Predicting the Need for Biopsy to Detect Clinically Significant Prostate Cancer in Patients with a Magnetic Resonance Imaging-detected Prostate Imaging Reporting and Data System/Likert ≥3 Lesion: Development and Multinational External Validation of the Imperial Rapid Access to Prostate Imaging and Diagnosis Risk Score.

BACKGROUND: Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy. OBJECTIVE: 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). DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTION: 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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). CONCLUSIONS: 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. PATIENT SUMMARY: 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.

The Mount Sinai Prebiopsy Risk Calculator for Predicting any Prostate Cancer and Clinically Significant Prostate Cancer: Development of a Risk Predictive Tool and Validation with Advanced Neural Networking, Prostate Magnetic Resonance Imaging Outcome Database, and European Randomized Study of Screening for Prostate Cancer Risk Calculator.

Background: 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. Objective: 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. Design setting and participants: Institutional review board-approved prospective data of 1902 men undergoing biopsy from October 2013 to September 2021 at Mount Sinai were collected. Outcome measurements and statistical analysis: 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. Results and limitations: 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. Conclusions: 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. Patient summary: 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.

Effect of information on prostate biopsy history on biopsy outcomes in the era of MRI-targeted biopsies.

PURPOSE: To describe the predictive value of information on previous benign biopsy for the outcome of MRI-targeted biopsies. METHODS: An exploratory analysis was conducted using data from a prospective, multicenter, paired diagnostic study of 532 men undergoing diagnostics for prostate cancer during 2016-2017. All men underwent 1.5 T MRI; systematic prostate biopsies; and MRI-targeted biopsies to MRI lesions with Prostate Imaging Reporting and Data System version 2, PI-RADS ≥ 3. The main outcome was numbers of detected prostate cancer characterized by grade group (GG) where GG ≥ 2 defined clinically significant cancer (csPCa). RESULTS: Men with previous biopsies had significantly more often negative MRI (26% vs. 17%, p < 0.05) compared to men without previous biopsies. Men with previous biopsies showed higher rates of benign biopsies (41% vs. 26%, p < 0.05) and lower rates of GG2 (17% vs. 30%, p < 0.05) and GG ≥ 3 (5% vs. 10%, p < 0.05) cancer. Biopsy-naïve men had higher proportions of highly suspicious MRI lesions (PIRADS 5; p < 0.05) and a higher proportion of significant cancer in those lesions (p = 0.05). In multivariate regression analysis, a previous benign prostate biopsy was associated with less than half the odds of csPCa (OR 0.38; 95% CI 0.20-0.71). CONCLUSION: In this large prospective multicenter trial, we showed that men with a previous prostate biopsy had higher proportions of MRIs without lesions and lower proportion of highly suspicious lesions than biopsy-naïve men. Further, biopsy-naïve men showed higher detection of clinically significant cancer when using MRI-targeted biopsies. Also, in the era of MRI-targeted biopsy strategies, biopsy history should be carefully considered in biopsy decisions. TRIAL REGISTRATION: NCT02788825 (ClinicalTrials.gov). Date of registration June 2, 2016.

Biomarker discrimination and calibration with MRI-targeted biopsies: an analysis with the Stockholm3 test.

BACKGROUND: The validated Stockholm3 test is used to improve PC detection. Stockholm3, however, was developed using systematic biopsies. We aimed to assess Stockholm3 operating performance when using MRI-targeted biopsies for PC detection. METHODS: A prospective cohort of 532 men was considered for prostate biopsy during 2016-2017. All men underwent Stockholm3 testing and MRI before biopsy. All PIRADs ≥3 lesion underwent targeted biopsy; all men underwent systematic biopsy. The primary outcome was ISUP Grade Group ≥2 (GG ≥ 2) PC. Detection strategies included: (1) systematic biopsies alone, (2) targeted biopsies alone, (3) targeted with associated systematic biopsies for MRI+, and (4) all biopsies in all men. For each strategy, the Stockholm3 operating characteristics were assessed with discrimination, calibration, and decision curve analysis (DCA). RESULTS: Median age was 65 years, median PSA was 6.2 ng/mL, median Stockholm3 score was 16.5%, and overall detection of GG ≥ 2 PC was 36% (193/532). Stockholm3 showed accurate discrimination for separating GG ≥ 2 cancer from benign and GG1, with an area under the curve of 0.84-0.86 depending on the biopsy strategy. Calibration analysis showed that Stockholm3 underestimated risks for GG ≥ 2 PC risk using MRI-targeted biopsies: there was a net benefit over biopsies in all men for Stockholm3 at risk thresholds varying from >3% in systematic biopsies to >15% in targeted with systematic biopsies in MRI+ men. When using a Stockholm3 score of >10% cutoff, a range of 32-38% of biopsies could be avoided while missing 5-11% of GG ≥ 2 PC and 0-3% of GG ≥ 3 PC. CONCLUSIONS: Stockholm3 shows high discriminatory performance in an MRI-targeted biopsy setting, however risks are underpredicted due to MRI-targeted biopsies being more sensitive than the systematic biopsies for which Stockholm3 was developed. Stockholm3, along with any risk prediction model developed for systematic prostate biopsy decisions, will need recalibration for optimal use in an MRI-driven biopsy setting.

Combined Use of Prostate-specific Antigen Density and Magnetic Resonance Imaging for Prostate Biopsy Decision Planning: A Retrospective Multi-institutional Study Using the Prostate Magnetic Resonance Imaging Outcome Database (PROMOD).

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. RESULTS AND LIMITATIONS: 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.

Prostate Cancer Diagnostics Using a Combination of the Stockholm3 Blood Test and Multiparametric Magnetic Resonance Imaging.

BACKGROUND: More specific diagnostic for prostate cancer is needed to decrease overdetection and number of diagnostic procedures. OBJECTIVE: To assess the performance of combining a blood-based biomarker panel and magnetic resonance imaging (MRI)-targeted biopsies for prostate cancer detection. DESIGN, SETTING, AND PARTICIPANTS: We used a prospective, multicenter, paired diagnostic study design. A total of 532 men aged 45-74 yr referred for prostate cancer workup were included during 2016-2017. INTERVENTION: Participants underwent blood sampling for analysis of the Stockholm3 test including protein biomarkers, genetic polymorphisms, and clinical variables; 1.5 T MRI; systematic prostate biopsies; and MRI-targeted biopsies to lesions with Prostate Imaging Reporting and Data System version 2 ≥3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcome was numbers of detected prostate cancer characterized by grade group (GG) and the number of performed biopsies using relative sensitivity (RS). RESULTS AND LIMITATIONS: Median prostate-specific antigen was 6.3 ng/ml, and mean age was 63.9 yr. Targeted and systematic biopsies detected 170 and 162 GG ≥2 tumors, respectively (RS 1.05; 95% confidence interval [CI] 0.96-1.14). Compared with performing systematic biopsies on all men, performing targeted and systematic biopsies only on men with >10% risk of GG ≥2 cancer, as predicted by the Stockholm3 test, required 62% (95% CI 58-66) of the biopsy procedures and detected 58% (95% CI 48-70) of GG 1 disease, with increased sensitivity for GG ≥2 detection (RS 1.10; 95% CI 1.02-1.17). Performing only targeted biopsies in men with elevated Stockholm3 test altered these results only slightly. Compared with performing systematic and targeted biopsies on all men, performing this only for men with an elevated Stockholm3 test decreased detection of GG ≥2 cancer slightly (RS 0.92; 95% CI 0.88-0.95). Limitations include lacking knowledge of true disease prevalence. CONCLUSIONS: These findings provide evidence that strategies combining the blood-based Stockholm3 test and MRI-targeted biopsies can be used to inform biopsy decision making. PATIENT SUMMARY: In this study, 532 men coming for prostate cancer workup underwent blood sampling, and both traditional and magnetic resonance imaging/fusion-guided prostate biopsies. We report that performing targeted biopsies only in men with an elevated risk as assessed by the Stockholm3 test saved biopsies, decreased overdetection, and maintained the number of detected high-grade cancers.

Detection of Prostate Cancer Using a Multistep Approach with Prostate-specific Antigen, the Stockholm 3 Test, and Targeted Biopsies: The STHLM3 MRI Project.

There is a distinct need for clinical improvements to the pipeline for prostate detection. The aim of the STHLM3 magnetic resonance imaging (MRI) study is to provide evidence of an improved and structured multistep pipeline for prostate cancer detection using the bloodbased Stockholm 3 test and MRI to achieve better specificity and reduce the risk of overdiagnosis.