Improve Prostate Cancer Research Articles

Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution.

Prostate cancer is a common malignancy that in 5%-30% leads to treatment-resistant and highly aggressive disease. Metastasis-potential and treatment-resistance is thought to rely on increased plasticity of the cancer cells-a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases. As cellular plasticity is largely driven by non-genetic events, complementary studies in cancer epigenomics are now being conducted to identify chromatin variants. These variants, defined as genomic loci in cancer cells that show changes in chromatin state due to the loss or gain of epigenomic marks, inclusive of histone post-translational modifications, DNA methylation and histone variants, are considered the fundamental units of epigenomic heterogeneity. In prostate cancer chromatin variants hold the promise of guiding the new era of precision oncology. In this review, we explore the role of epigenomic heterogeneity in prostate cancer, focusing on how chromatin variants contribute to tumor evolution and therapy resistance. We therefore discuss their impact on cellular plasticity and stochastic events, highlighting the value of single-cell sequencing and liquid biopsy epigenomic assays to uncover new therapeutic targets and biomarkers. Ultimately, this review aims to support a new era of precision oncology, utilizing insights from epigenomics to improve prostate cancer patient outcomes.

Impact of Genomic Classifiers on Risk Stratification and Treatment Intensity in Patients With Localized Prostate Cancer : A Systematic Review.

Tissue-based genomic classifiers (GCs) have been developed to improve prostate cancer (PCa) risk assessment and treatment recommendations. To summarize the impact of the Decipher, Oncotype DX Genomic Prostate Score (GPS), and Prolaris GCs on risk stratification and patient-clinician decisions on treatment choice among patients with localized PCa considering first-line treatment. MEDLINE, EMBASE, and Web of Science published from January 2010 to August 2024. Two investigators independently identified studies on risk classification and treatment choice after GC testing for patients with localized PCa considering first-line treatment. Relevant data extracted by 1 researcher and overread by a second. Risk of bias (ROB) was assessed in duplicate. Ten studies reported risk reclassification after GC testing. In low ROB observational studies, very low- or low-risk patients with PCa were more likely to have their risk levels classified as the same or lower (GPS, 100% to 88.1%; Decipher, 87.2% to 82.9%; Prolaris, 76.9%). However, 1 randomized trial found that GC testing with GPS reclassified 34.5% of very low-risk and 29.4% of low-risk patients to a higher risk category. Twelve observational studies indicated that treatment decisions after GC testing either remained unchanged or slightly favored active surveillance. In contrast, analyses from a single randomized trial found fewer choices for active surveillance after GPS testing. Heterogeneity in screening patterns, risk-determination cutoffs, pathology, and clinical practices. Studies on treatment choice were moderate to high ROB. Although GC tests do not consistently influence risk classification or treatment decisions, the differences observed between observational and randomized studies highlight a need for well-designed trials to explore the role of GC tests in patients with newly diagnosed PCa considering first-line treatment. U.S. Department of Veterans Affairs. (PROSPERO: CRD42022347950).

Impact of Nanoparticles on Oxidative Stress and Inflammatory Pathways in Human Prostate Cancer

Prostate cancer is one of the most prevalent cancers among men and is fueled by oxidative stress and inflammation that drive tumor progression and resistance to therapy. Production of reactive oxygen species (ROS) and pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) establish a pro-tumor microenvironment. Iron oxide nanoparticles are believed to be promising micro/nano therapy agents because NPs such as ferric oxide (Fe2O3) play a critical role in antioxidant and anti-inflammatory events. Herein, we examine influences of NPs on oxidative stress and inflammatory pathways in prostate cancer models. NP treatment was used for cells exposed to oxidative and inflammatory stressors. We measured a variety of key markers including ROS, MDA, GSH, and activities of antioxidant enzymes (catalase [CAT] and superoxide dismutase [SOD]). The levels of inflammatory cytokines were determined by widely used biochemical methods and spectrophotomedically. This resulted in significant reduction in ROS and MDA (oxidative damage markers) and significant elevation in the reduced GSH levels and these results were supported by the increased levels of antioxidant enzymes namely catalase (CAT) and superoxide dismutase (SOD) activity in NP-treated. Moreover, NPs also inhibited inflammation by downregulating the release of cytokines, such as TNF-α and IL-6. These effects suggest that NPs are capable of restoring oxidative homeostasis and suppressing inflammation, ultimately leading to a more tumor-hostile microenvironment. Abstract Nanoparticles that alleviate oxidative stress and overwrite inflammation pathways synergistically offer two critical blockade points in prostate cancer therapy to counter plasma phase-induced cellular malfunctions required for tumor progression. These results reinforce the prospect of NP as complements to cancer therapy. Optimizing NP formulations could improve their efficacy and safety for potential clinical applications in the future and provide new approaches for improving prostate cancer treatment. CuO NPs with Anti-cancer Effect on Prostate Cancer: In Vivo Study Oxidative Stress along with Inflammation as Potential Pathogenesis Prostate Cancer Responsive Ferric Oxide Nanoparticles Release ROS Assist in Treating Prostate Cancer.

Rethinking prostate cancer screening in transgender women

Introduction: Over the years, the number of people openly identifying as transgender has steadily increased, leading to a greater need for transgender-specific healthcare information. Among transgender women (TW), there remains a risk of prostate cancer since the prostate is not removed during gender-affirming hormone therapy (GAHT) or surgery; however, there is limited knowledge about prostate cancer screening in the transgender population. Although there are few reported cases of prostate cancer screening or prostate-specific antigen (PSA) testing in TW, the impact of hormone therapies on PSA levels is well-documented. Notably, GAHT for TW and hormone therapy for treating prostate cancer share similarities. Drawing on these similarities, we aimed to develop guidelines for baseline PSA levels and prostate cancer screening in TW. Methods: Through a systematic review, we examined the existing PubMed publications on PSA levels and prostate cancer screening in TW, as well as expected PSA levels in patients with prostate cancer undergoing hormone therapies. We also investigated other aspects considered for the diagnosis of prostate cancer. Given the limited research on TW, we also included relevant case studies. These publications and case reports were reviewed and analyzed to create a comprehensive overview of expected baseline PSA levels and prostate cancer screening guidelines for TW. Results: Currently, there are no established guidelines for PSA or prostate cancer screening in TW; however, these case studies indicated a range of PSA values from 3.3 to <100 ng/ml. Existing literature on expected PSA levels in prostate cancer patients undergoing hormone therapy shows a reduction in PSA of over 50% post-therapy. This evidence suggests that PSA values in TW presenting with prostate cancer may be lower than those observed in cisgender males with the disease. Conclusions: While TW exhibit lower prostate cancer incidence compared to cisgender men, the impact of hormone therapy on PSA levels presents significant challenges for screening and diagnosis. The parallels between PSA level reductions in TG women and cisgender men undergoing estrogen therapy highlight the need for revised screening protocols. Addressing these challenges through targeted research and personalized care approaches will be vital for improving prostate cancer management in transgender individuals.

Physician Payment Incentives and Active Surveillance in Low-Risk Prostate Cancer

Active surveillance in men with less aggressive prostate cancer is inconsistently used despite clinical guidelines. Renumeration generally favors treatment over conservative management and may contribute to the variable adoption of active surveillance, which suggests that value-based payment incentives may promote guideline-concordant care. To describe the adoption of active surveillance in low-risk prostate cancer, following the initiation of a novel payment incentive sponsored by a commercial payer to support its use. This cohort study included men with prostate cancer diagnosed between 2015 to 2021 with data registered with the Michigan Urological Surgery Improvement Collaborative (MUSIC), a statewide quality-improvement collaborative of practicing urologists. Eligible participants were men with newly diagnosed low-risk or low-volume, favorable intermediate-risk prostate cancer who were eligible for active surveillance. Data were analyzed from January 2015 through December 2021. Health insurance payment incentive established between June 9, 2017, and September 30, 2018, to encourage active surveillance adoption within MUSIC. Upon meeting the target (ie, at least 72% of men with low-risk disease consider or initiate surveillance), the insurer would provide enhanced reimbursement on claims covered by preferred provider organization plans independent of diagnosis. Active surveillance adoption relative to the preincentive period among men with low-risk prostate cancer. Secondary analyses examined practices by baseline surveillance use and proportion of patients with eligible insurance plans, as well as patients with favorable intermediate-risk disease. We identified 15 273 patients (median [IQR] age, 65 [59-70] years), of whom 10 457 (68.5%) had low-risk disease. The percentage of these men electing for surveillance increased, from 54.4% in 2015 (729 of 1340 men) to 84.1% in 2021 (1089 of 1295 men). Relative to the preincentive period, the payment incentive was not associated with increased surveillance use among patients with low-risk disease (odds ratio [OR], 0.96; 95% CI, 0.75-1.24) during its application. Secondary analyses similarly did not demonstrate an association between the payment incentive and active surveillance adoption. A payment incentive was not associated with increased active surveillance adoption in men with low-risk prostate cancer relative to the preincentive period. Value-based reimbursement incentives may require tailored implementation that considers existing reimbursement policy and practice characteristics to improve prostate cancer care quality.

Intergrating Radiosensitivity Index and Radiation Resistance Related Index Improves Prostate Cancer Outcome Prediction

Intergrating Radiosensitivity Index and Radiation Resistance Related Index Improves Prostate Cancer Outcome Prediction

Multimodal AI Combining Clinical and Imaging Inputs Improves Prostate Cancer Detection.

Deep learning (DL) studies for the detection of clinically significant prostate cancer (csPCa) on magnetic resonance imaging (MRI) often overlook potentially relevant clinical parameters such as prostate-specific antigen, prostate volume, and age. This study explored the integration of clinical parameters and MRI-based DL to enhance diagnostic accuracy for csPCa on MRI. We retrospectively analyzed 932 biparametric prostate MRI examinations performed for suspected csPCa (ISUP ≥2) at 2 institutions. Each MRI scan was automatically analyzed by a previously developed DL model to detect and segment csPCa lesions. Three sets of features were extracted: DL lesion suspicion levels, clinical parameters (prostate-specific antigen, prostate volume, age), and MRI-based lesion volumes for all DL-detected lesions. Six multimodal artificial intelligence (AI) classifiers were trained for each combination of feature sets, employing both early (feature-level) and late (decision-level) information fusion methods. The diagnostic performance of each model was tested internally on 20% of center 1 data and externally on center 2 data (n = 529). Receiver operating characteristic comparisons determined the optimal feature combination and information fusion method and assessed the benefit of multimodal versus unimodal analysis. The optimal model performance was compared with a radiologist using PI-RADS. Internally, the multimodal AI integrating DL suspicion levels with clinical features via early fusion achieved the highest performance. Externally, it surpassed baselines using clinical parameters (0.77 vs 0.67 area under the curve [AUC], P < 0.001) and DL suspicion levels alone (AUC: 0.77 vs 0.70, P = 0.006). Early fusion outperformed late fusion in external data (0.77 vs 0.73 AUC, P = 0.005). No significant performance gaps were observed between multimodal AI and radiologist assessments (internal: 0.87 vs 0.88 AUC; external: 0.77 vs 0.75 AUC, both P > 0.05). Multimodal AI (combining DL suspicion levels and clinical parameters) outperforms clinical and MRI-only AI for csPCa detection. Early information fusion enhanced AI robustness in our multicenter setting. Incorporating lesion volumes did not enhance diagnostic efficacy.

Kaempferol modulates ɑ2M secretion in bone marrow-derived macrophages by downregulating GR/PER1-mediated lipid metabolism to attenuate the emotional stress-aggravated metastasis of prostate cancer

Ethnopharmacological relevanceProstate cancer patients often suffer from depression during androgen deprivation therapy. Chaihu-Shugan-San (CSS) can prevent prostate cancer metastasis caused by chronic unpredictable mild stress (CUMS), but its active ingredients and molecular mechanism remain unelucidated. Aim of studyThis study aims to explore the potential targets and molecular mechanisms of CSS in the treatment of emotional stress-aggravated metastasis of prostate cancer. ResultsStress induces nuclear translocation of GR, initiating the transcription of PER1, which leads to an enhanced lipid metabolism and decreased secretion of α2M in BMDMs. CSS, a classical Traditional Chinese Medicine (TCM) formula for alleviating depression, can improve prostate cancer metastasis caused by CUMS. Of the active ingredients in CSS, kaempferol demonstrated the highest potency for enhancing α2M secretion in BMDMs and inhibiting prostate cancer cell migration. Kaempferol also inhibited nuclear translocation of GR and the GR/PER1 pathway in Per1-overexpressed BMDMs. ConclusionsThese findings reveal that emotional stress-aggravated prostate cancer growth and metastasis rely on the GR/PER1 pathway and lipid metabolism, as the suppression of this pathway ultimately leads to an increase in α2M secretion in BMDMs and inhibition of PC-3 cell metastasis.

A pilot randomized clinical trial of a smartphone-based application to support at-home PSA screening and culturally tailored prostate cancer education for African American men: A study protocol

BackgroundProstate cancer is the most diagnosed cancer in Black/African American men (AA) and the second‑leading cause of cancer-related deaths. A prostate-specific antigen (PSA) blood test is an early detection screening tool for prostate cancer, but uptake of PSA screening remains low among AA men. Greater PSA screening rates among AA men, coupled with earlier treatment, may reduce disparities in prostate cancer outcomes, including mortality. The current pilot study will test the first-of-its-kind mobile health (mHealth) app to improve prostate cancer knowledge and increase PSA screening uptake among AA men using home-based screening methods. MethodsAA men aged 55 to 69 and are not up to date with PSA screening will be randomly assigned 1:1 to receive a prostate cancer screening app: Prevention Taskforce App (Taskforce App; control condition) or the Prostate Cancer Genius App (Genius App; intervention condition), which was developed specifically for AA men. ResultsWe will evaluate the preliminary efficacy of the apps via post-intervention group differences on the validated 18-item Prostate Cancer Knowledge Scale (primary outcome). We will also explore post-intervention group differences in perceived engagement, accessibility, and acceptability between the apps. Finally, we will derive preliminary estimates of PSA screening rates between study conditions and identify mechanisms of screening adherence. DiscussionmHealth apps offer promise to improve prostate cancer knowledge and screening rates among AA men. Demonstrating the preliminary efficacy of the Genius App will support future fully-powered mHealth interventions to address health disparities.

Commercial prices and their influence on urology practices: Prostate cancer care among men with Medicare.

For men with prostate cancer, there is substantial variation in the use of conservative management, such as active surveillance. Commercial prices, which vary across urology practices, may afford incentives that foster physician behaviors associated with utilization. Such behaviors may "spillover" to the Medicare population and affect quality. This study evaluated the effects of practice-level commercial prices on health care utilization and quality in men with prostate cancer insured by traditional Medicare. From a 20% Medicare sample, the authors identified men with newly diagnosed prostate cancer between 2014-2019 (n=44,653). Using commercial payments from the MarketScan database, they developed a practice-level commercial price index (ratio of commercial prices to Medicare prices). They examined the association of the price index with price standardized spending, overtreatment (treatment among those with >50% noncancer mortality within 10 years), and underuse of diagnostic testing in active surveillance (at least one prostate-specific antigen test and one confirmatory test-MRI, prostate biopsy, genomic test-within 12 months of diagnosis). Practice-level commercial price indices varied from 1.34 (134% of Medicare prices), for practices in the bottom decile, to 3.00, for practices in the top decile. Increasing price index was associated with lower odds of overtreatment (odds ratio, 0.86; 95% confidence interval, 0.76-0.97; p=.01), but not price standardized spending or underuse of diagnostic testing in active surveillance. Commercial prices vary markedly across urology practices. Among newly diagnosed men with traditional Medicare, those managed by practices with higher commercial price indices had lower odds of overtreatment, suggesting improved prostate cancer care quality.

Graphene oxide@chitosan for urinary sarcosine extraction in prostate cancer detection: Method development and adsorption isotherm studies

Sarcosine has emerged as a potential prostate cancer marker, yet current detection methods have limitations, necessitating the development of non-invasive approaches for early and accurate diagnosis. To develop a novel, sensitive method combining dispersive micro-solid phase extraction with high-performance liquid chromatography for sarcosine determination in urine samples. A meso-sized graphene oxide@chitosan adsorbent was synthesized via a template-free, freeze-drying method. The adsorption mechanism was investigated using Langmuir and Freundlich isotherm models, and extraction parameters were optimized for maximum efficiency. Under optimized conditions, the method showed linearity over 0.05-5 µg/mL with precision better than 10%. The adsorption data demonstrated better correlation with the Langmuir model, indicating monolayer adsorption. Regeneration studies using acetonitrile and water washing cycles demonstrated the adsorbent’s reusability for up to 5 extraction cycles, with approximately 70% retention of initial extraction capacity. The method exhibited high sensitivity and good precision using a simple setup. This approach offers a practical, non-invasive method for sarcosine determination in urine, potentially contributing to improved prostate cancer screening and monitoring. The reusability of the adsorbent enhances its economic viability and aligns with green chemistry principles, though some capacity loss occurs after multiple cycles, likely due to memory effects or structural changes in the porous framework.

Association between smoking and prostate cancer survivors' long-term quality of life and function: an analysis of the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study.

There is limited evidence of tobacco smoking's effect on cancer survivors' quality of life (QOL) and function. As the natural history of localized prostate cancer (PCa) is protracted, there is a need to identify modifiable risk factors that can influence PCa survivorship, such as tobacco smoking. We used up to 10-year survey data from the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study, a prospective, population-based, observational study of patients diagnosed with localized PCa in 2011-2012. Survivors were categorized as never, former, and current smokers during survivorship. Adjusted multivariable linear regression models were used to assess the association between smoking and 5-year and 10-year scores on the 26-Item Expanded Prostate Index Composite (EPIC-26; PCa-specific domains) and 5-year scores on the Medical Outcomes Study 36-Item Short Form Survey (SF-36; general health domains). We included 2426 patients of whom 142 (6%) were current smokers, 1039 (43%) were former smokers, and 1245 (51%) were never smokers. Current smokers were more likely to be Black, low-income, and less formally educated (all p < 0.01). After adjustments, there was no association between smoking history with disease-specific functional outcomes (EPIC-26) at 5years or 10years (all p > 0.05). However, in adjusted analyses assessing general health domains (SF-36), compared to participants who never smoked, current smokers during survivorship had worse physical function (- 10.96, 95% CI - 16.37 to - 5.55, p < 0.01) at 5years. PCa survivors who continue to smoke experience worse physical functioning though there is no significant independent effect on PCa-specific functional domains. Prostate cancer survivors who continue to smoke experience worse physical functioning though there is no significant independent effect on PCa-specific functional domains. Smoking cessation may improve prostate cancer survivorship.

7906 Nanoencapsulated Curcumin-Piperine Complex: A Breakthrough In Targeting CYP17A1 For Castration Resistant Prostate Cancer Therapy

Abstract Disclosure: J. Yakubu: None. Nanoencapsulated Curcumin-Piperine Complex: A Breakthrough in Targeting CYP17A1 for Castration Resistant Prostate Cancer Therapy. Jibira Yakubu a,b,c, Oya Taritd, Evangelos Natsaridisd, Amit V. Pandey a,ba Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, b Paediatric Endocrinology, Diabetology and Metabolism, University Children’s Hospital, Inselspital, Bern, c Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. d Biointerfaces, Institute of Chemistry and Bioanalytics, University of Life Sciences FHNW, Muttenz, Switzerland. Abstract: Androgens play a pivotal role in prostate cell survival and are implicated in both early-stage and advanced, castration-resistant prostate cancer (CRPC). In CRPC patients on CYP17A1 inhibitors, the development of drug resistance and hypertensive crisis through the inhibition of CYP21A2 and or its substrate are a recognized challenge. Given its crucial role in androgen production, CYP17A1 has become a major target for cancer therapies. In this study, we employed a mini-evaporation technique to nanoencapsulate curcumin, exploring its impact on CYP17A1 activity in human adrenal NCI-H295R cells. We performed steroid profiling with LC-MS, as well as gene and protein expression studies. Initial results demonstrated that curcumin nanoparticles exhibited superior efficacy in reducing CYP17A1 activity compared to known drug Abiraterone acetate. Curcumin and piperine combined in nano-capsules greatly increased the inhibitory effects on CYP17A1 activity. Furthermore, ongoing studies include western blot investigation of the drug's interaction with the CYP17A1 protein and cell cycle effects. We confirmed the efficacy of our nano formulation by testing its impact on the growth of androgen-sensitive prostate cancer cell lines. Notably, nanoencapsulation improved curcumin's inhibitory effects on DHEA production via CYP17A1. Surprisingly, the curcumin-piperine nano-capsules enhanced these effects while having no effect on CYP21A2, offering a promising option for prostate cancer treatment. Our study reveals the promise of nanoencapsulated curcumin-piperine as a game-changing method for targeting CYP17A1 for improved prostate cancer therapy. The synergistic benefits observed in our study open new avenues for addressing the difficulties associated with androgen deprivation therapy. Funding: Cancer Research Switzerland grant number: KFS 5557-02-2022 Presentation: 6/3/2024

Partial prostatectomy for localized prostate cancer.

Localized prostate cancer treatment aims to balance cancer control with preserving urinary and erectile function. While focal ablative therapies have emerged, their uncertain prognosis prompts exploration of partial prostatectomy. We systematically reviewed its efficacy as a primary treatment, particularly in low-to-intermediate-risk patients. Our review comprehensively analyzed existing studies on partial prostatectomy for localized cancer. We focused on patient selection, surgical techniques, and postoperative outcomes, emphasizing tumor control, continence, and erectile function. Studies involving multiparametric MRI and targeted biopsies for candidate selection were included. Partial prostatectomy, encompassing various techniques, demonstrates promising short-term outcomes in tumor control and functional preservation. Preoperative imaging and biopsy aid in candidate selection. However, longer-term data on cancer recurrence are limited, warranting further investigation. Heterogeneity among studies and the lack of standardized follow-up protocols are notable limitations. Partial prostatectomy offers a minimally invasive and effective treatment option for localized prostate cancer, particularly in selected patients. Preoperative imaging and biopsy play crucial roles in patient selection, while standardized follow-up protocols are needed to assess long-term outcomes. Future research should focus on elucidating its precise role and optimizing patient selection criteria, contributing to improved prostate cancer management strategies. Partial prostatectomy is explored for localized prostate cancer treatment, aiming to balance cancer control with preserving function. Short-term outcomes are promising, but long-term data on recurrence are lacking. Further research is needed to optimize patient selection and standardize follow-up protocols.

Contemporary Update on Clinical and Experimental Prostate Cancer Biomarkers: A Multi-Omics-Focused Approach to Detection and Risk Stratification.

Prostate cancer remains a significant health challenge, being the most prevalent non-cutaneous cancer in men worldwide. This review discusses the critical advancements in biomarker discovery using single-omics and multi-omics approaches. Multi-omics, integrating genomic, transcriptomic, proteomic, metabolomic, and epigenomic data, offers a comprehensive understanding of the molecular heterogeneity of prostate cancer, leading to the identification of novel biomarkers and therapeutic targets. This holistic approach not only enhances the specificity and sensitivity of prostate cancer detection but also supports the development of personalized treatment strategies. Key studies highlighted include the identification of novel genes, genetic mutations, peptides, metabolites, and potential biomarkers through multi-omics analyses, which have shown promise in improving prostate cancer management. The integration of multi-omics in clinical practice can potentially revolutionize prostate cancer prognosis and treatment, paving the way for precision medicine. This review underscores the importance of continued research and the application of multi-omics to overcome current challenges in prostate cancer diagnosis and therapy.

PIONEER big data platform for prostate cancer: lessons for advancing future real-world evidence research.

Prostate Cancer Diagnosis and Treatment Enhancement through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer. PIONEER brings together 34 private and public stakeholders from 9 countries in one multidisciplinary research consortium with the aim of positively transforming the field of prostate cancer clinical care by answering pressing questions related to prostate cancer screening, diagnosis and treatment. PIONEER has developed a unique state-of-the-art big data analytic platform by integrating existing data sources from patients withprostate cancer. PIONEER leveraged this platform to address prioritized research questions, filling knowledge gaps in the characterization, management and core outcomes of prostate cancer across the different disease stages. The network has benefited from sustained patient and stakeholder involvement and engagement, but many challenges remain when using real-world data for big data projects. To continue to advance prostate cancer care, data need to be available, suitable methodologies should be selected and mechanisms for knowledge sharing must be in place. Now acting as the prostate cancer arm of the European Association of Urology's new endeavour, UroEvidenceHub, PIONEER maintains its goal of maximizing the potential of big data to improve prostate cancer care.

Epidemiology of Prostate Cancer in Africa: An In-Depth Review

Prostate cancer is a major health challenge in Africa, presenting significant regional disparities in incidence and outcomes. This review provides an in-depth examination of the epidemiology of prostate cancer on the continent, considering a range of factors that influence its prevalence and management. Genetic predispositions, including mutations in BRCA1, BRCA2, and HOXB13, play a crucial role, with African populations displaying unique genetic variants contributing to higher incidence rates. Environmental and lifestyle factors, such as diet, physical activity, and substance use, also impact prostate cancer risk. Traditional African diets, rich in fruits and vegetables, may offer protective benefits, while modern dietary patterns and sedentary lifestyles are linked to increased risk. Socioeconomic determinants, including access to healthcare, educational attainment, and financial barriers, significantly affect diagnosis and treatment, often leading to late-stage presentations. Hormonal and biological factors, such as androgen levels and age-related changes, further influence disease development. Infections, inflammatory conditions, and occupational exposures also contribute to risk. Cultural and behavioral influences, including traditional beliefs and health-seeking behaviors, impact prevention and management strategies. The review highlights the challenges faced by healthcare infrastructure and screening programs, emphasizing the need for improved access, public awareness, and tailored interventions. Addressing these factors through comprehensive public health strategies, including enhanced screening, lifestyle modifications, and cultural sensitivity, is essential for improving prostate cancer outcomes across Africa. Keywords: Epidemiology, Prostate Cancer, Africa, Genetic, Biological factor.

Advancing Prostate Cancer Diagnosis: A Deep Learning Approach for Enhanced Detection in MRI Images.

Prostate cancer remains a leading cause of mortality among men globally, necessitating advancements in diagnostic methodologies to improve detection and treatment outcomes. Magnetic Resonance Imaging has emerged as a crucial technique for the detection of prostate cancer, with current research focusing on the integration of deep learning frameworks to refine this diagnostic process. This study employs a comprehensive approach using multiple deep learning models, including a three-dimensional (3D) Convolutional Neural Network, a Residual Network, and an Inception Network to enhance the accuracy and robustness of prostate cancer detection. By leveraging the complementary strengths of these models through an ensemble method and soft voting technique, the study aims to achieve superior diagnostic performance. The proposed methodology demonstrates state-of-the-art results, with the ensemble model achieving an overall accuracy of 91.3%, a sensitivity of 90.2%, a specificity of 92.1%, a precision of 89.8%, and an F1 score of 90.0% when applied to MRI images from the SPIE-AAPM-NCI PROSTATEx dataset. Evaluation of the models involved meticulous pre-processing, data augmentation, and the use of advanced deep-learning architectures to analyze the whole MRI slices and volumes. The findings highlight the potential of using an ensemble approach to significantly improve prostate cancer diagnostics, offering a robust and precise tool for clinical applications.

Evaluating the Initial Experience and Clinical Impact of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) Scans in Prostate Cancer Management: A Retrospective Study in Iraq.

Background Prostate cancer is a significant health concern globally, especially in the Middle East, including Iraq. This study explores the adoption and impact of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scans in Erbil, Iraq, from 2020 to 2023, marking a pivotal advancement in prostate cancer diagnostics in a region where the disease's prevalence is rising. Materials and methods Through a retrospective analysis at Medya Diagnostic Center in Erbil, Iraq, involving 172 patients, we assessed the feasibility, applicability, and clinical utility of PSMA PET/CT in the local population. Results The study highlights the modality's enhanced sensitivity and specificity in detecting prostate cancer and its metastases, with bone being the most frequent metastasis site. Despite positive outcomes, challenges such as integration into clinical practice, adherence to guidelines, and financial implications were identified. The majority of referrals came from medical oncologists, primarily for staging and response evaluation, indicating PSMA PET/CT's critical role in managing prostate cancer. The findings suggest a need for national guidelines, interdisciplinary collaboration, and educational initiatives to optimize the use of PSMA PET/CT in Iraq's healthcare setting. Conclusions This study contributes valuable insights into the early experiences with PSMA PET/CT, paving the way for improved prostate cancer diagnostics and management in similar contexts.

Docosahexaenoic acid enhances the treatment efficacy for castration-resistant prostate cancer by inhibiting autophagy through Atg4B inhibition

Autophagy induction in cancer is involved in cancer progression and the acquisition of resistance to anticancer agents. Therefore, autophagy is considered a potential therapeutic target in cancer therapy. In this study, we found that long-chain fatty acids (LCFAs) have inhibitory effects on Atg4B, which is essential for autophagosome formation, through screening based on the pharmacophore of 21f, a recently developed Atg4B inhibitor. Among these fatty acids, docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibited the most potent Atg4B inhibitory activity. DHA inhibited autophagy induced by androgen receptor signaling inhibitors (ARSI) in LNCaP and 22Rv1 prostate cancer cells and significantly increased apoptotic cell death. Furthermore, we investigated the effect of DHA on resistance to ARSI by establishing darolutamide-resistant prostate cancer 22Rv1 (22Rv1/Dar) cells, which had developed resistance to darolutamide, a novel ARSI. At baseline, 22Rv1/Dar cells showed a higher autophagy level than parental 22Rv1 cells. DHA significantly suppressed Dar-induced autophagy and sensitized 22Rv1/Dar cells by inducing apoptotic cell death through mitochondrial dysfunction. These results suggest that DHA supplementation may improve prostate cancer therapy with ARSI.