Negative Multiparametric Magnetic Resonance Imaging Research Articles

The effect of the combination of prostate-specific antigen derivatives with multiparametric prostate magnetic resonance imaging scores on the negative predictive value of it in grey zone patients

ObjectiveTo calculate the negative predictive value (NPV) of negative multiparametric prostate magnetic resonance imaging (mpMRI), accepted as no lesions on images, when combined with prostate-specific antigen density (PSAD) and free/total prostate-specific antigen ratio (f/t PSA) in grey zone patients. Methods191 patients with PSA levels between 4−10 mg/mL and negative mpMRI were analyzed. The NPV of negative mpMRI was calculated according to a PSAD level of <0.15 ng/mL/mL, f/t PSA ratio of >0.15, and a combination of both. Patients were divided into three risk groups according to these two parameters, which were PSAD 0.01−0.07 ng/mL/mL and f/t PSA ratio ≥25 in a low-risk group, PSAD 0.08−0.15 ng/mL/mL, and f/t PSA ratio 0.15−0.24 in an intermediate-risk group and high-risk group, in which PSAD > 0.15 ng/mL/mL and f/t PSA ratio <15. ResultsNPV of negative mpMRI was 92.6% for clinically significant prostate carcinoma (CSPCa). It increased to 97.5% in a low-risk group and decreased to 33.3% for CSPCa in a high-risk group. NPV of negative mpMRI results were so close when combined with PSAD < 0.15 ng/mL/mL and f/t PSA > 15. Conclusionf/t PSA ratio might also be used to increase the NPV of mpMRI, like PSAD. We advise not to avoid prostate biopsy when PSAD is >0.15 ng/mL/mL and the f/t PSA ratio is <0.15. However, we need randomized controlled studies with more patients to confirm our study.

Evaluación del valor predictivo negativo de la resonancia magnética multiparamétrica de próstata al combinar su puntuación con parámetros del antígeno prostático específico en pacientes con PSA en zona gris

ObjectiveTo calculate the negative predictive value (NPV) of negative multiparametric prostate magnetic resonance imaging (mpMRI), accepted as no lesions on images, when combined with prostate-specific antigen density (PSAD) and free/total prostate-specific antigen ratio (f/t PSA) in grey zone patients. MethodsOne hundred ninety-one patients with PSA levels between 4-10mg/ml and negative mpMRI were analyzed. The NPV of negative mpMRI was calculated according to a PSAD level of <0.15 ng/ml/ml, f/t PSA ratio of >0.15, and a combination of both. Patients were divided into three risk groups according to these two parameters:•PSAD 0.01-0.07 ng/ml/ml and f/t PSA ratio ≥25 in a low-risk group.•PSAD 0.08-0.15 ng/ml/ml, and f/t PSA ratio 0.15-0.24 in an intermediate-risk group and high-risk group.•PSAD>0.15 ng/ml/ml and f/t PSA ratio <15 in high-risk group, ResultsNPV of negative mpMRI was 92.6% for clinically significant prostate carcinoma (CSPCa). It increased to 97.5% in a low-risk group and decreased to 33.3% for CSPCa in a high-risk group. NPV of negative mpMRI results were so close when combined with PSAD <0.15 ng/ml/ml and f/t PSA>15. Conclusionf/t PSA ratio might also be used to increase the NPV of mpMRI, like PSAD. We advise not to avoid prostate biopsy when PSAD is >0.15 ng/ml/ml and the f/t PSA ratio is <0.15. However, we need randomized controlled studies with more patients to confirm our study.

Detection Rate of Prostate Cancer in Repeat Biopsy after an Initial Negative Magnetic Resonance Imaging/Ultrasound-Guided Biopsy.

A negative multiparametric magnetic resonance imaging (mpMRI)-guided prostate biopsy in patients with suspected prostate cancer (PC) results in clinical uncertainty, as the biopsy can be false negative. The clinical challenge is to determine the optimal follow-up and to select patients who will benefit from repeat biopsy. In this study, we evaluated the rate of significant PC (sPC, Gleason score ≥7) and PC detection in patients who received a follow-up mpMRI/ultrasound-guided biopsy for persistent PC suspicion after a negative mpMRI/ultrasound-guided biopsy. We identified 58 patients at our institution that underwent repeat targeted biopsy in case of PI-RADS lesions and systematic saturation biopsy between 2014 and 2022. At the initial biopsy, the median age was 59 years, and the median prostate specific antigen level was 6.7 ng/mL. Repeat biopsy after a median of 18 months detected sPC in 3/58 (5%) patients and Gleason score 6 PC in 11/58 (19%). Among 19 patients with a downgraded PI-RADS score at the follow-up mpMRI, none had sPC. In conclusion, men with an initial negative mpMRI/ultrasound-guided biopsy had a high likelihood of not harboring sPC at repeat biopsy (95%). Due to the small size of the study, further research is recommended.

Assessing the Role of High-resolution Microultrasound Among Naïve Patients with Negative Multiparametric Magnetic Resonance Imaging and a Persistently High Suspicion of Prostate Cancer

BackgroundMultiparametric magnetic resonance imaging (mpMRI) is an invaluable diagnostic tool in the decision-making for prostate biopsies (PBx). However, a non-negligible proportion of patients with negative MRI (nMRI) may still harbour prostate cancer (PCa). ObjectiveTo assess whether microultrasound (micro-US) can help in substratifying the presence of PCa and clinically significant PCa (csPCa; ie, any Gleason score ≥7 PCa) in patients with nMRI despite a persistently high clinical suspicion of PCa. Design, setting, and participantsA total of 125 biopsy-naïve patients who underwent micro-US–guided PBx with the ExactVu system for a persistently high suspicion of PCa despite nMRI were prospectively enrolled. InterventionThe Prostate Risk Identification using micro-US (PRI-MUS) protocol was used to identify suspicious areas; PBx included targeted sampling of PRI-MUS ≥3 areas and systematic sampling. Outcome measurements and statistical analysisThe primary endpoint was the assessment of micro-US diagnostic accuracy in detecting csPCa. Secondary endpoints included determining the proportion of patients with nMRI who may avoid PBx after micro-US or transrectal US, presence of cribriform and intraductal patterns on biopsy core examination, predictors of csPCa in patients presenting with nMRI, and comparing micro-US–targeted and systematic PBx in identifying csPCa. Results and limitationsConsidering csPCa detection rate, micro-US showed optimal sensitivity and negative predictive value (respectively, 97.1% and 96.4%), while specificity and positive predictive value were 29.7% and 34.0%, respectively. Twenty-eight (22.4%) patients with a negative micro-US examination could have avoided PBx with one (2.9%) missed csPCa. Cribriform and intraductal patterns were found in 14 (41.2%) and four (11.8%) of csPCa patients, respectively. In multivariable logistic regression models, positive micro-US, age, digital rectal examination, and prostate-specific antigen density ≥0.15 emerged as independent predictors of PCa. Targeted and systematic sampling identified 33 (97.1%) and 26 (76.5%) csPCa cases, respectively. The main limitation of the current study is represented by its retrospective single-centre nature on an operator-dependent technology. ConclusionsMicro-US represents a valuable tool to rule out the presence of csPCa among patients with a persistent clinical suspicion despite nMRI. Patient summaryAccording to our results, microultrasound (micro-US) may represent an effective tool for the diagnosis of clinically significant prostate cancer in patients with negative magnetic resonance imaging (nMRI), providing high sensitivity and negative predictive value. Further randomised studies are needed to confirm the potential role of micro-US in the diagnostic pathway of patients with a persistent suspicion of prostate cancer despite nMRI.

Negative multiparametric magnetic resonance imaging for prostate cancer: further outcome and consequences

PurposeEAU guidelines recommend multiparametric MRI of the prostate (mpMRI) prior to biopsy to increase accuracy and reduce biopsies. Whether biopsy can be avoided in case of negative mpMRI remains unclear. Aim of this study is to evaluate predictors of overall prostate cancer (PCa) in negative mpMRI.MethodsA total of 216 patients from 2018 to 2020 with suspicion of PCa and negative mpMRI (PI-RADS ≤ 2) were interviewed by telephone about outcome and further follow-up. Clinically significant PCa (csPCa) was defined as ISUP ≥ 2. Patients with vs. without biopsy and with vs. without PCa were compared. Univariate and multivariate analyses were performed to evaluate predictors of PCa occurrence in patients with negative mpMRI.Results15.7% and 5.1% of patients with PI-RADS ≤ 2 on mpMRI showed PCa and csPCa, respectively. PCa patients had higher PSAD (0.14 vs. 0.09 ng/ml2; p = 0.001) and lower prostate volume (50.5 vs. 74.0 ml; p = 0.003). Patients without biopsy (25%) after MRI were older (69 vs. 65.5 years; p = 0.027), showed lower PSA (5.7 vs. 6.73 ng/ml; p = 0.033) and lower PSA density (0.09 vs. 0.1 ng/ml2; p = 0.027). Multivariate analysis revealed age (OR 1.09 [1.02–1.16]; p = 0.011), prostate volume (OR 0.982 [0.065; 0.997]; p = 0.027), total PSA level (OR 1.22 [1.01–1.47], p = 0.033), free PSA (OR 0.431 [0.177; 0.927]; p = 0.049) and no PI-RADS lesion vs PI-RADS 1–2 lesion (OR 0.38 [0.15–0.91], p = 0.032.) as predictive factors for the endpoint presence of PCa.ConclusionsBiopsy for selected patient groups (higher age, prostate volume and free PSA as well as lower PSA-Density) with negative mpMRI can be avoided, if sufficient follow-up care is guaranteed. Detailed counseling regarding residual risk for undetected prostate cancer should be mandatory.

Population-based randomized trial of screening for clinically significant prostate cancer ProScreen: a pilot study.

ObjectivesTo evaluate the feasibility of a population‐based screening trial using prostate‐specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit.Patients and MethodsFeasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI‐RADS] score 3–5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies.ResultsOf the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA‐positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]‐positive) had a suspicious MRI finding (PI‐RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%.ConclusionThe findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal.

Diagnosis of clinically significant prostate cancer after negative multiparametric magnetic resonance imaging.

The diagnostic pathway after a negative magnetic resonance imaging (nMRI) exam is not clearly defined. The aim of the present study is to define the risk of prostate adenocarcinoma (PCa) at the prostate biopsy after a negative multiparametric magnetic resonance imaging (mpMRI) exam. Patients with nMRI Prostate Imaging Reporting & Data System (PI-RADS) ≤2 and without a previous diagnosis of PCa were identified among all patients undergoing mpMRI in a single referral center between 01/2016-12/2019. Detailed data about prostate biopsy after nMRI were collected, including any PCa diagnosis and clinically significant PCa diagnosis. [Gleason score (GS) ≥7]. In addition to descriptive statistics, uni and multivariable logistic regression assessed the potential predictors of any PCa and clinically significant prostate cancer (csPCa) at the biopsy after a negative mpMRI. Of 410 patients with nMRI, 73 underwent saturation biopsy. Only prostate-specific antigen (PSA) levels were significantly higher in patients undergoing biopsy (5.2 ng/ml vs 6.4, p <0.001), while Prostate Cancer Research Foundation (SWOP - Stichting Wetenschappelijk Onderzoek Prostaatkanker) risk score and other variables did not differ. A total of 22 biopsies (30.1%) were positive for PCa, GS 6 was diagnosed in 14 patients, GS 7 in 3, GS 8 in 1 and GS 9-10 in 4. csPCa was found in 8 (11%) patients. No significant predictors of any PCa or csPCa were identified at multivariate regression analysis. Despite the good negative predictive value of mpMRI in the diagnosis of prostate cancer, 11% of the patients had csPCa. Specific predictive models addressing this setting would be useful.

The role of prostate-specific antigen density and negative multiparametric magnetic resonance imaging in excluding prostate cancer for biopsy-naïve men: clinical outcomes from a high-volume center in China.

This study aimed to assess the role of prostate-specific antigen density (PSAD) and negative multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer for biopsy-naïve men based on a large cohort of the Chinese population. From a prostate biopsy database between March 2017 and July 2021, we retrospectively identified 240 biopsy-naïve patients with negative prebiopsy mpMRI (Prostate Imaging Reporting and Data System version 2 [PI-RADS v2] score <3). Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer (csPCa). Receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) were performed to assess the diagnostic accuracy. The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8% (201/240) and 90.8% (218/240), respectively. ROC curve analysis indicated that PSAD was the most promising predictor, with an AUC value of 0.786 (95% confidence interval [CI]: 0.699-0.874), and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa (odds ratio [OR]: 10.99, 95% CI: 2.75-44.02, P < 0.001). Combining negative mpMRI and PSAD below 0.20 ng ml-2 obviously increased the predictive value in excluding PCa (91.0%, 101/111) or csPCa (100.0%, 111/111). If a PSAD below 0.20 ng ml-2 was set as the criterion to omit biopsy, nearly 46.3% of patients (463 per 1000) with negative mpMRI could safely avoid unnecessary biopsy, with approximately 4.2% of patients (42 per 1000) at risk of missed diagnosis of PCa and no patients with csPCa missed. A PI-RADS v2 score <3 and a PSAD <0.20 ng ml-2 could be potential criteria for the Chinese population to omit prompt biopsy safely.

How Many Cores Should Be Sampled during Systematic Prostate Biopsy in Case of Negative Multiparametric Magnetic Resonance Imaging? Analysis of 274 Men with Clinical Suspicion of Prostate Cancer

Introduction: This study aimed to investigate the number of cores needed in a systematic biopsy (SB) in men with clinical suspicion of prostate cancer (PCa) but negative prebiopsy multiparametric magnetic resonance imaging and to test prostate-specific antigen (PSA) density as an indicator for reduced SB. Methods: Two hundred and seventy-four patients were analyzed, extracted from an institutional database. Detection rates of any PCa and clinically significant (CS) PCa for different reduced biopsy protocols were compared by using Fisher’s exact test. Results: In total, 12-core SB revealed PCa in 103 (37.6%) men. Detection rates of reduced biopsy protocols were 74 (27%, 6-core) and 82 (29.9%, 8-core). Regarding CSPCa, 12-core SB revealed a detection rate of 26 (9.5%). Reduced biopsy protocols detected less CSPCa: 15 (5.5%) and 18 (6.6%), respectively. All differences were statistically significant, p < 0.05. PSA density ≥0.15 did not help to filter out men in whom a reduced biopsy may be sufficient. Conclusions: Twelve-core SB still has the highest detection rate of any PCa and CSPCa compared to reduced biopsy protocols. If the investigator and patient agree – based on individual risk calculation – to perform a biopsy, this SB should contain at least 12 cores regardless of PSA density.

Clinical Utility of Negative Multiparametric Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer and Clinically Significant Prostate Cancer

BackgroundMultiparametric magnetic resonance imaging (MRI) is increasingly used to diagnose prostate cancer (PCa). It is not yet established whether all men with negative MRI (Prostate Imaging-Reporting and Data System version 2 score <3) should undergo prostate biopsy or not. ObjectiveTo develop and validate a prediction model that uses clinical parameters to reduce unnecessary prostate biopsies by predicting PCa and clinically significant PCa (csPCa) for men with negative MRI findings who are at risk of harboring PCa. Design, setting, and participantsThis was a retrospective analysis of 200 men with negative MRI at risk of PCa who underwent prostate biopsy (2014–2020) with prostate-specific antigen (PSA) >4 ng/ml, 4Kscore of >7%, PSA density ≥0.15 ng/ml/cm3, and/or suspicious digital rectal examination. The validation cohort included 182 men from another centre (University of Miami) with negative MRI who underwent systematic prostate biopsy with the same criteria. Outcome measurements and statistical analysiscsPCa was defined as Gleason grade group ≥2 on biopsy. Multivariable logistic regression analysis was performed using coefficients of logit function for predicting PCa and csPCa. Nomogram validation was performed by calculating the area under receiver operating characteristic curves (AUC) and comparing nomogram-predicted probabilities with actual rates of PCa and csPCa. Results and limitationsOf 200 men in the development cohort, 18% showed PCa and 8% showed csPCa on biopsy. Of 182 men in the validation cohort, 21% showed PCa and 6% showed csPCa on biopsy. PSA density, 4Kscore, and family history of PCa were significant predictors for PCa and csPCa. The AUC was 0.80 and 0.87 for prediction of PCa and csPCa, respectively. There was agreement between predicted and actual rates of PCa in the validation cohort. Using the prediction model at threshold of 40, 47% of benign biopsies and 15% of indolent PCa cases diagnosed could be avoided, while missing 10% of csPCa cases. The small sample size and number of events are limitations of the study. ConclusionsOur prediction model can reduce the number of prostate biopsies among men with negative MRI without compromising the detection of csPCa. Patient summaryWe developed a tool for selection of men with negative MRI (magnetic resonance imaging) findings for prostate cancer who should undergo prostate biopsy. This risk prediction tool safely reduces the number of men who need to undergo the procedure.

The role of multiparametric MRI in active surveillance for low-risk prostate cancer: The ROMAS randomized controlled trial

BackgroundWe aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial. Materials and methodsBetween 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading. ResultsA total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001). ConclusionsThe early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy.

EP011 - Factors predicting positive saturation biopsy in prostate cancer patients with prior negative multiparametric magnetic resonance imaging

EP011 - Factors predicting positive saturation biopsy in prostate cancer patients with prior negative multiparametric magnetic resonance imaging

Clinical Utility of 4Kscore ® , ExosomeDx™ and Magnetic Resonance Imaging for the Early Detection of High Grade Prostate Cancer

We aimed to evaluate 4Kscore® and ExosomeDx™ with multiparametric magnetic resonance imaging in the detection of high grade prostate cancer and number of biopsies avoided. Patients had 1 liquid biomarker test with or without multiparametric magnetic resonance imaging. High grade prostate cancer was defined as Gleason grade group 2 or greater. The overall number of avoided biopsies (with Gleason grade 1 or less), and number of missed Gleason grade 2 or greater cancer among the biopsied patients, were determined. Of the 783 patients in the overall cohort 419 (53.5%) underwent biopsy. 4Kscore and ExosomeDx scores higher than the manufacturers' cut point were associated with PI-RADS™ scores 3 to 5 and Gleason grade 2 or greater prostate cancer. Limiting biopsy to the men with liquid biomarker scores above the manufacturers' cut point would have resulted avoiding 29.5% to 39.9% unnecessary biopsies overall, while missing 4.0% to 4.8% Gleason grade 2 or greater prostate cancer in the biopsy group. Screening algorithms with up-front liquid biomarker testing followed by multiparametric magnetic resonance imaging if the biomarker is above the manufacturers' cut point, then followed by biopsy if the multiparametric magnetic resonance imaging is positive or if 4Kscore 20 or greater or ExosomeDx 19 or greater would have missed 4.8% to 5.6% of Gleason grade 2 or greater prostate cancer in the biopsy group while avoiding 39.4% to 43.0% biopsies and 29.5% to 39.9% multiparametric magnetic resonance imaging overall. Similar algorithms with up-front multiparametric magnetic resonance imaging followed by liquid biomarker testing for negative multiparametric magnetic resonance imaging would have missed 2.4% of Gleason grade 2 or greater prostate cancer in the biopsy group but only avoided 17.2% 19.3% biopsies overall. Screening algorithms with up-front liquid biomarker testing followed by multiparametric magnetic resonance imaging and biopsy at certain biomarker thresholds could reduce unnecessary biopsies, multiparametric magnetic resonance imaging and overdetection of Gleason grade 1 prostate cancer.

Abstract 2301: Indications for systematic prostate biopsy in men with negative multi-parametric magnetic resonance imaging

Abstract Introduction: Multiparametric Magnetic Resonance Imaging (mpMRI) is a valuable tool in the prostate cancer diagnostic pathway, and MRI-influenced biopsy has been shown to be superior to systematic biopsy alone for detecting clinically significant prostate cancer (csPCa), defined as the presence of any Gleason ≥ 4. Negative predictive value of mpMRI for csPCa varies widely in published reports, with a median of approximately 88%. Counselling patients with negative mpMRI (PIRADS score &amp;lt;3)to decide whether or not to proceed with systematic biopsy or PSA monitoring could be challenging. Several studies have shown that a PSA density (PSAD) ≥ 0.15 is an indication for systematic biopsy. We analysed the clinical, radiological and pathological features of patients with negative mpMRI but csPca on systematic biopsy to identify other criteria that may inform the need for systematic biopsy when mpMRI is negative. Methods: For 18 months between Nov 2017 and May 2019, all men on our prostate diagnostic pathway with negative mpMRI were offered systematic biopsy. The criteria for pre-biopsy mpMRI was any man suitable for radical surgery or radiotherapy, plus one or more of PSA ≥ 3, palpable lesion on digital rectal examination, or family history of PCa in a first degree relative (father or brother). mpMRI was performed with a 1.5-Tesla magnet and included T2, DWI and DCE sequences. Systematic biopsy was TRUS-guided, with 8-16 biopsy cores. Results: Of 589 mpMRI scans in 573 men, 216 (37%) had negative mpMRI. Of these, 141 (65%) proceeded with systematic biopsy. Among the men that had biopsy, Gleason 3+3 was detected in 12 men (9%) and Gleason ≥ 4 in six (4%). Important pre-biopsy features in men with Gleason ≥ 4 were PSAD ≥ 0.15 (n=3), artefact on MRI from hip joint prosthesis (n=1), and family history (n=2). There were no unusual histological variants seen on the positive biopsy cores. Conclusion: Most men with negative mpMRI can avoid prostate biopsy and be managed with PSA monitoring. Based on our experience, we recommend systematic biopsy in men with negative mpMRI who have PSAD ≥ 1.5, family history or any imaging artifact that may alter image interpretation. Citation Format: Chidi N. Molokwu, Christos Gkikas, Harry Bardgett, Nicola Lee, Faisal Ali, Rohit Chahal, Rajindra Singh. Indications for systematic prostate biopsy in men with negative multi-parametric magnetic resonance imaging [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2301.

Comparing Prostate Imaging-Reporting and Data System Version 2 (PI-RADSv2) Category 1 and 2 Groups: Clinical Implication of Negative Multiparametric Magnetic Resonance Imaging.

Objectives To evaluate the clinicopathological differences between Prostate Imaging-Reporting and Data System (PI-RADS) version 2 (v2) category 1 and 2 groups. Materials and Methods. We retrospectively reviewed our two institutional clinical databases: (1) transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) fusion biopsy cohort (n = 706) and (2) radical prostatectomy (RP) cohort (n = 1403). Subsequently, we performed comparative analyses between PI-RADSv2 category 1 and 2 groups. Clinically significant prostate cancer (csPCa) was defined as the presence of Gleason score (GS) ≥ 3 + 4 in a single biopsy core, and adverse pathology (AP) was defined as high-grade (primary Gleason pattern 4 or any pattern 5) and/or non-organ-confined disease (pT3/N1). We also performed multivariate logistic regression analyses for AP. Results In the TRUS/MRI fusion biopsy cohort, no significant differences in detection rates of all cancer (18.2% vs. 29.0%, respectively, P = 0.730) or csPCa (9.1% vs. 9.9%, respectively, P = 0.692) were observed between PI-RADSv2 category 1 and 2 groups. There were no significant differences in pathologic outcomes including Gleason score (≥4 + 3, 21.2% vs. 29.9%, respectively, P = 0.420) or detection rate of AP (27.3% vs. 33.8%, respectively, P = 0.561) between the two groups in the RP cohort either. PI-RADSv2 category 1 or 2 had no significant association with AP, even in univariate analysis (P = 0.299). Conclusions PI-RADSv2 categories 1 and 2 had similar performance to predict clinicopathological outcomes. Consequently, these two categories may be unified into a single category. Negative mpMRI does not guarantee the absence of AP, as with csPCa.

Multiparametric magnetic resonance imaging and follow-up to avoid prostate biopsy in 4259 men.

To determine the proportion of men avoiding biopsy because of negative multiparametric magnetic resonance imaging (mpMRI) findings in a prostate MRI expert centre, and to assess the number of clinically significant prostate cancers (csPCa) detected during follow-up. Retrospective study of 4259 consecutive men having mpMRI of the prostate between January 2012 and December 2017, with either a history of previous negative transrectal ultrasonography-guided biopsy or biopsy naïve. Patients underwent mpMRI in a referral centre. Lesions were classified according to Prostate Imaging Reporting And Data System (PI-RADS) versions 1 and 2. Negative mpMRI was defined as an index lesion PI-RADS ≤2. Follow-up until 13 October 2018 was collected by searching the Dutch Pathology Registry (PALGA). Gleason score ≥3 + 4 was considered csPCa. Kaplan-Meier analysis and univariable logistic regression models were used in the cohort of patients with negative mpMRI and follow-up. Overall, in 53.6% (2281/4259) of patients had a lesion classified as PI-RADS ≤2. In 320 patients with PI-RADS 1 or 2, follow-up mpMRI was obtained after a median (interquartile range) of 57 (41-63)months. In those patients, csPCa diagnosis-free survival (DFS) was 99.6% after 3years. Univariable logistic regression analysis revealed age as a predictor for csPCa during follow-up (P<0.05). In biopsied patients, csPCa was detected in 15.8% (19/120), 43.2% (228/528) and 74.5% (483/648) with PI-RADS 3, 4 and 5, respectively. More than half of patients having mpMRI of the prostate avoided biopsy. In those patients, csPCa DFS was 99.6% after 3years.

Negative Predictive Value of Prostate Multiparametric Magnetic Resonance Imaging among Men with Negative Prostate Biopsy and Elevated Prostate Specific Antigen: A Clinical Outcome Retrospective Cohort Study.

We estimated the negative predictive value of prostate multiparametric magnetic resonance imaging to detect clinically significant (Gleason 7 or greater) prostate cancer at long-term followup (median 6.7 years, range 2.6 to 10.7), in men with negative biopsy findings before magnetic resonance imaging. We also assessed the diagnostic performance of multiparametric magnetic resonance imaging to detect clinically significant prostate cancer during this time. Following Institutional Research Ethics Board approval we retrospectively identified men who underwent prostate multiparametric magnetic resonance imaging after biopsy between 2004 and 2009 using a cancer registry database and magnetic resonance imaging reports. Multiparametric magnetic resonance imaging sequences comprised T2-weighted and dynamic contrast-enhanced series from 2004 to 2005 with diffusion-weighted imaging from 2006 and thereafter. Clinical outcomes were assessed up to July 2015 by reviewing subsequent pathology results, prostate specific antigen levels and electronic patient records. The primary outcome was clinically significant prostate cancer diagnosis during followup. We also estimated the sensitivity, specificity, and positive and negative predictive values of all prostate multiparametric magnetic resonance imaging during this period. A total of 502 multiparametric magnetic resonance imaging scans with a prior biopsy were included in study. Of these scans 121 were done in men with a prior systematic biopsy negative for cancer. In these men median prostate specific antigen was 9.5 ng/dl and median age was 60 years. At a median followup of 6.7 years (95% CI 2.6 to 10.7) 70 of 73 (96%) men with negative multiparametric magnetic resonance imaging findings remained free of clinically significant prostate cancer. In this period the overall negative and positive predictive values of multiparametric magnetic resonance imaging were 86% (range 80% to 91%) and 54% (range 52% to 57%), respectively, in the entire cohort regardless of biopsy status before magnetic resonance imaging. Prostate multiparametric magnetic resonance imaging has high clinical negative predictive value. In men with a negative biopsy before magnetic resonance imaging and negative magnetic resonance imaging findings the risk of clinically significant prostate cancer was extremely low at a median of 6.7 years.

MP13-08 RADIOGENOMIC DISSECTION OF MULTIFOCAL PROSTATE CANCER

INTRODUCTION AND OBJECTIVES:Up to 20% of patients with negative multiparametric magnetic resonance imaging (MRI) harbor Gleason score ≥7 prostate cancer (PCa). In this study, we sought to elucidate...

546 - Radiogenomic characterization of multifocal prostate cancer

126Background: Up to 20% of patients with negative multiparametric magnetic resonance imaging (MRI) harbor Gleason score ≥7 prostate cancer (PCa). We sought to elucidate the molecular basis of and ...

Radiogenomic characterization of multifocal prostate cancer.

126 Background: Up to 20% of patients with negative multiparametric magnetic resonance imaging (MRI) harbor Gleason score ≥7 prostate cancer (PCa). We sought to elucidate the molecular basis of and determine the prognostic significance of PCa visibility on MRI. Methods: We identified a retrospective cohort of patients who underwent MRI prior to prostatectomy with both MRI visible (PIRADS 3 – 5) and invisible PCa. MRI for each patient was re-reviewed and co-registered with whole-mount histopathology. DNA and RNA were co-isolated from all tumor foci pre-identified on FFPE specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each tumor focus using the Oncomine Comprehensive Panel (DNA) and a custom targeted RNAseq panel assessing PCa relevant alterations. A multigene RNAseq model was developed and validated in two independent cohorts to predict MRI visible PCa and to determine the prognostic significance of MRI visibility. Results: A total of 26 primary tumor foci from 10 patients were analyzed. Of the 14 (54%) invisible lesions on MRI, 5 (36%) were Gleason 3+4 = 7 and the remainder were Gleason 6. We detected high-confidence prioritized PCa relevant mutations in 54% (14/26) of tumor foci, 43% (6/14) of which were in MRI invisible lesions. Notable point mutations were in APC, AR, ARID1B, ATM, ATRX, BRCA2, FAT1, MAP3K1, NF1, SPEN, SPOP, and TP53. A 9-gene RNA signature, the majority of which were under-expressed cellular organization and structure genes, was developed to predict MRI visibility with an AUC of 0.89. Validation of this signature in an independent data set (n = 16) yielded an AUC of 0.88 with a specificity of 100% for predicting MRI visible tumors. Using this signature in a cohort of 375 patients with clinical follow up, we found that predicted MRI visibility status was not an independent predictor of biochemical recurrence, metastasis-free survival, or PCa specific mortality (all p &gt; 0.05). Conclusions: We observed under-expression of cellular organization and structural genes in MRI visible tumors compared to MRI invisible cancer foci. Using our validated signature to predict MRI visibility status, we found that MRI visibility is not a significant predictor of oncological outcomes.