Search Results (1,015)

Objectives: To investigate whether radiomics features extracted from iliac bone marrow on prostate MRI can differentiate patients with monoclonal gammopathy of undetermined significance (MGUS) alone from those with concomitant MGUS and prostate cancer (PCa). Methods: This retrospective study included 28 patients with hematologically confirmed MGUS who underwent multiparametric prostate MRI and MRI/ultrasound fusion-guided biopsy, stratified into MGUS + PCa (n = 16) and MGUS-only (n = 12). The right iliac bone marrow was manually segmented on axial T2-weighted images. A total of 107 radiomics features were extracted using PyRadiomics. A hybrid descriptive-inferential approach was applied for feature selection, followed by discriminant analysis with 5-fold cross-validation. Diagnostic performance was evaluated using sensitivity, specificity, accuracy, PPV, NPV, and AUROC with 95% bootstrap confidence intervals. Results: ANOVA identified two features with significant group differences. After hybrid feature selection, original_glcm_ClusterShade was the most discriminative feature. The model achieved sensitivity of 87.5%, specificity of 41.7%, accuracy of 67.9%, PPV of 66.7%, NPV of 71.4%, and AUROC of 0.745 (95% CI: 0.54–0.91; p = 0.013). Conclusions: Radiomics analysis of the iliac bone marrow on routine prostate MRI may reveal microstructural differences between patients with isolated MGUS and those with concomitant MGUS and PCa. These hypothesis-generating findings warrant prospective validation in larger multicenter cohorts before clinical application. Full article

Background/Objectives: Systemic inflammation and nutritional status influence cancer progression and prognosis. The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel biomarker reflecting inflammation, immune response, and nutritional status; however, its prognostic value in metastatic hormone-sensitive prostate cancer (mHSPC) remains unclear. Methods: This retrospective multicenter cohort study included 159 patients with de novo mHSPC diagnosed between January 2018 and April 2025. Baseline CALLY, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) were calculated. Results: The optimal CALLY cut-off was 0.58. A low CALLY was associated with significantly shorter progression-free survival (PFS) and overall survival (OS). It correlated with higher tumor burden, higher Gleason grade, elevated prostate-specific antigen levels, and poorer performance status. In univariate analysis, a low CALLY predicted worse OS (HR 5.20; p = 0.021), although this effect was attenuated in multivariate analysis (HR 2.15; 95% CI 0.52–8.90; p = 0.290), and its absolute discriminatory performance in receiver operating characteristic analysis remained modest (AUC = 0.558). Complete response rates differed significantly (high-CALLY 41.7% vs. low-CALLY 5.9%, p < 0.001), suggesting a potential link between baseline CALLY and treatment response. Conclusions: Among the indices evaluated, CALLY demonstrated the highest, though still modest, discriminatory ability for overall survival (AUC 0.558), and was the only marker to reach statistical significance in survival analysis. Its prognostic effect was attenuated in multivariable analysis, suggesting that CALLY reflects, rather than independently drives, the systemic consequences of high-burden disease. These findings are exploratory, and prospective validation in larger cohorts is required to determine its potential clinical utility. Full article

Lutetium-177-PSMA-617 (Lu-PSMA) radioligand therapy (RLT) is established in metastatic castration-resistant prostate cancer (mCRPC), with regulatory approvals based on the VISION and TheraP trials. Subsequent trials have extended the evidence to taxane-naive mCRPC (PSMAfore) and demonstrated that combining Lu-PSMA with enzalutamide yields a significant overall survival benefit over enzalutamide alone (ENZA-p). However, higher and more homogeneous PSMA expression in treatment-naive disease, combined with lower tumor burden and preserved bone marrow reserve, provides a biological rationale for deploying RLT earlier in the disease course. In metastatic hormone-sensitive prostate cancer (mHSPC), the Phase III PSMAddition trial reported improved radiographic progression-free survival when Lu-PSMA was added to standard androgen deprivation therapy (ADT) plus androgen receptor pathway inhibitor (ARPI), and the Phase II UpFrontPSMA trial demonstrated enhanced biochemical responses with Lu-PSMA induction before docetaxel. In oligometastatic and oligorecurrent disease, the BULLSEYE and LUNAR trials have shown progression-free survival benefits, raising the possibility of deferring androgen deprivation therapy and its associated morbidity. Meanwhile, next-generation radionuclides, including actinium-225 (WARMTH) and the dual beta-Auger emitter terbium-161 (VIOLET), are entering clinical development to address the radiobiological limitations of Lutetium-177. This review synthesizes the evidence for PSMA-targeted radioligand therapy across the prostate cancer disease continuum and discusses patient selection, treatment sequencing, and the access and cost-effectiveness considerations that will shape adoption in earlier disease settings. Full article

Unc-51-like kinase 3 (ULK3) is a key member of the ULK serine/threonine kinase family. Aberrant ULK3 expression has been increasingly linked to tumorigenesis and malignant progression in multiple cancer types. However, the precise role of ULK3 in tumor initiation and progression remains incompletely understood. Leveraging integrated multi-omics data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), we systematically characterized the expression of ULK3 at both the transcript and protein levels across 33 cancer types. We also evaluated genomic alterations, prognostic significance, alternative splicing, pathway enrichment, tumor stemness, immune infiltration, and immunotherapy-related biomarkers. In parallel, we investigated the function of ULK3 in prostate cancer PC-3 cells using cellular localization analysis, wound-healing assays, and MTT assays. We further applied Connectivity Map (CMap) screening and molecular docking to identify candidate ULK3 activators. ULK3 was significantly upregulated in 13 cancer types, including Bladder Urothelial Carcinoma, Breast Invasive Carcinoma, and Lung Adenocarcinoma. In contrast, ULK3 was downregulated in Cholangiocarcinoma and Head and Neck Squamous Cell Carcinoma. High ULK3 expression was associated with poor overall survival in Adrenocortical Carcinoma, Kidney Renal Clear Cell Carcinoma, and Skin Cutaneous Melanoma. Copy number amplification contributed to ULK3 overexpression. A recurrent A206V missense mutation was detected in the protein kinase (Pkinase) domain. Genes co-expressed with ULK3 were enriched in RNA splicing, methylation, oxidative phosphorylation, and energy metabolism. ULK3 expression showed positive correlations with tumor stemness indices and m1A/m5C/m6A RNA modification regulators. From an immunological perspective, high ULK3 expression was associated with lower Immune Score, increased M2 macrophage infiltration, and co-expression of PD-L1, CTLA4, and LAG3 in most cancers. ULK3 expression was also correlated with Tumor Mutational Burden in Kidney Renal Clear Cell Carcinoma and Rectum Adenocarcinoma. In addition, ULK3 expression was associated with Microsatellite Instability in Brain Lower Grade Glioma, Lung Adenocarcinoma, and Uterine Corpus Endometrial Carcinoma. ULK3 overexpression promoted proliferation and migration in PC-3 cells. Cephaeline was screened as a putative ULK3 activator. Overall, ULK3 expression and amplification were associated with poor clinical outcomes, tumor stemness, immunosuppression, and RNA dysregulation. These findings highlight the potential value of ULK3 as a pan-cancer diagnostic and prognostic biomarker and as a predictor of immunotherapy response, particularly in prostate cancer. Full article

Introduction: Prostate cancer (PC) is a highly prevalent malignant tumour associated with significant morbidity and mortality. While physical activity has been linked to a lower risk of PC and exercise has been shown to reduce mortality, the evidence for the association between physical activity and mortality is limited. Objective: This study aimed to assess the association between physical activity and mortality risk in men with or at risk of PC. Methods: A systematic search was conducted in Medline, Scopus and Web of Science from inception until April 2026. Observational studies analysing physical activity and all-cause and PC-specific mortality were included. The data were synthesised and interpreted using a synthesis without meta-analysis (SWiM) approach. The quality of the studies was assessed using the NHLBI tool. The certainty of the evidence was assessed using the GRADE framework. Results: Fifteen observational studies were included. The hazard ratio (HR) was the predominant effect measure. Physical activity was associated with a reduction in all-cause mortality (HRs: 0.40–0.88; highest versus lowest categories), and a dose–response gradient was observed within two cohorts. Associations with PC-specific mortality were less consistent, with significant inverse findings concentrated in post-diagnosis assessments. The quality of the studies was generally poor, and the certainty of the evidence was very low for both outcomes. Conclusions: Physical activity was associated with lower all-cause mortality risk in men with or at risk of PC, and the most consistent inverse estimates were observed in post-diagnostic assessments. These findings are observational and should not be interpreted as a clinical recommendation. A dose–response pattern was noted within individual studies, although the certainty of evidence was very low for this outcome. Additionally, evidence for PC-specific mortality was inconsistent and of very low certainty. Prospective studies with standardised, objective measures of physical activity are required. Full article

Background: Prostate cancer represents one of the greatest challenges in modern urology. The definitive diagnosis relies on prostate biopsy. The traditional transrectal (TR) approach carries a significant risk of infectious complications and drives antimicrobial resistance. For this reason, the transperineal (TP) approach is increasingly being considered the method of choice. This literature review aims to comparatively analyze both methods (TP vs. TR) in terms of oncological efficacy, infectious and non-infectious safety, patient-reported pain tolerance, and cost-effectiveness. Materials and Methods: A comprehensive search of the PubMed and Embase databases was conducted, including English-language clinical studies published after 2011. Studies directly comparing TP and TR biopsies regarding diagnostic parameters and/or complication profiles were eligible for inclusion and subsequently underwent qualitative methodological assessment. Additionally, to outline a broader background and fuller clinical context, other supplementary publications were included in the review. Results: Ultimately, 14 publications representing 10 unique clinical trials were included in the main analysis. The overall cancer detection rate is comparable for both methods; however, the TP approach demonstrates an advantage in detecting anterior zone lesions and—especially in combination with MRI—clinically significant prostate cancer (csPCa). Both techniques differ in their safety and tolerance profiles: TP minimizes the risk of infection and rectal bleeding but is associated with higher short-term discomfort during local anesthesia administration and more frequent hematuria. Conversely, TR is associated with prolonged post-procedural discomfort. Economic analyses yield inconclusive results depending on the time horizon adopted. Conclusions: The choice of biopsy technique requires a conscious clinical compromise. The TP method is becoming the preferred option due to its more favorable infectious safety profile. The development of modern urology should aim towards fully personalized diagnostics, where the decision regarding the biopsy approach is based on the patient’s best interest and is individually tailored to their anatomy, risk profile, and personal preferences. Full article

Background: Prostate cancer remains one of the most prevalent malignancies worldwide, with high mortality in advanced and metastatic stages. Drug repurposing offers a cost-effective and time-efficient strategy to identify new therapeutic options. Objectives: This study aimed to apply physiologically based pharmacokinetic (PBPK) modeling to evaluate repurposed antiretroviral drugs efavirenz (EFV), etravirine (ETV), and saquinavir (SAQ) in prostate cancer, and to assess potential drug–drug interactions (DDIs) between EFV and ETV. Methods: PBPK models for EFV and SAQ were obtained and an ETV was developed and validated using literature and ADMET Predictor^® data. Prostate tissue models were modified to simulate malignant conditions, and population-based simulations examined the influence of age and obesity. The GastroPlus^® DDI module was applied to explore mechanistic interactions between EFV and ETV under different physiological scenarios. Results: Tumor-specific prostate tissue alterations produced minimal systemic pharmacokinetic changes but increased total drug accumulated in simulated tissue, with differences in unbound concentrations, while demographic variables such as age and weight significantly affected drug exposure, which are comorbidities in prostate cancer. Lighter individuals exhibited higher plasma concentrations across all drugs, consistent with known previously reported pharmacokinetic trends in obese individuals. DDI simulations indicated only minor changes in ETV pharmacokinetics when combined with EFV, with no clinically significant interaction detected. Conclusions: The integration of PBPK modeling, population variability, and DDI analysis highlights the potential of SAQ, EFV, and ETV as viable drugs for prostate cancer repurposing, but with a heavy focus on dosing personalization. In silico approaches provide a useful framework for early preclinical evaluation and the optimization of repurposed drugs, supporting the early evaluation of repurposed drug candidates in oncology. Full article

Background/Objectives: Metastatic hormone-sensitive prostate cancer (mHSPC) is a biologically heterogeneous disease in which treatment intensification with androgen receptor pathway inhibitors has significantly improved clinical outcomes. However, direct comparative evidence between abiraterone and enzalutamide remains limited. We aimed to evaluate radiographic progression-free survival (rPFS) in patients with mHSPC treated with first-line abiraterone or enzalutamide and to perform exploratory subgroup analyses according to baseline clinical and laboratory characteristics. Methods: This retrospective single-center study included patients with mHSPC who received first-line abiraterone or enzalutamide in combination with androgen deprivation therapy. Baseline demographic, clinical, and laboratory characteristics were collected retrospectively. The primary endpoint was rPFS. Survival was analyzed using the Kaplan–Meier method and compared using the log-rank test. Results: A total of 172 patients were included, of whom 84 received abiraterone and 88 received enzalutamide. The median follow-up duration was 24.7 months (95% CI 21.5–27.9). In the overall population, median rPFS was comparable between the abiraterone and enzalutamide groups (50 vs. 49 months, p = 0.21). However, enzalutamide was associated with significantly longer rPFS among patients aged <70 years (HR 0.25, 95% CI 0.07–0.89; p = 0.02), those with baseline hemoglobin ≥12 g/dL (HR 0.36, 95% CI 0.15–0.85; p = 0.01), and those with baseline ALP < 147 U/L (HR 0.43, 95% CI 0.19–0.98; p = 0.04). No significant differences were observed in other subgroups. Conclusions: rPFS was comparable between abiraterone and enzalutamide in the overall mHSPC population. However, enzalutamide was associated with longer rPFS in patients aged <70 years and in those with preserved hemoglobin and lower ALP levels. These findings suggest that baseline clinical and laboratory characteristics may influence treatment outcomes and should be prospectively validated. Full article

Background/Objectives: Iatrogenic nerve injury is a significant challenge in urologic surgery, with radical prostatectomy posing a high risk due to complex pelvic neural anatomy. Despite advances in robotic-assisted and nerve-sparing techniques, postoperative urinary incontinence and erectile dysfunction remain prevalent, adversely affecting patients’ quality of life and imposing substantial healthcare costs. Methods: A narrative review was conducted using PubMed, MEDLINE, and the Cochrane Library (searches through February 2026) for studies on radical prostatectomy epidemiology, mechanisms of nerve injury, functional outcomes, and economic burden. Emerging intraoperative fluorescence imaging technologies, surgical strategies to mitigate iatrogenic nerve injuries, and the financial costs of post-prostatectomy complications were assessed. Results: Robotic-assisted radical prostatectomy now accounts for >80% of procedures in the United States, and has been associated in observational studies with improved early recovery of erectile function compared with open and laparoscopic approaches. However, the lack of real-time nerve visualization remains a limiting factor. Recent milestones (January 2026) include the Food and Drug Administration Investigational New Drug clearance for the nerve-specific fluorophore LGW16-03 (NerveTrace), which enables real-time identification of sub-millimeter nerve branches, and the 510(k) premarket clearance of Dendrite imaging (November 2025). Conclusions: Enhanced intraoperative nerve discrimination via molecularly targeted imaging has the potential to reduce iatrogenic complications and improve long-term functional and economic outcomes in prostate cancer surgery, although these benefits have yet to be demonstrated in prospective clinical and health-economic studies. Full article

Focal therapy is emerging as an organ-preserving strategy for selected patients with localized prostate cancer, aiming to preserve urinary and sexual function while maintaining acceptable cancer control. However, patient and technology selection remain complex because prostate cancer is often multifocal, clinically significant lesions may be missed by imaging or biopsy, and long-term comparative oncological data are limited. This narrative review summarizes current evidence and consensus recommendations on oncological suitability, histopathological risk features, tumor burden, imaging assessment, anatomical considerations, functional priorities, and follow-up. We also discuss the complementary roles of multiparametric magnetic resonance imaging, prostate-specific membrane antigen positron emission tomography, micro-ultrasound, and artificial intelligence-assisted planning. Finally, we review how tumor location and proximity to critical structures guide selection among high-intensity focused ultrasound, cryotherapy, irreversible electroporation, transurethral ultrasound ablation, laser ablation, and photodynamic therapy. Focal therapy remains promising but requires careful selection, shared decision-making, and structured follow-up. Full article

Background/Objectives: Cancer, a multifactorial disease with uncontrolled cell growth, oxidative stress, inflammation, genomic instability, and molecular signaling pathways, is a global health concern, leading to the ~20 million newly diagnosed cases annually. Although conventional therapy has been shown to enhance the survival rates of cancer patients, its clinical efficacy is limited by certain side effects that occur as a result of treatment, thus necessitating the exploration of plant-derived bioactive compounds for their potential as safer and alternative supportive therapeutic agents. Aloe vera, known as the plant of immortality, comprises phytochemicals, such as anthraquinones (aloe-emodin, emodin, and aloin), polysaccharides (acemannan), flavonoids, and phenolic acids, which contribute to the pharmacological effect of the compound. Methods: This review summarizes the anticancer potential of Aloe vera, and the data were retrieved from databases, such as PubMed, Google Scholar, ScienceDirect, Web of Science, and Wiley Online Library, during the time period of 2015 to 2025. Results: The literature revealed that Aloe vera and its bioactive compounds have dose-dependent cytotoxic and anti-proliferative properties against hepatocellular, cervical, colorectal, lung, breast, prostate, and hematological cancers, which are significantly mediated by apoptosis and pyroptosis induction, reactive oxygen species (ROS) production, mitochondrial dysfunction, inhibition of angiogenesis and metastasis, and the modulation of key signaling pathways, particularly PI3K/Akt, MAPK, NF-кB, p53, and Wnt/β-catenin. Furthermore, anthraquinones, including Aloe-emodin, demonstrate potent anticancer effects at micro-molar doses, and polysaccharides increase immune reactions and provide tumor immunity. Conclusions: Conclusively, Aloe vera is a promising multi-target natural compound, particularly efficient in the treatment of cancer. However, despite significant therapeutic potential, more research on pharmacokinetics, standard dose, and controlled clinical trials of Aloe vera is required to validate clinical applicability. Full article

Background/Objectives: Enzalutamide and abiraterone acetate are commonly used androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC), including after docetaxel. However, real-world outcomes remain heterogeneous, and simple prognostic markers may help describe this variability. This study aimed to describe survival outcomes with enzalutamide and abiraterone acetate after docetaxel and to explore the prognostic value of a routine clinical-inflammatory risk classification. Methods: This retrospective single-center study included 136 patients with mCRPC treated with enzalutamide or abiraterone acetate after docetaxel. A composite risk classification was defined using four routinely available variables: pan-immune-inflammation value (PIV) > 457.99, time to castration resistance < 12 months, baseline hemoglobin ≤ 12 g/dL, and Gleason score ≥ 8. One point was assigned for each adverse factor, and patients were classified as low, moderate, or high risk. Overall survival (OS) was assessed using Kaplan–Meier estimates and Cox regression. The prognostic score and Cox regression-based nomogram were evaluated as exploratory tools. Results: Of the 136 patients, 8 (5.9%) were classified as low risk, 67 (49.3%) as moderate risk, and 61 (44.9%) as high risk. Median OS was not reached in the low-risk group, compared with 33.84 months in the moderate-risk group and 9.66 months in the high-risk group. In multivariable analysis, high-risk status was independently associated with worse OS (HR = 9.87; 95% CI: 2.38–40.92; p = 0.002). No statistically significant OS difference was observed between enzalutamide and abiraterone acetate in this non-randomized cohort (HR = 1.36; 95% CI: 0.90–2.06; p = 0.142). Conclusions: In this real-world post-docetaxel mCRPC cohort, no statistically significant OS difference was observed between enzalutamide and abiraterone acetate; however, the study was not designed to establish comparative effectiveness or therapeutic equivalence. The exploratory risk classification based on routine clinical and inflammatory variables was associated with distinct survival outcomes. External validation is required before clinical application. Full article

Background/Objectives: Clinical studies of prostate cancer treated with radically hypofractionated high-dose-rate brachytherapy (HDR-BT) have reported a significant loss of tumor control that contradicts the standard linear-quadratic (LQ) and low-$\alpha /\beta$-ratio paradigm for prostate cancer. In a previous study by our group, we showed that the linear–quadratic–linear (LQL) model could describe this response, but the underlying biological drivers remained unclear. In this follow-up study, we further investigate whether the interplay between hypoxia and reoxygenation kinetics can explain the poor response to extreme hypofractionation. Methods: We analyzed a large dataset of 3239 patients (44 schedules) using a three-compartment reoxygenation model (the MSK model) that simulates the dynamics of oxic, intermediate, and hypoxic cell populations. Results: The results show that the MSK model achieves an excellent fit to the clinical data ($p>0.99$) while maintaining a biologically plausible low $\alpha /\beta$ ratio (≤8 Gy). The reoxygenation model provided a performance comparable to the LQL model for low-risk prostate cancer and slightly inferior for intermediate-risk. Conclusions: This suggests that the observed reduction in tumor control may not necessarily be a failure of the LQ formalism but, rather, a consequence of oxygen dynamics associated with ultra-hypofractionated schedules. Nonetheless, neither this nor our previous work can provide insight into the driving mechanism and should only be interpreted as showing that both hypotheses are compatible with the clinical data. Full article

Background and Clinical Significance: Many diagnostic radiopharmaceuticals are excreted in the urine. This can pose a diagnostic challenge when urine-containing structures are in atypical locations, particularly in review of planar imaging without anatomical details from cross-sectional imaging. This case highlights a challenging ^99mTc-methylene diphosphonate (^99mTc-MDP) bone scan in a patient with an inguinal hernia containing a portion of the urinary bladder. Subsequently, we review diagnostic challenges on conventional and molecular imaging following surgical repair of the inguinal hernia. Case Presentation: A 79-year-old man with prostate cancer underwent initial staging prior to prostatectomy with ^99mTc-MDP bone scintigraphy. Anterior and posterior images showed focal uptake overlying the pubic symphysis. Lateral views showed that the activity was extraosseous. Follow-up CT urography showed a bladder hernia as the cause of the abnormality on bone scan. Prostatectomy and inguinal hernia repair were performed as a combination case. Four years postoperatively, follow-up ⁶⁸Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) showed no recurrence. The CT component of the exam showed an intermediate-density focus at the right inguinal hernia repair site, corresponding to a plugoma related to a polypropylene mesh plug, and a hyperattenuating Gore-Tex mesh repair of the left inguinal hernia. Conclusions: This case highlights the importance of lateral projections in resolving scintigraphic pitfalls and recognizing mesh-related imaging appearances to prevent misinterpretation. Full article

Background and Objectives: Metastatic castration-resistant prostate cancer (mCRPC) remains a clinically heterogeneous condition despite ongoing advances in systemic treatment. Androgen receptor pathway inhibitors (ARPIs), including abiraterone acetate and enzalutamide, have been associated with improved clinical outcomes; however, early identification of patients deriving limited benefit continues to be challenging. Prostate-specific antigen (PSA) kinetics may serve as a practical indicator of treatment response over time. This study aimed to examine the prognostic significance of achieving a ≥50% reduction in PSA levels at three months in patients with mCRPC treated with ARPIs in routine clinical practice. Materials and Methods: In this retrospective single-center study, patients with mCRPC who received abiraterone acetate or enzalutamide between February 2015 and March 2024 were included. Patients were stratified according to PSA decline at three months (≥50% vs. <50%). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared with the log-rank test. Prognostic variables were subsequently examined using univariate and multivariate Cox proportional hazards models. Results: A total of 60 patients were included. At three months, 44 patients (73.3%) achieved a ≥50% decline in PSA levels. Patients reaching this level had longer PFS and OS than those with <50% decline, and the differences between groups were statistically significant. In multivariate analysis, early PSA decline remained significantly associated with improved survival outcomes. Conclusions: A ≥50% decline in PSA levels at three months represents a simple and clinically meaningful indicator of treatment response in patients with mCRPC receiving ARPIs. Early PSA kinetics may assist in timely risk stratification and closer clinical monitoring in routine clinical practice. Full article