Prostate Cancer Outcomes Research Articles

Post-prostatectomy Magnetic Resonance-guided Radiotherapy on a 1.5 Tesla Magnetic Resonance Integrated Linear Accelerator: Feasibility, Toxicity, and Preliminary Clinical Outcomes.

This study aimed to prospectively investigate magnetic resonance (MR)-guided radiotherapy (MRgRT) for post-prostatectomy prostate cancer and report preliminary clinical outcomes. All included patients underwent salvage or adjuvant adaptive MRgRT on a 1.5T MR integrated linear accelerator (MR-LINAC). Gastrointestinal and genitourinary toxicities were assessed. The primary endpoint was the progression-free survival (PFS) rate estimated by Kaplan-Meier (KM) survival analysis. A progression event was defined as the first occurrence of biochemical failure, radiological progression, or death. Secondary endpoints were biochemical failure-free survival (bFFS) rate, radiological PFS (rPFS) rate, and ≥G2 adverse events. Thirty post-prostatectomy patients were enrolled and followed (median follow-up: 32.0 months; 3.0-48.1 months). Three patients had biochemical failure during follow-up. One patient developed pelvic node metastases. All patients were alive. The estimated PFS rates were 96.4% (95% confidence interval [95%CI]: 89.8%-100.0%) at 2 years and 78.8% (95%CI: 61.3%-100%) at 3 years. The estimated bFFS rates were 96.4% (95%CI: 89.8%-100%) /86.6%(95%CI: 73.4%-100%) at 2/3 years, respectively. The corresponding rPFS rates were 100% at 2 years and 92.3% (95%CI: 78.9%-100%) at 3 years, respectively. There was only one acute G2 GI adverse event (1/30, 3.33%) of abdominal pain occurred. Two late G2 events (one rectal bleeding and one urinary frequency) were scored (2/30, 6.67%). No ≥G3 events were observed. Our findings suggest the feasibility, excellent patient tolerance, and encouraging efficacy of post-prostatectomy MRgRT, extending our knowledge of the clinical outcomes of MRgRT and serving as a benchmark for future investigation.

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.

Tumor characteristics, treatments, and oncological outcomes of prostate cancer in men aged ≤60 years: real-world data from a single urological center over a 10-year period.

Prostate cancer (PCa) has emerged as one of the most common malignancies among men globally. However, its pathogenesis, clinical features, and treatment responses in younger patients (aged 60 years or below) remain underexplored. This study aims to evaluate the distinctive clinical features, treatment strategies, and oncological outcomes of PCa in men aged 60 years or younger over a 10-year period at a single urological center. We retrospectively analyzed data from The Second Hospital of Tianjin Medical University, spanning January 2010 to June 2020. The study included patients aged ≤60 years who underwent prostate biopsies. We examined clinical characteristics, pathological findings, treatment approaches, and survival outcomes using t-tests and chi-square tests. Adjusted linear regression models evaluated the relationships between treatment modalities and outcomes, while Kaplan-Meier survival analysis and Cox regression assessed progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Of the 5,686 patients who underwent prostate biopsy, 643 (11.3%) were ≤60 years old. Among these, 42.8% (275/643) were diagnosed with PCa, with 59.6% presenting at advanced stages. Compared to those with negative pathology, patients with PCa were older and more likely to have hypertension, alcohol consumption, and metabolic syndrome. Most patients (69.8%) received definitive local therapy, while 22.2% opted for palliative care and 8.0% were loss to follow-up. The median follow-up period for the entire cohort was 28.0 months and the median PFS was 77.0 months. For patients receiving definitive local therapy, the median CSS and OS were not reached, while those undergoing palliative therapy had median CSS and OS of 52.0 and 59.0 months, respectively. Multivariable analysis identified prostate-specific antigen >20 ng/mL, International Society of Urological Pathology >3, bone metastasis, and localized treatment as independent factors affecting PFS. Propensity score matching showed that definitive therapy led to superior PFS compared to palliative therapy for patients with localized PCa and a life expectancy of over 5 years. Our findings highlight the influence of incidence, diagnostic characteristics, and treatment methods in younger men with PCa, emphasizing the need to identify specific risk factors and treatment response patterns. Further large-scale, multi-center research is necessary to improve diagnosis and outcomes for PCa patients in this age group.

Prostate cancer in people with HIV

Purpose of review Prostate cancer burden has been rising among people with HIV (PWH), yet it remains understudied in the context of HIV infection. The objective of this review article is to summarize contemporary information on the burden, risk, and outcomes of prostate cancer for people living with HIV. Recent findings Despite a lower apparent incidence of prostate cancer in early studies for PWH compared to uninfected persons, this malignancy is now likely to be the most common tumor for US PWH. Tumor characteristics and stage appear to have limited differences by HIV status. The optimal approach to early detection of prostate cancer remains controversial, and there are little HIV-specific data surrounding screening. Prostate cancer outcomes may have been worse for PWH in the early antiretroviral era but may have improved in more recent years. Summary Prostate cancer is an increasingly common clinical issue for PWH. Lower than expected incidence rates in the early ART-era may be increasing, and oncologic outcomes may also be improving. Treatment tolerability is still a key question for this patient group. Given the clinical and biological complexity of chronic HIV infection, strategies for both early detection and treatment will need continued evaluation specifically in the setting of HIV.

Investigation of radiomic features on MRI images to identify extraprostatic extension in prostate cancer

Background and ObjectiveDetection of extraprostatic extension (EPE) preoperatively is of critical importance in the context of prostate cancer (PCa) management and outcomes. This study aimed to characterize the radiomic features of malignant prostate lesions based on multi-paramagnetic magnetic resonance imaging (mpMRI). MethodsWe analyzed 20 patients who underwent mpMRI followed by radical prostatectomy. Two experienced radiologists manually segmented the 3D lesions using the T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) imaging sequences. A total of 210 radiomic features were extracted from each lesion. We used the Recursive Feature Elimination with Cross-Validation to select key features. Using the selected radiomic features, we developed a Multilayer Perceptron (MLP) neural network to classify the EPE and non-EPE lesions. The pathology results were accepted as gold standard for EPE. We measured the performance of the classifier, calculating the area-under-curve (AUC), sensitivity, and specificity. ResultsA total of 25 lesions were segmented, including 12 lesions with EPE and 13 lesions without EPE, based on the pathology reports. We selected 18 radiomic features (18/210). The MLP classifier using these features provided a good sensitivity (0.75), specificity (0.79), and AUC of 0.82, 95 % CL [0.59 - 0.96] in identifying the EPE lesions. ConclusionsThis pilot study presents 18 radiomic features derived from T2-weighted and ADC images and demonstrates their potential in the preoperative prediction of EPE in PCa using an MLP model.

Association of Race and Area of Deprivation Index with Prostate Cancer Incidence and Lethality.

Socio-economic and demographical factors contribute to disparity in prostate cancer (PCa) outcomes. We examined the impact of area of deprivation index (ADI) and race on PCa incidence and lethality in a North-American cohort. Our cohort included men who received at least one PSA test within our Health System (1995-2022). An ADI score was assigned to each patient based on their residential census block, ranked as a percentile of deprivation relative to the national level. Individuals were further categorized into quartiles, where the fourth one (ADI 75-100) represented those living in the most deprived areas. We investigated PCa incidence and lethality, using cumulative incidence estimates and competing-risk regression. An ADIxRace interaction term examined whether the relationship between ADI and outcomes varied based on race. We included 134,366 patients, 25% of whom were NHB. Median (IQR) follow-up was 8.8 (5-17) years. At multivariate analysis, individuals from the third (ADI 50-74, 95% CI: 0.83-0.95) and the fourth quartile (ADI ≥ 75, 95% CI: 0.75-0.86) showed significant reduced HRs for PCa incidence, when compared with the first quartile (ADI < 25, all p < .001). In contrast to the overall cohort, PCa incidence increased with ADI in NHB men, who were persistently at higher hazard for both PCa incidence and lethality than NHW, across all ADI strata (all p < .001). Living in more deprived areas was associated with lower PCa incidence and higher lethal disease rate. Conversely, PCa incidence increased with ADI for NHB, who consistently showed worse outcomes than NHW individuals, regardless of ADI.

Analysis of urinary function and prostate volume changes in localized prostate cancer patients treated with carbon-ion radiotherapy; a prospective study

BackgroundThe potential of carbon ion radiation therapy (CIRT) as a curative treatment for localized prostate cancer (PCa) has garnered attention due to its characteristic dose distribution. We prospectively collected and analyzed over five years to investigate the outcomes of localized PCa treated with CIRT at our institution.Patients and methodsThe study included patients with histologically confirmed prostate adenocarcinoma. CIRT treatment was administered at a total dose of 57.6 Gy (RBE) in 16 fractions over four weeks. Uroflowmetry (UFM) and residual urine measurements were performed at various time points: before CIRT treatment, one month after starting CIRT, three months after treatment, and annually for five years starting from 1 year after the completion of CIRT. Prostate volume was measured using transrectal ultrasonography (TRUS).ResultsA total of 304 prostate cancer patients were analyzed. UFM parameters were significantly worsened immediately after the treatment. However, they recovered to pretreatment levels after three months and remained stable until five years post-treatment. Notably, Average flow rate showed significant improvement after three years of treatment compared to before the treatment. Prostate volume decreased to 80% of baseline in patients treated with CIRT alone and to 60–70% of baseline in those receiving combined CIRT and either short- or long-term ADT. The logistic-binomial analysis identified post-voiding residual urine volume (PVR) as a significant factor for predicting adverse events in the acute phase.ConclusionsFollowing CIRT treatment, the voiding parameters in PCa patients significantly deteriorated immediately. However, after three months, they returned to their pre-treatment levels and remained stable for five years.

Effects of sulforaphane on prostate cancer stem cells-like properties: In vitro and molecular docking studies

The increasing incidence of prostate cancer worldwide has spurred research into novel therapeutics for its treatment and prevention. A critical factor contributing to its incidence and development is the presence of prostate cancer stem cells (PCSCs). Targeting PCSCs has become key in enhancing therapeutic and clinical outcomes of prostate cancer. Sulforaphane (SFN), a compound found in cruciferous vegetables, has shown effective antineoplastic activity in prostate cancer. Yet, its mechanisms of action in PCSCs remains unclear. In the present study, tumorsphere formation assay was used to isolate and enrich PCSCs from PC-3 cells. Our results found that SFN effectively reduced the activity of PCSCs, including the ability of tumorsphere formation, the number of CD133 positive cells, and the expression of PCSCs markers. Moreover, the data showed that SFN inhibited PCSCs through downregulating the activation of Wnt/β-catenin and hedgehog signaling pathways in PCSCs. Furthermore, the verification experiments showed that the activators of Wnt/β-catenin (LiCl) and hedgehog (purmorphamine) attenuated the effects of SFN on PCSCs, including the expression of stem cell markers, cell proliferation and apoptosis. Meanwhile, suppression of β-catenin or Smoothened enhanced the effects of SFN on PCSCs. In addition, molecular docking further indicated that SFN inhibited Wnt/β-catenin and hedgehog pathways by directly targeting β-catenin and Smoothened. Taken together, our results demonstrated that SFN targeted PCSCs through Wnt/β-catenin and hedgehog pathways to inhibit stemness and proliferation and induce apoptosis. Findings from this study could provide new insights into SFN as a dietary supplement or adjunct to chemotherapy.

AR (CAG)n Microsatellite and APEX1 c.444T>G (p.Asp148Glu) Polymorphisms as Independent Prognostic Biomarkers in Prostate Cancer: Insights from an Argentinian Cohort.

Prostate cancer (PCa) is the leading malignancy and the third most common cause of cancer-related death in Argentinian men. Predicting outcomes in localized PCa remains difficult due to tumor heterogeneity. In this study, we assessed the impact of AR (CAG)n and APEX1 c.444T>G polymorphisms on biochemical relapse in Argentine patients with localized PCa. We genotyped blood samples from 123 PCa patients for AR (CAG)n and APEX1 p.Asp148Glu (c.444T>G) polymorphisms. Associations with clinicopathological parameters and biochemical relapse-free survival (BRFS) were assessed. AR (CAG)20-23 was associated with a family history of breast/ovarian cancer (p = 0.0469). The combination of AR (CAG)20-23 and APEX1 c.444TT/GG correlated with a 2.89 times higher risk of biochemical relapse (log-rank p = 0.006). Multivariable analysis confirmed AR and APEX1 polymorphisms as independent predictors of biochemical relapse (HR = 3.95, p = 0.002). In patients with PSA levels <10 ng/mL, combined AR (CAG)20-23 and APEX1 c.444TT/GG genotypes were significantly associated with an increased risk of biochemical relapse (HR = 2.61, p = 0.044). Multivariable analysis confirmed the prognostic significance of these genotypes (HR = 3.44, p = 0.02). This study has identified AR (CAG)n and APEX1 c.444T>G polymorphisms as independent predictors of PCa relapse in Argentinian patients, suggesting their potential use in improving prognostic models.

Integrating PET/CT, radiomics and clinical data: An advanced multi-modal approach for lymph node metastasis prediction in prostate cancer

The involvement of lymph nodes critically affects patient outcomes in prostate cancer. While traditional risk models use factors like stage and PSA levels, the detection of lymph node involvement through modalities like PET targeting PSMA with 68Ga radiotracer plays a pivotal role in guiding treatments ranging from prostatectomy to pelvic radiotherapy. This study aims to create a deep learning model to predict lymph node involvement in intermediate to high-risk prostate cancer patients using 68Ga-PSMA PET/CT imagery, radiomics features, and various clinical parameters. For this study, 68Ga-PSMA PET/CT scans and corresponding clinical data from 229 prostate cancer patients were retrospectively collected. An artificial intelligence model, integrating PET/CT fusion images, clinical data, and radiomics features, was developed using a slice-wise feature extractor and MNASNet for spatial feature extraction. The model was trained on 181 cases and tested on 48 cases. To assess the model’s performance, a reader study was conducted on a balanced subset of the test data with five radiation oncologists. Among the 229 intermediate to high-risk patients with localized prostate cancer evaluated, 67 (30%) had lymph node metastasis, while 162 were non-metastatic. The proposed AI model achieved a mean accuracy of 0.85±0.03 and an F1 score of 0.73±0.03. In the reader study, radiation oncologists’ mean evaluations showed lower metrics (accuracy 0.71±0.08, F1 score 0.70±0.07), compared to the AI model’s mean accuracy of 0.79±0.02 and F1 score of 0.76±0.02. Our findings demonstrate the potential benefits of the proposed model in the clinical setting, particularly in enhancing decision-making by doctors in scenarios with high variability between readers, such as lymph node metastasis prediction.

Optimizing Multiparametric MRI Protocols for Prostate Cancer Detection: A Comprehensive Assessment Aligned with PI-RADS Guidelines.

Multiparametric magnetic resonance imaging (mpMRI) is recognized as the most indicative method for diagnosing prostate cancer. The purpose of this narrative review is to provide a comprehensive evaluation aligned with the Prostate Imaging and Reporting Data System (PI-RADS) guidelines, offering an in-depth insight into the various MRI sequences used in a standard mpMRI protocol. Additionally, it outlines the critical technical requirements necessary to perform a standard mpMRI examination of the prostate, as defined by the PI-RADS specifications. European Society of Urogenital Radiology has released PI-RADS guideline detailing its suggestions aimed at improving the standards of the procedure. The purpose of this guideline is to establish a standard strategy for MRI protocols and image interpretation, aiming to prevent variability in each of the imaging and interpretation stages. A standard mpMRI protocol comprises morphological sequences and functional sequences. Morphological sequences which encompass T1- and T2-weighted images, and various functional sequences include diffusion-weighted imaging, and dynamic contrast-enhanced MRI. The PI-RADS recommendations assert that having a standard and uniform protocol for all MRI centers is imperative. Furthermore, the existence of a standardized checklist for interpreting MRI images can foster greater consensus in the process of diagnosing and treating patients. Standardized protocols and checklists for mpMRI interpretation are essential for achieving greater consensus among radiologists, ultimately leading to improved diagnostic outcomes in prostate cancer.

P007 PRO-WAVE1: Monitoring patient reported outcomes (PROs) in prostate cancer through Wave Health, a novel ePRO health platform

P007 PRO-WAVE1: Monitoring patient reported outcomes (PROs) in prostate cancer through Wave Health, a novel ePRO health platform

The relationship between immune cells and prostate cancer, and the mediating role of metabolites: a Mendelian randomization study

Research has demonstrated the significant involvement of immune cells in the development and progression of prostate cancer (PCa). However, the precise causal relationship between immune cells and PCa remains unclear. This study utilized bidirectional Mendelian randomization (MR) analysis to investigate the causal link between immune cells and PCa. Additionally, employed mediation MR design to ascertain the potential mediating role of metabolites in the connection between immune cells and PCa outcomes. Unswitched memory B cell % lymphocyte and CD24 + CD27 + B cell % lymphocyte were positively related to PCa risk, while CD62L − monocyte absolute count and CD62L − monocyte % monocyte were negatively associated with PCa risk. Sensitivity analysis was conducted to validate these results. The mediation MR results indicate that 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) levels may be an independent risk factor for PCa, while the succinate to acetoacetate ratio (SA ratio) was found to be a mediator for the effect of CD62L − monocyte % monocyte on PCa, with a mediation proportion of 16.6% (mediation percentage: 16.6%, 95%CI − 163% − 196%). The research validates the genetic causality between particular immune cells and PCa, and has emphasized the potential intermediary function of SA ratio. These noteworthy discoveries provide fresh perspectives for the clinical management of PCa.

Rurality and outcomes in prostate cancer: role of socioeconomic status and educational attainment

Abstract Background/Introduction Patients diagnosed with prostate cancer (PC) have a higher cardiovascular disease (CVD) prevalence and mortality risk. Rurality have been associated with up to 33% higher CVD risk and 44% higher all-cause mortality risk in patients with PC. Purpose Analyze the impact of rurality (from both patient and provider perspectives) on the development of adverse outcomes after a PC diagnosis according to socioeconomic and educational status. Methods We included men aged ≥66 with a new primary PC diagnosis (defined as ICD-10 = C61) from 2009-2017 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The primary outcomes were CVD (comprising heart failure, atrial fibrillation, acute myocardial infarction, peripheral artery disease, and ischemic stroke), PC-specific mortality (PCsm), cardiovascular disease mortality (CVDm), and all-cause mortality. Patients living in areas with a population of &amp;lt;2,500 or &amp;lt;20,000, not adjacent to a metropolitan area, were considered to have a positive rural status. The provider status (metropolitan vs. non-metropolitan) was defined according to the 2013 National Center for Health Statistics' Urban-Rural Classification Scheme for Counties. Low socioeconomic status (SES) was defined according to Yost Index quintiles. Low educational status was defined according to percentiles of people &amp;gt;25 years old with less than a high school diploma. Multivariable Fine-Gray models, accounting for competing mortality/type of mortality, and Cox regression models were applied. Results We included 75,221 patients with PC (Picture 1), of which 1,828 were from rural areas and 362 were from rural areas with providers from non-metropolitan areas. Among patients from rural areas under the care of non-metropolitan providers, 82.6% had low SES (Yost Index ≤ 2). In this subgroup, patients from rural areas with non-metropolitan providers had 30% higher CVD risk (sHR 1.30; 95% CI 1.04-1.62) and 44% higher all-cause mortality risk (sHR 1.44; 95% CI 1.14-1.83; Picture 2) when compared to patients with low SES from urban or rural areas with providers from metropolitan areas. Additionally, within patients from rural areas with non-metropolitan providers, the median % of people with only high school diploma was 38.3 (IQR 36.2-40.9). Among those with low educational status (≤41% of high school county-rate), patients from rural areas with non-metropolitan providers had a 35% higher associated CVD risk (sHR 1.35; 95% CI 1.06-1.71), 54% higher associated CVDm risk (sHR 1.54; 95% CI 1.01-2.36), and a 32% higher associated all-cause mortality risk (sHR 1.32; 95% CI 1.04-1.66). Conclusion Patients with PC from rural areas with non-metropolitan providers have higher rates of low SES and low educational status and suffer from up to 54% higher associated risks of adverse outcomes, emphasizing the role of multiple domains of the Social Determinants of Health in health outcomes.

Educational attainment and cardiovascular outcomes in prostate cancer: observations from 3700 men in 6 countries in the RADICAL PC study

Abstract Background Educational attainment has been associated with improved cardiovascular outcomes in individuals with or at high risk for cardiovascular disease (CVD). There is little information on the relationship between education and CVD outcomes in individuals with cancer. Also, we have limited understanding of what mediates the relationship between education and these outcomes. Purpose To evaluate the relationship between educational attainment in patients with PC and CVD event (CVE) or all-cause mortality. Methods We prospectively studied 3,778 men with PC from 55 sites in 7 countries (median age 69 years), 46% on ADT. Inclusion criteria were one of: PC diagnosed in the past 12 months; started ADT within the past 6 months; or plan to start ADT in the next month. Educational attainment was classified as those who attained primary school education vs. those who attained high school education vs. those who attained greater than high school education. Participants were followed for a median of 2.5 years from enrolment to document CVE: myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism, and atrial fibrillation. The primary outcome for this analysis was CVE or death. All outcomes were evaluated by Cox proportional hazards models adjusted sequentially for age, race, physical activity levels, tobacco use, and alcohol use. Results Among 3,778 participants, 726 (19%) achieved primary school education, 1,001 (27%) high school, and 2,051 (54%) greater than high school education. On univariate analysis, as compared with participants with greater than high school education, those with high school education and primary school education had respective HR (95% CI) of 1.33 (1.05-1.69) and 2.19 (1.71-2.83). Adding age, race, tobacco, and alcohol use to the Cox model progressively attenuated the association between education and the primary outcome. Eventually, after adjustment for these characteristics and physical activity levels, the relationship between education and the primary outcome was no longer significant (Table). Conclusion This finding suggests that patterns of tobacco and alcohol use and physical activity, which are modifiable behaviors, account for the relationship between education and death or CVE in patients with prostate cancer.Table

Exploring Ethnic Variability in Aryl Hydrocarbon Receptor Signaling: Delineating Differences in Prostate Cancer Outcomes Between African American and Caucasian Populations.

Prostate cancer rates and outcomes show significant differences between African American (AA) and Caucasian men, with AA males experiencing higher incidence and mortality rates. These disparities result from a complex interaction of socioeconomic, environmental, and biological factors. This study explores how the Aryl Hydrocarbon Receptor (AHR) and Androgen Receptor (AR) signaling pathways contribute to these differences. AHR, traditionally recognized for its role in detoxifying environmental carcinogens, has recently been identified as playing a key role in prostate cancer progression. AA men tend to exhibit higher levels of AHR expression and activity, which may contribute to the aggressive nature of the disease in this population. The interaction between AHR and AR signaling pathways might promote tumor growth and lead to resistance to standard treatments. Additionally, genetic variations in the AHR and AR genes, along with environmental exposures, may exacerbate these disparities. This study emphasizes the importance of developing targeted therapies that address the specific genetic and molecular profiles of different populations. By gaining a deeper understanding of the roles of AHR and AR signaling in prostate cancer, particularly in the context of ethnic diversity, we aim to work toward reducing these disparities and improving outcomes for all patients.

LINC01518 predicts poor prognosis of prostate cancer and promotes its progression by regulating hsa-miR-320a/CNKSR2 axis

BackgroundProstate cancer (PCa) is the most common malignancy of the male genitourinary system. Understanding the molecular mechanism of PCa and its prognostic markers will assist in the selection of better treatment.AimTo explore the role of LINC01518 in the development of PCa and its prognostic value, and to understand its specific regulatory mechanism.MethodsThe levels of LINC01518, hsa-miR-320a, and CNKSR2 mRNA were detected by RT-qPCR. ROC curve was constructed to evaluate the prognostic value of LINC01518 in PCa. The effects of LINC01518 on the functions of PCa cells were demonstrated by CCK-8, Transwell test, and the detection of apoptotic markers, after LINC01518 knockdown. The interaction between hsa-miR-320a and LINC01518 or CNKSR2 mRNA was examined by constructing luciferase vectors.ResultsLINC01518 was abnormally expressed in PCa cells and tumor tissues, and knockdown of it inhibited the growth of PCa cells. LINC01518 predicted castration-resistant prostate cancer (CRPC) outcomes in PCa patients with AUC of 0.803, sensitivity and specificity of 75.4% and 74.6%, respectively. Hsa-miR-320a mimics reduced luciferase activity in PCa cells transfected with WT-LINC01518/CNKSR2 plasmids. Knocking down LINC01518 reduced CNKSR2 level, and this regulatory effect disappeared with the inhibition of hsa-miR-320a.ConclusionHigh levels of LINC01518 predicted poor prognosis in PCa patients and promoted CNKSR2 expression by competitively binding hsa-miR-320a, contributing to the progression of PCa.

The mendelian randomized study revealed the association of prostatitis with prostate cancer risk

In recent observational studies, a potential link between prostatitis and prostate cancer (PCa) has been hinted at, yet the causality remains ambiguous. In our endeavor to scrutinize the conceivable causal nexus between prostatitis and PCa, we embarked upon a Mendelian randomization (MR) study. MR circumvents arbitrary groupings by employing genetic variations that have a strong association with the exposure as instrumental variables to infer causal relationships between exposures and outcomes. The etiology of PCa remains elusive. Given that prostatitis and prostate cancer occupy the same anatomical region, MR can more effectively delineate their relationship by mitigating confounding variables. This method can indirectly elucidate disease correlations, thereby contributing to cancer prevention strategies. FinnGen Consortium data were used for the prostatitis genome-wide association study (GWAS), including 74,658 participants. UK biobank baseline data (ncase = 3436, ncontrol = 459574), European Bioinformatics Institute Database (ncase = 79148, ncontrol = 61106), and IEU openGWAS database (ncase = 79148, ncontrol = 61106) were used for PCa outcomes, mostly for European population samples. Data from the GWSAs for prostatitis were compared with data from the three GWASs for PCa, respectively, in an analysis of an MR. Utilizing the inverse variance weighting (IVW) methodology as our primary analytical framework, we delved into a meticulous exploration of the conceivable causal association between prostatitis and PCa. Furthermore, we deployed supplementary methodologies, including Maximum Likelihood, MR-Egger, weighted median, and MR-PRESSO, to thoroughly assess and scrutinize the causality aspect comprehensively. Cochran’s Q statistic is employed as a metric to quantify the heterogeneity inherent in instrumental variables. The inverse variance weighted analysis revealed no discernible effect of prostatitis on PCa in the three PCa GWAS databases (odds ratio [OR]: 1.001, 95% Confidence Interval [CI]: 0.999–1.002, p = 0.28), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40). Similarly, employing MR-Egger did not yield substantial evidence (OR: 0.999, 95% CI: 0.999–1.002, p = 0.89), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07). The weighted median analysis also failed to provide convincing support for the impact of prostatitis on the incidence of PCa (OR: 1.001, 95% CI: 1.000-1.002, p = 0.064), (OR: 0.989, 95% CI: 0.946–1.034, p = 0.64), (OR: 0.989, 95% CI: 0.945–1.036, p = 0.65). The results of the MR showed no causality from prostatitis to PCa.

Ultralow Prostate-Specific Antigen (PSA) Levels and Improved Oncological Outcomes in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Patients Treated with Apalutamide: A Real-World Multicentre Study.

Background/Objectives: Androgen receptor-targeted agents have significantly improved the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific antigen (PSA) levels are key prognostic markers, with rapid and deep reductions associated with better outcomes. This study aims to assess the association between the new PSA cut-offs and survival in mHSPC patients treated with Apalutamide. Methods: We conducted a multicentre, retrospective analysis of mHSPC patients treated with Apalutamide between March 2021 and January 2023. Overall survival (OS) and radiographic progression-free survival (rFPS) were analyzed and stratified by the following PSA ranges: <0.02 ng/mL (ultralow), 0.02-0.2 ng/mL, and >0.2 ng/mL. Cox regression was applied to identify variables associated with OS and rPFS. Results: Among 193 patients, 34.2% had de novo mHSPC, with the majority classified as M1b. A total of 58.2% (110) of our cohort achieved ultralow PSA levels, with 20.6% between 0.02 and 0.2 ng/mL, and 21.2% of PSA levels > 0.2 ng/mL. Most patients reached ultralow PSA within six months. Low-volume, metachronous, and M1a subgroups displayed a higher prevalence of patients reaching ultralow PSA levels. At 18 months, OS was 100% in the ultralow PSA group, 94.4% for the 0.02-0.2 ng/mL group, and 67.7% in the >0.2 ng/mL group. Similarly, rPFS at 18 months was 100%, 93.5%, and 50.7%, respectively. Cox regression revealed that both ultralow PSA levels and ISUP grade had a significant impact on OS (HR of 8.256 and 0.164, respectively). For rPFS, only ultralow PSA levels had a significant impact (HR = 0.085). Conclusions: This real-world study of mHSPC patients treated with Apalutamide plus ADT revealed that achieving ultralow PSA levels is strongly associated with better oncological outcomes.

N-linked fucosylated glycans are biomarkers for prostate cancer with a neuroendocrine and metastatic phenotype.

Prostate cancer (PCa) is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged Matrix Assisted Laser Desorption Ionization (MALDI) imaging of formalin-fixed, paraffin embedded (FFPE) prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes. We found that N-glycan fucosylation was abundant in neuroendocrine prostate cancer as well as adenocarcinomas at time of prostatectomy that eventually developed recurrent metastatic disease. Analysis of patient derived xenografts revealed that this fucosylation signature was enriched differently across metastatic disease organ sites, with the highest abundance in liver metastases. These data suggest that N-linked fucosylated glycans could be an early tissue biomarker for poor PCa outcomes. Implications: These studies identify that hyper-fucosylated N-linked glycans are enriched in neuroendocrine prostate cancer and conventional prostate adenocarcinomas that progress to metastatic disease, thus advancing biomarker discovery and providing insights into mechanisms underlying metastatic disease.