Search Results (248)

Background: Aging is the strongest risk factor for prostate cancer (PCa). It is accompanied by progressive epigenomic divergence, known as epigenetic drift, particularly affecting DNA methylation at regulatory regions. However, the extent to which age-associated promoter methylation contributes to coordinated microRNA (miRNA) expression changes in PCa remains incompletely characterized. Methods: We conducted an integrative in silico analysis of 449 primary tumors from the TCGA-PRAD cohort. Age was modeled as a continuous variable. Age-related miRNA expression changes were estimated from miRNA-seq data using DESeq2. Promoter DNA methylation changes (±2 kb from transcription start sites) were assessed using Illumina 450K arrays and linear regression. MiRNAs showing significant age-associated alterations at both expression and methylation levels were classified as concordant or discordant based on directionality and prioritized using an effect size-based concordance score. We analyzed experimentally validated targets of prioritized miRNAs through functional enrichment and network-based approaches to identify convergent regulatory pathways. Results: Initially, we identified 105 age-associated miRNAs. After filtering, 65 candidates remained. Of these, we found 37 miRNAs with significant age-associated changes at both layers, including 20 concordant and 17 discordant miRNAs. These comprised well-characterized cancer-associated miRNAs and lesser-studied candidates enriched in CpG-rich regulatory regions. Network analyses revealed a limited set of genes under convergent regulation by multiple age-associated miRNAs. These implicated pathways are related to cell cycle control, apoptosis, stress response, and epigenetic regulation. Conclusions: Our findings support a model in which age-dependent promoter methylation drift contributes to coordinated miRNA deregulation in PCa. This convergence highlights biologically plausible miRNA biomarkers and age-sensitive epigenetic circuits relevant to prostate carcinogenesis. Full article

A 75-year-old man with newly diagnosed high-risk prostate cancer (cT3bN0M0) underwent ¹⁸F-PSMA PET/CT, which demonstrated intense tracer uptake in a left tracheal mass causing near-complete luminal obstruction, raising suspicion of a primary lung malignancy or metastatic disease. Endoscopic debulking was performed due to progressive respiratory symptoms with dyspnea. Histopathology and immunohistochemistry (p63, SMA, CK5/6 positive; PSA, NKX3.1, and AR negative, with downregulated PSMA-expression) established the diagnosis of low-grade epithelial–myoepithelial carcinoma of the trachea. Following debulking, the patient’s symptoms resolved, and a watchful-waiting strategy was adopted for the tracheal tumor, while curative-intent therapy for prostate cancer continued. This case highlights that ¹⁸F-PSMA PET/CT may reveal rare, intensely PSMA-avid non-prostatic neoplasms and underscores the importance of recognizing atypical uptake patterns to avoid misinterpretation during prostate cancer staging. Full article

Background and Objective: Positive surgical margins (PSMs) remain a major challenge during radical prostatectomy, particularly in patients with high-risk prostate cancer (HR-PCa), where extracapsular extension, multifocal disease, and aggressive tumor biology substantially increase the likelihood of incomplete resection. In this setting, PSMs are strongly associated with early biochemical recurrence and frequently prompt adjuvant or salvage treatments, potentially exposing patients to overtreatment and added morbidity. Materials and Methods: To review and critically appraise established and emerging intraoperative technologies for surgical margin assessment during radical prostatectomy, with a specific focus on their potential role and relevance in patients with HR-PCa. Evidence Acquisition: A non-systematic literature review was performed using Pubmed, MEDLINE, Web of Science, and Google Scholar, focusing on preoperative, intraoperative ex vivo, and intraoperative in vivo technologies for margin assessment. Emphasis was placed on techniques with potential applicability to HR-PCa, where real-time intraoperative decision-making is particularly consequential. Evidence Synthesis: Preoperative tools, including multiparametric MRI, PSMA-PET imaging, and predictive nomograms, aid surgical planning but show limited sensitivity for microscopic extracapsular extension, especially in high-risk disease. Intraoperative frozen section analysis reduces positive surgical margin rates while enabling selective nerve-sparing (defined as a side-specific, risk-adapted preservation strategy); however, its widespread adoption is constrained by substantial logistical and resource requirements, and robust oncological outcome data in high-risk populations remain limited. Novel ex vivo approaches, such as fluorescence confocal microscopy and specimen-based PSMA PET/CT imaging, offer rapid whole-gland or targeted margin assessment with reduced dependency on dedicated pathology workflows. In parallel, emerging in vivo technologies, particularly PSMA-targeted near-infrared-fluorescence-guided surgery, enable real-time detection of residual tumor and facilitate selective re-resection, representing a biology-driven approach that may be especially suited to HR-PCa. Conclusions: In high-risk prostate cancer, intraoperative margin assessment technologies may extend beyond functional preservation and play a central role in optimizing oncological radicality and multimodal treatment sequencing. While NeuroSAFE remains the reference standard, PSMA-based ex vivo and in vivo technologies are particularly promising in HR-PCa due to their ability to integrate tumor biology into surgical decision-making. Prospective studies focusing on high-risk-specific oncological and patient-reported outcomes are needed before widespread clinical implementation. Full article

Background: MRI-based radiomics has shown promise in men with prostate cancer (PCa); however, successful clinical implementation is contingent upon on reproducible measurements. Purpose: We assessed the reproducibility of radiomics features extracted from bi-parametric prostate MRI (bpMRI) in prostate lesions and non-tumoral prostate tissue in men with PCa undergoing active surveillance (AS). Methods: This retrospective study included 47 men with biopsy-proven PCa undergoing AS (mean 68.9 ± 8.2 years, mean PSA density [PSAD] 0.08 ± 0.03 ng/mL/mL) who underwent two bpMRI approximately 12 months apart (range, 10–14 months; December 2018 to April 2020). The reproducibility of radiomics measurements was assessed using the same MRI platform (3T Skyra, Siemens Healthineers; inter-platform) (n = 37), different MRI vendors (Skyra, Siemens Healthineers; 3T Discovery MR750, GE Healthcare; inter-platform) (n = 10), and between observers (n = 10). Shape/1st-/2nd-order radiomics features were extracted from regions of interest on axial T2-weighted (T2-WI), diffusion-weighted imaging (DWI, b1600), and apparent diffusion coefficient (ADC) maps on prostate lesions, non-tumoral peripheral zones (PZs), and transition zones (TZs) using software. Reproducibility was evaluated by calculating the intraclass correlation coefficient (ICC) and coefficient of variation (CV). Associations of clinical variables and prostate volume were assessed. Results: PCa diagnoses included Gleason grade groups 1 (n = 46) and 2 (n = 1)]. Thirty-seven lesions (mean size 0.9 ± 0.4 cm) in 31 patients had PI-RADS v2.1 scores of 2 (n = 3)/3 (n = 12)/4 (n = 21)/5 (n = 1); 16 patients demonstrated diffuse PI-RADS 2 changes. Lesion radiomics features from T2-WI yielded a high proportion of good/moderate ICCs (intra-platform, 77.8%; inter-platform, 56.5%), whereas most DWI/ADC features yielded poor reproducibility. Similar results were observed for non-tumoral PZ/TZ. Intra-platform CVs were lowest for T2-WI lesion features (13.6%) and background PZ/TZ (<13.3%), while DWI/ADC exceeded 20%. Inter-platform CVs were lowest for lesions on T2-WI and were <18% for DWI/ADC; all background PZ/TZ CVs were < 16.4%. Inter-observer analyses showed good/moderate ICCs across all sequences and regions (57.4–92.6%). The distribution of ICC and CV values did not differ between intra- and inter-platform analyses (p > 0.05). Higher reproducibility (ICC > 0.5) was associated with larger prostate volume (intra-platform diagnostic odds ratio [DOR] = 2.58, 95% confidence interval [95%CI], 1.35–3.80, p = 0.01; inter-platform DOR = 3.48, 95%CI 1.79–5.17, p = 0.01) and older age (inter-platform DOR = 5.30, 95%CI 3.75–6.85, p < 0.01). Conclusions: Radiomics measurements from T2-WI demonstrated better intra-/inter-platform reproducibility than DWI/ADC for prostate lesions and non-tumoral tissue. Patient factors (larger prostate volumes and older age) influence radiomics stability. The optimization of diffusion-based radiomics features is needed to improve reproducibility given the essential role of DWI in prostate MRI. Full article

Prostate cancer (PrCa), the second most common cancer diagnosed in men globally, remains a critical challenge in precision oncology. While PrCa can be deadly, it is highly treatable if detected early. Identifying associative factors influencing disease progression risks can help inform preliminary steps that will further the expedition of clinical therapeutic intervention decisions, which will improve treatment outcomes. While conventional PrCa progression assessment tools rely heavily on a few clinical parameters, the importance of genomic information is increasingly recognized. In this study, we evaluate the prognostic value of patients’ clinicogenomic profiles in modeling progression-free survival (PFS) of PrCa. Three survival models, namely the penalized Cox model, random survival forest, and a deep learning survival neural network, were deployed with extensive tuning applied to a dataset for a cohort of 494 patients with PrCa. This dataset, compiled from public data in The Cancer Genome Atlas (TCGA) accessed via cBioPortal, consists of relevant clinical features and single-nucleotide variant information on likely PrCa-related genes. The survival models demonstrated satisfactory discriminatory performance, with Harrell’s concordance index ranging from approximately 0.80 to 0.87 on held-out test data, indicating their ability to rank patients according to their relative progression risk among patients, while exhibiting distinct dynamics, all three models consistently identified clinical variables that indicated neoadjuvant treatment history, neoplasm cancer status, and tumor recurrence as well as the gene MYH6 as important predictor variables for PrCa PFS. Our findings suggest the incorporation of genomic data into the survival modeling workflow, thereby allowing the use of integrated clinicogenomics information to gain insights into progression risks for patients with PrCa. Full article

Background/Objectives: Robot-assisted radical prostatectomy (RARP) is widely used in contemporary prostate cancer surgery; however, surgeons enter robotic practice through heterogeneous training pathways. This study aimed to compare early oncological and functional outcomes after RARP between two experienced robotic surgeons with different surgical backgrounds after completion of the learning curve. Methods: We conducted a retrospective, consecutive, single-center study including patients undergoing RARP after completion of the learning curve (> 40 cases) by two experienced robotic surgeons with different surgical backgrounds. Baseline characteristics, perioperative variables, and early oncological and functional outcomes were compared between surgeons. Pentafecta achievement was assessed as an exploratory composite outcome. Appropriate non-parametric and categorical statistical tests were applied as appropriate. Results: Ninety-three patients were included (55 operated on by surgeon A and 38 by surgeon B). Preoperative clinical and pathological characteristics were largely comparable between groups, except for prostate volume. Median operative time was significantly shorter for surgeon A (70 vs. 120 min, p < 0.001). Postoperative morbidity was low, with no major complications and no differences in length of hospital stay. At 6 months, urinary continence and erectile function recovery rates were high and comparable between surgeons. Oncological outcomes, including positive surgical margin rates and biochemical recurrence, did not differ significantly, although recurrence events were infrequent and follow-up was limited. Overall pentafecta achievement was modest and similar between groups (23.6% vs. 21.1%, p = 0.77), with positive surgical margins emerging as the main limiting factor. Conclusions: In this exploratory post-learning curve analysis, early oncological and functional outcomes after RARP were similar between surgeons with different surgical backgrounds. These findings should be interpreted cautiously and considered hypothesis-generating. Full article

Triggering receptor expressed on myeloid cells-2 (TREM2) is a key myeloid immune checkpoint for macrophage plasticity. However, its functional landscape in urology is still incomplete. This review addresses this gap by providing the first systematic synthesis of TREM2 in urological malignancies (bladder, prostate, and renal cell carcinomas) and benign conditions. We find a strong correlation between TREM2 upregulation and adverse clinical outcomes in these cancers. Importantly, we highlight the phenomenon of “mechanistic convergence”: unlike the high context-dependency of other organ systems, TREM2 appears to drive progression in urological malignancies by a common convergent signaling hub, the PI3K/AKT pathway. This contrasts sharply with its metabolic role in benign prostatic hyperplasia and its protective role in non-malignant renal injury. We also consider the translational potential of TREM2 as a prognostic biomarker (specifically urine detection) and as a therapeutic target to reverse immunotherapy resistance. Full article

Background/Objectives: Prostate cancer is the second most common cause of cancer-related mortality among the male population worldwide. It is among the leading reasons for the increasing number of years of life lost, working years of life lost, and gross domestic product (GDP) loss in Bulgaria. The primary objective of this study is to evaluate the burden of prostate cancer in Bulgaria, including calculating years of life lost (YLL), years of working life lost (YWLL), and the associated indirect costs. Methods: An observational time-series study was conducted using official national data from the National Statistical Institute (NSI), the INFOSTAT database, and the National Social Security Institute. The study covered the period 2008–2023 and included all registered male deaths attributed to malignant neoplasm of the prostate (ICD-10: C61). YLL, YWLL, and indirect costs were calculated using the human capital approach. Due to restricted access to age-specific mortality files, additional mortality records were obtained through formal data requests to NSI. Results: Prostate cancer led to 127,457 YLL and 6345 YWLL, with productivity losses reaching €88.2 million. Mortality showed an overall increasing trend up to 2020, while YWLL declined due to deaths shifting to older age groups. Conclusions: Despite the advancements in prostate cancer diagnosis and treatment, our findings demonstrate a negative trend regarding YLL, YWLL, and indirect costs associated with the disease, in contrast to other European countries. Strengthening early screening, reducing diagnostic delays, and improving national cancer registry capacity are critical to mitigating future health and economic losses. Full article

Background/Objectives: The objective of this study is to compare nerve-sparing (NS) and non-nerve-sparing (NNS) robot-assisted radical prostatectomy (RARP) techniques used to treat localized prostate cancer. Numerous studies have evaluated the impact of NS techniques on patient-reported outcomes. However, there are unaddressed methodological issues making interpretation of results difficult. Therefore, we performed a comparison of the two techniques, accounting for methodological threats, including patient selection and confounding. Methods: We sampled 120 patients with similar disease burden who underwent RARP by the same surgeon, either with NS (n = 84) or NNS (n = 36) and assessed changes in lower urinary tract (LUT) function and bother, and bowel function/bother using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire and the six-item International Index of Erectile Function (IIEF-6) survey at 6 weeks and 12 months postoperatively. Multivariable linear regression models were used to adjust for differences in age, preoperative PSA levels, pathological tumor stage and Gleason-score of patients receiving either NS or NNS. Results: At 6 weeks postoperatively, the NNS group had a significantly larger decrease in LUT function compared to the NS group (−17.42; 95% Confidence Interval (CI): −31.31, −3.53; p = 0.0145). At 12 months, both groups recovered substantially, and no group differences were observed (p > 0.9). No significant differences were observed between the NS and NNS groups for the EPIC bowel subscores, whereas the IIEF-6 showed borderline significance at 12 months. Conclusions: The results suggest a small impact of NS vs. NNS RARP on important patient-reported outcomes when controlling for tumor biology, surgeon skill, and patient characteristics. These results need to be confirmed by larger studies using similar sampling strategies and design considerations. Full article

Background: Local recurrences following radical prostatectomy (RP) are typically attributed to incomplete surgical resection or positive surgical margins (PSMs). Yet approximately 70% of men with PSMs never experience BCR. Prostate-specific membrane antigen PET scans (PSMA PET) are useful in detecting the incidence and location of recurrence sites. This study explores the relationship between margin status and local and metastatic recurrences using PSMA PET scans. Methods: A retrospective study was conducted with prospectively collected data following RARP with BCR in 159 men undergoing PSMA PET (2017–2023). The primary outcome compared risk and location of recurrences between NSM vs. PSM. A total of 13 cases (8%) had “equivocal” PET scan findings which were assessed first as all positive and then all negative. Results: Of 159 men with BCR undergoing PSMA PET scans, 101 (63.5%) had NSMs and 58 (36.5%) had PSMs. Assuming all 13 “equivocal” scans were positive, the risk of a positive PSMA PET is NSMs vs. PSMs (73% vs. 69% p = 0.56). Local recurrence rates did not differ significantly (NSMs 39.2% vs. PSMs 45% p = 0.55), nor did lymph nodes (NSMs 61% vs. PSMs 58% p = 0.73) or bone lesions (NSMs 16.2% vs. PSMs 22.5% p = 0.41). Multivariate regression analysis showed that margin status was not a predictor of local recurrence (OR 1.40; 95% CI [0.65, 1.54]; p = 0.382). Conclusions: Local recurrence occurs at about the same rate independent of margin positivity status, suggesting that local recurrences appear to be more closely related to metastatic dissemination, not incomplete resection. These findings question the oncologic rationale for wider resections at the expense of functional outcomes. Full article

Background: There is a great deal of knowledge regarding the development of polyomavirus-associated nephropathy and polyomavirus-associated hemorrhagic cystitis in transplant recipients with active BKPyV infection. However, recent studies have revealed a potential association between BKPyV reactivation and certain malignancies, including transitional cell carcinoma, malignant melanoma, colorectal cancer, and prostate cancer. This study aimed to identify a potential link between BKPyV infection and oncogenic transformation in kidney transplant recipients. Methods: Presentation of a case series of kidney transplant recipients diagnosed with polyomavirus-associated nephropathy who developed neoplasms after transplantation. Results: Positive immunohistochemical reactions confirmed the presence of polyomavirus large T antigen in tissue samples from all three patients’ cancers. Furthermore, a case of chromophobe renal cell carcinoma presenting BKPyV proteins in cancer cells was observed for the first time in the literature. Conclusions: BKPyV reactivation was found to be associated with the development of both urothelial cancer, which originates directly from the BKPyV-infected site, and colorectal cancer. Full article

Background and Objectives: Prostate cancer (PC) is largely a disease of elderly men, and de novo metastatic presentations are increasingly reported in this population. Yet older patients remain underrepresented in clinical trials, limiting the applicability of guideline-based treatments. Materials and Methods: We retrospectively analyzed 90 patients aged ≥75 years with de novo metastatic castration-sensitive PC (mCSPC) to describe clinical features, treatment patterns, and survival outcomes. Results: Median age was 81 years; high-volume disease and Gleason grade 9–10 tumors predominated. A substantial portion of patients received androgen deprivation therapy (ADT) alone or with bicalutamide despite recommendations for intensified therapy. Enzalutamide was associated with the longest median progression-free survival (PFS, 25.4 months) and overall survival (OS, 30.5 months), though between-group differences were not significant. Castration resistance occurred only in the high-volume group (22.4%). Absence of hypertension was associated with a lower risk of progression (HR 0.46, 95% CI 0.23–0.92, p = 0.028). Conclusions: Elderly patients with de novo mCSPC often have aggressive forms of the disease. Enzalutamide was associated with numerically longer survival compared to other treatments, although the difference was not statistically significant. Additionally, the absence of hypertension appeared to be linked with a lower risk of progression, suggesting that comorbid conditions such as hypertension may influence treatment outcomes in elderly patients. Full article

Circulating tumor DNA (ctDNA) profiling offers non-invasive insights for personalized prostate cancer management. This systematic review provides the first comprehensive appraisal of ctDNA assay methods, genomic targets, and their clinical correlations and proposes practical recommendations to guide future standardization and validation. We searched PubMed, ScienceDirect, Scopus, and the Cochrane Library starting December 2024 following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. From 229 records, 44 studies (10,631 patients) met the inclusion criteria. Plasma ctDNA analyzed by NGS predominantly profiled TP53 (72.7%), AR (70.4%), BRCA1/2 (61.3%), ATM (50%), RB1 (47.7%), and PTEN (41%). ctDNA positivity and specific key alterations correlated with poorer overall and progression-free survival. BRCA1/2-mutant patients benefited from Olaparib plus Abiraterone, while persistent alterations predicted early progression. Beyond synthesizing existing evidence, we identify key gaps, such as inconsistent reporting of variant allele fractions, limited diversity in study populations, and underexplored rare alterations. We recommend unified reporting standards (e.g., variant allele frequency thresholds and panel composition) and prioritized prospective trials to validate high-impact targets. These steps will accelerate the integration of ctDNA into routine precision oncology practice worldwide. Full article

Urological cancers are associated with reduced quality of life and high psychological burden, yet affected patients receive less psychosocial support than other cancer groups. Electronic health literacy (eHL) may facilitate independent access to resources, but its role for psychological outcomes and quality of life in this group is unclear. This study examined associations between eHL, psychological symptoms, and quality of life during transition from inpatient to outpatient care. A prospective, single-centre observational study was conducted. Eligible inpatients (urological cancer, Distress Thermometer ≥5 and/or request for psycho-oncological support) received an initial psycho-oncology consultation and completed surveys during inpatient treatment (T1) and three months later (T2). Measures included socio-demographics, PO-BADO, eHL (eHEALS), distress, depression (PHQ-2), anxiety (GAD-2), and quality of life (EORTC QLQ-C30). Of 108 patients completing T1, 71 completed T2. After controlling for age, eHL was not significantly associated with distress, depression, anxiety, or quality of life. Age did not moderate these relationships. In this sample, eHL showed no significant associations with psychological outcomes or quality of life. However, higher age was linked to lower eHL, suggesting that older patients may face barriers to digital health engagement. Age-related differences in eHL should be considered when designing digital support services for urological cancer patients. Full article

Pancreatic neuroendocrine neoplasms (pNENs) are the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma. Germline mutations in DNA repair genes drive several hereditary and sporadic cancers; however, their role in pNENs remains poorly defined. This pilot study aimed to assess the frequency and clinical relevance of germline DNA repair gene mutations in patients with pNENs, both with and without a family history of cancer. Germline DNA from 57 Polish patients with pNENs was analyzed using targeted next-generation sequencing to identify variants in a panel of DNA repair genes. Variant classification followed the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Germline mutations were identified in 14 patients (24.6%), both with and without a family history of malignancy. Two patients carried pathogenic variants in BRCA2 and CHEK2, while seven carried variants of uncertain significance (VUS). The identified variants have been implicated in various cancer types, including breast, ovarian, prostate, gastric, colorectal, and pancreatic cancers. These findings indicate that germline mutations in DNA repair genes may contribute to the pathogenesis of pNENs, even in patients without a family history. Broader germline testing and population-specific studies are needed to clarify the genetic landscape and clinical implications of these alterations. Full article