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Background: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. Methods: In this observational retrospective cohort study, 400 de novo metastatic hormone‐sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow‐up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan–Meier methods estimated overall survival (OS) and castration‐resistant prostate cancer (CRPC)‐free survival from mHSPC diagnosis date and a log‐rank test compared these outcomes by oligometastatic status. Results: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non‐omHSPC had higher median prostate‐specific antigen at diagnosis (151.7) than omHSPC (44.1). First‐line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non‐omHSPC (14%). More omHSPC patients received metastasis‐directed therapy/prostate radiation therapy (14%) versus non‐omHSPC (2%). Median OS and CRPC‐free survival (in months) were higher in omHSPC versus non‐omHSPC (44.4; 95% confidence interval [CI], 33.9–not estimated vs. 26.2; 95% CI, 20.5–32.5, p =.0089 and 27.6; 95% CI, 22.1–37.2 vs. 15.3; 95% CI, 12.8–17.9, p =.0049), respectively. Conclusions: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non‐omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non‐omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies. In this observational retrospective Veterans Affairs cohort study, 20% of men had de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC). Although first‐line (1L) novel hormonal therapy was similar between groups, 1L chemotherapy use was lower in omHSPC, more omHSPC patients received metastasis‐directed therapy/prostate radiation therapy, and median overall survival and time to castration resistance was longer in men with omHSPC than non‐omHSPC. [ABSTRACT FROM AUTHOR]

Background: Despite the rise in gender‐affirming care, our understanding of prostate cancer (PCa) in transgender women (TGW) remains in its infancy. Health disparities and lack of PCa awareness and screening are possible barriers to providing quality care for this population. In addition, the implication of hormonal manipulation for the aggressiveness of PCa in TGW is yet to be determined. Here, this study sought to compare oncological characteristics and survival outcomes between transgender and cisgender (CG) patients with PCa via two national data sets. Methods: The Veterans Affairs Informatics and Computing Infrastructure database (1999–2020) and the Surveillance, Epidemiology, and End Results–Medicare database (2010–2017) were reviewed. Demographic and clinical details were analyzed. Logistic regression analysis was performed on propensity score–matched groups to identify predictors of high‐risk disease and metastasis in patients with PCa. Groups were matched 5:1 (CG:TGW) on the basis of age, race, year of diagnosis, and Charlson Comorbidity Index score. Primary outcomes included metastatic presentation, high‐risk localized disease, overall survival (OS), and prostate cancer–specific mortality (PCSM). Results: A total of 1194 patients were included (199 TGW; 995 CG). Associations between transgender identity and metastatic presentation (odds ratio [OR], 0.38; p =.2), high‐risk localized disease (OR, 1.19; p =.50), or PCSM (hazard ratio [HR], 0.65; p =.3) were not detected. Transgender identity was associated with improved OS (HR, 0.67; p =.014). Conclusions: PCa‐specific outcomes seem comparable between TGW and CG men, although the study was underpowered to detect modest differences. Further investigation into the incidence and outcomes of PCa in TGW is warranted. Despite the increasing availability of gender‐affirming care, our understanding of prostate cancer (PCa) in transgender women (TGW) is limited. This study comparing oncological characteristics and survival outcomes between transgender and cisgender patients with PCa suggests comparable outcomes, which indicates the need for further investigation into PCa incidence and outcomes in TGW. [ABSTRACT FROM AUTHOR]

Background: Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. Methods: Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time‐to‐event outcomes (multivariable Fine‐Gray regression, with mortality considered a competing event) and recurrent‐event outcomes (multivariable negative binomial regression). Results: Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow‐up of 10.6 months (interquartile range: 5.3–19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53–0.93], p =.014), pneumonia (adjusted SHR 0.76 [0.59–0.99], p =.040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39–0.79], p =.001), but not urinary tract infection (adjusted SHR 0.91 [0.62–1.35], p =.643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. Conclusions: Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess. This study compared the risk of infections in patients with prostate cancer taking enzalutamide versus abiraterone. The results showed that enzalutamide users had a lower risk of sepsis, pneumonia, and cellulitis or skin abscess compared to those on abiraterone. [ABSTRACT FROM AUTHOR]

The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes. Forty-five radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the RCT protocol. The probability of biochemical failure (BF) was determined using a model from the RCT. The primary metric evaluated was delta BF (DBF = Participant BF – Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful. Eight patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. Of participant plans, 37% were noted to have an absolute increase in BF of 5% or more. Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients. [ABSTRACT FROM AUTHOR]

To study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiation therapy. Patients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity-modulated radiation therapy (moderate hypofractionated radiation therapy [MHRT], stereotactic body radiation therapy [SBRT]), were included in this study. Severity and duration of urinary symptoms observed during serial follow-up after at least 3 months from radiation therapy were graded per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 using information from a prospectively maintained institutional database. Impact of hypofractionation and other potential contributory factors on cumulative grade 2+ late urinary toxicity was analyzed with univariable and multivariable binary logistic regression. A total of 203 eligible patients were included (MHRT = 114, 64-68 Gy/25#; SBRT = 89, 35-37.5 Gy/5#). Median time from TURP to radiation therapy was 10 months (IQR, 7-16 months), similar for MHRT and SBRT. Overall, mean cavity volume was 1.17 cc (IQR, 0.5-1.35 cc), whereas in MHRT and SBRT groups it was 1.03 cc (IQR, 0.4-1.15 cc) and 1.27 cc (IQR, 0.5-1.4 cc), respectively. At a median follow-up of 37 months, cumulative grade 3 and grade 2 late urinary toxicity was 8.4% (n = 17) and 23.2% (n = 47), respectively. Grade 3 symptoms were observed at median 29 months (IQR, 19-62 months) after radiation therapy completion, lasting for a median duration of 8 months (IQR, 2-14 months). Hematuria (6.4%) and urinary obstruction (3.4%) were the chief grade 3 symptoms. Multivariable analysis for age, diabetes, pelvic radiation therapy, fraction size, prostate volume, TURP to radiation therapy duration, and TURP cavity volume showed no significant association with late grade 2+ urinary toxicity. In this large cohort of patients with prior TURP and treated with hypofractionated prostate radiation therapy, incidence of severe late urinary adverse effects was <10%, mainly hematuria or urinary obstruction. Most of these were temporary, and no significant contributory factors were identified for late urinary morbidity after TURP and radiation therapy. [ABSTRACT FROM AUTHOR]

For men with intermediate-risk prostate cancer treated with definitive therapy, the addition of androgen deprivation therapy (ADT) reduces the risk of distant metastasis and cancer-related mortality. However, the absolute benefit of ADT varies by baseline cancer risk. Estimates of prognosis have improved over time, and little is known about ADT decision making in the modern era. We sought to characterize variability and identify factors associated with intended ADT use within the Michigan Radiation Oncology Quality Consoritum (MROQC). Patients with localized prostate cancer undergoing definitive radiation therapy were enrolled from June 9, 2020, to June 26, 2023 (n = 815). Prospective data were collected using standardized patient, physician, and physicist forms. Intended ADT use was prospectively defined and was the primary outcome. Associations with patient, tumor, and practice-related factors were tested with multivariable analyses. Random intercept modeling was used to estimate facility-level variability. Five hundred seventy patients across 26 facilities were enrolled with intermediate-risk disease. ADT was intended for 46% of men (n = 262/570), which differed by National Comprehensive Cancer Network favorable intermediate-risk (23.5%, n = 38/172) versus unfavorable intermediate-risk disease (56.3%, n = 224/398; P <.001). After adjusting for the statewide case mix, the predicted probability of intended ADT use varied significantly across facilities, ranging from 15.4% (95% CI, 5.4%-37.0%) to 71.7% (95% CI, 57.0%-82.9%), with P <.01. Multivariable analyses showed that grade group 3 (OR, 4.60 [3.20-6.67]), ≥50% positive cores (OR, 2.15 [1.43-3.25]), and prostate-specific antigen 10 to 20 (OR, 1.87 [1.24-2.84]) were associated with ADT use. Area under the curve was improved when incorporating MRI adverse features (0.76) or radiation treatment variables (0.76), but there remained significant facility-level heterogeneity in all models evaluated (P <.05). Within a state-wide consortium, there is substantial facility-level heterogeneity in intended ADT use for men with intermediate-risk prostate cancer. Future efforts are necessary to identify patients who will benefit most from ADT and to develop strategies to standardize appropriate use. [ABSTRACT FROM AUTHOR]

Background and Purpose: Prostate cancer remains a major public health burden worldwide. Polo like kinase 4 (PLK4) has emerged as a promising therapeutic target in prostate cancer due to its key roles in cell cycle regulation and tumour progression. This study aims to develop and characterize the novel curcumin analogue NL13 as a potential therapeutic agent and PLK4 inhibitor against prostate cancer. Experimental Approach: NL13 was synthesized and its effects were evaluated in prostate cancer cells and mouse xenograft models. Kinome screening and molecular modelling identified PLK4 as the primary target. Antiproliferative and proapoptotic mechanisms were explored via cell cycle, apoptosis, gene and protein analyses. Key Results: Compared with curcumin, NL13 exhibited much greater potency in inhibiting PC3 (IC50, 3.51 μM vs. 35.45 μM) and DU145 (IC50, 2.53 μM vs. 29.35 μM) prostate cancer cells viability and PLK4 kinase activity (2.32 μM vs. 246.88 μM). NL13 induced G2/M cell cycle arrest through CCNB1/CDK1 down‐regulation and triggered apoptosis via caspase‐9/caspase‐3 cleavage. These effects were mediated by PLK4 inhibition, which led to the inactivation of the AKT signalling pathway. In mice, NL13 significantly inhibited tumour growth and modulated molecular markers consistent with in vitro findings, including decreased p‐AKT and increased cleaved caspase‐9/3. Conclusion and Implications: NL13, a novel PLK4‐targeted curcumin analogue, exerts promising anticancer properties against prostate cancer by disrupting the PLK4‐AKT‐CCNB1/CDK1 and apoptosis pathways. NL13 represents a promising new agent for prostate cancer therapy. [ABSTRACT FROM AUTHOR]

Objectives: To compare the image quality of 1.5T and 3T prostate MRIs of the same post-hip arthroplasty patients, with a specific focus on the degree of susceptibility artifacts. Methods: This single-center retrospective study included post-hip arthroplasty patients who underwent 1.5T prostate MRIs between 2021 and 2023, as well as comparative 3T prostate MRIs. Three blinded abdominal radiologists retrospectively reviewed their diffusion-weighted imaging (DWI, 50 s/mm2), T2-weighted imaging (T2WI), and dynamic contrast-enhanced imaging (DCE) to evaluate the image quality. The degree of susceptibility artifacts was categorized using a three-point scale, with 3 indicating the least artifact and 1 indicating the most. Image quality was also evaluated using Prostate Imaging Quality (PI-QUAL) version 2. The median of the three raters' scores was compared between 1.5T and 3T prostate MRIs using the Wilcoxon signed-rank test. The inter-rater agreement was evaluated using the multi-rater generalized kappa. Results: Twenty pairs of 1.5T and 3T prostate MRI examinations from 20 unique patients were included. The DWI susceptibility artifact score at 1.5T was significantly higher than at 3T (mean score ± standard deviation, 2.80 ± 0.41 vs. 2.35 ± 0.93, p = 0.014). In contrast, no significant differences were observed in the susceptibility artifact scores in T2WI and DCE, or in the PI-QUAL score. The inter-reader agreement in the susceptibility artifact score was moderate (multi-rater generalized kappa: 0.60) in DWI, perfect in T2WI (not applicable), and substantial (0.65) in DCE. The inter-reader agreement was fair (0.27) in the PI-QUAL score. Conclusion: Using 1.5T scanners may be preferable to reduce susceptibility artifacts from hip prostheses in DWI. [ABSTRACT FROM AUTHOR]

Objectives: With the widespread clinical application of prostate magnetic resonance imaging (MRI), there has been an increasing demand for lesion detection and accurate diagnosis in prostate MR, which relies heavily on satisfactory image quality. Focusing on the primary sequences involved in Prostate Imaging Reporting and Data System (PI-RADS), this study have evaluated common quality issues in clinical practice (such as signal-to-noise ratio (SNR), artifacts, boundaries, and enhancement). The aim of the study was to determine the impact of image quality on clinically significant prostate cancer (csPCa) detection, positive predictive value (PPV) and radiologist's diagnosis in different sequences and prostate zones. Methods: This retrospective study included 306 patients who underwent prostate MRI with definitive pathological reports from February 2021 to December 2022. All histopathological specimens were evaluated according to the recommendations of the International Society of Urological Pathology (ISUP). An ISUP Grade Group ≥ 2 was considered as csPCa. Three radiologists from different centers respectively performed a binary classification assessment of image quality in the following ten aspects: (1) T2WI in the axial plane: SNR, prostate boundary conditions, the presence of artifacts; (2) T2WI in the sagittal or coronal plane: prostate boundary conditions; (3) DWI: SNR, delineation between the peripheral and transition zone, the presence of artifacts, the matching of DWI and T2WI images; (4) DCE: the evaluation of obturator artery enhancement, the evaluation of dynamic contrast enhancement. Fleiss' Kappa was used to determine the inter-reader agreement. Wilson's 95% confidence interval (95% CI) was used to calculate PPV. Chi-square test was used to calculate statistical significance. A p-value < 0.05 was considered statistically significant. Results: High-quality images had a higher csPCa detection rate (56.5% to 64.3%) in axial T2WI, DWI, and DCE, with significant statistical differences in SNR in axial T2WI (p 0.002), the presence of artifacts in axial T2WI (p 0.044), the presence of artifacts in DWI (p < 0.001), and the matching of DWI and T2WI images (p < 0.001). High-quality images had a higher PPV (72.5% to 78.8%) and showed significant statistical significance in axial T2WI, DWI, and DCE. Additionally, we found that PI-RADS 3 (24.0% to 52.9%) contained more low-quality images compared to PI-RADS 4-5 (20.6% to 39.3%), with significant statistical differences in the prostate boundary conditions in axial T2WI (p 0.048) and the presence of artifacts in DWI (p 0.001). Regarding the relationship between csPCa detection and image quality in different prostate zones, this study found that significant statistical differences were only observed between high- (63.5% to 75.7%) and low-quality (30.0% to 50.0%) images in the peripheral zone (PZ). Conclusion: Prostate MRI quality may have an impact on the diagnostic performance. The poorer image quality is associated with lower csPCa detection rates and PPV, which can lead to an increase in radiologist's ambiguous diagnosis (PI-RADS 3), especially for the lesions located at PZ. [ABSTRACT FROM AUTHOR]

The broad range of disease aggressiveness together with imperfect screening, diagnostic, and treatment options in prostate cancer (PCa) makes medical decision-making complex. The primary goal of a multidisciplinary conference is to improve patient outcomes by combining evidence-based data and expert opinion to discuss optimal management, including for those patients with challenging presentations. The primary purpose of the genitourinary imaging specialist in the prostate cancer multidisciplinary conference is to use imaging findings to reduce uncertainty by answering clinical questions. In this review, we discuss the role and the opportunities for an imaging specialist to add value in the care of men with prostate cancer discussed at multidisciplinary conferences. [ABSTRACT FROM AUTHOR]

Introduction: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is revolutionizing the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) patients. This study aimed to establish patient-specific radiation dosimetry for [177Lu]Lu-PSMA-617 RLT in Iranian patients with mCRPC. Method: Twelve biopsy-proven prostate cancer patients (aged 68.73 ± 5.26 yr) underwent 6.62 ± 0.36 GBq [177Lu]Lu-PSMA-617 RLT. Post-therapy whole-body planar scans were acquired approximately at 4, 48, and 72 h post-administration, alongside a single SPECT/CT around 48 h using Siemens Symbia T2 to obtain cumulated activity. An imaging protocol and dosimetry approach were designed to balance between time efficacy and accuracy in post-therapeutic dosimetry. Using accurate activity calibration, S-values were calculated by importing SPECT/CT images as the source/geometry into the Geant4 application for the tomographic emission (GATE) Monte Carlo (MC) toolkit. The Medical Internal Radiation Dose (MIRD) scheme was followed for subsequent absorbed dose (AD) calculations in organs at risk (OAR) and tumoral lesions using the dose actor and accumulated activities for precise dose estimations. Results: Using the MC approach, the mean ADs to the liver, spleen, right and left kidneys, and tumor lesions were 0.11 ± 0.04 Gy/GBq, 0.08 ± 0.03 Gy/GBq, 0.34 ± 0.09 Gy/GBq, 0.34 ± 0.10 Gy/GBq, and 0.83 ± 0.54 Gy/GBq, respectively. Notably, tumoral lesions demonstrated significantly higher ADs, indicating enhanced uptake of radiopharmaceuticals by malignant cells. Conclusions: This study indicates that the ADs of OARs and tumoral lesions from [177Lu]Lu-PSMA-617 RLT in patients with mCRPC are consistent with existing literature. The dosimetry findings suggest that increasing the administered activity of [177Lu]Lu-PSMA-617 RLT is feasible and does not pose a significant risk of adverse effects on OARs, as supported by our data. However, to validate the safety and efficacy of higher doses, further clinical follow-up studies are recommended. [ABSTRACT FROM AUTHOR]

MRI has gained prominence in the diagnostic workup of prostate cancer (PCa) patients, with the Prostate Imaging Reporting and Data System (PI-RADS) being widely used for cancer detection. Beyond PI-RADS, other MRI-based scoring tools have emerged to address broader aspects within the PCa domain. However, the multitude of available MRI-based grading systems has led to inconsistencies in their application within clinical workflows. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) assesses the likelihood of clinically significant radiological changes of PCa during active surveillance, and the Prostate Imaging for Local Recurrence Reporting (PI-RR) scoring system evaluates the risk of local recurrence after whole-gland therapies with curative intent. Underlying any system is the requirement to assess image quality using the Prostate Imaging Quality Scoring System (PI-QUAL). This article offers practicing radiologists a comprehensive overview of currently available scoring systems with clinical evidence supporting their use for managing PCa patients to enhance consistency in interpretation and facilitate effective communication with referring clinicians. Key Points: Assessing image quality is essential for all prostate MRI interpretations and the PI-QUAL score represents the standardized tool for this purpose. Current urological clinical guidelines for prostate cancer diagnosis and localization recommend adhering to the PI-RADS recommendations. The PRECISE and PI-RR scoring systems can be used for assessing radiological changes of prostate cancer during active surveillance and the likelihood of local recurrence after radical treatments respectively. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) incidence is reportedly lower in men with HIV compared to men without HIV for unknown reasons. We describe PCa incidence by HIV status in Medicaid beneficiaries, allowing for comparison of men with and without HIV who are similar with respect to socioeconomic characteristics and access to healthcare. Men (N = 15,167,636) aged 18–64 with ≥7 months of continuous enrollment during 2001–2015 in 14 US states were retained for analysis. Diagnoses of HIV and PCa were identified using non-drug claims. We estimated cause-specific (csHR) comparing incidence of PCa by HIV status, adjusted for age, race-ethnicity, state of residence, year of enrollment, and comorbid conditions, and stratified by age and race-ethnicity. Hazard of PCa was lower in men with HIV than men without HIV (csHR = 0.89; 95% CI: 0.80, 0.99), but varied by race-ethnicity, with similar observations among non-Hispanic Black (csHR = 0.79; 95% CI: 0.69, 0.91) and Hispanic (csHR = 0.85; 95% CI: 0.67, 1.09), but not non-Hispanic white men (csHR = 1.17; 95% CI: 0.91, 1.50). Findings were similar in models restricted to men aged 50–64 and 40–49, but not in men aged 18–39. Reported deficits in PCa incidence by HIV status may be restricted to specific groups defined by age and race ethnicity. [ABSTRACT FROM AUTHOR]

Objectives: To test the performance of ex vivo fluorescence confocal microscopy (FCM; Vivascope 2500M‐G4), as compared to intra‐operative frozen section (IFS) analysis, to evaluate surgical margins during robot‐assisted radical prostatectomy (RARP), with final pathology as the reference standard. Methods: Overall, 54 margins in 45 patients treated with RARP were analysed with: (1) ex vivo FCM; (2) IFS analysis; and (3) final pathology. FCM margins were evaluated by two different pathologists (experienced [M.I.: 10 years] vs highly experienced [G.R.: >30 years]) as strongly negative, probably negative, doubtful, probably positive, or strongly positive. First, inter‐observer agreement (Cohen's κ) between pathologists was tested. Second, we reported the sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV) of ex vivo FCM. Finally, agreement between ex vivo FCM and IFS analysis (Cohen's κ) was reported. For all analyses, four combinations of FCM results were evaluated. Results: At ex vivo FCM, the inter‐observer agreement between pathologists ranged from moderate (κ = 0.74) to almost perfect (κ = 0.90), according to the four categories of results. Indeed, at ex vivo FCM, the highly experienced pathologist reached the best balance between sensitivity (70.5%) specificity (91.8%), PPV (80.0%) and NPV (87.1%). Conversely, on IFS analysis, the sensitivity, specificity, PPV and NPV were, respectively, 88.2% vs 100% vs 100% vs 94.8%. The agreement between the ex vivo FCM and IFS analyses ranged from moderate (κ = 0.62) to strong (κ = 0.86), according to the four categories of results. Conclusion: Evaluation of prostate margins at ex vivo FCM appears to be feasible and reliable. The agreement between readers encourages its widespread use in daily practice. Nevertheless, as of today, the performance of FCM seems to be sub‐par when compared to the established standard of care (IFS analysis). [ABSTRACT FROM AUTHOR]

Objectives: To assess artificial intelligence (AI) ability to evaluate intraprostatic prostate cancer (PCa) on prostate‐specific membrane antigen positron emission tomography (PSMA PET) scans prior to active treatment (radiotherapy or prostatectomy). Materials and Methods: This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO identifier: CRD42023438706). A search was performed on Medline, Embase, Web of Science, and Engineering Village with the following terms: 'artificial intelligence', 'prostate cancer', and 'PSMA PET'. All articles published up to February 2024 were considered. Studies were included if patients underwent PSMA PET scan to evaluate intraprostatic lesions prior to active treatment. The two authors independently evaluated titles, abstracts, and full text. The Prediction model Risk Of Bias Assessment Tool (PROBAST) was used. Results: Our search yield 948 articles, of which 14 were eligible for inclusion. Eight studies met the primary endpoint of differentiating high‐grade PCa. Differentiating between International Society of Urological Pathology (ISUP) Grade Group (GG) ≥3 PCa had an accuracy between 0.671 to 0.992, sensitivity of 0.91, specificity of 0.35. Differentiating ISUP GG ≥4 PCa had an accuracy between 0.83 and 0.88, sensitivity was 0.89, specificity was 0.87. AI could identify non‐PSMA‐avid lesions with an accuracy of 0.87, specificity of 0.85, and specificity of 0.89. Three studies demonstrated ability of AI to detect extraprostatic extensions with an area under curve between 0.70 and 0.77. Lastly, AI can automate segmentation of intraprostatic lesion and measurement of gross tumour volume. Conclusion: Although the current state of AI differentiating high‐grade PCa is promising, it remains experimental and not ready for routine clinical application. Benefits of using AI to assess intraprostatic lesions on PSMA PET scans include: local staging, identifying otherwise radiologically occult lesions, standardisation and expedite reporting of PSMA PET scans. Larger, prospective, multicentre studies are needed. [ABSTRACT FROM AUTHOR]

This article from BJU International presents a case study of a 74-year-old patient with castration-resistant prostate cancer who underwent stereotactic body radiotherapy (SBRT) for 20 metastatic lesions. The patient had a complex treatment history involving various therapies before receiving SBRT, which served as a bridge therapy while awaiting 177Lu-PSMA-617 therapy. The SBRT treatment was delivered without reported side effects, resulting in a decrease in PSA levels and a partial or complete response at treated sites. The article discusses the efficacy and challenges of SBRT in treating multiple metastatic sites, highlighting the evolving landscape of prostate cancer therapy. [Extracted from the article]

Summary: Androgen Deprivation Therapy (ADT) increases long-term fracture risk in prostate cancer. Our study showed a higher fracture risk within six months of ADT use, and current use was associated with a higher risk of fragility fractures. Attention is needed for the prevention of fragility fractures at the start of ADT. Purpose: Androgen Deprivation Therapy (ADT) is known to increase long-term fracture risk in men with prostate cancer (PCa), although the risk of fragility fractures remains unclear. This study aims to evaluate the risk of fragility and malignancy-related fractures in men with PCa treated with ADT. Methods: We conducted a retrospective cohort study of men with PCa. Follow-up time was divided into 30-day intervals and exposure (current, past, or no-ADT use). Current ADT use was stratified by duration of ADT use (≤ 182 days, 183–730 days, and > 730 days). Cause-specific Cox proportional hazard models were used to estimate the risk of fractures. Results: We included 471 patients (mean age 70.5 (± 8.3) years). The mean follow-up time was 5.0 (± 1.7) years in patients who never started ADT, 3.4 (± 2.3) years and 4.1 (± 2.0) years in patients who started ADT at baseline and during follow-up, respectively. In total, 60 patients had a fracture, 48 (80%) fragility, and 12 (20%) malignancy-related fractures. Current ADT use was associated with a higher risk of all fractures (HR 5.10, 95% CI 2.34–11.13) and fragility fractures (HR 3.61, 95% CI 1.57–8.30). The association with malignancy-related fractures could not be studied due to no events during no-ADT use. There was an increased risk of all fractures with longer duration of ADT use. Conclusions: Current ADT use was associated with a higher risk of fragility fractures than no-ADT use. A higher fracture risk was observed within the first six months of ADT use and persisted for longer durations. [ABSTRACT FROM AUTHOR]

Purpose: Robotic-assisted radical prostatectomy (RARP) impairs erectile function (EF) due to the surgical procedure and non-surgical factors. Non-surgical factors may contribute to recovery of erectile function (EFR) after RARP. This study assessed the role of non-surgical factors including physical activity in baseline EF and EFR after prostatectomy. Methods: Patient Reported Measure Outcomes questionnaires from patients with localized prostate carcinoma who underwent a RARP with a postoperative follow up (FU) of 3 years. EFR was defined as at least 70% EF recovery of baseline IIEF-EF. Physical activities was defined as no activity at all, once a week and ≥ 2 a week. Results: In total 804 patients were included. At baseline, age, lower urinary tract symptoms (LUTS), having a partner and former smoking were significantly associated (p <.001) of EF. Postoperatively, the extent of nerve sparing and baseline EF were strongly associated with EFR (p <.001). Physical activity ≥ 2 a week predicted EF but only beyond 6 months of FU (p =.005, p =.028 and p =.007 at 1, 2 and 3 year FU respectively). Comorbidities, BMI and the use of medications known to affect EF were not predictive of EFR. Conclusions: Age, LUTS, having a partner and former smoking were baseline associated with EF prior to RARP. Baseline EF and extent of nerve sparing jointly predicted EFR. Intensive physical activity was an independent predictor of EFR beyond the first year after RARP. Our findings suggests that besides clinical factors, lifestyle may also play a role in recovery of erectile function. [ABSTRACT FROM AUTHOR]

Introduction: Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer. Method: We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008–2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008–2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3 years after cancer with Cochram-Armitage tests and multivariable logistic regression. Cancer cohorts were analyzed separately. Results: We included 3595 patients in all six cohorts (in Clinformatics® 503 with colorectal, 468 with lung, and 440 with prostate cancer; in SEER-Medicare 580 with colorectal, 1010 with lung, and 594 with prostate cancer). No significant increase was observed in bDMARD or TNFi utilization over time. Overall, use of bDMARD within the first 3 years of follow-up ranged from 16.7% (Clinformatics® lung cohort) to 29.7% (SEER-Medicare colorectal cohort). The major predictor of bDMARD utilization was prior use in the 3 months before cancer diagnosis (p < 0.001 for all cancers) and earlier cancer stage (p < 0.001 in colorectal and lung cancer and p = 0.05 in prostate cancer). Conclusions: Use of bDMARD in patients with RA and recently diagnosed common cancers has not increased since 2008. Additional evidence on the safety of bDMARD in patients with early cancer is needed to ensure appropriate management of their RA. Key Points • Use of bDMARD and TNFi in patients with RA and early colorectal, lung, or prostate cancer has been stable since 2008, with no significant increases over time. • The major determinant of receiving bDMARD after cancer diagnosis was prior treatment with bDMARD in the prior 3 months before cancer. • Patients with advanced cancer stage and distant metastases were less likely to receive bDMARD and TNFi than those at early stages of disease. [ABSTRACT FROM AUTHOR]

Background: Phospholipase A2 (PLA2) is a large family of enzymes involved in the inflammatory process that catalyzes the hydrolysis of membrane phospholipids, leading to the production of free fatty acids and lysophospholipids, starting the arachidonic acid cascade. Their expression has been related to the behavior of several cancers. Our objective is to search for PLA2 expression in prostate cancer (PCa) tissue that correlates with prognosis and survival. Methods: Using qRT-PCR, we analyzed the expression levels of PLA2G1B, PLA2G2A, PLA2G2D, PLA2G4A, PLA2G4B, PLA2G4C, PLA2G4D, PLA2G4E, PLA2G4F, PLA2G6, PLA2G7, PLA2G16, PNPLA1, and PNPLA2 in PCa tissue from 108 patients submitted to radical prostatectomy, followed by a mean time of 163 months. Results: All PLA2 was overexpressed in PCa compared to normal tissue. Interestingly, higher expression of some PLA2 was related to favorable prognostic factors: lower levels of PSA (PLA2G2A, PLA2G4D), lower rates of lymph node metastasis (PLA2G16 and PLA2G1B), and organ-confined disease (PLA2G4A). Most importantly, PLAG4B was independently related to longer disease-free survival. Conclusion: This is the first study exploring comprehensively the expression levels of PLA2 in PCa, showing that the higher expression of some PLA2 should be used as biomarkers of good prognosis and longer disease-free survival. [ABSTRACT FROM AUTHOR]

Radionuclide therapy, in particular peptide receptor radionuclide therapy (PRRT), has emerged as a valuable means to combat malignant tumors. The specific affinity of ACUPA peptide toward prostate-specific membrane antigen (PSMA) renders the successful development of PRRT for prostate cancer. The clinical outcome of PRRT is, however, generally challenged by moderate tumor uptake and off-target toxicity. Here, we report on a novel design of Sigma-1 receptor and PSMA dual-receptor targeted peptide (S1R/PSMA-P) for superior radionuclide imaging and therapy of prostate cancer. S1R/PSMA-P was acquired with good purity and could efficiently be labeled with 177Lu to yield 177Lu-S1R/PSMA-P with high specific activity and radiostability. Interestingly, 177Lu-S1R/PSMA-P revealed greatly enhanced affinity to LNCaP cells over single-targeted control 177Lu-PSMA-617. The single photon emission computed tomography (SPECT) imaging demonstrated exceptional uptake and retention of 177Lu-S1R/PSMA-P in LNCaP tumor, affording about 2-fold better tumor accumulation while largely reduced uptake by most normal tissues compared to 177Lu-PSMA-617. The selective uptake in LNCaP tumor was also visualized by positron emission tomography (PET) with 68Ga-S1R/PSMA-P. In accordance, a single and low dosage of 177Lu-S1R/PSMA-P at 11.1 MBq effectively suppressed tumor growth without causing apparent side effects. This dual-targeting strategy presents an appealing radionuclide therapy for malignant tumors. Sigma-1 receptor and PSMA dual-receptor targeted peptide (S1R/PSMA-P) labeled with 177Lu or 68Ga can efficiently target and bind to LNCaP prostate cancer cells, inducing superior radionuclide therapy and imaging of prostate tumor in mice. [Display omitted] [ABSTRACT FROM AUTHOR]

Sustained release microspheres loaded with goserelin are regarded as a promising candidate for treating prostate cancer and other sex hormone diseases. However, their widespread adoption has been hindered by issues such as wide particle size distribution and unstable release characteristics. To address these challenges, we employed a combination of the solid-in-oil-in-water microspheres preparation approach (S/O/W) and innovative premix membrane emulsification technology and deeply investigated the effects of four key parameters on the loaded performance of microspheres and the microscopic mechanisms behind them. With this approach, we successfully produced goserelin-loaded sustained release microspheres of narrow particle size distribution (Span 0.642), remarkable encapsulation efficiency (DL = 4.23 %, EE = 93.98 %), low initial burst release (about 0.50 % within 2 h), and compatibility with small injection needles (23-G, inner diameter 0.33 mm, outer diameter 0.64 mm, maximal force 59 N). In the animal model(administered dose, 2.4 mg·Kg−1), goserelin long-acting sustained release microspheres sustained release for over 32 days, maintaining effective concentrations above 2 ng·mL−1, and effectively reduced serum testosterone concentrations to castration levels (<1.0 ng·mL−1) by day 4, maintaining this inhibition for up to 21 days, exhibiting comparable efficacy to the positive control group. In vivo release kinetics analysis revealed that goserelin-loaded sustained release microspheres exhibited a release pattern dominated by diffusion with corrosion assistance in vivo. In summary, the systematic and comprehensive evaluation of uniform-sized goserelin-loaded sustained release microspheres has highlighted their excellent translational potential, and the study herein may provide new strategies and ideas for the development of microsphere dosage forms. [Display omitted] • Developed uniform-sized goserelin microspheres (GOS-M) with high encapsulation efficiency. • Achieved low initial burst release and sustained release for over 32 days in vivo. • Uniform-sized GOS-M adapted to 23-G needles, ideal for low-pain administration. • Offers New strategies for microsphere release regulation and prescription screening. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationships between eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations and prostate cancer development and progression. This study included 88 patients diagnosed with prostate cancer and 91 healthy controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to determine the genotype distributions of eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations. In our study, the CC homozygous genotype of eNOS T786C gene variation was determined to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 2.343, 95%Cl: 0.990–5.544, p = 0.026), while the CT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was found to be significantly higher (OR: 0.589, 95%Cl: 0.325–1.068, p = 0.041). In addition, while the TT homozygous genotype of the eNOS G894T gene variation was found to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 9.068, 95%Cl: 4.396–18.777, p < 0.001), the GT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was determined significantly higher (OR: 0.227, 95%Cl: 0.121–0.427, p < 0.001). For eNOS (4VNTR (4a/b) - G894T) gene variations, aa-TT (p = 0.042) and bb-TT (p < 0.001) haplotype frequencies were significantly higher in the prostate cancer patient group, while aa-GT (p = 0.017), bb-GG (p = 0.049) and bb-GT (p < 0.001) haplotype frequencies were found to be significantly higher in the healthy control group. For eNOS (4VNTR (4a/b) - T786C) gene variations, the bb-CC haplotype frequency was determined to be significantly higher in the patient group (p = 0.049), while the bb-CT haplotype frequency was determined to be significantly higher in the control group (p = 0.008). For eNOS (T786C -G894T) gene variations, TT-TT (p < 0.001) and CC-TT (p = 0.025) haplotype frequencies were found to be significantly higher in the patient group. On the other hand, TT-GT (p = 0.002) and CT-GT (p < 0.001) haplotype frequencies were determined to be significantly higher in the control group. The aa genotype of the intron 4 VNTR (4a/b) gene variation was determined to be significantly higher at Gleason score ≥7 compared to Gleason score <7 (OR: 0.184, 95%Cl: 0.050–0.677, p = 0.005). PSA levels were determined significantly higher in patients with Gleason score 7 and above (p = 0.008). The risk of developing prostate cancer was found to be significantly higher in patients carrying the CC homozygous mutant genotype of the eNOS T786C gene variation (p = 0.024) and in patients carrying the TT homozygous genotype of the G894T gene variation (p = 0.021). In our study, the CC homozygous genotype of the eNOS T786C gene variation was determined as a genetic risk factor for the development of prostate cancer, while the CT heterozygous genotype was determined as a protective factor against prostate cancer. For the eNOS G894T gene variation, the TT homozygous genotype was determined as a genetic risk factor for the development of prostate cancer, while the GT heterozygous genotype was determined as a protective factor against prostate cancer. Additionally, for eNOS (4VNTR (4a/b) - G894T) gene variations, aa-TT and bb-TT haplotypes have been identified as genetic risk factors for the development of prostate cancer, while aa-GT, bb-GG and bb-GT haplotypes have been identified as protective factors against the disease has been determined. For eNOS (4VNTR (4a/b) - T786C) gene variations, the bb-CC haplotype was determined as a genetic risk factor in the development of prostate cancer, while the bb-CT haplotype was determined as a protective factor against the disease. TT-TT and CC-TT haplotypes for eNOS (T786C -G894T) gene variations have been identified as genetic risk factors for the development of prostate cancer. In contrast, TT-GT and CT-GT haplotypes were found to be protective factors against the disease. The aa genotype of the intron 4 VNTR (4a/b) gene variation has also been identified as an important genetic risk factor in prostate cancer progression. Significantly increased PSA levels in patients with Gleason score 7 and above, and significantly increased PSA levels in patients carrying the CC and TT homozygous mutant genotype for T786C and G894T gene variations were determined as important risk factors. It is thought that the genetic biomarkers in our study may play a role as personalized therapeutic agents in slowing down the development of prostate cancer, increasing the effectiveness of treatment in prostate cancer, affecting the responses to drugs that regulate NO signaling, predetermining genetic predisposition to prostate cancer, and risk assessment in patients with prostate cancer. • In our study, the CC homozygous genotype of the eNOS T786C gene variation was determined as a genetic risk factor for the development of prostate cancer, while the CT heterozygous genotype was determined as a protective factor against prostate cancer. For eNOS G894T gene variation, the TT homozygous genotype was determined as a genetic risk factor for the development of prostate cancer, while the GT heterozygous genotype was determined as a protective factor against prostate cancer. • For (4a/b - G894T) gene variations, aa-TT and bb-TT haplotypes have been identified as genetic risk factors for development of prostate cancer, while aa-GT, bb-GG and bb-GT haplotypes have been determined as protective factors against the disease. For (4a/b - T786C) gene variations, the bb-CC haplotype was determined as a genetic risk factor in the development of prostate cancer, while the bb-CT haplotype was determined as a protective factor against the disease. TT-TT and CC-TT haplotypes for (T786C-G894T) gene variations have been identified as genetic risk factors in the development of prostate cancer. In contrast, TT-GT and CT-GT haplotypes were found to be protective factors against the disease. • The aa genotype of the (4a/b) gene variation has also been identified as an important genetic risk factor in prostate cancer progression. • PSA levels were determined significantly higher in prostate cancer patients with a Gleason score of 7 and above. In addition, the risk of developing prostate cancer was determined to be significantly higher in patients carrying the CC homozygous mutant genotype of the T786C gene variation and the TT homozygous mutant genotype of the G894T gene variation. • Due to its versatile and diverse effects, NO is important as new anticancer strategies in slowing down cancer growth and increasing cancer treatment efficacy. eNOS regulation and NO production are affected by eNOS functional genetic variations, and these genetic variations are important in affecting the response to drugs that regulate NO signaling. It is thought that our findings may be effective in risk assessment and development of personalized therapeutic strategies in prostate cancer patients. [ABSTRACT FROM AUTHOR]

Propofol has become a microtubule‐stabilizing drug for prostate cancer (PC) therapy, but propofol resistance impairs the therapeutic effect. This study aimed to explore the regulatory mechanism of propofol in the pathogenesis of PC through mechanisms involving N6‐methyladenosine (m6A) modification. The changes in PC cell malignancy were evaluated by means of transwell, cell counting kit 8 (CCK‐8), western blotting and tumour xenograft model assays. Long noncoding RNA TRHDE‐AS1 and m6A methyltransferase METTL14 expression levels were determined via reverse transcription quantitative polymerase chain reaction (RT‐qPCR). The m6A modification of TRHDE‐AS1 which was mediated by METTL14 was confirmed by conducting methylated RNA immunoprecipitation (MeRIP) assay. We observed that propofol (200 μM) inhibited PC cell malignancy in vivo and in vitro, elucidating that it impaired cell proliferation, migration and tumour growth but induced apoptosis. TRHDE‐AS1 expression was observed to be lower in PC cells and tissues, and propofol induced TRHDE‐AS1 upregulation in PC cells. Propofol was capable of reversing the tumour‐promoting effect of TRHDE‐AS1 knockdown in PC cells. Additionally, METTL14 was upstream of TRHDE‐AS1 to induce m6A modification of TRHDE‐AS1 in PC cells. Collectively, our results show that propofol prevents PC progression by upregulating TRHDE‐AS1 expression and METTL14 is involved in the m6A modification of TRHDE‐AS1. These findings suggest that TRHDE‐AS1 may be a potential therapeutic target for the improvement of propofol's therapeutic effect. [ABSTRACT FROM AUTHOR]

Extraprostatic extension (EPE) of prostate cancer is usually reported as either focal (F‐EPE) or established (E‐EPE), but data on the implication for outcomes of this subdivision are conflicting and no systematic review (SR) evaluating this exists. This SR aims to address this gap in the literature, focusing on the impact of F‐EPE and E‐EPE on outcome in radical prostatectomy (RP) patients. Searches on Embase, Medline(R), and Pubmed databases were conducted. Studies were included if they investigated the extent of EPE in RP patients and correlated this with defined outcomes (biochemical recurrence [BCR], death, metastasis). Quality was assessed using the Newcastle‐Ottawa Scale. A random effects model was used for studies reporting hazard ratios (EPE extent and biochemical recurrence). 24 studies, including 49,187 men, were included. Six studies were of high quality. 20 studies reported how they measured EPE. 13 studies reported that the extent of EPE was associated significantly with BCR. Meta‐analysis showed there was a significant correlation between BCR and both F‐EPE and E‐EPE when compared to organ‐confined disease; no significant difference was found between F‐EPE and E‐EPE. This is the only SR to investigate the extent of EPE on outcomes after RP. EPE alone predicts outcome, but the value of subdivision by extent could not be demonstrated. Comparisons are limited due to variability in EPE assessment and in the methods used to report outcomes in the literature. Further work to standardize EPE reporting methods, in larger cohorts, may be helpful to resolve remaining questions. [ABSTRACT FROM AUTHOR]

Intraoperative frozen section (IFS) is used with the intention to improve functional and oncological outcomes for patients undergoing radical prostatectomy (RP). High resource requirements of IFS techniques such as NeuroSAFE may preclude widespread adoption, even if there are benefits to patients. Recent advances in fresh‐tissue microscopic digital imaging technologies may offer an attractive alternative, and there is a growing body of evidence regarding these technologies. In this narrative review, we discuss some of the familiar limitations of IFS and compare these to the attractive counterpoints of modern digital imaging technologies such as the speed and ease of image generation, the locality of equipment within (or near) the operating room, the ability to maintain tissue integrity, and digital transfer of images. Confocal laser microscopy (CLM) is the modality most frequently reported in the literature for margin assessment during RP. We discuss several imitations and obstacles to widespread dissemination of digital imaging technologies. Among these, we consider how the 'en‐face' margin perspective will challenge urologists and pathologists to understand afresh the meaning of positive margin significance. As a part of this, discussions on how to describe, categorize, react to, and evaluate these technologies are needed to improve patient outcomes. Limitations of this review include its narrative structure and that the evidence base in this field is relatively immature but developing at pace. [ABSTRACT FROM AUTHOR]

Background and purpose: Castration‐resistant prostate cancer (CRPC) is a common male malignancy that requires new therapeutic strategies due to acquired resistance to its first‐line treatment, docetaxel. The benefits of vitamin D on prostate cancer (PCa) progression have been previously reported. This study aimed to investigate the effects of vitamin D on chemoresistance in CRPC. Experimental approach: Structure function relationships of potent vitamin D analogues were determined. The combination of the most potent analogue and docetaxel was explored in chemoresistant primary PCa spheroids and in a xenograft mouse model derived from a patient with a chemoresistant CRPC. Key results: Here, we show that Xe4MeCF3 is more potent than the natural ligand to induce vitamin D receptor (VDR) transcriptional activities and that it has a larger therapeutic window. Moreover, we demonstrate that VDR agonists restore docetaxel sensitivity in PCa spheroids. Importantly, Xe4MeCF3 reduces tumour growth in a chemoresistant CRPC patient‐derived xenograft. In addition, this treatment targets signalling pathways associated with cancer progression in the remaining cells. Conclusion and implications: Taken together, these results unravel the potency of VDR agonists to overcome chemoresistance in CRPC and open new avenues for the clinical management of PCa. [ABSTRACT FROM AUTHOR]

Biochemical recurrence (BCR) is common in prostate cancer (PCa), and patients with BCR usually have a poor prognosis. Cuproptosis is a unique type of cell death, and copper homeostasis is crucial to the occurrence and development of malignancies. The present study aimed to explore the prognostic value of cuproptosis-related long non-coding RNAs (lncRNAs; CRLs) in PCa and to develop a predictive signature for forecasting BCR in patients with PCa. Using The Cancer Genome Atlas database, transcriptomic, mutation and clinical data were collected from patients with PCa. A total of 121 CRLs were identified using Pearson's correlation coefficient. Subsequently, a 6-CRL signature consisting of AC087276.2, CNNM3-DT, AC090198.1, AC138207.5, METTL14-DT and LINC01515 was created to predict the BCR of patients with PCa through Cox and least absolute shrinkage and selection operator regression analyses. Kaplan-Meier curve analysis demonstrated that high-risk patients had a low BCR-free survival rate. In addition, there was a substantial difference between the high- and low-risk groups in the immune microenvironment, immune therapy, drug sensitivity and tumor mutational burden. A nomogram integrating the Gleason score, 6-CRL signature and clinical T-stage was established and evaluated. Finally, the expression of signature lncRNAs in PCa cells was verified through reverse transcription-quantitative PCR. In conclusion, the 6-CRL signature may be a potential tool for making predictions regarding BCR in patients with PCa, and the prognostic nomogram may be considered a practical tool for clinical decision-making. [ABSTRACT FROM AUTHOR]

The incidence of prostate cancer is increasing, and its poor prognosis is associated with metadherin overexpression; however, its molecular mechanisms are unclear. This study used Western blot, quantitative real-time polymerase chain reaction, immunofluorescence, and tumorigenicity assays to investigate metadherin and epithelial-mesenchymal transition in prostate cancer. We found that metadherin was highly expressed in prostate cancer tissues, especially PC-3 cells. Metadherin overexpression promoted t epithelial-mesenchymal transition and tumor growth. Bioinformatics analysis and assays revealed that lymphoid enhancer-binding factor 1 directly activates the metadherin promoter. The epithelial- mesenchymal transition and tumorigenicity were suppressed by the silencing of lymphoid enhancer-binding factor 1; however, these effects were reversed by metadherin overexpression. Vitamin D treatment downregulated metadherin and lymphoid enhancer-binding factor 1, counteracting lymphoid enhancer-binding factor 1-induced metadherin upregulation. Our findings indicate that metadherin enhances epithelial-mesenchymal transition and tumorigenicity through lymphoid enhancer-binding factor 1, with vitamin D modulating this interaction in prostate cancer. [ABSTRACT FROM AUTHOR]

A deep neural network (DNN) was trained to generate a multiparametric ultrasound (mpUS) volume from four input ultrasound-based modalities (acoustic radiation force impulse [ARFI] imaging, shear wave elasticity imaging [SWEI], quantitative ultrasound-midband fit [QUS-MF], and B-mode) for the detection of prostate cancer. A DNN was trained using co-registered ARFI, SWEI, MF, and B-mode data obtained in men with biopsy-confirmed prostate cancer prior to radical prostatectomy (15 subjects, comprising 980,620 voxels). Data were obtained using a commercial scanner that was modified to allow user control of the acoustic beam sequences and provide access to the raw image data. For each subject, the index lesion and a non-cancerous region were manually segmented using visual confirmation based on whole-mount histopathology data. In a prostate phantom, the DNN increased lesion contrast-to-noise ratio (CNR) compared to a previous approach that used a linear support vector machine (SVM). In the in vivo test datasets (n = 15), the DNN-based mpUS volumes clearly portrayed histopathology-confirmed prostate cancer and significantly improved CNR compared to the linear SVM (2.79 ± 0.88 vs. 1.98 ± 0.73, paired-sample t -test p < 0.001). In a sub-analysis in which the input modalities to the DNN were selectively omitted, the CNR decreased with fewer inputs; both stiffness- and echogenicity-based modalities were important contributors to the multiparametric model. The findings from this study indicate that a DNN can be optimized to generate mpUS prostate volumes with high CNR from ARFI, SWEI, MF, and B-mode and that this approach outperforms a linear SVM approach. [ABSTRACT FROM AUTHOR]

• Ask prostate cancer patients about sexual orientation, gender identity, and sexual behaviors. • Consider receptive anal intercourse at every stage in the cancer continuum. • Gender affirming hormone therapy can influence prostate specific antigen levels. • Consider patient interest in genital affirming surgery when recommending prostate cancer treatment. At every stage of the cancer continuum, the management of sexual and gender minorities with prostate cancer requires a thoughtful and multidisciplinary approach. For example, it is important to recognize that receptive anal intercourse, common among sexual minority men—i.e. gay and bisexual men—can potentially elevate prostate-specific antigen (PSA) leading to overdiagnosis and overtreatment. Additionally, it is important to understand that sexual minority men with prostate cancer might engage in insertive and/or receptive anal intercourse, as opposed to insertive vaginal intercourse, requiring a treatment conversation that expands beyond the usual discussion of sexual health in prostate cancer patients. For gender minorities—i.e. transgender women or trans feminine individuals (those recorded male at birth with feminine gender identities)—it is important to consider gender affirming hormones and pelvic surgeries as they can cause diagnostic and treatment challenges, including PSA suppression, more aggressive disease, and anatomical changes. Furthermore, it is essential to recognize that gender minorities are a diverse cohort and may or may not be on gender affirming hormone therapy and may or may not have received or intend to receive pelvic affirming surgery. In this seminar article, we highlight considerations for personalized management of prostate cancer in sexual and gender minorities to improve care for this understudied cohort and enhance health equity. [ABSTRACT FROM AUTHOR]

Background and objective: Prostate cancer (PCa) was the leading incident cancer and 3rd leading cause of cancer death in men in France in 2015 with inter-regional disparities. The objectives were to describe PCa incidence and mortality in France and by region, using real life data from the National Health Data System and to identify the factors associated with all-cause or PCa-specific mortality. Methods: Men aged ≥ 18years hospitalized and/or on long-term care for PCa (ICD-10 code C61) in France between 2010 and 2021 were included. An incident case was defined by the absence of any cancer in the five years preceding the first coding. Incidence and mortality estimates were age-standardized: France 2018f standardized rates (FSR), all-cause mortality (SMR) and PCa-specific mortality (SMRspe). Factors associated with death were identified using cause-specific Cox models. Results: The mean annual incidence was 47,081cases/year (FSR:179.6/100,000men), increasing over the period except 2020. All-cause mortality was 20,259 deaths/year (77.3/100,000men), and PCa-specific mortality was 7,265 deaths/year (27.7/100,000men). A PCa-specific mortality excess was found in Centre-Val-de-Loire (SMRspe = 1.21), Bretagne (1.18), Hauts-de-France (1.17) Normandie (1.15). After adjustment, significant PCa mortality excess was observed in Bretagne (HR = 1,29;95%IC[1.09–1.46]) and Hauts-de-France (HR = 1.19[1.03–1.34]). The other factors associated with death were an age ≥ 60years, an increasing comorbidity index, metastatic disease at onset (major weight in specific mortality with hazard ratio HR = 16.1[15.2–17.0]), precariousness, affiliation to the agricultural scheme, and the COVID period in all-cause mortality. Conclusion: This study updated incidence and mortality data in France. It showed differences in mortality between regions in France. The adjustment moderates regional findings based on raw mortality data. [ABSTRACT FROM AUTHOR]

In the over 80 years since androgens were found to play a pivotal role in prostate cancer (PCa) progression, androgen deprivation therapy (ADT) has been a cornerstone in treating advanced PCa. Castration‐resistant PCa persists, however, with some of these tumors evolving to androgen receptor (AR)‐independent forms like neuroendocrine PCa. The development of novel diagnostic and therapeutic approaches to PCa is therefore crucial. This review provides an overview of recent basic research in PCa, focusing on two main areas: PCa cells and their tumor microenvironments. The first section describes current knowledge on the intricate mechanisms of AR signaling pathways, emphasizing the roles of coactivators and chromatin state alterations in gene regulation. Genomic analyses have revealed recurrent mutations and copy number alterations critical for precision medicine. Liquid biopsy has become a promising tool for real‐time tumor monitoring, identifying genetic alterations in circulating‐tumor DNA or extracellular vesicles. The second section describes the tumor microenvironment of PCa, highlighting its immunosuppressive landscape and the potential of combining ADT with immunotherapy. Advanced techniques, including single‐cell RNA sequencing and spatial transcriptomics offer insights into cellular heterogeneity and interactions within the tumor microenvironment, paving the way for novel therapeutic strategies. Integration of these diverse research areas will provide a comprehensive understanding of the current state and future directions of PCa research, underscoring the importance of personalized medicine and the dynamic nature of cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Transforming growth factor β1 (TGF‐β) is a cytokine with pleiotropic biological functions. Recently, its signaling pathway has been highlighted for its implicative paradoxical roles in prostate cancer (PCa). Suppressing downstream effects of this pathway by interfering with receptor complex formation through inhibition of the TGF‐β1 leads to its antitumor effects, illuminating the TGF‐β1 as a viable therapeutic target for PCa. Our compound library—established by a literature‐based approach that identified phytochemicals with published evidence against the TGF‐β1—was screened by employing molecular docking, density functional theory (DFT), and molecular dynamic (MD) simulations to identify TGF‐β1 inhibitors. Eight of the 24 phytochemicals docked from our compound library had a good binding affinity (ranging from −11.7 to −10 kcal/mol) to the TGF‐β1 (PDB: 1PY5). The phytochemicals displayed good stability and reactivity as revealed by the DFT analysis and a desirable pharmacokinetic profile. The top four phytochemical complexes with high binding energies maintained stability throughout the 100 ns simulation. Qualitative studies on the drug repurposing attributes of bisindolylmaleimide, flavopiridol, baicalin, and gefitinib as inhibitors of TGF‐β1 are recommended; most importantly, suggest further wet‐lab studies to corroborate these phytochemicals—SB 202190, SB 203580, silymarin, and cryptotanshinone—in TGF‐β1 targeted drug development. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is a leading malignancy among men globally, with rising incidence rates emphasizing the critical need for better detection and therapeutic approaches. The roles of HSP90AB1 and PARP1 in prostate cancer cells suggest potential targets for enhancing treatment efficacy. Methods: This study investigated the overexpression of HSP90AB1 and PARP1 in prostate cancer cells and the impact of HSP90AB1 knockdown on the sensitivity of these cells to the PARP inhibitor olaparib. We also explored the combined effect of olaparib and celastrol, an HSP90 inhibitor, on the clonogenic survival, migration, proliferation, and overall viability of prostate cancer cells, alongside the modulation of the PI3K/AKT pathway. An in vivo PC3 xenograft mouse model was used to assess the antitumor effects of the combined treatment. Results: Our findings revealed significant overexpression of HSP90AB1 and PARP1 in prostate cancer cells. Knockdown of HSP90AB1 increased cell sensitivity to olaparib. The combination of olaparib and celastrol significantly reduced prostate cancer cell survival, migration, proliferation, and enhanced cumulative DNA damage. Celastrol also downregulated the PI3K/AKT pathway, increasing cell susceptibility to olaparib. In vivo experiments demonstrated that celastrol and olaparib together exerted strong antitumor effects. Conclusions: The study indicates that targeting both HSP90AB1 and PARP1 presents a promising therapeutic strategy for prostate cancer. The synergistic combination of celastrol and olaparib enhances the efficacy of treatment against prostate cancer, offering a potent approach to combat this disease. [ABSTRACT FROM AUTHOR]

Background: Interpreting genetic variants remains a challenge in prostate cancer (PCa). Although many annotation tools are available for prioritizing causal variants, the clinical relevance of these variants is rarely studied. Methods: We collected a cohort study that included 274 PCa patients from June 2017 to December 2020 and sequenced 19 DNA damage repair (DDR) genes in these patients and explored the clinical consequence of these different approaches. We also examined all-cause and PCa-specific survival in DDR gene mutation carriers compared to non-carriers after androgen receptor (AR)-directed therapy. Results: We identified 13 variants from 19 DDR genes in a total of 14 (5.1%) patients who had at least one presumed pathogenic mutation using different annotation methods. Four variants were annotated as pathogenic, 11 variants were predicted as protein-truncating variants (PTVs), four variants received proxy-deleterious (Combined Annotation-Dependent Depletion scores of > 30), and only one variant was identified as a pathogenic variant or as having a functional effect by all three methods. PCa patients with PTVs were significantly associated with early onset, high cancer stage, and a worse response to AR-directed treatment. However, patients carrying a proxy-deleterious variant were only associated with a higher T (tumor) stage and N (node) stage than those without such a variant, but not associated with other clinical characteristics. In patients treated with AR-directed therapy, patients with a PTV showed an increased risk of all-cause death (adjusted hazard ratio (aHR) = 3.51, 95% confidence interval (CI): 1.06 ~ 11.56) and PCa-specific death (aHR = 4.49, 95% CI: 1.87 ~ 10.77) compared to non-PTV carriers after adjustment. We were unable to examine gene-specific risks due to the small number of patients. Conclusions: PTVs may assist in guiding treatment and early screening in PCa, while population-specific data for pathogenic variants are still being amassed. [ABSTRACT FROM AUTHOR]

Background: Spatial proteomics seeks to understand the spatial organization of proteins in tissues or at different subcellular localization in their native environment. However, capturing the spatial organization of proteins is challenging. Here, we present an innovative approach termed Spatial Proteomics through On-site Tissue-protein-labeling (SPOT), which combines the direct labeling of tissue proteins in situ on a slide and quantitative mass spectrometry for the profiling of spatially-resolved proteomics. Materials and Methods: Efficacy of direct TMT labeling was investigated using seven types of sagittal mouse brain slides, including frozen tissues without staining, formalin-fixed paraffin-embedded (FFPE) tissues without staining, deparaffinized FFPE tissues, deparaffinized and decrosslinked FFPE tissues, and tissues with hematoxylin & eosin (H&E) staining, hematoxylin (H) staining, eosin (E) staining. The ability of SPOT to profile proteomes at a spatial resolution was further evaluated on a horizontal mouse brain slide with direct TMT labeling at eight different mouse brain regions. Finally, SPOT was applied to human prostate cancer tissues as well as a tissue microarray (TMA), where TMT tags were meticulously applied to confined regions based on the pathological annotations. After on-site direct tissue-protein-labeling, tissues were scraped off the slides and subject to standard TMT-based quantitative proteomics analysis. Results: Tissue proteins on different types of mouse brain slides could be directly labeled with TMT tags. Moreover, the versatility of our direct-labeling approach extended to discerning specific mouse brain regions based on quantitative outcomes. The SPOT was further applied on both frozen tissues on slides and FFPE tissues on TMAs from prostate cancer tissues, where a distinct proteomic profile was observed among the regions with different Gleason scores. Conclusions: SPOT is a robust and versatile technique that allows comprehensive profiling of spatially-resolved proteomics across diverse types of tissue slides to advance our understanding of intricate molecular landscapes. [ABSTRACT FROM AUTHOR]

To determine the synergistic effect and mechanism of AO/854, a new Bloom syndrome protein (BLM) helicase inhibitor, and cisplatin (CDDP), a DNA-crosslinking agent, cell viability assays, neutral comet assays, and Western blotting (WB) were performed on prostate cancer (PCa) cells. According to our findings, combining AO/854 and CDDP enhanced the antiproliferative capabilities of PC3 cell lines. As evidenced by the upregulation of γH2AX, cleaved caspase-3/caspase-3, and BAX/Bcl-2, AO/854 dramatically increased PC3 apoptosis and DNA damage induced by CDDP. Furthermore, combining AO/854 and CDDP synergistically inhibited PC3 cell migration and invasion. In addition, AO/854 inhibited CDDP-induced S-phase cell-cycle arrest in PC3 cells while enhancing G2/M-phase cell-cycle arrest. In vivo, the antitumor efficacy of the combination therapy group was greater than that of the groups treated with AO/854 or CDDP alone. Our findings indicate that synergistic chemotherapy with AO/854 and CDDP may be a novel anticancer strategy for PCa. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most common cancer among men and the fifth leading cause of cancer death. Circulating tumor cell (CTC) enumeration and characterisation in PCa has been shown to provide valuable information on prognosis of disease, therapy management and detection of resistance. Here, Cellsway's microfluidic platform for high-throughput enrichment of intact CTC populations was used to isolate CTCs from the blood of 20 localised PCa patients and 10 healthy donor samples to evaluate the clinical performance of the technology. To enumerate and characterise CTCs, a multi-parameter flow cytometry analysis was performed on the enriched CTC suspension using CTC-specific biomarkers. CTCs were detected in 17 of 20 patient samples, which corresponds to 85% CTC positivity. The median CTC count per 7.5 ml blood was 2 (1–9). In 80% of patients (n = 16), the number of CTCs ranged from 1 to 5, and in 5% of patients (n = 1) the number of CTCs was above 5. No CTCs were observed in the blood samples of 10 healthy volunteers, demonstrating the high specificity and low risk of false positives of the technology. [ABSTRACT FROM AUTHOR]

Objectives: For prostate cancer (PCa), hundreds of risk variants have been identified. It remains unknown whether the polygenic risk score (PRS) that combines the effects of these variants is also a sufficiently informative metric with relevance to the molecular mechanisms of carcinogenesis in prostate. We aimed to understand the biological basis of PRS and racial disparities in the cancer. Methods: We performed a comprehensive analysis of the data generated (deposited in) by several genomic and/or transcriptomic projects (databases), including the GTEx, TCGA, 1000 Genomes, GEO and dbGap. PRS was constructed from 260 PCa risk variants that were identified by a recent trans-ancestry meta-analysis and contained in the GTEx dataset. The dosages of risk variants and the multi-ancestry effects on PCa incidence estimated by the meta-analysis were used in calculating individual PRS values. Results: The following novel results were obtained from our analyses. (1) In normal prostate samples from healthy European Americans (EAs), the expression levels of 540 genes (termed PRS genes) were associated with the PRS (P <.01). (2) Ubiquitin–proteasome system in high-PRS individuals' prostates was more active than that in low-PRS individuals' prostates. (3) Nine PRS genes play roles in the cancer progression-relevant parts, which are frequently hit by somatic mutations in PCa, of PI3K-Akt/RAS-MAPK/mTOR signaling pathways. (4) The expression profiles of the top significant PRS genes in tumor samples were capable of predicting malignant PCa relapse after prostatectomy. (5) The transcriptomic differences between African American and EA samples were incompatible with the patterns of the aforementioned associations between PRS and gene expression levels. Conclusions: This study provided unique insights into the relationship between PRS and the molecular mechanisms of carcinogenesis in prostate. The new findings, alongside the moderate but significant heritability of PCa susceptibility contributed by the risk variants, suggest the aptness and inaptness of PRS for explaining PCa and disparities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To determine the diagnostic test accuracy of multiparametric magnetic resonance imaging (mpMRI) in detecting seminal vesicle invasion (SVI).The Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed, the Excerpta Medica dataBASE (EMBASE) and Cochrane databases were search up to May 2023. We included studies that investigated the accuracy of mpMRI in detecting SVI when compared to radical prostatectomy specimens as the reference standard. Data extraction was performed by two independent reviewers to construct 2 × 2 tables, as well as patient and study characteristics. The methodological quality of the included studies was assessed with the Quality of Assessment of Diagnostic Accuracy Studies‐2 tool. Sensitivity and specificity were pooled and presented graphically with summary receiver operator characteristic (SROC) plots.A total of 27 articles with 4862 patients were included for analysis. The summary sensitivity and specificity were 0.57 (95% confidence interval [CI] 0.45–0.68) and 0.95 (95% CI 0.92–0.99), respectively. Meta‐regression indicated that there was no evidence that coil strength (P = 0.079), coil type (P = 0.589), year of publication (P = 0.503) or use of the Prostate Imaging‐Reporting and Data System (P = 0.873) significantly influenced these results. The summary diagnostic odds ratio was 28.3 (95% CI 15.0–48.8) and the area under the curve for the SROC curve was 0.87. The I2 statistic was a modest 11.9%. In general, methodological quality was good.The use of mpMRI in detecting SVI has excellent specificity but poor sensitivity. Both endorectal coils and magnetic field strength do not significantly impact the accuracy of MRI. These findings suggest that mpMRI cannot reliably rule out SVI in patients with prostate cancer. [ABSTRACT FROM AUTHOR]

The Gleason score is the gold standard for grading of prostate cancer (PCa) and is assessed by assigning specific grades to different microscopical growth patterns. Aside from the Gleason grades, individual growth patterns such as cribriform architecture were recently shown to have independent prognostic value for disease outcome. PCa grading is performed on static tissue samples collected at one point in time, whereas in vivo epithelial tumour structures are dynamically invading, branching and expanding into the surrounding stroma. Due to the lack of models that are able to track human PCa microscopical developments over time, our understanding of underlying tissue dynamics is sparse. We postulate that human PCa expansion utilizes embryonic and developmental tubulogenetic pathways. The aim of this study is to provide a comprehensive overview of developmental pathways of normal epithelial tubule formation, elongation, and branching, and relate those to the static microscopical PCa growth patterns observed in daily clinical practise. This study could provide a rationale for the discerned pathological interobserver variability and the clinical outcome differences between PCa growth patterns. [ABSTRACT FROM AUTHOR]

AbstractProstate cancer is one of the most common malignancies in men. The tumour microenvironment (TME) has a critical role in the initiation, progression, and metastasis of prostate cancer. TME contains various cell types, including cancer-associated fibroblasts (CAFs), endothelial cells, immune cells such as macrophages, lymphocytes B and T, natural killer (NK) cells, and other proteins such as extracellular matrix (ECM) components. The interactions and communications between these cells within the TME are crucial for the growth and response of various solid tumours, such as prostate cancer to different anticancer modalities. In this review article, we exemplify the various mechanisms by which the TME influences prostate cancer progression. The roles of different cells, cytokines, chemokines, and growth factors in modulating the immune response and prostate tumour growth will be discussed. The impact of these cells and factors and other ECM components on tumour cell invasion and metastasis will also be discussed. We explain how these interactions in TME can affect the response of prostate cancer to therapy. We also highlight the importance of understanding these interactions to develop novel therapeutic approaches for prostate cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND Whether stereotactic body radiotherapy (SBRT) is noninferior to conventionally demoderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear. METHODS We conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage Tl or T2 prostate cancer, a Gleason score of 3+4 Or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgendeprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population. RESULTS A total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.696. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (9596 confidence interval ICI], 93.3 to 97.4) in the SBRI group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P=0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RIOG) grade or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P-0.94). CONCLUSIONS Five-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.). [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is among prevalent cancers in men. Numerous strategies have been proposed to intervene with the important prostate cancer-related signaling pathways. Among the most promising strategies is CRISPR/Cas9 strategy. This strategy has been used to modify expression of a number of genes in prostate cancer cells. Aims: This review summarizes the most recent progresses in the application of CRISPR/Cas9 strategy in modification of prostate cancer-related phenotypes with an especial focus on pathways related to androgen receptor signaling. Conclusion: CRISPR/Cas9 technology has successfully targeted several genes in the prostate cancer cells. Moreover, the efficiency of this technique in reducing tumor burden has been tested in animal models of prostate cancer. Most of targeted genes have been related with the androgen receptor signaling. Targeted modulation of these genes have affected growth of castration-resistant prostate cancer. PI3K/AKT/mTOR signaling and immune response-related genes have been other targets that have been successfully modulated by CRISPR/Cas9 technology in prostate cancer. Based on the rapid translation of this technology into the clinical application, it is anticipated that novel treatments based on this technique change the outcome of this malignancy in future. [ABSTRACT FROM AUTHOR]

Background: Docetaxel (DTX) resistance attenuates anti-tumor effects of DTX on prostate cancer (mCRPC) and drug resistance was related to Treg expansion in tumors. ZNF667-AS1 played a suppressing role in various tumors and tumor-derived exosomes carry lncRNAs to participate in tumor progression. Here, the effects of ZNF667-AS1 on malignant characteristics and DTX resistance in PC and the effect and its underlying molecular mechanism of tumor-derived exosomes carrying ZNF667-AS1 on Treg expansion were investigated. Methods: The identification of exosomes were determined using TEM, NTA and western blot. The abundance of genes and proteins were evaluated using IHC, RT-qPCR, western blot and FISH. Malignant phenotypes of PC cells were evaluated by means of Edu, scratch test, transwell, CCK-8 and flow cytometry. The percentage of CD4+CD25+Foxp3+ Tregs was detected using flow cytometry. The location of ZNF667-AS1 was detected using nuclear-cytoplasmic fractionation. The co-location of ZNF667-AS1 and U2AF1 protein was detected using IF-FISH assay. The interactions among ZNF667-AS1, TGFBR1 and U2AF1 were verified using RNA pull-down, RIP and dual luciferase activity. Results: ZNF667-AS1 expression in PC samples was lowered, which was negatively relative to poor prognosis and DTX resistance. ZNF667-AS1 overexpression inhibited malignant phenotypes of PC cells, tumor growth and DTX resistance. Besides, DTX resistant cell-derived exosomes expressed lower ZNF667-AS1 expression. Exosomes carrying exogenously high ZNF667-AS1 expression derived PC cells or serum of mice suppressed Treg expansion. On the mechanism, ZNF667-AS1 interacted with U2AF1 to destabilize TGFBR1 mRNA and reduce TGFBR1 expression in CD4+T cells. Conclusion: ZNF667-AS1 suppressed cell growth of PC cells, tumor growth of mice and DTX resistance to PC cells and exogenously high ZNF667-AS1 expression in tumor-derived exosomes destabilized TGFBR1 mRNA and reduce TGFBR1 expression through interacting with U2AF1, thus resulting in attenuated Treg expansion, which was related to DTX resistance. [ABSTRACT FROM AUTHOR]

The primary cilium, a non‐motile organelle present in most human cells, plays a crucial role in detecting microenvironmental changes and regulating intracellular signaling. Its dysfunction is linked to various diseases, including cancer. We explored the role of ciliated cells in prostate cancer by using Gefitinib and Jasplakinolide compounds to induce ciliated cells in both normal and tumor‐like prostate cell lines. We assessed GLI1 and IFT20 expression and investigated YAP1 protein's role, which is implicated in primary cilium regulation. Finally, we examined these compounds in 3D cell models, aiming to simulate in vivo conditions. Our study highlights YAP1 as a potential target for novel genetic models to understand the primary cilium's role in mediating resistance to anticancer treatments. [ABSTRACT FROM AUTHOR]

Introduction: Clinical decision‐making in oncology is a complex process, with the primary goal of identifying the most effective treatment tailored to individual cancer patients. Many factors influence the treatment decision: disease‐ and patient‐specific criteria, the increasingly complex treatment landscape, market authorization and drug availability, financial aspects, and personal treatment expertise. In the domain of genitourinary cancers, particularly prostate cancer, decision‐making is challenging. Despite the prevalence of this malignancy, there are few in‐depth explorations of these factors within real‐world scenarios. Understanding and refining this intricate decision‐making process is essential for future successful clinical decisions and the integration of computerized decision support into clinicians' workflows. Aim: The objective of this study is to improve the current knowledge base and evidence of the factors that influence treatment decision‐making for patients with genitourinary cancers. Methods: Assessment of how routine treatment decisions are made for genitourinary cancers was performed by a mixed‐methods study, encompassing field observations and focus group discussions. Results: In total, we identified 59 factors that influence clinical decision‐making in oncology, specifically for genitourinary and prostate cancer. Of these, 23 criteria can be classified as decision‐maker‐related criteria encompassing personal, cognitive, and emotional attributes and factors of both, healthcare professionals and patients. Moreover, 20 decision‐specific criteria have been identified that refer to clinical and disease‐related factors, followed by 16 contextual decision factors that describe the relevant criteria introduced by the specific circumstances and environment in which the treatment decision is made. Conclusion: By presenting an exhaustive set of decision factors and providing specific examples for genitourinary cancers, this observational study establishes a possible framework for a better understanding of decision‐making. Moreover, we specify and expand the set of decision factors, while emphasizing the importance of cognitive, emotional, and human factors, as well as the quality and accessibility of decision‐relevant information. [ABSTRACT FROM AUTHOR]