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.
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.
IMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial.
ClinicalTrials.gov NCT02241122.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
We aimed to develop and externally validate a nomogram based on MRI volumetric parameters and clinical information for deciding when SBx should be performed in addition to TBx in man with ...suspicious prostate MRI.
Materials and methods
Retrospective analyses of single (IMPROD, NCT01864135) and multi-institution (MULTI-IMPROD, NCT02241122) clinical trials. All men underwent a unique rapid biparametric magnetic resonance imaging (IMPROD bpMRI) consisting of T2-weighted imaging and three separate DWI acquisitions. Men with IMPROD bpMRI Likert scores of 3–5 were included. Logistic regression models were developed using IMPROD trial (
n
= 122) and validated using MULTI-IMPROD trial (
n
= 262) data. The model’s performance was evaluated in the terms of PCa detection with Gleason Grade Group 1 (clinically insignificant prostate cancer, iPCa) and > 1 (clinically significant prostate cancer, csPCa). Net benefits and decision curve analyses (DCA) were compared. Combined biopsies were used for reference.
Results
The developed nomogram included age, PSA, prostate volume, MRI suspicion score (IMPROD bpMRI Likert or PIRADsv2.1 score), MRI-suspicion lesion volume percentage, and lesion location. All these variables were significant predictors of csPCa in SBx in multivariable analysis. In the validation cohort (
n
= 262) using different nomogram cutoffs, 19–43% of men would have avoided SBx while missing 1–4% of csPCa and avoiding detection of 9–20% of iPCa. Similar performance was found for nomograms using IMPROD bpMRI Likert score or v2.1.
Conclusions
The developed nomogram demonstrated potential to select men with a clinical suspicion of PCa who would benefit from performing SBx in addition to TBx. Public access to the nomogram is provided at:
https://petiv.utu.fi/multiimprod/
.
Gut microbiota of the prostate cancer patients is altered significantly compared with that of benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential ...mechanisms of action. These findings support the previously observed association of lifestyle, geography, and prostate cancer incidence.
Although prostate cancer (PCa) is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies, or differences in lifestyle. Gut microbiota has recently been associated with cancer progression, but its role in PCa is unclear.
Characterization of the gut microbiota and its functions associated with PCa.
In a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing.
Sequences were assigned to operational taxonomic units, differential abundance analysis, and α- and β-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated.
Of 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level.
Gut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence.
In this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.
Prostate Magnetic Resonance Imaging (MRI) is increasingly being used in men with a clinical suspicion of prostate cancer (PCa). Performing prostate MRI without the use of an intravenous contrast (IV) ...agent in men with a clinical suspicion of PCa can lead to reduced MRI scan time. Enabling a large array of different medical providers (from mid-level to specialized radiologists) to evaluate and potentially report prostate MRI in men with a clinical suspicion of PCa with a high accuracy could be one way to enable wide adoption of prostate MRI in men with a clinical suspicion of PCa. The aim of this pictorial review is to provide an insight into acquisition, quality control and reporting of prostate MRI performed without IV contrast agent in men with a clinical suspicion of PCa, aimed specifically at radiologists starting reporting prostate MRI, urologists, urology/radiology residents and mid-level medical providers without experience in reporting prostate MRI. Free public access (http://petiv.utu.fi/improd/and http://petiv.utu.fi/multiimprod/) to complete datasets of 161 and 338 men is provided. The imaging datasets are accompanied by clinical, laboratory and histopathological findings. Several topics are simplified in order to provide a solid base for the development of skills needed for an unsupervised review and potential reporting of prostate MRI in men with a clinical suspicion of PCa. The current review represents the first step towards enabling a large array of different medical providers to review and report accurately prostate MRI performed without IV contrast agent in men with a clinical suspicion of PCa.
We developed the Mount Sinai Prebiopsy Risk Calculator (MSP-RC) to assess the likelihood of any prostate cancer and clinically significant disease based on a combination of clinical and imaging ...characteristics. MSP-RC is applicable to all patient settings and accessible online.
The European Association of Urology guidelines recommend the use of imaging, biomarkers, and risk calculators in men at risk of prostate cancer. Risk predictive calculators that combine multiparametric magnetic resonance imaging with prebiopsy variables aid as an individualized decision-making tool for patients at risk of prostate cancer, and advanced neural networking increases reliability of these tools.
To develop a comprehensive risk predictive online web-based tool using magnetic resonance imaging (MRI) and clinical data, to predict the risk of any prostate cancer (PCa) and clinically significant PCa (csPCa) applicable to biopsy-naïve men, men with a prior negative biopsy, men with prior positive low-grade cancer, and men with negative MRI.
Institutional review board–approved prospective data of 1902 men undergoing biopsy from October 2013 to September 2021 at Mount Sinai were collected.
Univariable and multivariable analyses were used to evaluate clinical variables such as age, race, digital rectal examination, family history, prostate-specific antigen (PSA), biopsy status, Prostate Imaging Reporting and Data System score, and prostate volume, which emerged as predictors for any PCa and csPCa. Binary logistic regression was performed to study the probability. Validation was performed with advanced neural networking (ANN), multi-institutional European cohort (Prostate MRI Outcome Database PROMOD), and European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC RC) 3/4.
Overall, 2363 biopsies had complete clinical information, with 57.98% any cancer and 31.40% csPCa. The prediction model was significantly associated with both any PCa and csPCa having an area under the curve (AUC) of 81.9% including clinical data. The AUC for external validation was calculated in PROMOD, ERSPC RC, and ANN for any PCa (0.82 vs 0.70 vs 0.90) and csPCa (0.82 vs 0.78 vs 0.92), respectively. This study is limited by its retrospective design and overestimation of csPCa in the PROMOD cohort.
The Mount Sinai Prebiopsy Risk Calculator combines PSA, imaging and clinical data to predict the risk of any PCa and csPCa for all patient settings. With accurate validation results in a large European cohort, ERSPC RC, and ANN, it exhibits its efficiency and applicability in a more generalized population. This calculator is available online in the form of a free web-based tool that can aid clinicians in better patients counseling and treatment decision-making.
We developed the Mount Sinai Prebiopsy Risk Calculator (MSP-RC) to assess the likelihood of any prostate cancer and clinically significant disease based on a combination of clinical and imaging characteristics. MSP-RC is applicable to all patient settings and accessible online.
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.
What's new?
The discovery of germline biomarkers to predict outcome in prostate cancer could greatly aid disease management. One such marker of particular interest in this regard is the prostate‐specific gene ANO7, which previous studies have associated with high‐grade prostate cancer. Here, specific germline ANO7 genotypes were associated with increased prostate cancer risk. In patients, ANO7 expression correlated with disease severity, with elevated expression associated with decreased overall survival. The data suggest that ANO7 is a susceptibility marker in prostate cancer and, with further characterization, could be used to inform patient selection strategies and therapeutic approaches.
The five-item Imperial Rapid Access to Prostate Imaging and Diagnosis risk score using age, prostate-specific antigen density, prior negative biopsy, prostate volume, and highest magnetic resonance ...imaging (MRI) score provides a standardised tool for the prediction of clinically significant prostate cancer in patients with an MRI-detected Prostate Imaging Reporting and Data System/Likert ≥3 lesion and can support the decision for prostate biopsy.
Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy.
To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa).
The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019.
Visual-registration or image-fusion targeted and systematic transperineal biopsies for an MRI score of ≥4 or 3 + PSA density ≥0.12 ng/ml/ml.
Fourteen variables were used in multivariable logistic regression for Gleason ≥3 + 4 (primary) and Gleason ≥4 + 3, and PROMIS definition 1 (any ≥4 + 3 or ≥6 mm any grade; secondary). Nomograms were created and a decision curve analysis (DCA) was performed. Models with varying complexity were externally validated in 2374 patients from six international cohorts.
The five-item Imperial RAPID risk score used age, PSA density, prior negative biopsy, prostate volume, and highest MRI score (corrected c-index for Gleason ≥3 + 4 of 0.82 and 0.80–0.86 externally). Incorporating family history, DRE, and Black ethnicity within the eight-item Imperial RAPID risk score provided similar outcomes. The DCA showed similar superiority of all models, with net benefit differences increasing in higher threshold probabilities. At 20%, 30%, and 40% of predicted Gleason ≥3 + 4 prostate cancer, the RAPID risk score was able to reduce, respectively, 11%, 21%, and 31% of biopsies against 1.8%, 6.2%, and 14% of missed csPCa (or 9.6%, 17%, and 26% of foregone biopsies, respectively).
The Imperial RAPID risk score provides a standardised tool for the prediction of csPCa in patients with an MRI-detected PIRADS/Likert ≥3 lesion and can support the decision for prostate biopsy.
In this multinational study, we developed a scoring system incorporating clinical and magnetic resonance imaging characteristics to predict which patients have prostate cancer requiring treatment and which patients can safely forego an invasive prostate biopsy. This model was validated in several other countries.
Background
Multiparametric MRI of the prostate has been shown to improve the risk stratification of men with an elevated prostate‐specific antigen (PSA). However, long acquisition time, high cost, ...and inter‐center/reader variability of a routine prostate multiparametric MRI limit its wider adoption.
Purpose
To develop and validate nomograms based on unique rapid biparametric MRI (bpMRI) qualitative and quantitative derived variables for prediction of clinically significant cancer (SPCa).
Study Type
Retrospective analyses of single (IMPROD, NCT01864135) and multiinstitution trials (MULTI‐IMPROD, NCT02241122).
Population
161 and 338 prospectively enrolled men who completed the IMPROD and MULTI‐IMPROD trials, respectively.
Field Strength/Sequence
IMPROD bpMRI: 3T/1.5T, T2‐weighted imaging, three separate diffusion‐weighted imaging (DWI) acquisitions: 1) b‐values 0, 100, 200, 300, 500 s/mm2; 2) b values 0, 1500 s/mm2; 3) values 0, 2000 s/mm2.
Assessment
The primary endpoint of the combined trial analysis was the diagnostic accuracy of the combination of IMPROD bpMRI and clinical variables for detection of SPCa.
Statistical Tests
Logistic regression models were developed using IMPROD trial data and validated using MULTI‐IMPROD trial data. The model's performance was expressed as the area under the curve (AUC) values for the detection of SPCa, defined as ISUP Gleason Grade Group ≥2.
Results
A model incorporating clinical variables had an AUC (95% confidence interval) of 0.83 (0.77–0.89) and 0.80 (0.75–0.85) in the development and validation cohorts, respectively. The corresponding values for a model using IMPROD bpMRI findings were 0.93 (0.89–0.97), and 0.88 (0.84–0.92), respectively. Further addition of the quantitative DWI‐based score did not improve AUC values (P < 0.05).
Data Conclusion
A prediction model using qualitative IMPROD bpMRI findings demonstrated high accuracy for predicting SPCa in men with an elevated PSA. Online risk calculator: http://petiv.utu.fi/multiimprod/
Level of Evidence: 1
Technical Efficacy Stage: 2
J. Magn. Reson. Imaging 2020;51:1556–1567.
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).
To define optimal diagnostic strategies based on the combined use of PSAd and MRI in patients at risk of prostate cancer (PCa).
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.
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.
According to DCA, the best strategy in biopsy-naive patients was #7 (PI-RADS/Likert 4–5 or PI-RADS/Likert 3 if PSAd >0.2), which avoided 41.2% PBs while missed 44% of GGG 1 and 10.9% of csPCa cases. From a clinical standpoint, however, strategies with a lower risk of missing csPCa included #10 (PI-RADS/Likert 4–5 or PI-RADS 3 if PSAd >0.10 or PSAd >0.2), which avoided 27% PBs while missing 24.4% GGG 1 and 4% csPCa cases, or #5 (PI-RADS/Likert 3-5 or PSAd>0.15), which avoided 14.7% PBs while missing 9.3% GGG 1 and 1.7% csPCa cases. Similar results were found in patients with a previous negative biopsy. This study is limited by its retrospective nature, and no central review of MRI and histopathological findings.
Combined PSAd and MRI findings allows individualization of the decision to perform PB on the basis of the risk of missing PCa that both patients and clinicians are ready to accept to avoid this procedure.
We compared several biopsy strategies based on a combination of prostate magnetic resonance imaging findings and prostate-specific antigen density, providing a readily available tool for each center and practicing urologist to counsel patients about their individual risk of significant prostate cancer.
Physicians should consider combining prostate-specific antigen density and magnetic resonance imaging findings to individualize the decision to perform prostate biopsy on the basis of the risk of missing prostate cancer that both patients and clinicians are ready to accept to avoid this procedure.
PDF
