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Keywords = Gleason cancer grading

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11 pages, 1246 KiB  
Article
Trends in Prostate Cancer Incidence and Survival by Gleason Score from 2000 to 2020: A Population-Based Study in Northeastern Italy
by Martina Taborelli, Diego Serraino, Federica Toffolutti, Ettore Bidoli, Sara De Vidi, Lucia Fratino, Luigino Dal Maso and the FVG Cancer Registry Working Group
Curr. Oncol. 2025, 32(8), 426; https://doi.org/10.3390/curroncol32080426 - 29 Jul 2025
Viewed by 392
Abstract
Background: Prostate cancer (PCa) trends have evolved due to changing screening practices. This study assessed long-term trends in PCa incidence and survival according to Gleason score (GS) in Friuli Venezia Giulia, northeastern Italy. Methods: A population-based study was conducted, encompassing 21,571 PCa cases [...] Read more.
Background: Prostate cancer (PCa) trends have evolved due to changing screening practices. This study assessed long-term trends in PCa incidence and survival according to Gleason score (GS) in Friuli Venezia Giulia, northeastern Italy. Methods: A population-based study was conducted, encompassing 21,571 PCa cases from the regional Cancer Registry, diagnosed between 2000 and 2020. Age-standardized incidence rates and 5-year overall (OS) and net survival (NS) were assessed by GS (2–6, 7, 8–10) and age group (<65, 65–74, ≥75). Trends were analyzed using Joinpoint regression. Results: PCa incidence increased from 2000 to 2007 (Annual Percent Change, APC = +1.8%), then declined sharply until 2010 (APC = −7.6%) and remained stable thereafter. Incidence of low-grade cancers (GS 2–6) decreased across all age groups, especially in men aged ≥ 75 years (APC = −8.1%). The incidence of GS 7 rose until 2007 and then stabilized. High-grade cancers (GS 8–10) showed a stable incidence, but their proportion increased from 20% to 29%, mainly in older men. Survival improved across all GS groups. For GS 2–6, OS increased from 81.4% to 88.2%; for GS 7, from 78.1% to 88.1%. GS 8–10 had smaller gains, but NS reached 82% in recent years. Among men aged ≥ 75 years, OS for GS 7 rose from 51.9% to 78.1%, and for GS 8–10, from 43.9% to 54.4%. NS remained high for GS ≤ 7. Conclusions: While overall outcomes improved, the increasing proportion of high-grade PCa, despite a stable incidence, raises concerns, particularly in older men, and calls for tailored clinical strategies. Full article
(This article belongs to the Section Genitourinary Oncology)
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13 pages, 1043 KiB  
Article
Radiation Chronotherapy in Prostate Cancer: Does Time of Day of Radiation Treatment Influence Disease Outcome or Symptom Burden?
by Greeshma Rajeev-Kumar, Aoi Shimomura, Yan Che, Christopher Stepaniak and Stanley L. Liauw
Cancers 2025, 17(15), 2441; https://doi.org/10.3390/cancers17152441 - 23 Jul 2025
Viewed by 304
Abstract
Background: Circadian rhythms regulate critical cellular processes, including DNA repair and cell cycle dynamics, potentially influencing the effectiveness of radiotherapy (RT). This study evaluated whether RT timing impacts clinical outcomes and symptom burden in prostate cancer patients. Patients/Methods: This retrospective study (n [...] Read more.
Background: Circadian rhythms regulate critical cellular processes, including DNA repair and cell cycle dynamics, potentially influencing the effectiveness of radiotherapy (RT). This study evaluated whether RT timing impacts clinical outcomes and symptom burden in prostate cancer patients. Patients/Methods: This retrospective study (n = 336, median follow-up 55 months) included men who received curative intent external beam RT between 2010 and 2019 (median age 69, 69% black, median PSA 11.3, 40% with Gleason 8–10). Treatment times (TTs) were averaged and analyzed by quartile/median. Outcomes included freedom from biochemical failure (FFBF) and distant metastasis (FFDM), GI and GU toxicity, and quality of life (QOL). Subgroup analyses by race and hormone therapy status were performed. Results: Across the overall cohort, TT was not associated with FFBF or FFDM. However, in white men, earlier TTs were significantly associated with higher 5-year FFBF (89% vs. 67%, p = 0.0139) and FFDM (93% vs. 72%, p = 0.0268). In the multivariate analysis (MVA), TT was not associated with FFBF or FFDM for all men, but in white men, earlier TT was associated with improved FFBF (HR 2.8, p = 0.06) in a model also including risk category (p = 0.21). Overall, no significant differences were observed for grade 2–3+ toxicity and TT. Trends for inferior QOL, and worse grade 2+ (p = 0.2) and 3+ GU toxicity (p = 0.1) were observed for later TTs. In white men, bowel, urinary continence, and irritative/obstructive urinary QOL were worse with later TTs (p < 0.05). Conclusions: TT may influence clinical outcomes and symptom burden, particularly in white men. These findings underscore the potential of chronoradiotherapy as a personalized treatment strategy and highlight the need for prospective trials. Full article
(This article belongs to the Special Issue New Insights into Prostate Cancer Radiotherapy)
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11 pages, 399 KiB  
Article
Multiple or More Severe Grade Prevalent Vertebral Fractures Are Associated with Higher All-Cause Mortality in Men with Nonmetastatic Prostate Cancer Receiving Androgen Deprivation Therapy
by Kashia Goto, Daisuke Watanabe, Hiromitsu Takano, Kazuki Yanagida, Norikazu Kawae, Hajime Kajihara and Akio Mizushima
Cancers 2025, 17(13), 2131; https://doi.org/10.3390/cancers17132131 - 25 Jun 2025
Viewed by 391
Abstract
Background/Objectives: Prognostic information for nonmetastatic prostate cancer (nmPC) patients with prevalent vertebral fractures (PVFs) is very limited. Vertebral fractures can impair physical function, limit activities of daily living, and decrease quality of life. Prevention of vertebral fractures may be important to improve [...] Read more.
Background/Objectives: Prognostic information for nonmetastatic prostate cancer (nmPC) patients with prevalent vertebral fractures (PVFs) is very limited. Vertebral fractures can impair physical function, limit activities of daily living, and decrease quality of life. Prevention of vertebral fractures may be important to improve patient prognosis. This study aims to investigate the impact of the presence and severity of PVFs on overall survival in patients with nmPC undergoing androgen deprivation therapy (ADT). Methods: A total of 275 men (median age: 73 years) with nmPC who underwent ADT were studied retrospectively. The median observation period was 55 months. Variables included age, body mass index, T classification, N classification, Gleason score, and pretreatment serum prostate-specific antigen levels. PVF was diagnosed from the sagittal computed tomography images of Th1 to L5 before initiating ADT, and the severity was determined by the number of PVFs and the Semiquantitative (SQ) method. Hazard ratios and 95% confidence intervals for overall survival were calculated using the Cox proportional hazards model. Results: During the observation period, 30 patients died from all causes. Multivariate Cox regression analysis identified multiple PVFs and high-grade PVFs, as determined by the SQ method, as significant predictors of overall survival. The analysis utilized two adjustment models: one adjusted for age only and the other adjusted for age, Gleason score, and clinical T stage. Conclusions: Multiple PVFs and high-grade PVF determined by the SQ method prior to ADT initiation were associated with higher all-cause mortality in nmPC patients treated with ADT. Full article
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26 pages, 13044 KiB  
Review
SIU-ICUD: Localized Prostate Cancer: Pathological Factors That Influence Outcomes and Management
by Gladell P. Paner, Eva M. Compérat, Samson W. Fine, James G. Kench, Glen Kristiansen, Rajal B. Shah, Steven Christopher Smith, John R. Srigley, Geert J. L. H. van Leenders, Murali Varma, Ming Zhou and Mahul B. Amin
Soc. Int. Urol. J. 2025, 6(3), 41; https://doi.org/10.3390/siuj6030041 - 7 Jun 2025
Cited by 1 | Viewed by 1939
Abstract
Background/Objectives: Pathological factors are integral in the risk stratification and management of localized prostate cancer. In recent years, there has been an upsurge of studies that uncovered novel approaches and have refined prognostic factors for prostate cancer in needle biopsy and radical prostatectomy [...] Read more.
Background/Objectives: Pathological factors are integral in the risk stratification and management of localized prostate cancer. In recent years, there has been an upsurge of studies that uncovered novel approaches and have refined prognostic factors for prostate cancer in needle biopsy and radical prostatectomy (RP) specimens. Methods: We conducted a review of literature and summarized the significant recent updates on pathological factors for localized prostate cancer. Results: Innovative factors derived from the traditional Gleason grading, such as the extent of Gleason pattern 4 and presence of cribriform pattern are now recognized to significantly improve discrimination of outcome. The components and rules of Gleason grading themselves underwent modifications, and the subsequent prognostic grouping of the different grades (Grade group) have resulted in enhanced stratification of behavior more meaningful in management decision. The approaches for grade reporting in systematic or targeted needle biopsies and in RP with multifocal cancers are also being optimized. Newer tumor growth pattern-based factors such as intraductal carcinoma and atypical intraductal proliferation can have ramifications in management, especially in the background of low to intermediate risk prostate cancers. Gleason grade considerations in the different post-treatment settings and for de novo and residual prostate cancers with varying treatment effects have also been explicated. Likewise, the application of more traditional factors in tumor extent and perineural invasion in biopsy, or positive surgical margin in RP, have also evolved. Conclusions: Some of these newer pathological factors are now officially recommended in standardized pathology reporting protocols and are applied in the management decision for localized prostate cancer. Full article
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12 pages, 4225 KiB  
Communication
Deletions of LPL and NKX3.1 in Prostate Cancer Progression: Game Changers or By-Standers in Tumor Evolution
by Tereza Vodičková, Mária Wozniaková, Vladimír Židlík, Jana Žmolíková, Jana Dvořáčková, Adéla Kondé, Jana Schwarzerová, Michal Grepl and Jan Bouchal
Biomolecules 2025, 15(6), 758; https://doi.org/10.3390/biom15060758 - 24 May 2025
Viewed by 583
Abstract
The tumor suppressor gene NKX3.1 and the LPL gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of LPL loss may be misinterpreted due to its co-deletion with NKX3.1, [...] Read more.
The tumor suppressor gene NKX3.1 and the LPL gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of LPL loss may be misinterpreted due to its co-deletion with NKX3.1, a well-established event in prostate carcinogenesis. This study investigates whether LPL deletion represents a biologically relevant event or occurs merely as a bystander to NKX3.1 loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed LPL deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of NKX3.1 and LPL in 54 patients. Notably, NKX3.1 loss without accompanying LPL deletion was observed in eight additional cases. These findings suggest that LPL deletion is a passenger event secondary to NKX3.1 loss and underscore the importance of cautious interpretation of cytogenetic findings involving the LPL locus. Full article
(This article belongs to the Special Issue Advances in the Pathology of Prostate Cancer)
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18 pages, 4426 KiB  
Article
TWIK Complex Expression in Prostate Cancer: Insights into the Biological and Therapeutic Significances of Potassium Ion Channels in Clinical Cancer
by Abdulaziz Alfahed
Biology 2025, 14(5), 569; https://doi.org/10.3390/biology14050569 - 19 May 2025
Viewed by 632
Abstract
Ion channels play ubiquitous roles in the maintenance of tumour cell homeostasis and hence are attractive targets in the molecular pathogenesis and progression of prostate cancer (PCa). This study aimed to investigate the roles of the potassium ion channel complex TWIK, a member [...] Read more.
Ion channels play ubiquitous roles in the maintenance of tumour cell homeostasis and hence are attractive targets in the molecular pathogenesis and progression of prostate cancer (PCa). This study aimed to investigate the roles of the potassium ion channel complex TWIK, a member of the two-pore-domain potassium channel subfamily, in clinical PCa. The clinicopathological, gene expression, and copy number data of three clinical PCa cohorts from cancer genomics databases were analysed to determine the clinicopathological, biological, and therapeutic significances of the TWIK expression signature using statistical correlations and gene enrichment techniques. The results show that the PCa subset with high TWIK expression exhibited associations with worse pathological tumours, nodes, and overall tumour stages, as well as with high Gleason scores, high prognostic grade groups, and poorer responses to androgen deprivation therapy. Furthermore, a combination of gene set and gene ontology enrichment analyses showed that the PCa subset with high TWIK complex expression was differentially enriched for known oncogenic signalling pathways, aberrant ubiquitination and glucuronidation activities, and for gene sets of ion channel blockers and chemotherapeutic agents. The implications of these findings with respect to cancer progression, therapeutic response, and opportunities for therapeutic targeting of the TWIK complex are discussed, along with the potential of the TWIK complex as a predictive biomarker for integrated, multitargeted therapy. Full article
(This article belongs to the Special Issue Ion Channels in Cancer Progression)
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20 pages, 1587 KiB  
Systematic Review
Normal Weight, Overweight and Obesity Conditions Associated to Prostate Neoplasm Stages—A Systematic Review and Meta-Analysis
by Elsa Vitale, Alessandro Rizzo, Kurvatteppa Halemani, Asha P. Shetty, Omar Cauli, Francesco Massari and Matteo Santoni
Biomedicines 2025, 13(5), 1182; https://doi.org/10.3390/biomedicines13051182 - 13 May 2025
Viewed by 692
Abstract
Background/Objective: Prostate cancer (PCa) represents the second-most common cancer among men worldwide. Obesity is generally considered as a risk factor for cancer and it has been associated with a 20–30% increased risk of PCa death. The present systematic review and meta-analyses aimed to [...] Read more.
Background/Objective: Prostate cancer (PCa) represents the second-most common cancer among men worldwide. Obesity is generally considered as a risk factor for cancer and it has been associated with a 20–30% increased risk of PCa death. The present systematic review and meta-analyses aimed to highlight any existing trends between prostate neoplasm stages according to normal weight, overweight and obesity conditions. Methods: All interventional records such as randomized clinical trials, quasi-experimental studies and observational studies were included in the present systematic review and meta-analysis which reported PCa stages according to Gleason (GS) or TNM scores according to the BMI-related incidence, as normal weight, overweight and obesity groups. Results: Twenty-nine studies were included in the present study. As regards the GS scoring system, 1.09% of high grade in GS was reported among PCa normal weights. Among PCa overweights, 0.98% of low grade was registered in GS. The same trend was recorded among obese PCa patients, since 0.79% of low grade in GS was also registered. As regards TNM scores, both normal weight, overweight and obese PCa patients registered a significant incidence in non-advanced TNM score, without any significant differences considering higher TNM assessments. Conclusions: Although the literature seemed to be more in favor of associations between BMI and GS, no specific mechanisms were highlighted between obesity and PCa progression. In this regard, the low androgen microenvironment in obese men could play an important role, but further studies will be necessary in this direction. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Steroid Hormone Action—2nd Edition)
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14 pages, 1697 KiB  
Article
The Impact of Obesity on Prostate Cancer and Progression to Castration Resistance—Real-World Data from a Romanian Center
by Theodor Mustață, Dan Corneliu Jinga, Ioana Lazăr, Sorina Carmen Martin, Anca Elena Sîrbu and Simona Fica
J. Clin. Med. 2025, 14(9), 3146; https://doi.org/10.3390/jcm14093146 - 1 May 2025
Viewed by 581
Abstract
Background: The primary endpoint was to assess the nutritional status in patients diagnosed with prostate cancer (PCa) in Romania. The secondary endpoint was to analyze the impact of obesity on mortality and disease recurrence. Methods: In this retrospective cohort study, we [...] Read more.
Background: The primary endpoint was to assess the nutritional status in patients diagnosed with prostate cancer (PCa) in Romania. The secondary endpoint was to analyze the impact of obesity on mortality and disease recurrence. Methods: In this retrospective cohort study, we analyzed the files of 354 patients diagnosed with PCa between August 2001 and May 2022 and referred to the Medical Oncology Department of Neolife Medical Center. A total of 257 patients fulfilled the inclusion criteria and were the subject of this study. Results: Excess weight was seen in 190 (73.9%) patients, with 119 (46.3%) being overweight and 71 (27.6%) having obesity. Subgroup analysis showed that at diagnosis, patients with obesity (PwO) were younger (p = 0.022), had lower PSA (p = 0.016), and had lower 10-year all-cause mortality rates (p = 0.04) than patients without obesity. Patients with metastases had lower weight (p = 0.001) and BMI (p = 0.033), higher PSA (p < 0.001), Gleason scores (p = 0.002), ISUP grade group (p < 0.001), and 10-year all-cause mortality rate (p < 0.001) than patients without metastases. Weight (AUROC = 0.637, 95% CI: 0.557–0.717, p = 0.001; cut-off = 77.5 kg, Se = 52.5%, Sp = 71.2%) and BMI (AUROC = 0.591, 95% CI: 0.507–0.676, p = 0.033; cut-off = 23.5 kg/m2, Se = 25.4%, Sp = 91.9%) were independent predictors of the presence of metastases at diagnosis. In the androgen deprivation therapy (ADT) group, PwO had a shorter time to castration resistance than patients without obesity (Log Rank test: χ2 = 4.395, p = 0.036). Conclusions: Weight and BMI are accessible tools that could be useful in determining the presence of metastatic disease. PwO on ADT may develop castration resistant PCa faster than patients without obesity. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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23 pages, 7017 KiB  
Review
Hot Spots in Urogenital Basic Cancer Research and Clinics
by Claudia Manini, Gorka Larrinaga, Javier C. Angulo and José I. López
Cancers 2025, 17(7), 1173; https://doi.org/10.3390/cancers17071173 - 31 Mar 2025
Cited by 1 | Viewed by 836
Abstract
Urogenital cancer is very common in the male population of Western countries, a problem of major concern for public health systems, and a frequent test subject for oncological research. In this narrative, we identify the main hot topics for clinics and the basic [...] Read more.
Urogenital cancer is very common in the male population of Western countries, a problem of major concern for public health systems, and a frequent test subject for oncological research. In this narrative, we identify the main hot topics for clinics and the basic science of urological cancer in the last few years (from 2021 onwards), considering the information given in the abstracts of almost 300 original articles published in outstanding journals of pathology, urology, and basic science. Once defined, for the top ten list of hot topics (the 2022 WHO update on the classification of urinary and male genital tumors, new entities in kidney cancer, urinary cancer-omics, update on the Gleason grading system, targeted therapies and other novel therapies in renal cancer, news on non-muscle invasive urothelial carcinoma, artificial intelligence in urologic cancer, intratumor heterogeneity influence in therapeutic failures in urologic neoplasms, intratumor microbiome and its influence in urologic tumor aggressiveness, and ecological principles and mathematics applied to urogenital cancer study), each issue is independently reviewed in an attempt to put together the most relevant updates and/or useful features accompanied by selected illustrations. This review article addresses some of the most interesting and current hot spots in urogenital basic cancer research and clinics and is mainly aimed toward clinicians, including pathologists, urologists, and oncologists. Readers are invited to explore each topic for further, more detailed information, in addition to the references provided. Full article
(This article belongs to the Special Issue Insights from the Editorial Board Member)
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14 pages, 2884 KiB  
Case Report
Pleural Metastasis as an Initial Presentation of Prostate Cancer: Case Report and Literature Review
by Katarzyna Skrobisz, Kevin Miszewski, Laura Miszewska, Michał Bieńkowski, Marcin Matuszewski and Michał Studniarek
Diagnostics 2025, 15(6), 666; https://doi.org/10.3390/diagnostics15060666 - 10 Mar 2025
Viewed by 1449
Abstract
Background and Clinical Significance: Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men worldwide. While bone and lymph nodes are the most frequent metastatic sites, prostate cancer cells have the potential to spread to virtually any organ, including the [...] Read more.
Background and Clinical Significance: Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men worldwide. While bone and lymph nodes are the most frequent metastatic sites, prostate cancer cells have the potential to spread to virtually any organ, including the pleura, which is an exceedingly rare initial site of presentation that can mimic mesothelioma or primary lung cancer. Case Presentation: We describe a 77-year-old man who presented with exertional dyspnea and intermittent cough, initially suggesting a cardiopulmonary etiology. Imaging revealed multiple pleural nodules and an extensive right-sided pleural effusion. Despite a borderline serum prostate-specific antigen (PSA) level of 2.91 ng/mL, histopathology and immunohistochemistry of pleural biopsies confirmed metastatic prostate adenocarcinoma. Subsequent imaging identified a PIRADS 5 lesion in the prostate, and a biopsy confirmed ISUP Grade Group 5 disease (Gleason score 4 + 5 = 9). A bone scan showed no skeletal metastases, and a contrast-enhanced CT of the abdomen found no additional metastatic lesions. The patient was started on androgen deprivation therapy followed by abiraterone. This case underscores the diagnostic challenge posed by atypical metastatic presentations of prostate cancer. Low or moderately elevated PSA can obscure suspicion of prostate origin, especially with pleural-based lesions suggestive of mesothelioma. Immunohistochemical markers, including androgen receptors, AMACR, and Prostein, are critical for accurate diagnosis. Conclusions: Clinicians must maintain a high index of suspicion for prostate cancer in older men with unexplained pleural effusions, nodules, or masses, even with low-normal PSA levels. Early recognition and prompt treatment can improve outcomes, despite the rarity and aggressiveness of pleural metastases. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Urological Diseases)
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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 907
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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18 pages, 2354 KiB  
Article
Extracellular Microvesicle MicroRNAs and Imaging Metrics Improve the Detection of Aggressive Prostate Cancer: A Pilot Study
by Kapil K. Avasthi, Jung W. Choi, Tetiana Glushko, Brandon J. Manley, Alice Yu, Jong Y. Park, Joel S. Brown, Julio Pow-Sang, Robert Gantenby, Liang Wang and Yoganand Balagurunathan
Cancers 2025, 17(5), 835; https://doi.org/10.3390/cancers17050835 - 27 Feb 2025
Cited by 1 | Viewed by 1101
Abstract
Background/Objectives: Prostate cancer (PCa) is the most diagnosed cancer in men worldwide. Early diagnosis of the disease provides better treatment options for these patients. Recent studies have demonstrated that plasma-based extracellular vesicle microRNAs (miRNAs) are functionally linked to cancer progression, metastasis, and aggressiveness. [...] Read more.
Background/Objectives: Prostate cancer (PCa) is the most diagnosed cancer in men worldwide. Early diagnosis of the disease provides better treatment options for these patients. Recent studies have demonstrated that plasma-based extracellular vesicle microRNAs (miRNAs) are functionally linked to cancer progression, metastasis, and aggressiveness. The use of magnetic resonance imaging (MRI) as the standard of care provides an overall assessment of prostate disease. Quantitative metrics (radiomics) from the MRI provide a better evaluation of the tumor and have been shown to improve disease detection. Methods: We conducted a study on prostate cancer patients, analyzing baseline blood plasma and MRI data. Exosomes were isolated from blood plasma samples to quantify miRNAs, while MRI scans provided detailed tumor morphology. Radiomics features from MRI and miRNA expression data were integrated to develop predictive models, which were evaluated using ROC curve analysis, highlighting the multivariable model’s effectiveness. Results: Our findings indicate that the univariate feature-based model with the highest Youden’s index achieved average areas under the receiver operating characteristic (ROC) curve of 0.76, 0.82, and 0.84 for miRNA, MR-T2W, and MR-ADC features, respectively, in identifying clinically aggressive (Gleason grade) disease. The multivariable feature-based model yielded an average area under the curve (AUC) of 0.88 and 0.95 using combinations of miRNA markers with imaging features in MR-ADC and MR-T2W, respectively. Conclusions: Our study demonstrates that combining miRNA markers with MRI-based radiomics improves the identification of clinically aggressive prostate cancer. Full article
(This article belongs to the Special Issue New Insights into Urologic Oncology)
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9 pages, 579 KiB  
Article
The Effect of Pre-Biopsy Prostate MRI on the Congruency and Upgrading of Gleason Grade Groups Between Prostate Biopsy and Radical Prostatectomy
by Peter Stapleton, Thomas Milton, Niranjan Sathianathen and Michael O’Callaghan
Soc. Int. Urol. J. 2024, 5(6), 876-884; https://doi.org/10.3390/siuj5060069 - 17 Dec 2024
Viewed by 1049
Abstract
Introduction: Prostate biopsy results form the mainstay of patient care. However, there is often significant discordance between the biopsied histology and the ‘true’ histology shown on a radical prostatectomy (RP). Discordance in pathology can lead to the mismanagement of patients, potentially missing clinically [...] Read more.
Introduction: Prostate biopsy results form the mainstay of patient care. However, there is often significant discordance between the biopsied histology and the ‘true’ histology shown on a radical prostatectomy (RP). Discordance in pathology can lead to the mismanagement of patients, potentially missing clinically significant cancer and delaying treatment. There have been many advancements to improve the concordance of pathology and more accurately counsel patients; most notably, the induction of pre-biopsy mpMRIs has become a gold standard to aid in triaging and identifying clinically significant cancers, and also to facilitate ‘targeted’ biopsies. Although there have been multiple reviews on MRI-targeted biopsies, upgrading remains an ongoing phenomenon. Aim: To assess the rates of prostate cancer upgrading and the clinical implication of upgrading on NCCN stratification. Methods: We conducted a retrospective audit of 2994 men with non-metastatic prostate cancer diagnosed between 2010 and 2019 who progressed to a radical prostatectomy within 1 year of diagnosis without alternative cancer treatment from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. The study compared the histological grading between the biopsies and radical prostatectomies of men with prostate cancer and the varying rates of upgrading and downgrading for patients with and without a pre-biopsy MRI. Data were also obtain on suspected confounding variables; age, PSA, time to RP, T-stage at diagnosis and RP, number of cores, number of positive cores, prostate size, tumour volume and procedure type. The results were assessed through cross tabulation and uni- and multi-variate logistic regression while adjusting for confounders. Results: Upgrading occurred in (926) 30.9% of patients and downgrading in (458) 15.3% of patients. In total, 71% (410/579) of grade group 1 and 24.9% (289/1159) of grade group 2 were upgraded following a radical prostatectomy. By contrast, 33.4% (373/1118) of patients without prebiopsy MRI were upgraded at RP compared to 29.5% (553/1876) of the patients who received a pre-biopsy MRI. When analysed on a uni-variate level, the inclusion of a pre-biopsy MRI demonstrated a statically significant decrease in upgrading of the patient’s pathology and NCCN risk stratification (p = 0.026, OR 0.83, CI 0.71–0.98) (p = 0.049, OR 0.82, CI 0.64–1.01). However, when adjusted for confounders, the use of an MRI did not maintain a statistically significance. Conclusions: When considering the multiple variables associated with tumour upgrading, a pre-biopsy MRI did not show a statistically significant impact. However, upgrading of Gleason Grade Group following a prostatectomy is an ongoing phenomenon which can carry significant treatment implications and should remain a consideration with patients and clinicians when making decisions around treatment pathways. More research is still required to understand and improve biopsy grading to prevent further upgrading from affecting treatment choices. Full article
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13 pages, 2560 KiB  
Article
CD44 Immunohistochemical Expression in Central and Peripheral Parts of Prostatic Adenocarcinoma: An Institutional Study
by Romano Oguic, Antun Grskovic, Josip Spanjol, Ivana Mikolasevic and Gordana Djordjevic
Medicina 2024, 60(12), 2032; https://doi.org/10.3390/medicina60122032 - 9 Dec 2024
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Abstract
Background and Objectives: Prostate cancer is one of the most commonly diagnosed cancers in the male population and the fifth leading cause of cancer death worldwide in men as of 2022. One of the potential biomarkers that can predict the progression of [...] Read more.
Background and Objectives: Prostate cancer is one of the most commonly diagnosed cancers in the male population and the fifth leading cause of cancer death worldwide in men as of 2022. One of the potential biomarkers that can predict the progression of the disease is the transmembrane adhesion molecule CD44s. The aims of this study were to determine the expression of CD44s in prostate cancer in the central tumor mass and in the tumor periphery of the disease and to compare it with the clinicopathological parameters (PSA, Gleason score, surgical margins, and biochemical recurrence of the disease) in patients treated with radical prostatectomy. Materials and Methods: The research was randomized retrospectively during the period from 2001 to 2006. Tissue microarrays of 121 archival acinar prostate carcinoma samples were immunohistochemically evaluated for CD44s expression. The immunoexpression was determined semiquantitatively, taking into account the percentage (0 (0–5%), 1 (6–24%), 2 (26–75%), and 3 (76–100%) and intensity of the membranous staining of the tumor cells (0 absent; 1 weak at 400×; 2 intermediates at 100×; 3 strong at 40×) and calculated to obtain a final score (0–3 were regarded as negative; 4–6 were regarded as positive). Results: For statistical purposes, we divided the tumors into two categories: Gleason grade group 1 makes up 80.7% and grade group 2, which includes all the remaining Gleason grade groups (out of 2–5), accounts for 19.3% of the tumors. Grade group 1 had the highest incidence of score 4 (positive expression). There were statistically significantly more positive expressions in those tumors with negative prostatectomy margins (chi square: p = 0.001; Cramer V: 0.319). There was no correlation between CD44s expression and biochemical recurrence (p = 0.218), nor with the preoperative PSA values (p = 0.165). In the grade group 1 tumors, the CD44s immunoexpression and status of prostatectomy margin were statistically significantly related with negative margins (p = 0.028). An analysis of the expression of CD44s according to the localization in the central part of the tumor mass and on the periphery of the cancer in the group of tumors with a positive margin did not show a significant correlation because the sample was too small. Descriptively, it can be noted that the expression on the periphery was higher, and the central/peripheral expression ratio was higher in favor of the periphery. Conclusions: Our results provide insight into the possible value of CD44s expression for predicting the behavior of prostate tumors and the justification of therapy after a prostatectomy. Also hypothetically, they indicate a protective role of CD44s in a group of well-differentiated tumors at the periphery of the tumor mass. Therefore, it is useful to study the CD44s molecule further in this sense. Full article
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19 pages, 3232 KiB  
Article
Survival Outcomes for Men over 80 Years Undergoing Transrectal Ultrasound-Guided Prostate Biopsy: A Prospective Analysis
by Dareen Alghamdi, Neil Kernohan, Chunhui Li and Ghulam Nabi
Cancers 2024, 16(23), 3995; https://doi.org/10.3390/cancers16233995 - 28 Nov 2024
Viewed by 1713
Abstract
Introduction: Prostate cancer is the second most prevalent cancer among elderly males in Western countries. TRUS biopsy remains a standard diagnosing approach for prostate cancer but poses notable risks, particularly in older men, including complications such as sepsis, acute retention, and rectal bleeding, [...] Read more.
Introduction: Prostate cancer is the second most prevalent cancer among elderly males in Western countries. TRUS biopsy remains a standard diagnosing approach for prostate cancer but poses notable risks, particularly in older men, including complications such as sepsis, acute retention, and rectal bleeding, which can lead to substantial morbidity and mortality. This study aimed to evaluate cancer-specific survival outcomes in men aged over 80 years and whether there is any cancer-specific survival advantage for TRUS biopsy procedure. Methods: Between January 2005 and December 2015, we studied outcomes of 200 patients (median age, 82 years) with elevated prostate-specific antigen (PSA) levels (>4.0 ng/mL) and/or abnormal digital rectal examination (DRE) who underwent TRUS biopsy. Each participant was followed up until death using an electronic system and a unique identifier in a defined geographical area. Cancer-specific and overall survival analyses were carried out utilising SPSS, while R Project was employed to construct and evaluate two nomograms survival duration and predict the risk of death post-biopsy. All statistical tests were two-tailed, with significance set at p < 0.05. Results: Amongst the participants, only 24 patients were alive at the end of follow-up (median age, 91 years). The PSA levels ranged from 4.88 to 102.7 ng/mL. Log-rank and Breslow tests indicated that higher PSA levels, the development of metastases, and ISUP grade group 8–10 were associated with shorter survival times. Age, co-morbid conditions, and tumour type were incorporated into the nomogram due to their clinical significance. Patients aged <81 years had lower mortality risk, while those aged >88 years faced higher mortality risks. Complications from the biopsy increased mortality risks in both cancerous and benign cases, and metastasis significantly heightened the likelihood of death. However, co-morbid conditions did not influence survival probability. Conclusions: Our findings underscore that older age (specifically 80 years and above), high Gleason score, metastasis, and elevated PSA levels are predictive of poorer survival outcomes in elderly men following TRUS biopsy. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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