The CONFIRM trial protocol: the utility of prostate-specific membrane antigen positron emission tomography/computed tomography in active surveillance for prostate cancer.

OBJECTIVES: Primary objectives: To determine the additive value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the risk stratification of men with newly diagnosed prostate cancer (PCa) who 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. SECONDARY OBJECTIVES: to determine the additive value of PSMA PET/CT to repeat multiparametric magnetic resonance imaging (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 mpMRI of the prostate (Prostate Imaging-Reporting and Data System score of <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. Also, a blood sample will be taken to perform a Prostate Health Index test at the time of confirmatory biopsy. Furthermore, a portion of this blood will be stored at a biobank for up to 5 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. PATIENTS AND METHODS: The CONFIRM trial is a prospective, multicentre, 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). RESULTS: 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. CONCLUSIONS: 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.

Comparison of 18F-based PSMA radiotracers with [68Ga]Ga-PSMA-11 in PET/CT imaging of prostate cancer-a systematic review and meta-analysis.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has become an increasingly established imaging modality in the staging of prostate cancer (PCa). Numerous PSMA-based tracers are currently available, however, there is a lack of consensus on the optimal radiotracer(s) for PSMA PET/CT. This study aims to investigate whether Fluorine-18 (18F)-labelled PSMA PET/CT is significantly different from Gallium-68 (68Ga) in primary diagnosis and/or secondary staging of prostate cancer following biochemical recurrence. METHODS: A critical review of MEDLINE, EMBASE, PubMed and Web of Science databases was performed in May 2023 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Studies that directly compared 18F-based PSMA radiotracers and [68Ga]Ga-PSMA-11 in terms of the normal organ SUV or the lesion SUV or the detection rate were assessed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). RESULTS: Twenty-four studies were analysed. [18F]DCFPyL and [18F]PSMA-1007 were the two most commonly studied 18F based PSMA tracers. [18F]JK-PSMA-7, [18F]rhPSMA-7, [18F]AlF-PSMA-11 were the new tracers evaluated in a limited number of studies. Overall, [18F]DCFPyL was observed to have a similar lesion detection rate to [68Ga]Ga-PSMA-11 with no increase in false positive rates. [18F]PSMA-1007 was found to have a greater local lesion detection rate because of its predominant hepatobiliary excretory route. However, [68Ga]Ga-PSMA-11 was observed to have a similar local lesion detection rate in studies that administer patients with furosemide prior to the scan. In addition, [18F]PSMA-1007 was found to have a significant number of benign bone uptakes. CONCLUSIONS: [18F]DCFPyL was observed to be similar to [68Ga]Ga-PSMA-11. [18F]PSMA-1007 was observed to be less preferrable to [68Ga]Ga-PSMA-11 due to its high benign bone uptakes. Overall, there was not enough evidence in differentiating the radiotracers based on their clinical impacts.

Irreversible Electroporation for Prostate Cancer.

Although it can be lethal in its advanced stage, prostate cancer can be effectively treated when it is localised. Traditionally, radical prostatectomy (RP) or radiotherapy (RT) were used to treat all men with localised prostate cancer; however, this has significant risks of post-treatment side effects. Focal therapy has emerged as a potential form of treatment that can achieve similar oncological outcomes to radical treatment while preserving functional outcomes and decreasing rates of adverse effects. Irreversible electroporation (IRE) is one such form of focal therapy which utilises pulsatile electrical currents to ablate tissue. This modality of treatment is still in an early research phase, with studies showing that IRE is a safe procedure that can offer good short-term oncological outcomes whilst carrying a lower risk of poor functional outcomes. We believe that based on these results, future well-designed clinical trials are warranted to truly assess its efficacy in treating men with localised prostate cancer.