Search Results (511)

Background/Objectives: Randomised trials show that screening with prostate-specific antigen (PSA) and systematic prostate biopsies can reduce prostate cancer mortality but leads to high rates of overdiagnosis. Today, improved diagnostic methods more selectively detect potentially lethal, high-grade prostate cancer. Methods: This is a narrative review of modern diagnostic methods, ongoing trials, national policies and knowledge gaps related to screening and early detection of prostate cancer. Results: Screening intervals can be prolonged in men with PSA values below around 1 ng/mL as these men are at very low long-term risk of prostate cancer death. Overdiagnosis can be reduced by magnetic resonance imaging (MRI) and lesion-targeted prostate biopsies. Risk calculators and ancillary biomarkers can select men for further investigation and thereby reduce resource needs. These new methods are evaluated in large, randomised screening trials. The remaining knowledge gaps include optimal PSA cut-offs, screening intervals, start and stop ages, and the long-term balance between benefits and harm. Until recently, almost no national healthcare authority recommended population-based screening for prostate cancer. Now, the European Union Council recommends an evaluation of the feasibility of organised, risk-stratified screening. This has led to several pilot projects. In some other parts of the world, such as sub-Saharan Africa and the Caribbean, such initiatives are lacking despite high prostate cancer mortality rates. Conclusions: Risk-stratified prostate cancer screening including MRI and targeted biopsy reduces overdiagnosis. Results from ongoing research are needed to optimise screening protocols and to define long-term benefits and harms. Initiatives for early detection and screening are emerging across the world but are still lacking in many countries with high prostate cancer mortality. Full article

In photoelectrochemical (PEC) biosensing, efficient electron-hole separation is crucial to obtain preferred photocurrent response and analytical performance; thus, constructing developed heterointerfaces with high carrier transfer efficiency is an effective method for sensitive evaluation of analytes. Herein, a 1D ZnIn₂S₄ nanosheet-decorated 2D In₂O₃ tube was developed to integrate with a prostate antigen (PSA)-sensitive aptamer for sensitive PSA antigen detection. 1D In₂O₃ tubes were first prepared by two-step hydrothermal and annealing methods, followed by the in-situ growth of ZnIn₂S₄ nanosheets. Morphology, optical properties, structure, and PEC performance of prepared In₂O₃-ZnIn₂S₄ were characterized by scanning electron microscopy, transmission electron microscopy, ultraviolet–visible spectrophotometry, X-ray diffraction, X-ray photoelectron spectroscopy, and an electrochemical workstation. Benefiting from the photoelectric effect and specific 1D/2D hierarchical structure, In₂O₃-ZnIn₂S₄ displayed enhanced optical absorption and photocarrier separation, thus a superior photoelectrochemical response. Proposed bioassay protocol possessed a linear range from 0.001 to 50 ng/mL and a detection limit at 0.00037 ng/mL. In addition, this biosensor exhibited satisfactory anti-interface ability and stability, which also could be extended to other quantitative platforms for detecting other proteins. Full article

Prostate cancer (PCa) is one of the most common malignancies among men worldwide. While prostate-specific antigen (PSA) screening has improved early detection, it has also led to significant challenges regarding overdiagnosis and overtreatment. Overdiagnosis involves identifying indolent tumors unlikely to affect a patient’s lifespan, while overtreatment refers to unnecessary interventions that can cause adverse effects such as urinary incontinence, erectile dysfunction, and a reduced quality of life. This review highlights contributing factors, including the limitations of PSA testing, advanced imaging techniques like multi-parametric MRI (mpMRI), medical culture, and patient expectations. The analysis emphasizes the need for refining screening protocols, integrating novel biomarkers (e.g., PCA3, TMPRSS2-ERG), and adopting conservative management strategies such as active surveillance to minimize harm. Risk-based screening and shared decision-making are critical to balancing the benefits of early detection with the risks of unnecessary treatment. Additionally, systemic healthcare factors like financial incentives and malpractice concerns exacerbate overuse. This review advocates for updated clinical guidelines and personalized approaches to optimizing patient outcomes while reducing the strain on healthcare resources. Addressing overdiagnosis and overtreatment through targeted interventions will improve the quality of life for PCa patients and enhance the efficiency of healthcare systems. Full article

Despite substantial improvement in the definitive management of primary prostate cancer, a significant number of patients experience biochemical recurrence—a clinical state in which serum prostate-specific antigen (PSA) levels rise prior to the development of physical signs or symptoms. The early detection and localization of biochemical recurrence may confer eligibility for salvage therapy; therefore, imaging techniques that provide accurate disease visualization are imperative. In this review, we discuss various imaging methods for localizing disease in the context of biochemical recurrence in prostate cancer. Particularly, we describe available or investigational positron emission tomography (PET) radiotracers, such as ¹⁸F-FDG, ¹⁸F-NaF, choline (both ¹⁸F and ¹¹C), the ¹⁸F-labeled amino acid derivative fluciclovine, prostate-specific membrane antigen (PSMA) radioligands, and the short peptide compound bombesin. Generally, PET radiotracers such as ¹⁸F-FDG, ¹⁸F-NaF, and ¹⁸F/¹¹C choline have fallen out of favor because of their inferior sensitivity and/or specificity in relation to more recently developed radiotracers. ¹⁸F-fluciclovine has addressed these shortcomings by exploiting the upregulation of amino acid transporters in tumors; however, PSMA-targeting agents have significantly advanced the management of biochemical recurrence of prostate cancer through their high sensitivity and specificity, enabling the identification of candidates for radionuclide therapy. Investigational agents, such as bombesin-based radiotracers, may address the shortcomings of treating prostate cancer with little to no PSMA expression. Full article

Objective: To review the efficacy and safety of reduced dose compared to standard dose Enzalutamide treatment for patients with castration-resistant prostate cancer (CRPC). Methods: PubMed, Scopus, Web of Science, and Cochrane databases were searched for randomized controlled trials and cohort studies reporting the use of Enzalutamide in reduced and standard doses in patients with castration-resistant prostate cancer. Searches were limited to articles published in the English language. Outcome assessments included progression-free survival (PFS), overall survival (OS), adverse events, and serum prostate-specific antigen (PSA) response. Results: Ten studies met the inclusion criteria, including 2481 patients treated with Enzalutamide. Seven studies were retrospective cohorts, two were prospective trials, and one was a prospective cohort. No consistent relationship was identified between OS and PFS and the Enzalutamide dosage. Reduced doses of Enzalutamide decreased the incidence of adverse events, particularly among elderly patients. Conclusions: This systematic review suggests that reduced doses of Enzalutamide in CRPC may maintain therapeutic efficacy in selected patients while improving tolerability. However, inconsistent findings and methodological limitations highlight the need for prospective randomized trials to define optimal and individualized dosing strategies. Full article

Prostate cancer with bone metastasis exhibits significant heterogeneity, complicating prognosis, and treatment. This study explores the potential of plasma, serum, and urine biomarkers to stratify patients and evaluate their prognostic value. Using two-step clustering, we analyzed baseline levels of Platelet-derived growth factor-BB (PDGF-BB), Insulin-like growth factor-binding protein 1 (IGFBP-1), Bone Morphogenetic Protein 2 (BMP-2), Vascular endothelial growth factor (VEGF) (plasma and urine), prostate-specific antigen (PSA), neuron-specific enolase (NSE), chromogranin A (CgA) and bone-specific alkaline phosphatase (BAP) (serum) and creatinine (Cr), and type I collagen-cross-linked N telopeptide (NTx) (urine) in 29 patients with prostate cancer and bone metastasis. Longitudinal biomarker dynamics were assessed at baseline, 6 months, and 12 months. Clinical outcomes were evaluated using Kaplan–Meier and multivariate analyses. Three distinct groups (C1, C2, and C3) were identified. C1 exhibited elevated pPDGF-BB and pVEGF levels, C3 had increased pBAP and uNTx/Cr, and C2 showed lower biomarker levels. Prior treatments influenced biomarker levels, with bisphosphonates reducing bone turnover markers and radiotherapy correlating with long-term changes in growth factors. Longitudinal analysis revealed unique biomarker dynamics within each group, with a tendency for pPDGF-BB and pVEGF levels to decrease over time in C1, and distinct trends in uNTx/Cr between groups. Despite individual biomarkers failing to predict survival, C3 patients demonstrated significantly worse survival than C1 and C2. Molecular clustering of peripheral blood and urinary biomarkers identifies distinct subgroups with metastatic castration-resistant prostate cancer patients outperforming traditional models in outcome prediction and supporting its potential for personalized treatment and prognosis. Full article

Background: The testosterone-to-PSA (T/PSA) ratio has been proposed as a novel biomarker to enhance the diagnostic specificity of prostate-specific antigen (PSA) in prostate cancer (PCa) detection. The objective of this study was to evaluate the diagnostic performance of the T/PSA ratio in distinguishing PCa from benign conditions in men undergoing prostate biopsy. Materials and Methods: Eighty men who underwent systematic and targeted transrectal prostate biopsy were retrospectively studied. Clinical variables included serum PSA, testosterone, prostate volume, PSA density (PSAD), and the T/PSA ratio. Diagnostic accuracy was assessed using Receiver Operating Characteristic (ROC) curve analysis. Optimal cutoffs were determined using Youden’s index. Results: PCa was diagnosed in 53 patients (66.3%). Median T/PSA was significantly lower in PCa versus non-PCa patients (0.46 vs. 0.86; p < 0.01). T/PSA showed good diagnostic performance (AUC = 0.75) with an optimal cutoff of 0.81 (sensitivity: 59.3%, specificity: 86.8%). In patients with PSA ≤10 ng/mL, T/PSA retained strong discriminatory ability (AUC = 0.76), with sensitivity and specificity of 82.4% and 72.7%, respectively. Among all parameters, PSAD showed the highest diagnostic accuracy (AUC = 0.813). T/PSA was not significantly associated with Gleason score (p = 0.48). Conclusions: The T/PSA ratio is a clinically accessible and cost-effective biomarker that may improve PCa risk stratification and reduce unnecessary biopsies, particularly in patients with borderline PSA levels. Although it does not correlate with tumor aggressiveness, its combination with PSAD could enhance diagnostic accuracy in routine clinical practice. Full article

Prostate cancer is one of the world’s leading causes of cancer-related mortalities. There are several diagnostic tools and treatment plans readily available, such as prostate-specific antigen (PSA) tests and androgen deprivation therapy (ADT). However, these all come with their setbacks. Therefore, alternatives must be developed to assist those patients for whom standardised treatment does not work. There are many genes whose mutations lead to prostate cancer development and progression. These mutations may also lead to higher resistance/vulnerability to specific therapies. In this in silico study, four genes, AR, ATM, PTEN, and TP53, were assessed, and mutations were chosen for qPCR primer and probe design. A total of 28 mutations were selected from the four genes, with PTEN (13) making up the majority of the mutations, followed by TP53 (six), then ATM (five), and finally, AR (four). All primer/probe combinations fall within the desired ranges for this study and provide valuable additions to prostate cancer’s diagnostic/prognostic landscape. These assays will require further experimental validation, but they are the first step toward a better future in the fight against this horrible disease. Full article

Background/Objectives: Prostatic lymphoma is a rare malignant tumour that frequently causes urinary tract obstruction. It is uncommon for patients to present with systemic features or B-symptoms. As a result, it is often diagnosed incidentally during surgical lower urinary tract symptoms (LUTS) treatment. This systematic review aims to identify any common clinical features of prostatic lymphoma diagnosed incidentally during surgical LUTS treatment and summarise disease treatment and outcomes. Methods: The study protocol was registered with Prospective Register of Systematic Reviews (PROSPERO). A search was performed across the following electronic databases: MEDLINE, Embase, Web of Science, and Cochrane Database of Systematic Reviews. Full texts of eligible studies were analysed and data were extracted. The review was performed in accordance with PRISMA guidelines. Results: A total of 24 case reports compromising 25 cases were included. The median (IQR) age was 67 (61–73) years. All patients reported LUTS as their primary complaint, and the median duration of LUTS prior to diagnosis was 17 (4–44) months. Serum prostate-specific antigen (PSA) was normal in 10 cases and prostatomegaly present on imaging in 16 cases. A total of 10 different subtypes of lymphoma were reported. Extra-prostatic involvement was reported in eight patients. Chemotherapy, with or without adjuvant radiotherapy, was the mainstay of lymphoma treatment. The majority of articles reported positive outcomes, with complete remission in 17 cases. Conclusions: Prostatic lymphoma is a difficult clinical diagnosis due to its similar presentation to benign prostatic hyperplasia (BPH). Although rare, prostatic lymphoma may need to be considered as a diagnosis in patients with an atypical presentation of BPH. Prognosis is often favourable after prompt referral to haematology or oncology. Full article

Background/Objectives: To understand the clinical characteristics, risk factors, diagnosis, treatment, and outcomes of xanthogranulomatous prostatitis. Methods: A comprehensive search was conducted across PubMed, Embase, and Medline following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, including case reports and case series. Study quality and risk of bias were assessed using the Oxford Centre for Evidence-Based Medicine (CEBM) document. The systematic review process aimed to gather and synthesize all available research evidence on the topic. Results: We included 24 articles reporting on 33 patients, with a median age of 64 years. The most common presenting symptoms were lower urinary tract symptoms (81.8%), and only one patient was asymptomatic. The mean prostate-specific antigen (PSA) level upon presentation was 6.5 ng/mL. Notably, 51.5% of patients were suspected of harbouring clinically significant prostate carcinoma, and only one patient had concurrent prostate adenocarcinoma. All diagnoses were based on changes associated with xanthogranulomatous prostatitis demonstrated upon histopathological examination. A variety of pathogens were isolated, including Escherichia coli, Pseudomonas aeruginosa, Proteus species, and Enterobacter species. Transurethral resection of the prostate (60.6%) was the mainstay approach to management. In total, 27.3% of patients were successfully managed with non-surgical therapy. Conclusions: The majority of patients were suspected of prostate carcinoma prior to the histopathological diagnosis of xanthogranulomatous prostatitis. One patient underwent unnecessary radical prostatectomy as a result. The management of xanthogranulomatous prostatitis includes transurethral resection of the prostate and conservative management with the use of antibiotics. This outlines the importance of following well-established protocols upon suspicion of prostate carcinoma in order to avoid unnecessary radical prostatectomy. Full article

Focal Therapy (FT) is an emerging treatment modality for prostate cancer (PCa). Due to its novelty, the research exploring how patients should be followed-up after treatment is limited. There is currently no established role for non-prostate-specific-antigen (PSA) biomarkers and PSMA PET. However, a combination of PSA testing, multiparametric magnetic resonance imaging (mpMRI), and systematic and targeted biopsies should routinely be used for surveillance after FT. PSA values that rise 1.0 ng/mL over the nadir after twelve months or rise 1.5 ng/mL over nadir after twenty-four to thirty-six months should raise suspicion for recurrence. The standard imaging technique is mpMRI, but it can often be difficult to interpret after FT, so using a scoring system such as prostate imaging after focal ablation (PI-FAB) or the transatlantic recommendations for prostate gland evaluation with magnetic resonance imaging after focal therapy (TARGET) allows for greater consistency between readers. This review seeks to summarize the current literature regarding surveillance after FT as it relates to biomarkers, imaging, biopsies, and consensus statements. Full article

Background/Objectives: Prostate-specific antigen (PSA) persistence, defined as a postoperative PSA level ≥ 0.1 ng/mL measured within 4–8 weeks after radical prostatectomy (RP), predicts biochemical recurrence (BCR) and adverse oncological outcomes. The influence of nerve-sparing (NS) surgical techniques on PSA persistence remains debated, especially among patients with high-risk pathological features. This study aimed to evaluate the impact of NS techniques on PSA persistence following robot-assisted radical prostatectomy (RARP), considering tumor characteristics, surgical parameters, and patient-specific factors. Methods: A retrospective cohort analysis was performed on 779 patients who underwent RARP at a single institution between January 2002 and December 2015. The inclusion criteria consisted of histologically confirmed prostate cancer with available preoperative and postoperative data, including PSA measurements taken 4–8 weeks after surgery. PSA persistence served as the primary outcome. Statistical analyses included descriptive statistics, univariate and multivariable logistic regression models to identify predictors of PSA persistence, and Spearman’s correlation along with the Kruskal–Wallis H test to evaluate associations. Results: Of the 779 patients included, 55% underwent NS surgery (51% unilateral, 49% bilateral). The mean preoperative PSA was 11.85 ng/mL (SD: 7.63), while the mean postoperative PSA was 0.70 ng/mL (SD: 4.42). An elevated postoperative PSA was associated with a larger tumor size (r = 0.1285, p < 0.001), advanced pathological stages (χ² = 45.10, p = 3.79 × 10⁻⁹), and higher Gleason scores (χ² = 24.74, p = 1.57 × 10⁻⁴). NS surgery correlated with a lower postoperative PSA (mean: 0.20 ng/mL) compared to non-NS procedures (mean: 0.65 ng/mL), with slight differences between unilateral (mean: 0.30 ng/mL) and bilateral (mean: 0.35 ng/mL) NS approaches. Multivariable regression analysis identified advanced pathological stage (coefficient = 1.16, p = 0.04) as an independent predictor of PSA persistence, while NS techniques had no significant independent effect (coefficient = −0.01, p = 0.99). Conclusions: Nerve-sparing surgical techniques do not independently predict PSA persistence after RARP when adjusting for tumor-related factors and confounders. Advanced pathological stage, particularly stage pT3b, primarily determines PSA persistence. These findings highlight the necessity of personalized surgical planning informed by preoperative imaging and patient-centered decision making to optimize oncological and functional outcomes. Full article

Background: A previous phase I/II study demonstrated potent and long-term immune responses in men with prostate cancer following vaccination with a 20mer synthetic peptide (RV001) derived from the Ras homolog gene family member C protein (RhoC). Moreover, a fraction of patients experienced prostate-specific antigen (PSA) responses, which prompted the initiation of a phase II double-blind randomized trial (NCT04114825). The primary endpoint was to study whether vaccination could postpone PSA progression. Furthermore, the study included an evaluation of vaccination-induced immune responses, and in-depth in vitro studies of RhoC-specific CD4⁺ T cell responses. Methods: Men with non-metastatic biochemical recurrence after either radical prostatectomy or radiation therapy were eligible for the study. Participants were randomized 1:1 to either subcutaneous injections of 0.1 mg/mL RV001 emulsified in Montanide ISA 51, or a placebo. Vaccinations were administered every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. Blood samples were collected from a subset of patients (n = 38) over the course of vaccination, and peripheral blood mononuclear cells (PBMCs) isolated for immunological assessment of vaccine-induced immune responses. Experiments using PBMCs from a healthy donor and a patient were performed to study the phenotype and function of RV001-specific CD4⁺ T cells. Results: A total of 192 men entered the study. There was no difference in time to PSA doubling, with 7.5 versus 9.3 months, or in time to initiating further therapies, 11.2 versus 17.6 months for treatment and control groups, respectively. At long-term follow-up, 12.9% of the patients in the vaccination arm had developed metastasis compared to 12% in the placebo arm. No serious treatment-related side effects were observed, and treatment-related adverse events did not differ between groups. Immunological examinations in a subset of patients demonstrated that the vaccination induced potent, long-lasting CD4⁺ T cell responses capable of proliferation and cytokine production. RV001-specific CD4⁺ T cells were shown to mediate cytotoxicity against a RhoC-expressing cancer cell line in an HLA-class II-dependent manner. Conclusions: Men randomized to active treatment with RV001V demonstrated the induction of potent, functionally capable, anti RhoC-CD4⁺ T cell responses. However, there was no benefit in time to biochemical progression, and no difference in time to the initiation of second-line therapies. Full article

Background/Objectives: Metastatic prostate cancer remains a major clinical challenge, with limited therapeutic options. Doxycycline, a tetracycline antibiotic with anti-inflammatory properties, has shown potential as an adjunctive therapy. This study aimed to evaluate its efficacy in reducing prostate-specific antigen (PSA) levels and improving quality of life in patients receiving standard treatment for metastatic prostate cancer. Methods: This phase II, double-blind, randomized controlled trial included 45 participants (aged 57–81 years) assigned to doxycycline (100 mg daily) or a placebo for six months. The primary outcome was the percentage change in PSA levels at 3 and 6 months. Secondary outcomes included quality of life (EQ-5D-5L), cognitive function (Mini-Mental State Examination), and glucose levels. Additionally, a structure–activity relationship (SAR) analysis was performed through an extensive bibliographic review to identify pharmacophores responsible for doxycycline’s biological activity, particularly its tetracyclic core. The SAR analysis included tetracyclines and derivatives, androgen-targeting agents, and other pharmacologically relevant molecules used in prostate cancer therapy. Statistical analysis was conducted using multivariate logistic regression. Results: At six months, the doxycycline group showed a median PSA reduction of 60% compared to 10% in the placebo group (p = 0.043). A ≥50% reduction in PSA levels was observed in 71.4% of patients receiving doxycycline versus 20.8% in the placebo group (p = 0.001), with an adjusted relative risk of 10.309 (95% CI: 2.359–45.055, p = 0.002). Quality of life improved, with 7.1% of doxycycline-treated patients reporting poor quality of life compared to 42.9% in the placebo group (p = 0.028). A slight improvement in cognitive function was also noted (p = 0.037). SAR analysis suggested that the tetracyclic ring of doxycycline may play a crucial role in its observed biological effects. Conclusions: Doxycycline demonstrates potential as an adjunctive therapy in metastatic prostate cancer by reducing PSA levels and improving quality of life. The SAR analysis supports the hypothesis that its tetracyclic structure may be responsible for its therapeutic effects. Further large-scale trials are warranted to confirm these findings. Full article

Background/Purpose: to assess the inter-reader agreement of the PIFAB (Prostate Imaging after Focal Ablation) score, a new MRI-based standardized system for evaluating post-focal therapy prostate mpMRI, among radiologists in a single large cohort of patients treated with focal therapy (HIFU) in a tertiary care referral University Hospital. Methods: In total, 68 consecutive patients who underwent HIFU were included in this single-center retrospective observational study. A total of 109 post-HIFU follow-up mpMRIs were evaluated by three radiologists with varying levels of experience (12, 8, and 3 years, respectively). All patients underwent their first follow-up mpMRI at 6 months post-treatment, with 30 patients receiving additional evaluations at 18 months and 11 at 30 months. Results: The patients had a mean age of 70.6 ± 8.31 years, a mean pre-treatment PSA (prostate-specific antigen) of 7.85 ± 1.21 ng/mL, and a mean post-treatment PSA of 4.64 ± 4.2 ng/mL. The inter-reader agreement for PI-FAB among the three radiologists showed a Gwet’s AC2 value of 0.941 (95% confidence interval: 0.904–0.978, p < 0.0001). For the most experienced radiologist, at the 6-month follow-up 64 (94.14%) patients were scored as PI-FAB 1, 1 (1.47%) as PI-FAB 2, and 3 (4.41%) as PI-FAB 3. At the 18-month and 30-month follow-ups all patients were scored as PI-FAB 1 (no suspicion of recurrence). Conclusions: Our study demonstrates excellent inter-reader agreement among radiologists with varying levels of experience, confirming that the PI-FAB score is highly reproducible when evaluating post-treatment mpMRI scans. The low rate of PI-FAB 2 and PI-FAB 3 lesions observed at the first follow-up, coupled with the absence of significant recurrence in subsequent evaluations, suggests that HIFU is a reliable technique for prostate cancer treatment in selected patients. Full article