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21 pages, 3096 KB  
Review
Hybrid Surgical Guidance in Urologic Robotic Oncological Surgery
by Gijs H. KleinJan, Erik J. van Gennep, Arnoud W. Postema, Fijs W. B. van Leeuwen and Tessa Buckle
J. Clin. Med. 2025, 14(17), 6128; https://doi.org/10.3390/jcm14176128 - 29 Aug 2025
Abstract
Urologic oncological surgery increasingly makes use of robotic systems to realize precise and minimally invasive resections, convent to shorter hospital stays and faster recovery times. The dexterity gains enabled through procedures such as robot-assisted (RA) prostatectomy have helped realize significant advancements in recent [...] Read more.
Urologic oncological surgery increasingly makes use of robotic systems to realize precise and minimally invasive resections, convent to shorter hospital stays and faster recovery times. The dexterity gains enabled through procedures such as robot-assisted (RA) prostatectomy have helped realize significant advancements in recent years. Complementing these effects via the used of hybrid tracers that illuminate surgical targets, i.e., cancerous tissue, has helped advance the surgical decision making via enhanced visualization. A well-known example is Indocyanine green (ICG)-Technetium-99m (99mTc)-nanocolloid, a hybrid extension of the radiopharmaceutical 99mTc-nanocolloid. These hybrid tracers provide a direct link between preoperative imaging roadmaps and intraoperative target identification, and improve efficiency, accuracy, and confidence of the urologist in procedures such as sentinel lymph node biopsy (SLNB). Receptor-targeted hybrid tracer analogues, for e.g., prostate specific membrane antigen (PSMA), are also being explored as an extension of the ongoing efforts that use radiotracers such as 99mTc-PSMA-I&S. Together, these efforts jointly pave the way for novel techniques in intraoperative lesion localization in other urological malignancies. This narrative review discusses the potential use of hybrid tracers in robotic oncological urology, including different imaging techniques and their applications for tumor localization for prostate, bladder, and kidney cancer. Full article
(This article belongs to the Special Issue The Current State of Robotic Surgery in Urology)
18 pages, 16540 KB  
Article
E-CMCA and LSTM-Enhanced Framework for Cross-Modal MRI-TRUS Registration in Prostate Cancer
by Ciliang Shao, Ruijin Xue and Lixu Gu
J. Imaging 2025, 11(9), 292; https://doi.org/10.3390/jimaging11090292 - 27 Aug 2025
Viewed by 150
Abstract
Accurate registration of MRI and TRUS images is crucial for effective prostate cancer diagnosis and biopsy guidance, yet modality differences and non-rigid deformations pose significant challenges, especially in dynamic imaging. This study presents a novel cross-modal MRI-TRUS registration framework, leveraging a dual-encoder architecture [...] Read more.
Accurate registration of MRI and TRUS images is crucial for effective prostate cancer diagnosis and biopsy guidance, yet modality differences and non-rigid deformations pose significant challenges, especially in dynamic imaging. This study presents a novel cross-modal MRI-TRUS registration framework, leveraging a dual-encoder architecture with an Enhanced Cross-Modal Channel Attention (E-CMCA) module and a LSTM-Based Spatial Deformation Modeling Module. The E-CMCA module efficiently extracts and integrates multi-scale cross-modal features, while the LSTM-Based Spatial Deformation Modeling Module models temporal dynamics by processing depth-sliced 3D deformation fields as sequential data. A VecInt operation ensures smooth, diffeomorphic transformations, and a FuseConv layer enhances feature integration for precise alignment. Experiments on the μ-RegPro dataset from the MICCAI 2023 Challenge demonstrate that our model significantly improves registration accuracy and performs robustly in both static 3D and dynamic 4D registration tasks. Experiments on the μ-RegPro dataset from the MICCAI 2023 Challenge demonstrate that our model achieves a DSC of 0.865, RDSC of 0.898, TRE of 2.278 mm, and RTRE of 1.293, surpassing state-of-the-art methods and performing robustly in both static 3D and dynamic 4D registration tasks. Full article
(This article belongs to the Special Issue Celebrating the 10th Anniversary of the Journal of Imaging)
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20 pages, 2506 KB  
Article
Urinary Metabolome Study for Monitoring Prostate Cancer Recurrence Following Radical Prostatectomy
by Sabur Badmos, Elizabeth Noriega Landa, Kiana L. Holbrook, George E. Quaye, Xiaogang Su and Wen-Yee Lee
Cancers 2025, 17(17), 2756; https://doi.org/10.3390/cancers17172756 - 24 Aug 2025
Viewed by 417
Abstract
Background/objectives: Prostate cancer (PCa) is the most common cancer among males. Approximately 20–40% of patients with clinically localized PCa will present with a biochemical recurrence after a radical prostatectomy (RP), while some will present with recurrent metastasis. Monitoring the disease post-treatment is crucial [...] Read more.
Background/objectives: Prostate cancer (PCa) is the most common cancer among males. Approximately 20–40% of patients with clinically localized PCa will present with a biochemical recurrence after a radical prostatectomy (RP), while some will present with recurrent metastasis. Monitoring the disease post-treatment is crucial for detecting a potential cancer recurrence early. Urinary volatile organic compounds (VOCs) have shown potential to detect PCa. However, their application in disease monitoring remains unexplored. Methods: A total of 165 urine samples were collected from male adults with biopsy-designated PCa-positive results before (n = 55) and after a RP (n = 55), and with biopsy-designated PCa-negative diagnosis (n = 55). The post-RP cohort was subdivided into three groups based on their health status after surgery as recovered healthy, biochemical recurrence, and recurrent metastasis. VOCs in the urine samples were extracted by stir bar sorptive extraction and analyzed using gas chromatography and mass spectrometry. We explored the use of metabolomics and a machine learning algorithm tool to investigate the potential of using VOCs for differentiating PCa diagnoses before and after the RP procedure with different outcomes. Results: Over 100 potential VOCs were identified to differentiate PCa patients before and after a RP, and those with biochemical recurrence and recurrent metastasis. Conclusions: Urinary VOCs are promising biomarkers that could be used to differentiate PCa patients pre- and post-RP. The findings from this research provide preliminary insights and could aid future investigations in developing tools for PCa patients after treatment. The absence of a validation cohort limits the reproducibility and translational impact of these findings; therefore, the results should be considered exploratory and require confirmation in larger, independent cohorts. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based “Omics” Approaches in Cancer Research)
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14 pages, 390 KB  
Article
Focal Therapy for Localized Prostate Cancer: A Case Series with Cost Analysis
by Maxwell Sandberg, David Thole, Jackson Nowatzke, Gavin Underwood, Emily Ye, Soroush Rais-Bahrami, Ronald Davis and Alejandro Rodriguez
Curr. Oncol. 2025, 32(9), 476; https://doi.org/10.3390/curroncol32090476 - 23 Aug 2025
Viewed by 424
Abstract
Focal therapy for prostate cancer (PCa) provides approaches to treat PCa patients in a less invasive manner than traditional whole-gland surgical or radiation modalities. This manuscript provides a case series of high-intensity focused ultrasound (HIFU), cryoablation, and irreversible electroporation (IRE) for PCa at [...] Read more.
Focal therapy for prostate cancer (PCa) provides approaches to treat PCa patients in a less invasive manner than traditional whole-gland surgical or radiation modalities. This manuscript provides a case series of high-intensity focused ultrasound (HIFU), cryoablation, and irreversible electroporation (IRE) for PCa at a single institution and cost analysis with a review of the literature. All patients who underwent HIFU, cryoablation, or IRE for localized PCa were retrospectively reviewed, excluding patients who received whole-gland therapy. Functional outcomes were erectile dysfunction and lower urinary tract symptoms. Cost data were collected. A total of 45 patients were included in the study with focal therapy ranging from 2023 to 2025 (4 HIFU, 20 cryoablation, 21 IRE). A total of 30 patients had focally treated lesions, and 15 patients had hemi-gland treatment. The mean preoperative PSA was 7.7 ng/mL. On the paired sample t-test, there was no significant difference between pre-focal and post-focal therapy PSA. Three patients experienced biochemical recurrence requiring prostate biopsy after focal treatment. Mean cost was USD 3804.50 and not significantly different by focal treatment. No metastatic events occurred nor deaths at a median follow-up of 6 months. Patients in this series had largely unaltered functional outcomes. Cost analysis in contemporary publications is lacking. Although follow-up was short, cancer control was adequate. Full article
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12 pages, 1764 KB  
Article
Transperineal MRI-US Fusion-Guided Biopsy with Systematic Sampling for Prostate Cancer: Diagnostic Accuracy and Clinical Implications Across PI-RADS
by Valèria Richart, Meritxell Costa, María Muní, Ignacio Asiain, Rafael Salvador, Josep Puig, Leonardo Rodriguez-Carunchio, Belinda Salinas, Marc Comas-Cufí and Carlos Nicolau
Cancers 2025, 17(17), 2735; https://doi.org/10.3390/cancers17172735 - 22 Aug 2025
Viewed by 420
Abstract
Background/Objectives: Magnetic resonance imaging (MRI) and MRI–ultrasound (US) fusion-targeted biopsy have improved prostate cancer diagnosis, particularly for clinically significant disease. However, the added value of combining systematic biopsy with targeted biopsy remains debated. This study aimed to evaluate the diagnostic accuracy of [...] Read more.
Background/Objectives: Magnetic resonance imaging (MRI) and MRI–ultrasound (US) fusion-targeted biopsy have improved prostate cancer diagnosis, particularly for clinically significant disease. However, the added value of combining systematic biopsy with targeted biopsy remains debated. This study aimed to evaluate the diagnostic accuracy of MRI–US fusion-targeted and systematic transperineal biopsies in detecting prostate cancer and explore the correlation between PI-RADS score and histology. Methods: We retrospectively analyzed 356 patients with 452 MRI-detected lesions who underwent both MRI–US fusion-targeted and transperineal systematic biopsies between 2020 and 2023. Clinically significant prostate cancer (csPCa) was defined as International Society of Urological Pathology (ISUP) grade ≥ 2. Diagnostic performance metrics (sensitivity, specificity, and accuracy) were calculated for each technique using the combined result as a reference. Subgroup analysis was performed for patients under active surveillance. Results: Prostate cancer was diagnosed in 323 of 452 lesions (71%) and csPCa in 223 lesions (49%). Targeted biopsy demonstrated higher sensitivity (93.7%) and accuracy (79.9%) than systematic biopsy (85.7% sensitivity and 77.6% accuracy), although systematic biopsy provided slightly higher specificity. Systematic biopsy alone identified 8.2% of PCa cases missed by targeted biopsy and upgraded 9.9% of lesions to csPCa. csPCa detection increased with PI-RADS score (23% in PI-RADS 3 and 73% in PI-RADS 5). In active surveillance patients, csPCa was found in 65% of lesions. Conclusions: MRI–US fusion-targeted biopsy improves csPCa detection, but systematic biopsy remains valuable, especially for identifying additional or higher-grade disease. The combined approach provides an optimal diagnostic yield, supporting its continued use in both initial and repeat biopsy settings. Full article
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26 pages, 1075 KB  
Article
Early Activation of a Multilevel Prostate Cancer Screening Model: Pilot Phase Results and Strategic Perspectives in Lombardy Region
by Elena Azzolini, Danilo Cereda, Sara Piccinelli, Michela Viscardi and Silvia Deandrea
Healthcare 2025, 13(16), 2041; https://doi.org/10.3390/healthcare13162041 - 18 Aug 2025
Viewed by 395
Abstract
Background/Objectives: Prostate cancer is the most frequently diagnosed cancer among men in Italy, yet no national population-based screening program exists. In response to new European Council recommendations, the Lombardy Region launched a pilot in November 2024 to assess the feasibility of a [...] Read more.
Background/Objectives: Prostate cancer is the most frequently diagnosed cancer among men in Italy, yet no national population-based screening program exists. In response to new European Council recommendations, the Lombardy Region launched a pilot in November 2024 to assess the feasibility of a digitally enabled, risk-adapted screening model. Methods: Men turning 50 were invited to voluntarily self-enroll through the regional electronic health record (FSE). A digital questionnaire assessed eligibility and family history (FH); eligible individuals (97,849 men without a PSA test in the past two years in the regional database) were offered free PSA testing. Risk stratification guided follow-up: men with PSA >3 ng/mL or a positive FH were referred to urology; others were assigned 2- or 5-year recall based on PSA level. Results: By June 2025, 8558 men had enrolled (8.7% uptake), 6072 were eligible; 644 (10.6%) reported a positive FH. Among those tested, 58.4% had PSA < 1 ng/mL and were FH-negative, 25.8% had PSA > 1 and <3 ng/mL and were FH-negative, and 15.9% met referral criteria. Digital triage was efficient and ensured care continuity without burdening specialists. Participation varied by local health authority (ATS), depending on implementation context. Preliminary data show a 25.9% reduction in urology consultations and a 35% reduction in MRI use compared to standard care, with no biopsy rate increase. Conclusions: The pilot demonstrates the technical feasibility, safety, low administrative burden, and potential sustainability of digital, risk-stratified prostate cancer screening. While participation was low without active invitations, early results support expansion with improved outreach. Lombardy’s experience offers a scalable, EU-aligned model for broader implementation across Italy and other health systems seeking to balance early detection with resource efficiency. Full article
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9 pages, 813 KB  
Communication
Differences in PI-RADS Classification of Prostate Cancer Based on mpMRI Scans Taken 6 Weeks Apart
by Justine Schoch, Viola Düring, Michael Wiedmann, Daniel Overhoff, Daniel Dillinger, Stephan Waldeck, Hans-Ulrich Schmelz and Tim Nestler
Tomography 2025, 11(8), 92; https://doi.org/10.3390/tomography11080092 - 18 Aug 2025
Viewed by 312
Abstract
Objectives: This study aimed to investigate the consistency of lesion identification by Prostate Imaging Reporting and Data System (PI-RADS) and the related clinical and histological characteristics in a high-volume tertiary care center. Materials and methods: The analysis used real-world data from 111 patients [...] Read more.
Objectives: This study aimed to investigate the consistency of lesion identification by Prostate Imaging Reporting and Data System (PI-RADS) and the related clinical and histological characteristics in a high-volume tertiary care center. Materials and methods: The analysis used real-world data from 111 patients between 2018 and 2022. Each patient underwent two multiparametric magnetic resonance imaging (MRI) scans of the prostate at different institutions with a median interval of 42 days between the scans, followed by an MRI-fused biopsy conducted 7 days after the second MRI. Results: The PI-RADS classifications assigned to the index lesions in the in-house prostate MRI were as follows: PI-RADS V, 33.3% (n = 37); PI-RADS IV, 49.5% (n = 55); PI-RADS III, 12.6% (n = 14); and PI-RADS II, 4.5% (n = 5). Cancer detection rates for randomized and/or targeted biopsies were 91.9% (n = 34) for PI-RADS V, 65.5% (n = 36) for PI-RADS IV, 21.4% (n = 3) for PI-RADS III, and 20% (n = 1) for PI-RADS II. Overall, malignant histology was observed in 64.9% (n = 72) of the targeted lesions and 57.7% (n = 64) of the randomized biopsies. In the first performed, external MRI, 18% (n = 20) and 10.8% (n = 12) of the patients were classified in the higher and lower PI-RADS categories, respectively. The biopsy plan was adjusted for 57 patients (51.4%); nevertheless, any cancer could have possibly been identified regardless of the adjustments. Conclusion: The 6-week interval between the MRI scans did not affect the quality of the biopsy results significantly. Full article
(This article belongs to the Special Issue New Trends in Diagnostic and Interventional Radiology)
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16 pages, 381 KB  
Review
Prognostic Role of B7-H3 (CD276) Expression in Initial Biopsies of Metastatic Prostate Cancer
by Adam Yusuf and Paramahansa Pramanik
Onco 2025, 5(3), 38; https://doi.org/10.3390/onco5030038 - 14 Aug 2025
Viewed by 254
Abstract
Prostate cancer exhibits highly variable behavior, from slow-growing localized tumors to aggressive metastatic disease, yet early prognostic indicators remain limited. In this study, we examined B7-H3 (CD276) expression, a molecule linked to immune suppression and cancer progression in diagnostic biopsy specimens from 248 [...] Read more.
Prostate cancer exhibits highly variable behavior, from slow-growing localized tumors to aggressive metastatic disease, yet early prognostic indicators remain limited. In this study, we examined B7-H3 (CD276) expression, a molecule linked to immune suppression and cancer progression in diagnostic biopsy specimens from 248 patients with localized or metastatic prostate cancer. We found that elevated B7-H3 levels were significantly more common in metastatic cases and independently associated with reduced overall and disease-specific survival. Moreover, high B7-H3 expression correlated with increased PSA values and higher Gleason grades. These findings endorse B7-H3 as a robust prognostic marker and potential therapeutic target in advanced prostate cancer management. Full article
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11 pages, 1626 KB  
Article
Integrating PSA Change with PSA Density Enhances Diagnostic Accuracy and Helps Avoid Unnecessary Prostate Biopsies
by Yi-Ju Chou, Bor-En Jong and Yao-Chou Tsai
Diagnostics 2025, 15(16), 2027; https://doi.org/10.3390/diagnostics15162027 - 13 Aug 2025
Viewed by 460
Abstract
Background: Prostate-specific antigen (PSA) levels can be transiently elevated in benign conditions. Therefore, guidelines recommend repeat PSA testing before a biopsy. However, PSA should be adjusted for the prostate volume to improve its predictive accuracy for prostate cancer. This study aimed to compare [...] Read more.
Background: Prostate-specific antigen (PSA) levels can be transiently elevated in benign conditions. Therefore, guidelines recommend repeat PSA testing before a biopsy. However, PSA should be adjusted for the prostate volume to improve its predictive accuracy for prostate cancer. This study aimed to compare the diagnostic performance of the PSA density and PSA change for prostate cancer and to evaluate whether their combination can further reduce unnecessary biopsies. Methods: We retrospectively analyzed patients who underwent a prostate biopsy between January 2020 and December 2024. Inclusion criteria were an initial PSA level between 3 and 20 ng/mL and two PSA measurements within an eight-week interval prior to the biopsy. Patients using 5-alpha reductase inhibitors before the biopsy were excluded. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to compare the diagnostic performance of each predictor for prostate cancer and clinically significant prostate cancer (csPCa). Results: A total of 291 patients were included. Patients with prostate cancer had higher PSA levels, smaller PSA declines, and a higher PSA density. The PSA density showed a superior diagnostic accuracy compared with the PSA change for both prostate cancer and csPCa. The PSA density calculated by a transrectal ultrasound or MRI yielded a similar diagnostic performance. However, the accuracy of the PSA density decreased in patients with a large prostate volume. Incorporating a criterion of a >20% PSA decline to exclude biopsy candidates improved the performance of the PSA density and further reduced unnecessary biopsies. Conclusions: The PSA density demonstrates good diagnostic accuracy for predicting prostate cancer. However, incorporating the PSA change further reduces unnecessary biopsies. Therefore, combining both factors provides a more effective approach for determining the need for a prostate biopsy. Full article
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12 pages, 673 KB  
Article
Comparative Performance of the CamPROBE Local Anaesthetic Transperineal Biopsy Device Versus an In-Line Device for Detection of Significant Prostate Cancer
by Kieran Sandhu, Syed Shah, Hannah Thorman, Kasra Saeb-Parsy, Vincent J. Gnanapragasam, Saiful Miah and Adham Ahmed
J. Clin. Med. 2025, 14(16), 5702; https://doi.org/10.3390/jcm14165702 - 12 Aug 2025
Viewed by 418
Abstract
Background/Objective: The CamPROBE device offers a simple, low-cost method to facilitate double-free-hand local anaesthetic transperineal prostate biopsies (LATPBx). Here we present data from prospective implementation of its use for first biopsy cancer detection. Methods: The outcomes of two centres who adopted the [...] Read more.
Background/Objective: The CamPROBE device offers a simple, low-cost method to facilitate double-free-hand local anaesthetic transperineal prostate biopsies (LATPBx). Here we present data from prospective implementation of its use for first biopsy cancer detection. Methods: The outcomes of two centres who adopted the CamPROBE were compared to a retrospective series of biopsies using an in-line (single-free-hand) device. All biopsies were done by clinicians new to the device. Outcomes were the detection of any cancer and clinically significant prostate cancer (csPCa) defined as ≥Grade Group 2 and ≥Grade Group 3 (GG2/3) and composite ≥NICE Cambridge Prognostic Group 2 and 3 (CPG2/3), as well as sampling accuracy of MRI-defined lesions. Results: Device cohorts were well matched for pre-biopsy PSA, T stage, and MRI visibility in both centres. In centre 1 (100 CamPROBE vs. 97 in-line biopsies), there were no differences in detection of any cancer or csPCa: ≥GG2 60.0% vs. 56.7% (p = 0.64), ≥GG3 31% vs. 20.6% (p = 0.09), ≥CPG2 62.0% vs. 60.8% (p = 0.86), and ≥CPG3 (p = 0.55). There were also no differences between devices in target biopsy positivity: 67.4% vs. 63.5% (p = 0.59). Data from centre 2 (38 CamPROBE vs. 44 in-line) re-capitulated these findings. The MRI target detection rate of the CamPROBE (assessed in Centre 1) was not affected by prostate volume, lesion laterality, anatomical position, or lesion size. Limitations include modest sample sizes, lack of randomization, and patient-reported outcomes. Conclusions: These data demonstrate that the CamPROBE device is a highly effective method of performing prostate biopsies with excellent cancer detection rates and accuracy, supporting its wider dissemination and use. Full article
(This article belongs to the Section Nephrology & Urology)
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9 pages, 604 KB  
Article
Diagnostic Superiority of Transperineal Combined Fusion Biopsy Versus Transrectal Ultrasound-Guided Biopsy: Lower Upgrading Rates and Better Concordance with Post-Surgical Histopathology
by Emil Kania, Maciej Janica, Bartłomiej Kazimierski, Michał Wiński, Paweł Samocik, Robert Kozłowski, Wojciech Modzelewski, Mateusz Cybulski and Jacek Robert Janica
J. Clin. Med. 2025, 14(16), 5698; https://doi.org/10.3390/jcm14165698 - 12 Aug 2025
Viewed by 333
Abstract
Background/Objectives: Accurate histopathological grading of prostate cancer at the time of biopsy is essential for guiding treatment decisions and minimizing the risks of both overtreatment and undertreatment. A key challenge in prostate cancer diagnostics is the phenomenon of upgrading, wherein the cancer appears [...] Read more.
Background/Objectives: Accurate histopathological grading of prostate cancer at the time of biopsy is essential for guiding treatment decisions and minimizing the risks of both overtreatment and undertreatment. A key challenge in prostate cancer diagnostics is the phenomenon of upgrading, wherein the cancer appears more aggressive in the radical prostatectomy specimen than initially indicated by biopsy. Such discrepancies can compromise therapeutic planning. This study investigates whether transperineal combined fusion biopsy (ComBx), incorporating MRI-targeted and systematic sampling, achieves greater concordance with final prostatectomy histopathology compared to conventional transrectal ultrasound-guided systematic biopsy (TRUS-Bx). Methods: This retrospective cohort study analyzed 500 men aged 46 to 79 years (mean age 65) who underwent prostate biopsies between 2017 and 2022 at a single tertiary institution. Patients were stratified into two groups: 250 underwent TRUS-Bx using a 12-core systematic approach, and 250 underwent ComBx guided by software-based MRI–ultrasound fusion targeting PI-RADS ≥ 3 lesions, followed by systematic sampling. Histopathological grading from biopsies was compared with final pathology following radical prostatectomy. Concordance, upgrading, and downgrading rates were analyzed using appropriate statistical methods. Results: Prostate cancer was diagnosed in 113 patients in the TRUS-Bx group and 152 in the ComBx group. Among these, 89 TRUS-Bx and 68 ComBx patients underwent radical prostatectomy at our center. Histological upgrading occurred statistically significantly more often in the TRUS-Bx group (35%) compared to the ComBx group (16%) (p = 0.004). Concordance between biopsy and prostatectomy grading was statistically significantly higher in the ComBx group (63%) than in the TRUS-Bx group (49%) (p = 0.042). No significant difference in downgrading rates was observed between groups. Conclusions: Transperineal combined fusion biopsy substantially improves concordance with final prostatectomy histology and significantly reduces the risk of upgrading compared to transrectal systematic biopsy. These findings support the adoption of ComBx as a more reliable diagnostic strategy for accurate grading of clinically significant prostate cancer, with implications for improving treatment precision and patient outcomes. Full article
(This article belongs to the Section Nephrology & Urology)
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15 pages, 646 KB  
Review
A Brief Review of MicroRNA Profiling in Human Prostate Cancer Tissues and Plasma
by Georgios Kallinikas, Amin M. Ektesabi, Chirag M. Vaswani, Georgios Haronis, Eirini Kallinika, Diomidis Kozyrakis, Evangelos Rodinos, Athanasios Filios, Panagiotis Filios, Despoina Mityliniou, Konstantinos Safioleas, Dimitrios Bozios, Athanasios Karmogiannis, Vasileios Konstantinopoulos, Anna Maria Konomi and James N. Tsoporis
Biomolecules 2025, 15(8), 1156; https://doi.org/10.3390/biom15081156 - 12 Aug 2025
Viewed by 518
Abstract
(1) Background: The gold standard, prostate-specific antigen (PSA) screening lacks the sensitivity and specificity required for confident, early prostate-cancer detection. MicroRNAs (miRNAs) are small, highly stable, non-coding RNAs whose expression changes reproducibly in malignancy and therefore offer promise as minimally invasive biomarkers. Although [...] Read more.
(1) Background: The gold standard, prostate-specific antigen (PSA) screening lacks the sensitivity and specificity required for confident, early prostate-cancer detection. MicroRNAs (miRNAs) are small, highly stable, non-coding RNAs whose expression changes reproducibly in malignancy and therefore offer promise as minimally invasive biomarkers. Although prostate cancer biopsies are the gold standard for prostate cancer diagnosis, limitations in the field continue to persist. Since circulating fluids can also be a source of miRNA biomarkers, we investigated the overlap between miRNAs enriched in prostate cancer tissue and those isolated from the plasma of patients with prostate cancer. (2) Methods: We synthesized the published literature (PubMed, Google Scholar, ResearchGate, 2005–April 2025) and re-analyzed three Gene Expression Omnibus (GEO) datasets (GSE54516, GSE21032—tissue; GSE206793—plasma) to identify miRNAs consistently dysregulated in prostate cancer tissue and circulation. (3) Results: Of the 318 screened full-text articles, 24 met the inclusion criteria. From the GEO reanalysis (false-discovery-rate < 0.05, |log2FC| ≥ 1), 219 and 326 miRNAs were differentially expressed in tissue, whereas 12 were altered in plasma. Two miRNAs—miR-449b and miR-455-3p—were common in both compartments, highlighting their translational potential as liquid biopsy surrogates of tumor biology. (4) Conclusions: We summarize functional evidence for leading tumor-suppressive (e.g., miR-205, miR-23b, miR-455-3p) and oncogenic (e.g., miR-21, miR-182, miR-449b) candidates, discuss their intersection with the androgen-receptor, TGF-β, WNT/β-catenin, and PI3K-AKT signaling, and outline outstanding requirements for the clinical qualification of miRNA panels in prostate cancer. Full article
(This article belongs to the Collection Molecular Biology: Feature Papers)
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29 pages, 799 KB  
Review
The Evolving Landscape of Novel and Old Biomarkers in Localized High-Risk Prostate Cancer: State of the Art, Clinical Utility, and Limitations Toward Precision Oncology
by Lilia Bardoscia, Angela Sardaro, Mariagrazia Quattrocchi, Paola Cocuzza, Elisa Ciurlia, Ilaria Furfaro, Maria Antonietta Gilio, Marcello Mignogna, Beatrice Detti and Gianluca Ingrosso
J. Pers. Med. 2025, 15(8), 367; https://doi.org/10.3390/jpm15080367 - 11 Aug 2025
Viewed by 547
Abstract
High-risk prostate cancer (PC) accounts for 50–75% of 10-year relapse after primary treatment. Routine clinicopathological parameters for PC patient stratification have proven insufficient to inform clinical decisions in this setting. Tumor genomic profiling allowed overcoming the limits of diagnostic accuracy in the field [...] Read more.
High-risk prostate cancer (PC) accounts for 50–75% of 10-year relapse after primary treatment. Routine clinicopathological parameters for PC patient stratification have proven insufficient to inform clinical decisions in this setting. Tumor genomic profiling allowed overcoming the limits of diagnostic accuracy in the field of PC, integrated with radiomic features, automated platforms, evaluation of patient-related factors (age, performance status, comorbidity) and tumor-related factors (risk class, volume, T stage). In this scenario, the use of biomarkers to guide decision-making in localized, high-risk PC is evolving actively and rapidly. Additional tests for prostate-specific antigen have demonstrated superior sensitivity and specificity for detecting clinically significant PC, as well as commercially available genomic classifiers improving the risk prediction of disease recurrence/progression/metastasis, in combination with common clinical variables. This narrative review aimed to summarize the state of the art on the utility and evolution of old and emerging biomarkers in the diagnosis and prognosis of localized, high-risk PC, and the potential for their application in clinical practice. We focused on the theoretical molecular foundation of prostate carcinogenesis and explored the impact of genomic profiling, next-generation sequencing, and artificial intelligence in the extrapolation of customized features able to predict disease aggressiveness and possibly drive personalized therapeutic decisions. Full article
(This article belongs to the Special Issue Urological Cancer: Clinical Advances in Personalized Therapy)
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26 pages, 1870 KB  
Review
Biomarkers in Localized Prostate Cancer: From Diagnosis to Treatment
by Marta Lopez-Valcarcel, Fernando Lopez-Campos, Juan Zafra-Martín, Irene Cienfuegos Belmonte, José Daniel Subiela, María Ruiz-Vico, Sandra Fernandez Alonso, Jose Angel Garcia Cuesta and Felipe Couñago
Int. J. Mol. Sci. 2025, 26(16), 7667; https://doi.org/10.3390/ijms26167667 - 8 Aug 2025
Viewed by 565
Abstract
Prostate-specific antigen (PSA) has been the primary biomarker used for the detection and monitoring of prostate cancer for decades. However, its limited specificity and prognostic accuracy have led to the development of novel molecular and imaging biomarkers aimed at improving the clinical characterization [...] Read more.
Prostate-specific antigen (PSA) has been the primary biomarker used for the detection and monitoring of prostate cancer for decades. However, its limited specificity and prognostic accuracy have led to the development of novel molecular and imaging biomarkers aimed at improving the clinical characterization of localized disease. This review critically examines recent advances in urinary biomarkers (e.g., PCA3, SelectMDx), tissue-based genomic assays (Oncotype DX Prostate, Prolaris, Decipher), and imaging techniques such as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PET-PSMA). We evaluate their diagnostic performance, prognostic value, and clinical utility in risk stratification and individualized treatment decision-making. Methodological and clinical barriers to their routine implementation are also discussed. Current evidence supports the multidisciplinary integration of these biomarkers to overcome the limitations of PSA, improve biopsy decision-making, better distinguish indolent from aggressive tumors, and optimize therapeutic strategies. Finally, future research directions aimed at validating and incorporating emerging biomarkers into clinical practice are outlined, with the goal of improving outcomes in patients with localized prostate cancer. Full article
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28 pages, 3251 KB  
Article
Predictors of ISUP Grade Group Discrepancies Between Biopsy and Radical Prostatectomy: A Single-Center Analysis of Clinical, Imaging, and Histopathological Parameters
by Victor Pasecinic, Dorin Novacescu, Flavia Zara, Cristina-Stefania Dumitru, Vlad Dema, Silviu Latcu, Razvan Bardan, Alin Adrian Cumpanas, Raluca Dumache, Talida Georgiana Cut, Hossam Ismail and Ademir Horia Stana
Cancers 2025, 17(15), 2595; https://doi.org/10.3390/cancers17152595 - 7 Aug 2025
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Abstract
Background/Objectives: ISUP grade group discordance between prostate biopsy and radical prostatectomy (RP) impacts treatment decisions in over a third (~25–40%) of prostate cancer (PCa) patients. We aimed to identify ISUP grade migration predictors and assess the impact of preoperative imaging (MRI) in [...] Read more.
Background/Objectives: ISUP grade group discordance between prostate biopsy and radical prostatectomy (RP) impacts treatment decisions in over a third (~25–40%) of prostate cancer (PCa) patients. We aimed to identify ISUP grade migration predictors and assess the impact of preoperative imaging (MRI) in a contemporary Romanian PCa cohort. Methods: We retrospectively analyzed 142 PCa patients undergoing RP following biopsy between January 2021 and December 2024 at Pius Brinzeu County Hospital, Timișoara: 90 without and 52 with preoperative MRI. Clinical parameters, MRI findings (PI-RADS), and biopsy characteristics were evaluated. Machine learning models (gradient boosting, random forest) were developed with SHAP analysis for interpretability. Results: Grade migration occurred in 69/142 patients (48.6%): upstaging in 55 (38.7%) and downstaging in 14 (9.9%). In the non-MRI cohort, 37/90 (41.1%) were upstaged and 9/90 (10.0%) were downstaged, versus 18/52 (34.6%) upstaged and 5/52 (9.6%) downstaged in the MRI cohort. The MRI group showed a 6.5% absolute reduction in upstaging (34.6% vs. 41.1%), a promising non-significant trend (p = 0.469) that requires further investigation. Grade 1 patients showed the highest upstaging (69.4%), while Grades 3–4 showed the highest downstaging (11/43, 25.6%). PI-RADS 4 lesions had the highest upstaging (43.5%). PSA density > 0.20 ng/mL2 emerged as the strongest predictor. Gradient boosting achieved superior performance (AUC = 0.812) versus logistic regression (AUC = 0.721), representing a 13% improvement in discrimination. SHAP analysis revealed PSA density as the most influential (importance: 0.287). Grade migration associated with adverse pathology: extracapsular extension (52.7% vs. 28.7%, p = 0.008) and positive margins (38.2% vs. 21.8%, p = 0.045). Conclusions: ISUP grade migration affects 48.6% of Romanian patients, with 38.7% upstaged and 9.9% downstaged. The 69.4% upstaging in Grade 1 patients emphasizes the need for enhanced risk stratification tools, while 10% downstaging suggests potential overtreatment. Machine learning with SHAP analysis provides superior predictive performance (13% AUC improvement) while offering clinically interpretable risk assessments. PSA density dominates risk assessment, while PI-RADS 4 lesions warrant closer scrutiny than previously recognized. Full article
(This article belongs to the Special Issue Prostate Cancer: Contemporary Standards and Challenges)
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