Search Results (1,083)

Currently, new cultivation methods are increasingly sought to create functional foods that could reduce the risk of certain diseases. Benign prostatic hyperplasia represents significant health challenges worldwide and because of that, we investigated the effect of microgravity and total darkness on the anti-proliferative, anti-inflammatory, and anti-androgenic activity of white clover sprouts. The use of clover sprouts, a widely studied plant from the Fabaceae family, can be promising due to their rich phytochemical profile, including isoflavones, known for estrogenic properties. Anti-proliferation activity was determined using a crystal violet assay. Analysis of the prostate-specific antigen (PSA) and 5-α-reductase level was performed using ELISA kits, similarly to anti-inflammatory activity. White clover sprouts exerted anti-proliferative activity against PNT2 prostate cells stimulated by testosterone, and total darkness increased this activity. In addition, anti-androgenic activity of white clover sprouts was demonstrated, through the inhibition of PSA and 5-α-reductase activity, which was most visible in 7-days-old sprouts growing in conditions of microgravity and standard light. In turn, the anti-inflammatory activity of the tested sprouts was rather moderate, but most observed in the inhibition of pro-inflammatory interleukin 6 (IL-6). White clover sprouts cultivated in microgravity and darkness may represent a candidate for novel functional food with anti-androgenic activity. Full article

Background: Prostate cancer is one of the most common malignancies in men and a leading cause of cancer-related mortality. Early detection is essential to ensure curative treatment and favorable outcomes, but traditional diagnostic approaches—such as serum prostate-specific antigen (PSA) testing, digital rectal examination (DRE), and histopathological confirmation following biopsy—are limited by suboptimal accuracy and variability. Multiparametric magnetic resonance imaging (mpMRI) has improved diagnostic performance but remains highly dependent on reader expertise. Artificial intelligence (AI) offers promising opportunities to enhance diagnostic accuracy, reproducibility, and efficiency in prostate cancer detection. Objective: To evaluate the diagnostic accuracy and reporting timeliness of AI-based technologies compared with conventional diagnostic methods in the early detection of prostate cancer. Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, Web of Science, and Cochrane Library were searched for studies published between January 2015 and April 2025. Eligible designs included randomized controlled trials, cohort, case–control, and pilot studies applying AI-based technologies to early prostate cancer diagnosis. Data on AUC-ROC, sensitivity, specificity, predictive values, diagnostic odds ratio (DOR), and time-to-reporting were narratively synthesized due to heterogeneity. Risk of bias was assessed using the QUADAS-AI tool. Results: Twenty-three studies involving 23,270 patients were included. AI-based technologies achieved a median AUC-ROC of 0.88 (range 0.70–0.93), with median sensitivity and specificity of 0.86 and 0.83, respectively. Compared with radiologists, AI or AI-assisted readings improved or matched diagnostic accuracy, reduced inter-reader variability, and decreased reporting time by up to 56%. Conclusions: AI-based technologies show strong diagnostic performance in early prostate cancer detection. However, methodological heterogeneity and limited standardization restrict generalizability. Large-scale prospective trials are required to validate clinical integration. Full article

Background and Objectives: Benign prostatic hyperplasia (BPH) is one of the most common chronic conditions in older men, significantly impairing quality of life (QoL) by causing lower urinary tract symptoms (LUTSs). 5-alpha-reductase inhibitors (5-ARIs), including finasteride and dutasteride, remain a cornerstone of pharmacotherapy for BPH; however, comparative real-world data remain limited. The aim of this retrospective clinical study was to compare the therapeutic efficacy and safety of finasteride and dutasteride in patients with BPH. Materials and Methods: A total of 401 patients with BPH were retrospectively analyzed: 162 received finasteride and 239 received dutasteride. Clinical parameters, including the International Prostate Symptom Score (IPSS), Quality of Life (QoL) index, and International Index of Erectile Function-5 (IIEF-5) score; urodynamic outcomes, including maximum urinary flow rate (Qmax), average flow rate (Qave), and post-void residual urine volume (PVR); and biochemical markers, including prostate-specific antigen (PSA) and serum creatinine levels, were evaluated at baseline and after at least 6 months of continuous therapy. Statistical significance was defined as p < 0.05. Results: Both treatment groups demonstrated significant within-group improvements in LUTS severity and urodynamic outcomes (p < 0.001 for IPSS, Qmax, and QoL). Compared with finasteride, dutasteride achieved greater reductions in prostate volume (−26.3% vs. −18.1%, p = 0.008) and PSA levels (−43.7% vs. −32.5%, p = 0.014), as well as a slightly greater improvement in IPSS (−6.8 ± 3.9 vs. −5.9 ± 3.6, p = 0.042). Both drugs showed comparable effects on erectile function, as indicated by similar IIEF-5 score changes (Δ = −0.9 ± 2.8 vs. −0.7 ± 2.5, p = 0.51), confirming that neither agent demonstrated a clinically meaningful difference in sexual outcomes. Renal function parameters remained stable in both cohorts. Multivariate analysis identified higher BMI and older age as independent predictors of lower IIEF-5 scores in the finasteride group, while baseline prostate volume was the principal determinant of response in the dutasteride group. Conclusions: Both 5-ARIs effectively reduced LUTS severity and improved urodynamic parameters in men with BPH. Dutasteride demonstrated superior reductions in prostate volume and PSA, while both agents had comparable effects on sexual and renal function. These findings provide real-world evidence supporting the individualization of 5-ARI therapy according to patient-specific clinical characteristics. Full article

Prostate-specific membrane antigen (PSMA) targeting agents have been the cornerstone of advanced prostate cancer (PCa) management in theranostics due to their high sensitivity for detecting and treating metastatic disease. However, approximately one-third of metastatic castration-resistant PCa (mCRPC) lesions may exhibit low or absent PSMA expression due to tumor heterogeneity, prior androgen deprivation therapy, or loss of androgen receptor expression, subsequently altering their response to PSMA-targeted therapy. The molecular and biological mechanisms underlying PSMA downregulation remain elusive but may include neuroendocrine differentiation or epithelial-to-mesenchymal transition (EMT). This review addresses this knowledge gap by examining recent preclinical and clinical evidence on novel radiotracers with the potential to provide alternative strategies beyond PSMA for imaging and treating PCa. The diagnostic performance and therapeutic potential of three emerging radiotracer classes are discussed, including gastrin-releasing peptide receptor (GRPR) ligands, androgen receptor (AR) ligands, and amino acid analogs. This article further highlights the complementary roles of these radiotracers along with their utility in specific patient populations, such as those with low prostate-specific antigen (PSA), biochemical recurrence (BCR), or confirmed PSMA-negative disease. For instance, GRPR-targeted radiotracers have achieved sensitivity of up to 88% and specificity of up to 90% for detecting primary tumors in PCa. The radiolabeled androgen agonist, fluorine-18 (¹⁸F)-fluoro-5α-dihydrotestosterone (FDHT), has demonstrated 98% true-positive rate in predicting lesions on positron emission tomography (PET) scans of mCRPC patients. On the other hand, the synthetic amino acid analog ¹⁸F-fluciclovine demonstrated a lesion detection rate of 84% for PSA levels at or above 5, and 62.5% for PSA levels ranging from 0.7 to less than 1. This review concludes with future directions on the paradigm of multi-tracer and dual-targeting strategies, which can effectively address challenges associated with PCa tumor heterogeneity and facilitate personalized approaches in theranostics. Full article

Background/Objectives: Whole-gland surgery or radiotherapy for localized prostate cancer (PCa) can cure the disease but often impair urinary and sexual function. Focal therapy with high-intensity focused ultrasound (HIFU) seeks to eradicate the tumor while sparing uninvolved tissue. We prospectively evaluated oncological control, functional outcomes and safety of MRI-guided focal HIFU in patients with low- or intermediate-risk PCa. Methods: In this prospective, single-arm, phase II feasibility trial (three Austrian centres, 2021–2024), treatment-naive patients with D’Amico low/intermediate-risk, PSA ≤ 15 ng/mL, clinical stage ≤ T2 and MRI-targeted, biopsy-confirmed index lesions underwent lesion-targeted HIFU (Focal One™). The primary endpoint was failure-free survival (FFS: absence of salvage whole-gland or systemic therapy, metastasis or PCa-specific death). Secondary endpoints included biopsy-proven cancer, prostate-specific antigen (PSA), patient-reported symptoms as International Prostate Symptom Score (IPSS), 5-item International Index of Erectile Function (IIEF), Gaudenz Incontinence Questionnaire and adverse events. Planned follow-up was 24 months with PSA every 3 months, mpMRI and biopsies at 12 months, and imaging- or PSA-triggered biopsies thereafter. Results: Fifty-one men were analysed in the per-protocol cohort (median age 67 years, median PSA 7.55 ng/mL). Median treated volume was 12 mL; median procedure time 85 min. At 24 months, FFS was 94.1%: 3/51 patients (5.9%) required salvage radiotherapy. Among 31 patients who underwent follow-up biopsy, 26 (83.9%) had no cancer; the five positives included three ISUP 1, one ISUP2 and one ISUP 4 lesion. Mean PSA fell by 69% at 3 months (to 2.3 ng/mL) and then stabilized under 3 ng/mL, with a mean of 2.7 ± 1.5 ng/mL at 24 months. Transient acute urinary retention occurred in 11/51 (21.6%); no Clavien–Dindo grade ≥ 4 events were reported. IPSS returned to or improved beyond baseline, erectile function largely recovered by 6–12 months, and only one new case of grade 2 incontinence was observed. Conclusions: MRI-guided focal HIFU achieved high two-year failure-free survival with low morbidity and preserved quality of life in carefully selected patients with low- or intermediate-risk PCa. These data support further randomized and longer-term investigations of focal HIFU as an organ-sparing alternative to whole-gland treatment. Full article

Background: While prostate-specific membrane antigen (PSMA)-targeted imaging has revolutionized metastatic detection, unspecific bone uptake (UBU)—particularly in the ribs—is a common but diagnostically challenging finding in prostate cancer (PCa) patients. This review aims to synthesize current evidence on PSMA-avid rib lesions in PCa and to propose a structured approach for differentiating true metastases from benign mimics. Methods: A comprehensive literature search across PubMed, EMBASE, Scopus, and Web of Science identified relevant studies on PSMA imaging interpretation, tracer-specific patterns, rib lesion morphology, and clinical correlates. Data on uptake intensity, CT features, lesion number, location, tracer type, patient-specific risk factors, and follow-up behavior were extracted and analyzed. Results: Most solitary rib lesions are benign, particularly in low-risk patients or when located in the anterior/lateral arcs. Metastatic lesions are more likely to present as multiple foci, show cortical destruction on CT, exhibit high uptake intensity, and occur in patients with elevated PSA, high Gleason score, or ongoing androgen deprivation. ¹⁸F-PSMA-1007 is especially prone to UBU in the ribs compared to ⁶⁸Ga-PSMA-11. Based on these variables, we propose a clinical decision tree to guide interpretation of PSMA-avid rib lesions. Conclusions: Accurate interpretation of rib lesions on PSMA PET/CT requires a multimodal, context-sensitive approach. Our diagnostic decision tree guides precise differentiation of benign versus metastatic rib lesions, enhancing staging accuracy and clinical decision-making. Biomarker-guided therapies offer potential for personalized treatment, though rib-specific validation remains a critical need. Full article

Cognitive decline can result from various factors, including direct neurotoxic injury, brain tissue damage, inflammation, and disruptions in coagulation and fibrinolysis. This study aimed to examine the relationship between biochemical markers associated with cognitive function and cognitive performance in men with prostate cancer (PC) following radical prostatectomy. Participants underwent a comprehensive evaluation, including clinical assessments (demographic information, medical history, PC progression, and complications such as erectile dysfunction [IIEF-5] and urinary incontinence [ICIQ-UI]), biochemical testing (testosterone, prostate-specific antigen, phosphorylated neurofilament heavy chain [pNF-H], brain-derived neurotrophic factor [BDNF], neuroserpin [NSP], and interleukin-6 [IL-6]), and neuropsychological assessment of cognitive functions. Statistical analysis revealed significant positive correlations between BDNF and NSP levels and performance on delayed memory tasks, specifically the number of correct responses. No other significant associations were found between protein biomarkers and cognitive test outcomes. These findings suggest that the relationship between biochemical markers and cognitive function is complex. However, BDNF and NSP may serve as potential biomarkers for delayed memory impairment in men post-prostatectomy. Full article

Prostate cancer is the most frequently diagnosed solid-organ malignancy in men worldwide. Metastatic castration-resistant prostate cancer represents a rapidly fatal, end-stage form of the disease for which current therapies remain palliative rather than curative. The advent of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of refractory hematologic malignancies, and a growing number of studies are now exploring its potential in solid tumors. In this review, we first provide a concise overview of current immunotherapeutic strategies for prostate cancer, including checkpoint inhibitors, vaccine-based approaches, and bispecific antibodies. We then focus on the most recent and promising developments in CAR-T cell therapy for this malignancy. Specifically, we examine the key tumor-associated antigens targeted in prostate cancer-directed CAR-T cell therapy and summarize findings from preclinical research as well as ongoing and completed clinical trials. Finally, we discuss the main challenges that limit the efficacy of CAR-T therapy in prostate cancer, such as antigen heterogeneity, immunosuppressive tumor microenvironments, on-target/off-tumor toxicity, limited T-cell persistence, and inefficient trafficking to metastatic lesions, and outline potential strategies to overcome these barriers. Our aim is to define a translational roadmap for advancing CAR-T therapy toward clinical application in patients with metastatic castration-resistant prostate cancer. Full article

Background/Objectives: This study aimed to assess whether magnetic resonance elastography (MRE)-derived stiffness measurements of the central gland, entire gland, and lesions of the prostate differ among benign, premalignant, and malignant lesions and to evaluate their diagnostic performance in distinguishing these groups. Methods: This prospective study enrolled 113 men (mean age, 62.7 ± 7.2 years). Patients were categorized into benign (n = 75), premalignant (n = 15; atypical small acinar proliferation and high-grade prostatic intraepithelial neoplasia), and malignant (n = 23; adenocarcinoma) lesion groups based on histopathological findings. MRE-derived stiffness was measured at the lesion, central gland, and entire gland levels. Other evaluated parameters included diffusion restriction, contrast retention, prostate-specific antigen (PSA) levels, prostate volume, and Prostate Imaging Reporting and Data System (PI-RADS) score. Results: Mean central gland stiffness did not differ between benign and premalignant lesions, but was markedly higher in the malignant group (Benign: 3.3 ± 0.2 vs. Premalignant: 3.4 ± 0.2 vs. Malignant: 3.6 ± 0.3 kPa; p < 0.001). A similar pattern was observed for entire gland stiffness (Benign: 3.3 ± 0.4 vs. Premalignant: 3.3 ± 0.4 vs. Malignant: 4.1 ± 0.6 kPa; p < 0.001). Median lesion stiffness increased stepwise from benign to premalignant to malignant lesions (Benign: 3.6 vs. Premalignant: 5.8 vs. Malignant: 7.7 kPa; p < 0.001). Central and entire gland stiffness distinguished malignant lesions but failed to differentiate premalignant lesions from benign lesions. Lesion stiffness demonstrated superior diagnostic accuracy in distinguishing premalignant from benign (AUC 0.82; accuracy 83.3%) and malignant lesions from premalignant lesions (AUC 0.86; accuracy 82.5%) compared to central and entire gland stiffness. Conclusions: MRE-derived lesion stiffness is a promising diagnostic biomarker, effectively distinguishing benign, premalignant, and malignant prostate lesions. Prostate gland stiffness measured by MRE, especially lesion-specific measurements, may be considered as an additional candidate procedure that can be accommodated in multiparametric magnetic resonance imaging. Full article

Men with high-risk localized prostate cancer (PCa) often have poor long-term outcomes, underscoring the need for improved neoadjuvant strategies beyond the current standard of care. Radioligand therapy with ¹⁷⁷Lutetium-PSMA-617 (¹⁷⁷Lu-PSMA-617) has emerged as a promising method to eliminate occult micrometastases while enhancing immune-mediated clearance of the primary tumor. Initial trials have affirmed the treatment’s feasibility and safety; however, they have consistently reported a lack of pathological complete response. This absence of profound initial tumor reduction necessitates further therapeutic advancements. The underlying rationale for future strategies is clear, as ¹⁷⁷Lu-PSMA-617 promotes immunogenic cell death, potentially sensitizing immunologically “cold” tumors to checkpoint inhibitors. However, caution is warranted. The synergy observed between these therapies in advanced, metastatic castration-resistant PCa stems from a different biological context, and similar outcomes cannot be presumed in treatment-naïve, localized disease without rigorous validation. Continued progress hinges on developing improved metrics for success and patient selection. Simple prostate-specific antigen reductions have demonstrated minimal correlation with significant pathological outcomes in this setting, underscoring the critical need for validated surrogate endpoints and predictive biomarkers. Ultimately, large-scale randomized trials are essential to determine whether this investigational approach impacts key clinical outcomes—namely, metastasis-free and overall survival. While the strategy is theoretically sound, its capacity to enhance cure rates for high-risk localized PCa remains unverified. Full article

Background: Locally advanced prostate cancer (PCa) is commonly treated with multimodal therapy; however, long-term outcomes of surgery alone are poorly defined. We investigated the potential and limitations of robot-assisted radical prostatectomy (RARP) as primary treatment without perioperative systemic therapy in patients with locally advanced PCa. Methods: We retrospectively analyzed 258 patients who underwent RARP with extended pelvic lymph node dissection between 2012 and 2022 with locally advanced PCa, defined as present if at least one of the following was met: clinical stage cT3b–T4; primary Gleason pattern 5; >4 biopsy cores with Grade Group 4 or 5; or more than one NCCN high-risk characteristic. Patients who received neoadjuvant or adjuvant therapy were excluded. Endpoints included biochemical recurrence-free survival, metastasis-free survival, cancer-specific survival, and predictors of persistent PSA. Results: Median follow-up was 60.6 months. Pathological stage ≥ pT3a occurred in 63.6% and nodal involvement (pN1) in 27.1%. Five-year BRFS, MFS, and CSS were 36.6%, 88.9%, and 98.3%, respectively. Persistent PSA occurred in 21.3%. Preoperative predictors included PSA > 40 ng/mL, clinical stage ≥ cT3a, and >4 biopsy cores with a Gleason score of 8–10; patients with ≥2 features had significantly poorer BRFS and MFS. Postoperative predictors of recurrence were pathological stage, lymphovascular invasion, and nodal involvement. Conclusions: RARP alone provided durable long-term cancer control in selected men with locally advanced PCa, whereas patients with multiple adverse features were unlikely to be cured with surgery alone. Careful risk stratification may identify candidates for surgical monotherapy and help avoid overtreatment, while others may benefit from multimodal therapy. Full article

Background: This study aimed to develop and evaluate machine learning (ML) models to predict biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). Methods: We retrospectively analyzed clinical data from 1125 patients who underwent RARP between July 2013 and December 2023. The dataset was divided into a training set (70%) and a testing set (30%) using a stratified sampling strategy. Five ML models were developed using the training set. Model performance was evaluated on the testing set using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and F1 scores. Additionally, model interpretability was assessed using SHapley Additive exPlanations (SHAP) values to determine the contribution of individual features. Results: Among the five ML models, the LightGBM model achieved the best prediction ability with an AUC of 0.881 (95%CI: 0.840–0.922) in the testing set. For model interpretability, SHAP values explained the contribution of individual features to the model, revealing that pathological T stage (pT), positive surgical margin (PSM), prostate-specific antigen (PSA) nadir, initial PSA, systematic prostate biopsy positive rate, seminal vesicle invasion (SVI), pathological International Society of Urological Pathology Grade Group (pGG), and perineural invasion (PI) were the key contributors to the predictive performance. Conclusions: We developed and validated ML models to predict BCR following RARP and identified that the LightGBM model with 8 variables achieved promising performance and demonstrated a high level of clinical applicability. Full article

Background: MicroRNA-379 (miR-379) has been reported to play a tumour-suppressing role in several cancer types. Our previous work demonstrated that miR-379 overexpression attenuates the metastatic spread of prostate cancer (PCa) both in vitro and in vivo. However, the underlying mechanisms remain poorly understood. Methods: To elucidate the mechanisms by which miR-379 affects metastases, we performed a cytokine array to identify secreted proteins modulated by miR-379 dysregulation in a bone microenvironment model. We then assessed the levels of the key candidate, and performed functional studies, including reporter assays, of the transcriptional regulation. Results: Prostate-specific antigen (PSA)—the clinically widely used blood biomarker for PCa—emerged as the most significantly affected secreted protein. We observed that PSA secretion increased following miR-379 inhibition and decreased with miR-379 overexpression, with parallel changes in intracellular PSA levels. However, our data suggests that miR-379 does not directly regulate PSA expression. Instead, miR-379 appears to downregulate androgen receptor (AR) expression by targeting its 3′-untranslated region (3′-UTR), thereby indirectly reducing PSA transcription through diminished AR-mediated promoter activation. Supporting this indirect mechanism, analysis of clinical samples from prostate cancer patients revealed an inverse correlation between expression of miR-379 in prostatic tissue and serum PSA levels. Furthermore, reduced miR-379 expression was associated with increased levels of AR immunostaining in malignant tissues. Conclusions: Taken together, these findings suggest that miR-379 negatively regulates PSA secretion indirectly via suppression of AR, and that the interplay between miR-379, AR, and PSA may contribute to the metastatic progression of PCa to bone. Full article

Dendritic cells (DCs) are critical antigen-presenting cells that orchestrate the interface between innate and adaptive immunity, making them attractive approaches for cancer immunotherapy. Recent advances in the characterization of DC subsets, antigen delivery strategies, and adjuvant design have enabled the enhancement of DC-based vaccines for solid tumors. Clinical studies across melanoma, glioblastoma, prostate cancer, and non-small cell lung cancer have demonstrated safety and immunogenicity, with encouraging signals of clinical efficacy, particularly when DC vaccination is combined with immune checkpoint blockade or personalized neoantigen approaches. However, translational barriers remain, including the immunosuppressive tumor microenvironment, inefficient DC migration, and variability in manufacturing protocols. Developing solutions such as in vivo DC targeting, biomaterials-based delivery systems, high-resolution single-cell analyses, and artificial intelligence-driven epitope prediction are controlled to overcome these challenges. Together, these innovations highlight the evolving role of DC immunotherapy as a foundation of precision oncology, offering the potential to integrate personalized vaccination strategies into standard treatment paradigms for solid tumors. Therefore, in this review, we specifically focus on these advances in dendritic cell immunotherapy for solid tumors and their translational implications. Full article

Background: We evaluated the long-term treatment outcomes of patients with clinically localized and locally advanced prostate cancer (PC) who underwent high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT). The primary objective was to identify the optimal timing for discontinuing prostate-specific antigen (PSA) monitoring after HDR-BT. Methods: This analysis included 338 patients with PC who received HDR-BT combined with EBRT between 2006 and 2022 and had a minimum follow-up of 5 years. The patients were stratified based on their PSA levels, and factors associated with recurrence were identified. Results: The median observation period was 8.9 years (range, 5.0–19.0 years). The 10-year recurrence-free survival rate was 92.0%, with 26 recurrences. PSA levels at 5 and 7 years were significantly correlated with oncological outcomes after HDR-BT. Multivariate analysis revealed that a PSA level of >0.2 ng/mL at 5 years was an independent poor prognostic factor for recurrence (hazard ratio, 117.57; 95% confidence interval, 6.22–2223.37; p = 0.001). No patient with a PSA level of ≤0.2 ng/mL at 7 years developed recurrences. Conclusions: Based on our long-term data, we propose that PSA monitoring may be safely discontinued in patients with a PSA level of ≤0.2 ng/mL 7 years after HDR-BT because the risk of recurrence beyond this point is exceedingly low. Full article