{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:20:21Z","timestamp":1783938021847,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victor Babes University of Medicine and Pharmacy Timisoara"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Despite multiparametric MRI (mpMRI)-guided biopsy, clinically significant upgrading (CSU) of ISUP Grade Group (GG) at radical prostatectomy (RP) remains common in prostate cancer (PCa). We aimed to identify predictors of CSU (biopsy GG \u2264 2 to RP GG \u2265 3) using routine preoperative variables, and to benchmark a parsimonious logistic model against multiple machine learning (ML) classifiers. Methods: In this single-center exploratory analysis, 96 consecutive PCa patients underwent pre-biopsy mpMRI, systematic \u00b1 MRI-targeted biopsy, and RP. Predictive modeling was restricted to biopsy GG 1\u20132 patients (n = 64). LASSO-guided feature selection and Firth-penalized logistic regression were used to build a locked reference model, evaluated against ML classifiers using cross-validated discrimination, calibration, and decision curve analysis. Results: CSU occurred in 10\/64 patients (15.6%). Positive core ratio was the dominant independent predictor (adjusted OR 1.54 per 10% increase, 95% CI 1.10\u20132.17). PSA density (PSAD) showed a consistent positive association but did not retain independent significance. The locked two-variable model (AUC \u2248 0.75\u20130.79) outperformed all ML classifiers in discrimination, calibration, and net clinical benefit; however, the limited event count (n = 10) constrains model stability, and these findings require external validation. Conclusions: In a PCa mpMRI-informed diagnostic pathway, CSU is primarily driven by biopsy tumor burden. A simple logistic model based on positive core ratio and PSAD outperformed more complex ML approaches in this exploratory cohort, supporting integration of biopsy tumor burden metrics into preoperative risk stratification pending external validation.<\/jats:p>","DOI":"10.3390\/cancers18050730","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T16:58:18Z","timestamp":1771952298000},"page":"730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinically Significant ISUP Upgrading in the Multiparametric MRI Era: Biopsy Tumor Burden Outperforms Complex Machine Learning Models in a Single-Center Exploratory Cohort"],"prefix":"10.3390","volume":"18","author":[{"given":"Cristian","family":"Condoiu","sequence":"first","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelina","family":"Baloi","sequence":"additional","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"},{"name":"Department X\u2014Surgery II, Discipline Anesthesia and Intensive Care, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorel","family":"Sandesc","sequence":"additional","affiliation":[{"name":"Department X\u2014Surgery II, Discipline Anesthesia and Intensive Care, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alin Adrian","family":"Cumpanas","sequence":"additional","affiliation":[{"name":"Department XV, Discipline of Urology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silviu","family":"Latcu","sequence":"additional","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"},{"name":"Department XV, Discipline of Urology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0140-701X","authenticated-orcid":false,"given":"Vlad","family":"Dema","sequence":"additional","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"},{"name":"Department XV, Discipline of Urology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu","family":"Caprariu","sequence":"additional","affiliation":[{"name":"Department XV, Discipline of Radiology and Medical Imaging, University of Medicine and Pharmacy \u2018\u2019Victor Babes\u2019\u2019 Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Cristina","family":"Barb","sequence":"additional","affiliation":[{"name":"Department II of Microscopic Morphology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Ciucurita","sequence":"additional","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelina","family":"Marinescu","sequence":"additional","affiliation":[{"name":"Department XIII, Discipline of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-4407","authenticated-orcid":false,"given":"Talida Georgiana","family":"Cut","sequence":"additional","affiliation":[{"name":"Department XIII, Discipline of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razvan","family":"Bardan","sequence":"additional","affiliation":[{"name":"Department XV, Discipline of Urology, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"485","article-title":"Prostate Cancer Statistics, 2025","volume":"75","author":"Kratzer","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/PAS.0000000000000530","article-title":"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","volume":"40","author":"Epstein","year":"2016","journal-title":"Am. J. Surg. 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