CONFIRM trial Protocol: The utility of PSMA PET/CT in active surveillance for prostate cancer.

Abstract

Primary objectives: In this trial, we aim to determine the additive value of PSMA PET/CT in the risk-stratification of men with newly diagnosed prostate cancer (PCa) that would have otherwise been deemed suitable for active surveillance (AS). Specifically, we aim to determine if PSMA PET/CT can detect a cohort of men on AS that are in fact high risk and likely to experience unfavourable outcomes should they remain on their current treatment pathway. To determine the additive value of PSMA PET/CT to repeat mpMRI of the prostate and explore whether a confirmatory biopsy may be avoided in men with a negative PSMA PET/CT and a negative repeat MRI of the prostate (PIRADS <3). Furthermore, to develop a nomogram combining clinical, imaging and biomarker data to predict the likelihood of failure on AS in men with high-risk features. Furthermore, A blood sample will be taken to perform a prostate health index (PHI) test at the time of confirmatory biopsy. Furthermore, a portion of this blood will be stored at a biobank for up to five-years if a follow-up study on molecular biomarkers and genetic assays in this cohort of men is indicated, based on the results from the CONFIRM trial. The CONFIRM trial is a prospective, multi-centre, pre-test/post-test, cohort study across Victoria, Australia, involving men with newly diagnosed low-risk PCa with high-risk features, considered suitable for AS and undergoing confirmatory biopsy. The trial's goal is to provide high-quality evidence to establish whether PSMA PET/CT has a role in risk-stratifying men deemed suitable for AS despite having high-risk feature(s). The CONFIRM trial will measure the proportion of men deemed unsuitable for ongoing AS based on pathological upgrading and multidisciplinary team recommendation due to PSMA PET/CT scan and PSMA-targeted confirmatory biopsy. Additionally, the positive and negative predictive values, sensitivity, and specificity of PSMA PET/CT will be calculated in isolation and combined with repeat mpMRI of the prostate. This trial will provide robust prospective data to determine if PSMA-PET/CT and standard of care (prostate biopsy +/- repeat mpMRI) can improve diagnostic certainty in men undergoing confirmatory biopsy for low-grade PCa with high-risk features.