Context: MRI-targeted prostate biopsy (MRI-TB) may be an alternative to systematic biopsy for diagnosing prostate cancer.Objective: The primary aims of this systematic review and meta-analysis were to compare the detection rates of clinically significant and clinically insignificant cancer by MRI-TB to systematic biopsy in men undergoing prostate biopsy to identify prostate cancer. Evidence acquisition: A literature search was conducted using the PubMed, Embase, Web of Science, Cochrane library and Clinicaltrials.gov databases. We included prospective and retrospective paired studies where the index test was MRI-TB and the comparator test was systematic biopsy. We also included randomized controlled trials (RCTs) if one arm included MRI-TB and another arm included systematic biopsy. The risk of bias was assessed using a modified Quality Assessment of Diagnostic Accuracy Studies-2 checklist. In addition, the Cochrane risk of bias 2.0 tool was used for RCTs.Evidence Synthesis: We included 68 studies with a paired design and 8 RCTs, comprising a total of 14709 men who received either both MRI-TB and systematic biopsy or were randomized to receive one of the tests. MRI-TB detected more men with clinically significant cancer than systematic biopsy (Detection ratio (DR) 1.16 [95% CI 1.09-1.24], p < 0.0001) and fewer men with clinically insignificant cancer than systematic biopsy (DR 0.66 [95% CI 0.57-0.76], p < 0.0001). The proportion of cores positive for cancer was greater for MRI-TB than systematic biopsy, relative risk 3.17 [95% CI 2.82-3.56], p<0.0001.Conclusions: MRI-TB is an attractive alternative diagnostic strategy to systematic biopsy. Patient summary:We evaluated the published literature, comparing two methods of diagnosing prostate cancer. We found that biopsies targeted to suspicious areas on an MRI (MRI-Targeted biopsy) were better at detecting prostate cancer that needs to be treated and at avoiding the diagnosis of disease that doesn't need treatment than the traditional systematic biopsy.

BackgroundIntratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies.Patients and methodsForty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy. Seventy-nine tumour regions from 25 patients with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification.ResultsWe demonstrated extensive somatic nucleotide variation and somatic copy number alteration heterogeneity in high-risk PC. Overall, the mutational burden was low (0.93/Megabase), but two patients had hypermutation, with loss of mismatch repair (MMR) proteins, MSH2 and MSH6. Somatic copy number alteration burden was higher in patients with metastatic hormone-naive PC (mHNPC) than in those with high-risk localised PC (hrlPC), independent of Gleason grade. Mutations were rarely ubiquitous and mutational frequencies were similar for mHNPC and hrlPC patients. Enrichment of focal 3q26.2 and 3q21.3, regions containing putative metastasis drivers, was seen in mHNPC patients. We found evidence of parallel evolution with three separate clones containing activating mutations of β-catenin in a single patient. We demonstrated extensive intratumoural and intertumoural T-cell heterogeneity and high inflammatory infiltrate in the MMR-deficient (MMRD) patients and the patient with parallel evolution of β-catenin. Analysis of all patients with activating Wnt/β-catenin mutations demonstrated a low CD8+/FOXP3+ ratio, a potential surrogate marker of immune evasion.ConclusionsThe PROGENY (PROstate cancer GENomic heterogeneitY) study provides a diagnostic platform suitable for studying tumour ITH. Genetic aberrations in clinically high-risk PC are associated with altered patterns of immune infiltrate in tumours. Activating mutations of Wnt/β-catenin signalling pathway or MMRD could be considered as potential biomarkers for immunomodulation therapies.Clinical Trials.gov IdentifierNCT02022371

e17500 Background: IT heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease and patient outcomes are uncertain. Methods: This was a prospective, single-arm, translational study using targeted multi-region prostate biopsies to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. A pre-defined exploratory objective was to evaluate the association of ITH, median inflammatory infiltrate (MII), total, clonal and neoantigens, with overall survival (OS) and time-to-next-line of therapy (TTNL). Results: 49 men with elevated prostate-specific antigen (PSA) and multiparametric-magnetic resonance imaging (MRI) detected PC underwent image-guided multiregion transperineal biopsy. 79 tumour regions from 25 patients (pts) with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification. The median follow-up was 60 months (m) with 10 death events. For %ITH, MII, total, clonal and subclonal neoantigens, patients were split by the median. Conclusions: The PROGENY study provides a diagnostic platform suitable for studying tumour ITH and has the potential to identify poor outcome subgroups in PC. Larger sample numbers in prospective trials are warranted to further investigate this hypothesis. [Table: see text]

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