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      The Role of PSA Density among PI-RADS v2.1 Categories to Avoid an Unnecessary Transition Zone Biopsy in Patients with PSA 4-20 ng/mL

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          Abstract

          Objective

          To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL.

          Materials and Methods

          In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance.

          Results

          PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001).

          Conclusions

          For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.

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          Most cited references34

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          The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System.

          In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.
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            PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2.

            The Prostate Imaging - Reporting and Data System Version 2 (PI-RADS™ v2) is the product of an international collaboration of the American College of Radiology (ACR), European Society of Uroradiology (ESUR), and AdMetech Foundation. It is designed to promote global standardization and diminish variation in the acquisition, interpretation, and reporting of prostate multiparametric magnetic resonance imaging (mpMRI) examination, and it is based on the best available evidence and expert consensus opinion. It establishes minimum acceptable technical parameters for prostate mpMRI, simplifies and standardizes terminology and content of reports, and provides assessment categories that summarize levels of suspicion or risk of clinically significant prostate cancer that can be used to assist selection of patients for biopsies and management. It is intended to be used in routine clinical practice and also to facilitate data collection and outcome monitoring for research.
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              Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2

              The Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) was developed with a consensus-based process using a combination of published data, and expert observations and opinions. In the short time since its release, numerous studies have validated the value of PI-RADS v2 but, as expected, have also identified a number of ambiguities and limitations, some of which have been documented in the literature with potential solutions offered. To address these issues, the PI-RADS Steering Committee, again using a consensus-based process, has recommended several modifications to PI-RADS v2, maintaining the framework of assigning scores to individual sequences and using these scores to derive an overall assessment category. This updated version, described in this article, is termed PI-RADS v2.1. It is anticipated that the adoption of these PI-RADS v2.1 modifications will improve inter-reader variability and simplify PI-RADS assessment of prostate magnetic resonance imaging even further. Research on the value and limitations on all components of PI-RADS v2.1 is strongly encouraged.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2021
                11 October 2021
                : 2021
                : 3995789
                Affiliations
                1Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
                2Department of Radiology, Huai'an Hospital of Huai'an City, Huai'an 223200, China
                3Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
                4Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
                Author notes

                Academic Editor: Tobias De Zordo

                Author information
                https://orcid.org/0000-0003-3943-3164
                Article
                10.1155/2021/3995789
                8523253
                34671673
                0c47b5b5-d0c9-4d2d-9e3c-4c684996eee4
                Copyright © 2021 Zhi-bing Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 June 2021
                : 28 September 2021
                Funding
                Funded by: Second Affiliated Hospital of Soochow University
                Award ID: SDFEYQN1817
                Funded by: Suzhou Science and Technology Bureau Development Plan
                Award ID: SYS2020147
                Funded by: Suzhou Science and Technology Development Plan
                Award ID: SS2019012
                Funded by: National Natural Science Foundation of China
                Award ID: 81801754
                Categories
                Research Article

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