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Diagnostics
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Urologic Oncology: Biomarkers, Diagnosis, and Management
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Urologic Oncology: Biomarkers, Diagnosis, and Management

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 9351

Special Issue Editors

Dr. Roberto Contieri

E-Mail Website
Guest Editor
Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Interests: bladder cancer; urothelial carcinoma; non muscle-invasive bladder cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanni Lughezzani

E-Mail Website
Guest Editor
1. Department of Urology, Humanitas Clinical and Research Center, Rozzano, Italy
2. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
Interests: urologic cancers;prostate cancer

Special Issue Information

Dear Colleagues,

This Special Issue aims to comprehensively explore cutting-edge research in the field, with a particular focus on biomarkers, diagnostic advancements, and innovative management strategies. We invite contributions that delve into the latest developments that shape our understanding of urologic oncology, fostering a collaborative exchange of insights to advance patient care. As we navigate the intricate landscape of urologic malignancies, this Special Issue endeavors to spotlight emerging trends and breakthroughs, catalyzing impactful discussions within our scientific community.

Dr. Roberto Contieri
Dr. Giovanni Lughezzani
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • urologic oncology
  • biomarkers
  • diagnosis
  • management
  • urothelial carcinoma
  • prostate cancer
  • kidney cancer
  • testis cancer
  • penile cancer

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Published Papers (8 papers)

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Research

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17 pages, 2082 KiB  
Article
Comparing AI and Manual Segmentation of Prostate MRI: Towards AI-Driven 3D-Model-Guided Prostatectomy
by Thierry N. Boellaard, Roy van Erck, Sophia H. van der Graaf, Lisanne de Boer, Henk G. van der Poel, Laura S. Mertens, Pim J. van Leeuwen and Behdad Dashtbozorg
Diagnostics 2025, 15(9), 1141; https://doi.org/10.3390/diagnostics15091141 - 30 Apr 2025
Abstract
Background: Robot-assisted radical prostatectomy (RARP) is a common treatment option for prostate cancer. A 3D model for surgical guidance can improve surgical outcomes. Manual expert radiologist segmentation of the prostate and tumor in prostate MRI to create 3D models is labor-intensive and [...] Read more.
Background: Robot-assisted radical prostatectomy (RARP) is a common treatment option for prostate cancer. A 3D model for surgical guidance can improve surgical outcomes. Manual expert radiologist segmentation of the prostate and tumor in prostate MRI to create 3D models is labor-intensive and prone to inter-observer variability, highlighting the need for automated segmentation methods. Methods: This study evaluates the performance of the prostate and tumor segmentation using a commercially available AI tool without (fully automated) and with manual adjustment (AI-assisted) compared to manual segmentations on 120 patients, using several metrics, including Dice Coefficient and Hausdorff distance. Tumor detection rates were assessed with recall and precision. Results: For the prostate, both the fully automated AI model and AI-assisted model achieved a mean Dice score of 0.88, while AI-assisted had a lower Hausdorff distance (7.22 mm) compared to the fully automated (7.40 mm). For tumor segmentations, the Dice scores were 0.53 and 0.62, with Hausdorff distances of 9.53 mm and 6.62 mm obtained for fully automated AI and AI-assisted methods, respectively. The fully automated AI method had a recall of 0.74 and a precision of 0.76 in tumor detection, while the AI-assisted method achieved 0.95 recall and 0.94 precision. Fully automated segmentation required less than 1 min, while adjustments for the AI-assisted segmentation took an additional 81 s, and manual segmentation took approximately 15–30 min. Conclusions: The fully automated AI model shows promising results, offering high tumor detection rates and acceptable segmentation metrics. The AI-assisted strategy improved the relevant metrics with minimal additional time investment. Therefore, the AI-assisted segmentation method is promising for allowing 3D-model-guided surgery for all patients undergoing RARP. Full article
(This article belongs to the Special Issue Urologic Oncology: Biomarkers, Diagnosis, and Management)
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9 pages, 4831 KiB  
Article
Non-DRE Voided Urine Test to Diagnose Prostate Cancer: Updated Results
by Patrick T. Gomella, Joon Yau Leong, Leonard G. Gomella, Vivek S. Tomar, Hector Teran, Edouard J. Trabulsi and Madhukar L. Thakur
Diagnostics 2025, 15(5), 607; https://doi.org/10.3390/diagnostics15050607 - 3 Mar 2025
Viewed by 535
Abstract
Background: The standard diagnostic approach for prostate cancer (PCa) diagnosis consists of serum prostate-specific antigen (PSA) testing, digital rectal examination (DRE) and image-guided targeted biopsies. Given the invasive nature, potential adverse events and costs associated with these techniques, alternative approaches have been investigated, [...] Read more.
Background: The standard diagnostic approach for prostate cancer (PCa) diagnosis consists of serum prostate-specific antigen (PSA) testing, digital rectal examination (DRE) and image-guided targeted biopsies. Given the invasive nature, potential adverse events and costs associated with these techniques, alternative approaches have been investigated, specifically with serum and urine assays. The work presented here is intended to further validate a novel noninvasive optical technique for PCa detection, targeting the VPAC genomic receptors that are overexpressed on prostate cancer’s malignant cells (MC), in non-DRE voided urine. Methods: Patients (N = 62) who had image-guided biopsy and histologically confirmed localized PCa, and who were scheduled for radical prostatectomy, provided a non-DRE voided urine sample prior to surgery. Urine was cytocentrifuged and cells fixed on a glass slide, incubated with 0.5 μg TP4303 (a receptor-specific fluorophore developed in our laboratory with high affinity for VPAC), excess washed and treated with 4,6-diamidodino-2-phenylindole (DAPI) for nuclear staining. The field of cells on each slide was analyzed using a Zeiss AX10 Observer microscope (20×). The total number of cells and MC were then counted, and the florescent intensity around each MC was measured using Zeiss software. Additionally, non-DRE voided urine samples collected from clinically determined BPH patients (N = 97), were also analyzed similarly. Results: Urine samples from 62 patients were processed and analyzed. Mean PSA levels by Gleason grade (GG) group were 6.5 ± 4.1 ng/mL for GG1 (N = 10), 7.2 ± 3.8 for GG2 (N = 31), 13.2 ± 14.6 for GG3 (N = 13), 6.2 ± 2.2 for GG4 (N = 2) and 50.2 ± 104.9 for GG5 (N = 6). Like the PSA, % MC shed (66.7 ± 27.7) in voided urine and the fluorescent intensity (35.8 ± 5.7) were highest in patients with GG5 prostate cancer. All PCa patients in GG1 to GG5 shed MC in voided urine with increasing % of MC and increasing fluorescence intensity which correlated with the increasing GG for PCa. For BPH, the specificity for the assay was 89.6% (95% CI:81.9–94.9%), PPV was 0.0% and NPV was 100% (95.9% CI, 95.9–100%). Conclusions: These data indicate the following: (i) PCa MC shed in non-DRE voided urine can be detected by targeting VPAC receptors, (ii) MC are shed in non-DRE voided urine with increasing quantity, corresponding to the severity of the disease, and (iii) this non-DRE voided urine optical assay provides a simple, noninvasive, and reliable method for the preliminary detection of PCa with potentially a lower cost than the currently available pre-biopsy detection technologies. Full article
(This article belongs to the Special Issue Urologic Oncology: Biomarkers, Diagnosis, and Management)
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8 pages, 494 KiB  
Article
Role of Liquid Biopsy in Progressive PSA Patients after Radical Prostatectomy
by Marcel Figueras, Lourdes Mengual, Mercedes Ingelmo-Torres, Fiorella L. Roldán, Bernat Padullés, Héctor Alfambra, Sandra Herranz, Pilar Paredes, Gary Amseian, Joel Mases, Maria J. Ribal, Laura Izquierdo and Antonio Alcaraz
Diagnostics 2024, 14(20), 2293; https://doi.org/10.3390/diagnostics14202293 - 16 Oct 2024
Viewed by 1123
Abstract
Background/Objectives: Currently, the prediction of disease recurrence after radical prostatectomy (RP) in localized prostate cancer (PCa) relies on clinicopathological parameters, which lack accuracy in predicting clinical outcomes. This study focused on evaluating the utility of cfDNA levels and fragmentation patterns as prognostic biomarkers [...] Read more.
Background/Objectives: Currently, the prediction of disease recurrence after radical prostatectomy (RP) in localized prostate cancer (PCa) relies on clinicopathological parameters, which lack accuracy in predicting clinical outcomes. This study focused on evaluating the utility of cfDNA levels and fragmentation patterns as prognostic biomarkers in progressive prostate-specific antigen (PSA) patients, including those with persistent PSA and biochemical recurrence (BR), after primary treatment in localized PCa patients. Methods: Twenty-nine high-risk localized PCa patients were enrolled in the study between February 2022 and May 2023. Blood samples were obtained before robotic RP. cfDNA concentration and fragment size were quantified using the Quant-it PicoGreen dsDNA Assay kit and Agilent 2200 TapeStation System, respectively. Results: The mean PSA value at diagnosis was 9.4 ng/mL. Seven patients (24.1%) had stage pT2 and 22 (75.9%) pT3. Nine patients (31%) had detectable PSA at the first PSA control six weeks after surgery, and four patients (20%) had BR during a mean follow-up of 18.4 months. No associations were found between cfDNA levels or fragmentation patterns and clinicopathological data. Although not statistically significant, patients with detectable PSA levels post-surgery exhibited higher cfDNA levels and shorter fragments compared with those with undetectable PSA. Conclusions: Our study indicated a tendency toward more fragmented cfDNA levels in PCa patients with persistent PSA. Strikingly, biochemical recurrent PCa patients exhibited similar cfDNA levels and fragmentation patterns compared to non-recurrent patients. Further studies exploring liquid biopsy-derived biomarkers in localized PCa patients are needed to elucidate their clinical utility in predicting PSA persistence. Full article
(This article belongs to the Special Issue Urologic Oncology: Biomarkers, Diagnosis, and Management)
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11 pages, 2276 KiB  
Article
Utility of Ultrasound-Guided Attenuation Parameter (UGAP) in Renal Angiomyolipoma (AML): First Results
by Paul Christian Kranert, Paula Kranert, Miriam C. Banas, Ernst Michael Jung, Bernhard Banas and Franz Josef Putz
Diagnostics 2024, 14(18), 2002; https://doi.org/10.3390/diagnostics14182002 - 10 Sep 2024
Viewed by 968
Abstract
Angiomyolipoma (AML) are the most common benign solid renal mass. Differentiation from malignant tumours is essential. Imaging features in ultrasound may overlap between malignant lesions, especially between renal cell carcinoma (RCC) and AML. So far, sectional imaging has been necessary for reliable differentiation. [...] Read more.
Angiomyolipoma (AML) are the most common benign solid renal mass. Differentiation from malignant tumours is essential. Imaging features in ultrasound may overlap between malignant lesions, especially between renal cell carcinoma (RCC) and AML. So far, sectional imaging has been necessary for reliable differentiation. The aim of this study is to evaluate the use of the ultrasound-guided attenuation parameter (UGAP), a recently established tool for assessing hepatic steatosis, in the differentiation of AMLs from other renal masses. Therefore, 27 patients with unknown solid renal masses were examined by ultrasound including UGAP. The attenuation was assessed qualitatively by attenuation map and quantitatively in comparison to the surrounding renal tissue. UGAP was applicable in 26/27 patients. Findings were compared with CT/MRI as the current imaging standard. A total of 18 AML and 9 other renal tumours were found. The diagnostic performance of B-Mode (hyperechogenic lesion) ultrasound was 77.8% in identifying AML. The diagnostic performance of the attenuation map showed a diagnostic performance of 92.6%, whereby UGAP measurements were successful in 76.9% of cases. Quantitatively, we found a significant difference (p < 0.034) in mean measured attenuation between AML (0.764 ± 0.162 dB/cm/MHz) vs. other renal tumours (0.658 ± 0.155 dB/cm/MHz). The best performance was found by a combined parameter of a hyperechogenic lesion with a positive attenuation map with an accuracy of 95.0%. In conclusion, UGAP may represent a possibility for differentiating solid renal lesions more accurately by ultrasound, especially classic hyperechoic AMLs from other renal lesions. Further studies are needed to increase the diagnostic reliability further. Full article
(This article belongs to the Special Issue Urologic Oncology: Biomarkers, Diagnosis, and Management)
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10 pages, 1248 KiB  
Article
Diagnostic Value of SALL4 and OCT3/4 in Pediatric Testicular Tumors
by Ovidiu Bîcă, Carmen Iulia Ciongradi, Marius Ivănuță, Victor Ianole, Ioan Sârbu, Elena Cojocaru, Delia Elena Bîcă and Ludmila Lozneanu
Diagnostics 2024, 14(13), 1454; https://doi.org/10.3390/diagnostics14131454 - 8 Jul 2024
Cited by 1 | Viewed by 1172
Abstract
Testicular tumors (TTs) are rare in children, posing diagnostic and therapeutic challenges. This retrospective study evaluates the diagnostic and prognostic utility of SALL4 and OCT3/4 in pediatric TTs. We analyzed 18 cases of different types of TTs using immunohistochemistry (IHC) to assess SALL4 [...] Read more.
Testicular tumors (TTs) are rare in children, posing diagnostic and therapeutic challenges. This retrospective study evaluates the diagnostic and prognostic utility of SALL4 and OCT3/4 in pediatric TTs. We analyzed 18 cases of different types of TTs using immunohistochemistry (IHC) to assess SALL4 (Spalt-like transcription factor 4) and OCT3/4 (Octamer binding transcription factor 3/4) expression. SALL4 was positive in 83.3% of tumors, while OCT3/4 was positive in 38.9% of tumors, with a significantly higher prevalence in patients aged 12–18 years compared to those aged 0–11 years (p = 0.013). Mixed germinal cell tumors were significantly more frequently associated with OCT3/4 (p = 0.003), and a high immunostaining expression for SALL4 was observed primarily in yolk sac tumors and embryonal carcinoma. Our findings suggest that SALL4 and OCT3/4 immunostaining can aid in accurate diagnosis and treatment planning, and underscores the importance of OCT3/4 as a predictive factor in pediatric testicular tumors, highlighting its substantial correlation with tumor type and its impact on treatment response. These markers may guide personalized therapeutic strategies, potentially improving patient outcomes. Full article
(This article belongs to the Special Issue Urologic Oncology: Biomarkers, Diagnosis, and Management)
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Review

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22 pages, 2197 KiB  
Review
The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer
by Tatiana Cano Barbadilla, Martina Álvarez Pérez, Juan Daniel Prieto Cuadra, Mª Teresa Dawid de Vera, Fernando Alberca-del Arco, Isabel García Muñoz, Rocío Santos-Pérez de la Blanca, Bernardo Herrera-Imbroda, Elisa Matas-Rico and Mª Isabel Hierro Martín
Diagnostics 2024, 14(22), 2501; https://doi.org/10.3390/diagnostics14222501 - 8 Nov 2024
Cited by 1 | Viewed by 1886
Abstract
Background/Objectives: Bladder cancer (BC) is a highly heterogeneous disease, presenting clinical challenges, particularly in predicting patient outcomes and selecting effective treatments. Molecular subtyping has emerged as an essential tool for understanding the biological diversity of BC; however, its implementation in clinical practice remains [...] Read more.
Background/Objectives: Bladder cancer (BC) is a highly heterogeneous disease, presenting clinical challenges, particularly in predicting patient outcomes and selecting effective treatments. Molecular subtyping has emerged as an essential tool for understanding the biological diversity of BC; however, its implementation in clinical practice remains limited due to the high costs and complexity of genomic techniques. This review examines the role of immunohistochemistry (IHC) as a surrogate marker for molecular subtyping in BC, highlighting its potential to bridge the gap between advanced molecular classifications and routine clinical application; Methods: We explore the evolution of taxonomic classification in BC, with a particular focus on cytokeratin (KRT) expression patterns in normal urothelium, which are key to identifying basal and luminal subtypes. Furthermore, we emphasise the need for consensus on IHC markers to reliably define these subtypes, facilitating wider and standardised clinical use. The review also analyses the application of IHC in both muscle-invasive (MIBC) and non-muscle-invasive bladder cancer (NMIBC), with particular attention to the less extensively studied NMIBC cases. We discuss the practical advantages of IHC for subtyping, including its cost effectiveness and feasibility in standard pathology laboratories, alongside ongoing challenges such as the requirement for standardised protocols and external validation across diverse clinical settings; Conclusions: While IHC has limitations, it offers a viable alternative for laboratories lacking access to advanced molecular techniques. Further research is required to determine the optimal combination of markers, establish a consensus diagnostic algorithm, and validate IHC through large-scale trials. This will ultimately enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes. Full article
(This article belongs to the Special Issue Urologic Oncology: Biomarkers, Diagnosis, and Management)
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10 pages, 236 KiB  
Review
Artificial Intelligence in Uropathology
by Katia Ramos Moreira Leite and Petronio Augusto de Souza Melo
Diagnostics 2024, 14(20), 2279; https://doi.org/10.3390/diagnostics14202279 - 14 Oct 2024
Viewed by 1847
Abstract
The global population is currently at unprecedented levels, with an estimated 7.8 billion people inhabiting the planet. We are witnessing a rise in cancer cases, attributed to improved control of cardiovascular diseases and a growing elderly population. While this has resulted in an [...] Read more.
The global population is currently at unprecedented levels, with an estimated 7.8 billion people inhabiting the planet. We are witnessing a rise in cancer cases, attributed to improved control of cardiovascular diseases and a growing elderly population. While this has resulted in an increased workload for pathologists, it also presents an opportunity for advancement. The accurate classification of tumors and identification of prognostic and predictive factors demand specialized expertise and attention. Fortunately, the rapid progression of artificial intelligence (AI) offers new prospects in medicine, particularly in diagnostics such as image and surgical pathology. This article explores the transformative impact of AI in the field of uropathology, with a particular focus on its application in diagnosing, grading, and prognosticating various urological cancers. AI, especially deep learning algorithms, has shown significant potential in improving the accuracy and efficiency of pathology workflows. This comprehensive review is dedicated to providing an insightful overview of the primary data concerning the utilization of AI in diagnosing, predicting prognosis, and determining drug responses for tumors of the urinary tract. By embracing these advancements, we can look forward to improved outcomes and better patient care. Full article
(This article belongs to the Special Issue Urologic Oncology: Biomarkers, Diagnosis, and Management)

Other

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9 pages, 1287 KiB  
Brief Report
The Association between Specimen Neuromuscular Characteristics and Urinary Incontinence after Robotic-Assisted Radical Prostatectomy
by Tomer Bashi, Jonathan Margalioth, Ziv Savin, Ron Marom, Snir Dekalo, Ibrahim Fahoum, Rabab Naamneh, Roy Mano and Ofer Yossepowitch
Diagnostics 2024, 14(18), 2001; https://doi.org/10.3390/diagnostics14182001 - 10 Sep 2024
Viewed by 1004
Abstract
Urinary incontinence after robotic-assisted radical prostatectomy (RARP) has been associated with older age, a longer operative time, a higher BMI, a short membranous urethral length and preoperative erectile function. The authors sought to assess the association between the neuromuscular characteristics and postoperative urinary [...] Read more.
Urinary incontinence after robotic-assisted radical prostatectomy (RARP) has been associated with older age, a longer operative time, a higher BMI, a short membranous urethral length and preoperative erectile function. The authors sought to assess the association between the neuromuscular characteristics and postoperative urinary incontinence. Methods: RARP specimens from 29 men who underwent bilateral nerve sparing were reanalyzed. Urinary incontinence was evaluated using the International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF) at 6 weeks post surgery and last follow-up. Linear and logistic regression analyses were performed to assess neuromuscular characteristics and incontinence. Results: At the 1-year follow-up, 11 patients (38%) reported severe incontinence (>12 ICIQ-SF score). The median number of peripheral nerves observed at the base and apex in the specimens was 52 (IQR 13–139) and 59 (IQR: 28–129), respectively. Ganglia were present in 19 patients (65%) at the base and 12 patients (41%) at the apex. Additionally, the median proportional area of detrusor smooth muscle fibers at the base was 0.54 (IQR 0.31–1), while the median proportional area of striated muscle fibers at the apex was 0.13 (IQR 0.08–0.24). No statistically significant associations were found. Conclusions: Histologic neuromuscular characteristics were not associated with postoperative urinary incontinence. Enhanced intraoperative evaluation and larger-scale studies may prove useful for the prediction of postprostatectomy incontinence. Full article
(This article belongs to the Special Issue Urologic Oncology: Biomarkers, Diagnosis, and Management)
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