Zheng A, Chang R, Li Y, Gao J, Wang Z, Duan X. Evaluating the value of 18F-PSMA-1007 PET/CT in the detection and identification of prostate cancer using histopathology as the standard. Cancer Imaging. 2023 Nov 3;23(1):108. doi: 10.1186/s40644-023-00627-x. PMID 37924154

Identifiers

NCT: NCT07386496 · CRE-2025.094

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗