Background: Previous studies suggested that prostate-specific antigen (PSA) density (PSAd) combined with magnetic resonance imaging (MRI) may help avoid unnecessary prostate biopsy (PB) with a limited risk of missing clinically significant prostate cancer (csPCa; Gleason grade group [GGG] >1). Objective: To define optimal diagnostic strategies based on the combined use of PSAd and MRI in patients at risk of prostate cancer (PCa). Design, setting, and participants: A retrospective analysis of the international multicenter Prostate MRI Outcome Database (PROMOD), including 2512 men having undergone PSAd and prostate MRI before PB between 2013 and 2019, was performed. Outcome measurements and statistical analysis: Rates of avoided PB, missed GGG 1, and csPCa according to 10 strategies based on PSAd values and MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]/Likert/IMPROD biparametric prostate MRI Likert). Decision curve analysis (DCA) was used to statistically compare the net benefit of each strategy. Combined systematic and targeted biopsies were used for reference.
Background Magnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption. Methods and findings The aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3–5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1–2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy—including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value—of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score ≥ 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%–98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings. Conclusions IMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial. Trial registration ClinicalTrials.gov NCT02241122 .
Prostate cancer is one of the most common and heritable human cancers. Our aim was to find germline biomarkers that can predict disease outcome. We previously detected predisposing signals at 2q37, the location of the prostate specific ANO7 gene. To investigate, in detail, the associations between the ANO7 gene and PrCa risk and disease aggressiveness, ANO7 was sequenced in castration resistant tumors together with samples from unselected PrCa patients and unaffected males. Two pathogenic variants were discovered and genotyped in 1769 patients and 1711 unaffected males. Expression of ANO7 vs. PrCa aggressiveness was investigated. Different databases along with Swedish and Norwegian cohorts were used for validation. Case-control and aggressive vs. nonaggressive association analyses were performed against risk and/or cancer aggressiveness. The ANO7 mRNA level and patient survival were analyzed using expression data from databases. Variant rs77559646 showed both risk (OR 1.40; p = 0.009, 95% CI 1.09-1.78) and association with aggressive PrCa (Genotype test p = 0.04). It was found to be an eQTL for ANO7 (Linear model p-values for Finnish patients p = 0.009; Camcap prostate tumor p = 2.53E-06; Stockholm prostate tumor cohort p = 1.53E-13). rs148609049 was not associated with risk, but was related to shorter survival (HR 1.56; 95% CI 1.03-2.36). High ANO7 expression was independently linked to poor survival (HR 18.4; 95% CI 1.43-237). ANO7 genotypes correlate with expression and biochemical relapse, suggesting that ANO7 is a potential PrCa susceptibility gene and that its elevated expression correlates with disease severity and outcome.
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