Improving cancer immunotherapy in prostate cancer by modulating T cell function through targeting the galectin-1.

Our study aimed to elucidate the role of Galectin-1 (Gal-1) role in the immunosuppressive tumor microenvironment (TME) of prostate cancer (PCa). Our previous findings demonstrated a correlation between elevated Gal-1 expression and advanced PCa stages. In this study, we also observed that Gal-1 is expressed around the tumor stroma and its expression level is associated with PCa progression. We identified that Gal-1 could be secreted by PCa cells, and secreted Gal-1 has the potential to induce T cell apoptosis. Gal-1 knockdown or inhibition of Gal-1 function by LLS30 suppresses T cell apoptosis resulting in increased intratumoral T cell infiltration. Importantly, LLS30 treatment significantly improved the antitumor efficacy of anti-PD-1 in vivo. Mechanistically, LLS30 binds to the carbohydrate recognition domain (CRD) of Gal-1, disrupting its binding to CD45 leading to the suppression of T cell apoptosis. In addition, RNA-seq analysis revealed a novel mechanism of action for LLS30, linking its tumor-intrinsic oncogenic effects to anti-tumor immunity. These findings suggested that tumor-derived Gal-1 contributes to the immunosuppressive TME in PCa by inducing apoptosis in effector T cells. Targeting Gal-1 with LLS30 may offer a strategy to enhance anti-tumor immunity and improve immunotherapy.

Protecting Prostate Cancer Classification From Rectal Artifacts via Targeted Adversarial Training.

Magnetic resonance imaging (MRI)-based deep neural networks (DNN) have been widely developed to perform prostate cancer (PCa) classification. However, in real-world clinical situations, prostate MRIs can be easily impacted by rectal artifacts, which have been found to lead to incorrect PCa classification. Existing DNN-based methods typically do not consider the interference of rectal artifacts on PCa classification, and do not design specific strategy to address this problem. In this study, we proposed a novel Targeted adversarial training with Proprietary Adversarial Samples (TPAS) strategy to defend the PCa classification model against the influence of rectal artifacts. Specifically, based on clinical prior knowledge, we generated proprietary adversarial samples with rectal artifact-pattern adversarial noise, which can severely mislead PCa classification models optimized by the ordinary training strategy. We then jointly exploited the generated proprietary adversarial samples and original samples to train the models. To demonstrate the effectiveness of our strategy, we conducted analytical experiments on multiple PCa classification models. Compared with ordinary training strategy, TPAS can effectively improve the single- and multi-parametric PCa classification at patient, slice and lesion level, and bring substantial gains to recent advanced models. In conclusion, TPAS strategy can be identified as a valuable way to mitigate the influence of rectal artifacts on deep learning models for PCa classification.

MRI-guided in-bore biopsy of the prostate - defining the optimal number of cores needed.

BACKGROUND: Numerous studies have shown that magnetic resonance imaging (MRI)-targeted biopsy approaches are superior to traditional systematic transrectal ultrasound guided biopsy (TRUS-Bx). The optimal number of biopsy cores to be obtained per lesion identified on multiparametric MRI (mpMRI) images, however, remains a matter of debate. The aim of this study was to evaluate the incremental value of additional biopsy cores in an MRI-targeted "in-bore"-biopsy (MRI-Bx) setting. PATIENTS AND METHODS: Two hundred and forty-five patients, who underwent MRI-Bx between June 2014 and September 2021, were included in this retrospective single-center analysis. All lesions were biopsied with at least five biopsy cores and cumulative detection rates for any cancer (PCa) as well as detection rates of clinically significant cancers (csPCa) were calculated for each sequentially labeled biopsy core. The cumulative per-core detection rates are presented as whole numbers and as proportion of the maximum detection rate reached, when all biopsy cores were considered. CsPCa was defined as Gleason Score (GS) ≥ 7 (3 + 4). RESULTS: One hundred and thirty-two of 245 Patients (53.9%) were diagnosed with prostate cancer and csPCa was found in 64 (26.1%) patients. The first biopsy core revealed csPCa/ PCa in 76.6% (49/64)/ 81.8% (108/132) of cases. The second, third and fourth core found csPCa/ PCa not detected by previous cores in 10.9% (7/64)/ 8.3% (11/132), 7.8% (5/64)/ 5.3% (7/132) and 3.1% (2/64)/ 3% (4/132) of cases, respectively. Obtaining one or more cores beyond the fourth biopsy core resulted in an increase in detection rate of 1.6% (1/64)/ 1.5% (2/132). CONCLUSION: We found that obtaining five cores per lesion maximized detection rates. If, however, future research should establish a clear link between the incidence of serious complications and the number of biopsy cores obtained, a three-core biopsy might suffice as our results suggest that about 95% of all csPCa are detected by the first three cores.

Treatment escalation and de-escalation of de-novo metastatic castration-sensitive prostate cancer.

Androgen receptor signaling inhibitors combined with androgen deprivation therapy have become the standard of care for metastatic castration-sensitive prostate cancer (mCSPC), regardless of tumor volume or risk. However, survival of approximately one-third of these patients has not improved, necessitating further treatment escalation. On the other hand, for patients with oligometastatic mCSPC, there is an emerging role for local radiation therapy. Although data remain scarce, it is expected that treatment of both primary tumor as well as metastasis-directed therapy may improve survival outcomes. In these patients, systemic therapy may be de-escalated to intermittent therapy. However, precise risk stratification is necessary for risk-based treatment escalation or de-escalation. In addition to risk stratification based on clinical parameters, research has been conducted to incorporate genomic and/or transcriptomic data into risk stratification. In future, an integrated risk model is expected to precisely stratify patients and guide treatment strategies. Here, we first review the transition of the standard treatment for mCSPC over the last decade and further discuss the newest concept of escalating or de-escalating treatment using a multi-modal approach based on the currently available literature.

[Assessment of Incidental Prostate Carcinoma Cases and Predictors by Holmium Laser Enucleation of the Prostate].

Surgery for benign prostatic hyperplasia (BPH) has greatly advanced with the development of laser technology ; and holmium laser enucleation of the prostate (HoLEP), which can be performed safely and with minimal invasiveness regardless of prostate size. Incidental prostate carcinoma (iPCa) following HoLEP occurs at a certain rate. Predictors, include age, biopsy, history, preoperative prostate specific antigen, and prostate volume. We compared cases with and without incidental carcinoma detection among 257 patients with BPH who underwent HoLEP at our hospital from July 2015 to December 2022. Among the 257 patients, 29 (11.3%) were found to have incidental carcinoma. Although 1 patient switched to endocrine therapy the remaining patients showed good prognosis under surveillance therapy. The proportion of cases with magnetic resonance imaging (MRI) findings suggestive of carcinoma was significantly higher in the incidental carcinoma detection group (p＝0.009). Furthermore, univariate analysis of incidental carcinoma predictive factors revealed a significant difference in MRI findings (odds ratio [OR] 2.92 ; confidence interval [CI] 1.33-6.42), and multivariate analysis showed similar results (OR 2.92 ; CI 1.33-6.42). At our hospital, we currently perform MRI scans for preoperative morphological assessments but not for cancer diagnosis. However, based on the results obtained, we aim to proactively utilize MRI for preoperative malignant screening, in addition to PSA.

[A Case of Metastatic Prostate Cancer with Neuroendocrine Differentiation with Long-Term Survival after Multidisciplinary Therapy].

A 74-year-old man visited the urology clinic with the chief complaint of urinary retention in December 2014. Serum level of initial prostate specific antigen (PSA) was 50 ng/ml and he was diagnosed with Gleason Score 4＋4 prostate adenocarcinoma with regional lymphadenopathy (cT3aN1M0). PSA level had declined after the treatment with combined androgen blockade. In November 2018, he was diagnosed with castration resistant prostate cancer (CRPC) as local progression was detected by computed tomography (CT) while PSA level did not increase. Since local symptoms worsened, resulting in repeated hematuria after the treatment with enzalutamide, palliative radiation therapy to the prostate (45 Gy) was performed. Five months later, follow-up CT showed multiple metastasis in bilateral lung and left testicle. Serum level of neuron-specific enolase (NSE) was 24.4 ng/ml without an elevated in serum PSA level. He received rebiopsy of the prostate, but no malignant findings were observed. Consequently, bilateral orchiectomy was performed for diagnosis of left testicular tumor. Pathological examination revealed metastasis of neuroendocrine prostate cancer (NEPC). Chemotherapy using cisplatin and irinotecan was administered after orchiectomy. Complete response of lung lesions was achieved and serum level of NSE decreased within normal range. No recurrence has been confirmed for 4 years after the completion of chemotherapy.

Enhancing prostate cancer diagnosis and reducing unnecessary biopsies with [18F]DCFPyL PET/CT imaging in PI-RADS 3/4 patients.

For patients presenting with prostate imaging reporting and data system (PI-RADS) 3/4 findings on magnetic resonance imaging (MRI) examinations, the standard recommendation typically involves undergoing a biopsy for pathological assessment to ascertain the nature of the lesion. This course of action, though essential for accurate diagnosis, invariably amplifies the psychological distress experienced by patients and introduces a host of potential complications associated with the biopsy procedure. However, [18F]DCFPyL PET/CT imaging emerges as a promising alternative, demonstrating considerable diagnostic efficacy in discerning benign prostate lesions from malignant ones. This study aims to explore the diagnostic value of [18F]DCFPyL PET/CT imaging for prostate cancer in patients with PI-RADS 3/4 lesions, assisting in clinical decision-making to avoid unnecessary biopsies. 30 patients diagnosed with PI-RADS 3/4 lesions through mpMRI underwent [18F]DCFPyL PET/CT imaging, with final biopsy pathology results as the "reference standard". Diagnostic performance was assessed through receiver operating characteristic (ROC) analysis, evaluating the diagnostic efficacy of molecular imaging PSMA (miPSMA) visual analysis and semi-quantitative analysis in [18F]DCFPyL PET/CT imaging. Lesions were assigned miPSMA scores according to the prostate cancer molecular imaging standardized evaluation criteria. Among the 30 patients, 13 were pathologically confirmed to have prostate cancer. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of visual analysis in [18F]DCFPyL PET/CT imaging for diagnosing PI-RADS 3/4 lesions were 61.5%, 88.2%, 80.0%, 75.0%, and 76.5%, respectively. Using SUVmax 4.17 as the optimal threshold, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis were 92.3%, 88.2%, 85.7%, 93.8%, and 90.0%, respectively. The area under the ROC curve (AUC) for semi-quantitative analysis was 0.94, significantly higher than visual analysis at 0.80. [18F]DCFPyL PET/CT imaging accurately diagnosed benign lesions in 15 (50%) of the PI-RADS 3/4 patients. For patients with PI-RADS 4 lesions, the positive predictive value of [18F]DCFPyL PET/CT imaging reached 100%. [18F]DCFPyL PET/CT imaging provides potential preoperative prediction of lesion nature in mpMRI PI-RADS 3/4 patients, which may aid in treatment decision-making and reducing unnecessary biopsies.

Population-Specific gene expression profiles in prostate cancer: insights from Weighted Gene Co-expression Network Analysis (WGCNA).

This study investigates the genetic factors contributing to the disparity in prostate cancer incidence and progression among African American men (AAM) compared to European American men (EAM). The research focuses on employing Weighted Gene Co-expression Network Analysis (WGCNA) on public microarray data obtained from prostate cancer patients. The study employed WGCNA to identify clusters of genes with correlated expression patterns, which were then analyzed for their connection to population backgrounds. Additionally, pathway enrichment analysis was conducted to understand the significance of the identified gene modules in prostate cancer pathways. The Least Absolute Shrinkage and Selection Operator (LASSO) and Correlation-based Feature Selection (CFS) methods were utilized for selection of biomarker genes. The results revealed 353 differentially expressed genes (DEGs) between AAM and EAM. Six significant gene expression modules were identified through WGCNA, showing varying degrees of correlation with prostate cancer. LASSO and CFS methods pinpointed critical genes, as well as six common genes between both approaches, which are indicative of their vital role in the disease. The XGBoost classifier validated these findings, achieving satisfactory prediction accuracy. Genes such as APRT, CCL2, BEX2, MGC26963, and PLAU were identified as key genes significantly associated with cancer progression. In conclusion, the research underlines the importance of incorporating AAM and EAM population diversity in genomic studies, particularly in cancer research. In addition, the study highlights the effectiveness of integrating machine learning techniques with gene expression analysis as a robust methodology for identifying critical genes in cancer research.

Using multi-label ensemble CNN classifiers to mitigate labelling inconsistencies in patch-level Gleason grading.

This paper presents a novel approach to enhance the accuracy of patch-level Gleason grading in prostate histopathology images, a critical task in the diagnosis and prognosis of prostate cancer. This study shows that the Gleason grading accuracy can be improved by addressing the prevalent issue of label inconsistencies in the SICAPv2 prostate dataset, which employs a majority voting scheme for patch-level labels. We propose a multi-label ensemble deep-learning classifier that effectively mitigates these inconsistencies and yields more accurate results than the state-of-the-art works. Specifically, our approach leverages the strengths of three different one-vs-all deep learning models in an ensemble to learn diverse features from the histopathology images to individually indicate the presence of one or more Gleason grades (G3, G4, and G5) in each patch. These deep learning models have been trained using transfer learning to fine-tune a variant of the ResNet18 CNN classifier chosen after an extensive ablation study. Experimental results demonstrate that our multi-label ensemble classifier significantly outperforms traditional single-label classifiers reported in the literature by at least 14% and 4% on accuracy and f1-score metrics respectively. These results underscore the potential of our proposed machine learning approach to improve the accuracy and consistency of prostate cancer grading.

Association between lymphocyte-to-monocyte ratio and prostate cancer in men: A population-based study.

Using the novel inflammatory biomarker lymphocyte-to-monocyte ratio (LMR), this work aimed to look into any potential connections between LMR and prostate cancer (PCa). A cross-sectional research investigation was conducted on 7706 male participants involved in the National Health and Nutrition Examination Survey from 2001 to 2010. Multivariate logistic regression modeling investigated the relationship between LMR levels and PCa risk. Furthermore, threshold analysis, subgroup analysis, interaction testing, and smoothed curve fitting were carried out. A significant negative correlation was seen between LMR and PCa risk (OR = 0.79, 95% CI: 0.65-0.97, P = .0002), even after controlling for potential confounding factors. A significant nonlinear negative correlation with a threshold effect and a breakpoint of 4.86 was found by smooth curve fitting between LMR and PCa. Subgroup analysis revealed a significant interaction (P for interaction = 0.0448) between the negative correlation between PCa and LMR about hypertension. Moreover, additional stratified smoothed curve fitting demonstrated a statistically significant inverse relationship between PCa risk and LMR. According to our findings, there is a substantial inverse relationship between PCa risk and LMR level. The inflammatory response-related index is quick, easy to use, and offers some clinical references. However, more extensive prospective investigations are required to confirm the involvement of LMR levels in PCa.

The role of gut microbiota in prostate cancer progression: A Mendelian randomization study of immune mediation.

The potential relationship between the gut microbiota and prostate cancer, possibly influenced by immune cells, remains unclear. This study employed the mediation Mendelian randomization (MR) technique to investigate the causal link between the gut microbiota, immune cells, and prostate cancer. Data on immune cell activity were sourced from Valeria Orrù's research, whereas the genome-wide association study outcome dataset was obtained from the Integrative Epidemiology Unit database. The bidirectional MR analysis utilized 5 different methods: inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. In addition, the mediating effect of immune cells on the gut microbiota and prostate cancer was explored using mediation analysis. Eighty-three single nucleotide polymorphisms associated with prostate cancer were screened as instrumental variables. In a positive MR analysis with gut microbiota as the exposure factor, IVW showed an association between 8 gut microbiota and prostate cancer. Additionally, 9 types of immune cells have been found to be associated with prostate cancer using methods such as IVW. MR analysis of the gut microbiota on immune cells (beta1) revealed a negative correlation between Bifidobacterium and CD39+ T regulatory cells (Tregs; odds ratio [OR] = 0.785, 95% confidence interval [CI] = 0.627-0.983, P = .03). Furthermore, MR analysis of immune cells in prostate cancer disease (beta2) showed that CD39+Tregs are a risk factor for prostate cancer (OR = 1.215, 95% CI = 1.027-1.354, P = .04). Moreover, MR analysis of gut microbiota in prostate cancer (total effect) indicated that Bifidobacterium is a protective factor for prostate cancer (OR = 0.905, 95% CI = 0.822-0.977, P = .04). The sensitivity analysis verified the robustness of the above results. Mediation analysis demonstrated that CD39+Tregs partially mediate the causal relationship between Bifidobacterium and prostate cancer. This study demonstrates that Bifidobacterium inhibits prostate cancer progression through CD39+Tregs as mediators, providing new ideas and approaches for the treatment and prevention of prostate cancer.

Biomolecule-regulation of fluorescent probe signaling: Homogeneous rapid portable protease sensing in serum.

BACKGROUND: As is well documented, prostate cancer (PCa) being the second most prevalent cancer in men worldwide, emphasizing the importance of early diagnosis for prognosis. However, conventional prostate-specific antigen (PSA) testing lacks sufficient diagnostic efficiency due to its relatively low sensitivity and limited detection range. Mounting evidence suggests that matrix metalloproteinase 9 (MMP-9) expression increases with the aggressive behavior of PCa, highlighting the significance of detecting the serum level of MMP-9 in patients. Developing a non-immune rapid, portable MMP-9 detection strategy and investigating its representativeness of PCa serum markers hold considerable implications. RESULTS: Herein, our study developed a simple, homogeneous dual fluorescence and smartphone-assisted red-green-blue (RGB) visualization peptide sensor of MMP-9, utilizing cadmium telluride quantum dots (CdTe QDs) and calcein as signal reporters. The essence of our approach revolves around the proteolytic ability of MMP-9, exploiting the selective recognition of molecule-Cu2+ complexes with different molecular weights by CdTe QDs and calcein. Under optimized conditions, the limits of detection (LODs) for MMP-9 were 0.5 pg/mL and 6 pg/mL using fluorescence and RGB values readouts, respectively. Indeed, this strategy exhibited robust specificity and anti-interference ability. MMP-9 was quantified in 42 clinical serum samples via dual-fluorescence analysis, with 12 samples being visually identified with a smartphone. According to receiver operating characteristic curve (ROC) analysis, its sensitivity and specificity were 90 % and 100 %, respectively, with an area under curve (AUC) value of 0.903. SIGNIFICANCE AND NOVELTY: Of note, the results of the aforementioned analysis were highly consistent with the serum level of PSA, clinical color Doppler flow imaging (CDFI), and histopathological results. Therefore, this simple, rapid, homogeneous fluorescence and visualization strategy can reliably measure MMP-9 levels and exhibit promising potential in point-of-care testing (POCT) applications for PCa patients.

Early Prostate Cancer Deaths Among Men With Higher vs Lower Genetic Risk.

Importance: Prostate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic susceptibility. Objective: To explore differences in risk of early prostate cancer death among men with higher vs lower genetic risk to inform prevention efforts. Design, Setting, and Participants: This cohort study used a combined analysis of genotyped men without prostate cancer at inclusion and with lifestyle data in 2 prospective cohort studies in Sweden and the US, the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS), followed up from 1991 to 2019. Data were analyzed between April 2023 and April 2024. Exposures: Men were categorized according to modifiable lifestyle behaviors and genetic risk. A polygenic risk score above the median or a family history of cancer defined men at higher genetic risk (67% of the study population); the remaining men were categorized as being at lower genetic risk. Main Outcomes and Measures: Prostate cancer death analyzed using time-to-event analysis estimating hazard ratios (HR), absolute risks, and preventable deaths by age. Results: Among the 19 607 men included for analysis, the median (IQR) age at inclusion was 59.0 (53.0-64.7) years (MDCS) and 65.1 (58.0-71.8) years (HPFS). During follow-up, 107 early (by age 75 years) and 337 late (after age 75 years) prostate cancer deaths were observed. Compared with men at lower genetic risk, men at higher genetic risk had increased rates of both early (HR, 3.26; 95% CI, 1.82-5.84) and late (HR, 2.26; 95% CI, 1.70-3.01) prostate cancer death, and higher lifetime risks of prostate cancer death (3.1% vs 1.3% [MDCS] and 2.3% vs 0.6% [HPFS]). Men at higher genetic risk accounted for 94 of 107 early prostate cancer deaths (88%), of which 36% (95% CI, 12%-60%) were estimated to be preventable through adherence to behaviors associated with a healthy lifestyle (not smoking, healthy weight, high physical activity, and a healthy diet). Conclusions and Relevance: In this 20-year follow-up study, men with a genetic predisposition accounted for the vast majority of early prostate cancer deaths, of which one-third were estimated to be preventable. This suggests that men at increased genetic risk should be targeted in prostate cancer prevention strategies.

SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis.

Mutations that decrease or increase the activity of the tyrosine phosphatase, SHP2 (encoded by PTPN11), promotes developmental disorders and several malignancies by varying phosphatase activity. We uncovered that SHP2 is a distinct class of an epigenetic enzyme; upon phosphorylation by the kinase ACK1/TNK2, pSHP2 was escorted by androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation of histones H3 at Tyr54) epigenetic marks to trigger a transcriptional program of AR. Noonan Syndrome with Multiple Lentigines (NSML) patients, SHP2 knock-in mice, and ACK1 knockout mice presented dramatic increase in pY54-H3, leading to loss of AR transcriptome. In contrast, prostate tumors with high pSHP2 and pACK1 activity exhibited progressive downregulation of pY54-H3 levels and higher AR expression that correlated with disease severity. Overall, pSHP2/pY54-H3 signaling acts as a sentinel of AR homeostasis, explaining not only growth retardation, genital abnormalities and infertility among NSML patients, but also significant AR upregulation in prostate cancer patients.

Psychological distress and health behaviours in people living with and beyond cancer: a cross-sectional study.

This study aimed to examine whether psychological distress was cross-sectionally associated with meeting World Cancer Research Fund (WCRF) recommendations in people living with and beyond cancer. Participants were adults living with and beyond breast, prostate and colorectal cancer, participating in the baseline wave of the Advancing Survivorship after Cancer Outcomes Trial (ASCOT). Anxiety/depression was assessed using the EQ-5D-5L and dichotomised into any/no problems. WCRF recommendations were assessed via pedometers, 24-h dietary recalls, self-reported alcohol intake (AUDIT-C), and self-reported smoking status. Participants were categorised as meeting WCRF recommendations using the following cut-offs: average daily steps (≥ 10,000/day), average weekly aerobic steps (≥ 15,000/day), fruit and vegetables (≥ 400 g/day), fibre (≥ 30 g/day), red meat (< 500 g/week), processed meat (0 g/day), high calorie food (fat ≤ 33% of total daily energy intake and free sugar ≤ 5% of total daily energy intake), alcohol (≤ 14 units/week) and smoking (non-smoking). A composite health behaviour risk index (CHBRI) was calculated by summing the number of WCRF recommendations met (range: 0-9). Among 1348 participants (mean age = 64 years (SD = 11.4)), 41.5% reported anxiety/depression problems. The mean CHBRI score was 4.4 (SD = 1.4). Anxiety/depression problems were associated with lower odds of meeting WCRF recommendations for average daily steps (odds ratio (OR) = 0.73; 95% CI 0.55, 0.97), but not for any other health behaviour. Psychological distress is associated with lower adherence to WCRF recommendations for physical activity in people living with and beyond cancer. Physical activity may be a mechanism linking psychological distress and poorer outcomes among people living with and beyond cancer, and this should be explored in longitudinal studies.

Co-delivery of oncolytic virus and chemotherapeutic modality: Vincristine against prostate cancer treatment: A potent viro-chemotherapeutic approach.

Prostate cancer is a prevalent carcinoma among males, and conventional treatment options are often limited. Cytotoxic chemotherapy, despite its drawbacks, remains a mainstay. We propose a targeted co-delivery approach using nanoscale delivery units for Oncolytic measles virus (OMV) and vincristine (VC) to enhance treatment efficacy. The HA-coated OMV + VC-loaded TCs nanoformulation is designed for targeted oncolytic activity in prostate cancer. The CD44 expression analysis in prostate cancer cell lines indicates a significantly high expression in PC3 cells. The optimization of nanoformulations using Design of Expert (DOE) is performed, and the preparation and characterization of HA-coated OMV + VC-loaded TCs nanoformulations are detailed showing average particle size 397.2 ± 0.01 nm and polydispersity index 0.122 with zeta potential 19.7 + 0.01 mV. Results demonstrate successful encapsulation efficiency with 2.4 × 106 TCID50/Ml and sustained release of OMV and VC from the nanoformulation for up to 72 h. In vitro, assays reveal potent anticancer activity at 10 ± 0.71% cell viability in PC3 cells compared to 73 ± 0.66% in HPrEC and significant morphological changes at 90 µg/ml in dose and time-dependent manner. The co-formulation showed positive cell death 49.5 ± 0.02% at 50 µg PI/ml in PBS and 54.3% cell cycle arrest at the G2/M phase, 8.1% G0/G1 and 5.7% at S phase, with significant mitochondrial membrane potential (MMP) at 50 µg/ml, as assessed by flow cytometry (FACS). The surface-integrating ligand approach enhances the targeted delivery of the oncolytic virus and chemotherapeutic drug, presenting a potential alternative for prostate cancer treatment and suggested that co-administering VC and OMV in a nanoformulation could improve therapeutic outcomes while reducing chemotherapeutic drug doses.

Reducing Racial Inequalities in Prostate Cancer Treatment: Healthcare Access Barriers.

Inequalities in healthcare for patients with prostate cancer can result in treatment and mortality disparities. Despite Black men with prostate cancer having higher incidence and mortality from prostate cancer, the study by Hammarlund and colleagues found that they are less likely to receive appropriate treatment compared with their White counterparts. Given that Black men with prostate cancer have similar or better survival when participating in clinical trials or receiving equal treatment from an equal access to healthcare system, identifying factors contributing to inequitable treatment is essential to improve the overall health and survival of Black men with prostate cancer. See related article by Hammarlund and colleagues, Cancer Epidemiol Biomarkers Prev 2024;33:435-41.

Comparison of digital and analog [68Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

Seminal Papers in Urology: Darolutamide and survival in metastatic, hormone-sensitive prostate cancer.

The ARASENS trial recruited 1306 men with metastatic hormone sensitive prostate cancer. It investigated the effect of androgen deprivation therapy (ADT) and systemic therapy docetaxel in combination with a third novel drug - daralutamide, compared with placebo on overall survival. Triple therapy with ADT, docetaxel and darolutamide resulted in improved overall survival rates as compared with ADT, docetaxel and placebo (HR 0.68; 95% CI, 0.57-0.80; p < 0.001). The side effect profile for both treatments was similar. This randomised, double blinded, placebo controlled study, was assessed to have a low risk of bias using the Cochrane Risk of Bias 2 tool.

Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.