Image quality comparison of 1.5T and 3T prostate MRIs of the same post-hip arthroplasty patients: multi-rater assessments including PI-QUAL version 2.

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.

A Scoping Review of Stigma Related to Prostate Cancer in Black Men.

BACKGROUND: Prostate cancer (CaP) disproportionately affects 1-in-4 Black men and is a stigmatised disease within their communities. Yet, Black men are underrepresented in CaP research concerning stigma, which necessitates a scoping review to map available evidence on this topic to inform future research. AIMS: To map published literature on stigma related to CaP in Black men to understand their experiences and/or perceptions and identify directions for future research. METHODS: A scoping review was conducted using the five-step framework by Arksey and O'Malley. Studies published in English addressing stigma related to CaP from the perspectives of Black men and/or their families were included. We searched six databases including Medline, Embase, PsycInfo, CINAHL, Web of Science Core Collection and Google Scholar, from inception to April 2023. Citation searches were also conducted. Two independent reviewers conducted screening and data extraction. Data was synthesised using descriptive content analysis. RESULTS: Thirty-four eligible studies conducted in the USA, UK, Trinidad and Tobago, South Africa, Cameroon and Canada from 1995 to 2023 were included. A total of 1867 Black men with/without a CaP diagnosis and 145 adult partners were included. Review findings showed a complex intersection of self-stigma, public stigma and structural stigma impacted Black men's perceptions of their masculinity. While men's experiences/perceptions of stigma varied depending on their illness status, there were commonalities in their masculinity concerns (underpinned by stigma), which influenced their attitude towards digital rectal examination, post-treatment side effects and social interactions on CaP. These have implications for public health messaging on CaP within Black communities, as well as patient-provider interactions with the men. CONCLUSIONS: This novel review highlights the need to pay attention to how CaP is presented to Black men and their communities using avenues and languages that are culturally acceptable and empower them to negotiate self-stigma, public stigma and structural stigma related to CaP. Directions for further research were also identified.

Physiological biodistribution on Ga68-PSMA PET/CT and the factors effecting biodistribution.

AIM: The study aims to determine the physiological and pathophysiological distribution of the radiopharmaceutical (Ga68-PSMA-617) and investigate whether there are differences in distribution according to the laboratory, histopathological and clinical findings that can affect image evaluation. Also, we aimed to determine cut-off values to distinguish physiological and pathological uptake in prostate, bone, and lymph nodes. MATERIALS AND METHODS: 229 prostate cancer patients who underwent Ga68-PSMA PET/CT at our department were retrospectively analyzed. The patients were grouped according to PET/CT results, Gleason scores, PSA values, received treatments, metastatic status and other laboratory values. The SUV values of the organs, tissues, and pathological lesions of the patients in these subgroups were compared among themselves. RESULTS: No significant difference was detected in the physiological uptake of lymph nodes and bone between the groups. In the group with patients that received androgen deprivation therapy (ADT), the bone metastasis SUV values were found to be higher and the SUV values of the submandibular gland and renal cortex were found to be lower (Mann-Whitney U, p = 0.043; 0.004; 0.01, respectively). In the group with patients who received radiotherapy, the normal prostate tissue SUV values were determined to be higher (Mann-Whitney U, p = 0.009). The SUV values of the submandibular gland, muscle, liver, and blood pool were found to be lower in the group of patients with high serum LDH values. The cut-off SUVmax value was determined to be 6.945 (sensitivity 89.6%, specificity 98.1%) for primary prostate lesion; 4.72 for lymph node metastasis; 4.25 for bone metastasis. The serum PSA cut-off value to distinguish the negative/positive groups was found to be 1,505 (sensitivity 79.7%, specificity 77.3%). CONCLUSION: In conclusion, PSMA-617 demonstrates a similar biodistribution with other PSMA ligands. The physiological uptake of lymph nodes and bone which are mostly metastasized in prostate cancer, are not affected by the factors we examined. It should be kept in mind that the normal prostate tissue uptake may increase in patients receiving radiotherapy, and the physiological/pathological uptake of the organs may differ due to the changes in PSMA expression in patients receiving ADT, tumor burden, and kidney function may affect the biodistribution.

Elevating PLK1 overcomes BETi resistance in prostate cancer via triggering BRD4 phosphorylation-dependent degradation in mitosis.

Bromodomain-containing protein 4 (BRD4) has emerged as a promising therapeutic target in prostate cancer (PCa). Understanding the mechanisms of BRD4 stability could enhance the clinical response to BRD4-targeted therapy. In this study, we report that BRD4 protein levels are significantly decreased during mitosis in a PLK1-dependent manner. Mechanistically, we show that BRD4 is primarily phosphorylated at T1186 by the CDK1/cyclin B complex, recruiting PLK1 to phosphorylate BRD4 at S24/S1100, which are recognized by the APC/CCdh1 complex for proteasome pathway degradation. We find that PLK1 overexpression lowers SPOP mutation-stabilized BRD4, consequently rendering PCa cells re-sensitized to BRD4 inhibitors. Intriguingly, we report that sequential treatment of docetaxel and JQ1 resulted in significant inhibition of PCa. Collectively, the results support that PLK1-phosphorylated BRD4 triggers its degradation at M phase. Sequential treatment of docetaxel and JQ1 overcomes BRD4 accumulation-associated bromodomain and extra-terminal inhibitor (BETi) resistance, which may shed light on the development of strategies to treat PCa.

A vitamin D-based strategy overcomes chemoresistance in prostate cancer.

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.

Predictive Value of Preoperative PSA Levels Combined with MRI Features for BCR after Radical Prostatectomy: A Retrospective Study.

BACKGROUND: Existing models for predicting that biochemical recurrence (BCR) will occur in patients after radical prostatectomy (RP) vary in their predictive results from magnetic resonance imaging (MRI). This study aimed to assess the predictive value of preoperative prostate-specific antigen (PSA) levels combined with MRI features in determining BCR following radical prostatectomy. METHODS: A retrospective analysis was conducted on a cohort comprising 102 patients who underwent radical prostatectomy at our hospital between January 2019 and December 2019. On the basis of the outcomes observed during a 4-year follow-up after surgery, the patients were categorised into BCR group (n = 52) and non-BCR group (n = 50). Differences in preoperative PSA levels and MRI characteristics between the two groups were compared, and factors influencing postoperative BCR were analysed. The receiver operating characteristic curve was drawn, and the sensitivity, specificity, area under the curve (AUC) and Youden index were calculated to observe the predictive value of the combination of preoperative PSA level and MRI features for BCR following radical prostatectomy. RESULTS: Logistic regression analysis showed that preoperative PSA level, postoperative Gleason score, data system (Prostate Imaging-Reporting and Data System (PI-RADS)) score and clinical T stage were independent risk factors for BCR in patients following radical prostatectomy, with odds ratio (OR) greater than 1. The AUC value of preoperative PSA level combined with PI-RADS score was 0.921, surpassing the AUC values of 0.783, 0.822, 0.617 and 0.608 predicted by preoperative PSA level, postoperative Gleason score, PI-RADS score and clinical T stage alone, respectively. CONCLUSIONS: Postoperative BCR in patients with prostate cancer undergoing radical prostatectomy is associated with preoperative PSA level, postoperative Gleason score, PI-RADS score and clinical T stage. The combination of preoperative PSA level and MRI features can improve the predictive efficiency for postoperative BCR.

Clinical Study on Low-Frequency Electrical Pulse Acupoint Stimulation Combined with Pelvic Floor Muscle Exercise in the Treatment of Urinary Incontinence after Radical Prostatectomy.

BACKGROUND: Urinary incontinence (UI) is a common complication after radical prostatectomy (RP). It has a great influence on the postoperative quality of life of patients. This study aims to explore the clinical efficacy of low-frequency electrical pulse acupoint stimulation combined with pelvic floor muscle exercise in the treatment of UI after RP. METHODS: The clinical data of 129 patients with UI after receiving RP in our hospital from July 2020 to July 2023 were retrospectively analysed. A total of 65 patients who received pelvic floor muscle exercise from July 2020 to January 2022 were set as the reference group. Of these patients, four were excluded, resulting in the inclusion of 61 cases. A total of 64 patients who received low-frequency electrical pulse acupoint stimulation combined with pelvic floor muscle exercise from February 2022 to July 2023 were classified into the observation group. Of these patients, four were excluded, and 60 cases were finally included. SPSS 23.0 was used to analyse the use of urine pads, recovery time of urinary control and improvement of urination in the two groups. RESULTS: Before treatment, no significant difference existed in the use of urine pads, urination condition, maximum flow rate, maximum cystometric capacity, maximum urethral closure pressure, abdominal leak point pressure and scores on Short-Form-36 Health Survey (SF-36) in both groups (p > 0.05). After treatment, the observation group had significantly lower use of urinary pads, urination frequency and leakage times; Significantly shorter recovery time of urinary control (p < 0.05); And significantly higher maximum flow rate, maximum cystometric capacity, maximum urethral closure pressure, abdominal leak point pressure and SF-36 scores than the reference group (p < 0.05). CONCLUSIONS: The combination of low-frequency electrical pulse acupoint stimulation and pelvic floor muscle exercise can improve clinical symptoms, shorten the recovery time of urinary control and improve urodynamics and quality of life in patients with UI after RP.

Bi-Parametric Magnetic Resonance Imaging Analysis of Biochemical Recurrence of Prostate Cancer after Radical Surgery and Its Predictive Value: A Retrospective Study.

OBJECTIVE: This study aimed to analyse the characteristics of biochemical recurrence after radical prostatectomy via bi-parametric magnetic resonance imaging. METHODS: A total of 200 patients with radical prostatectomy admitted to our hospital from January 2016 to January 2021 were retrospectively enrolled as observation objects. According to whether there was biochemical recurrence after surgery, the patients were divided into the abnormal group (n = 62) and normal group (n = 138). Clinical data, encapsulation infiltration, seminal vesicle infiltration and prostate imaging report and data system (PI-RADS) were collected and compared between the two groups. Propensity score matching (PSM) was used to balance the baseline data of the two groups. Student's t-test and Chi-square test were used to analyse the data. RESULTS: PSM was performed in a 1:1 ratio, and a total of 72 patients were included in the abnormal and normal groups. The baseline data of the patients in each group were not statistically significant. The incidence of extraperitoneal invasion and seminal vesicle invasion was higher in the abnormal group than in the normal group, and we observed a significant difference in PI-RADS scores between the two groups (p < 0.05). Extracapsular invasion, seminal vesicle invasion, PI-RADS score and biochemical recurrence were significantly correlated (p < 0.05). The PI-RADS score has a high value for predicting biochemical recurrence, with an area under the curve value of 0.824, sensitivity of 0.667, specificity of 0.861 and Youden index of 0.528. CONCLUSIONS: Bi-parametric magnetic resonance imaging has a high predictive value in biochemical recurrence after radical prostatectomy, which can provide reference for early intervention measures.

Impact of homologous recombination repair/BReast CAncer (BRCA) gene alterations on survival in a real-world setting of metastatic prostate cancer.

OBJECTIVE: To investigate alterations of homologous recombination repair (HRR) and especially BReast CAncer 1/2 (BRCA1/2) gene on overall survival (OS). Moreover, to explore the effect of inhibition of poly(ADP-ribose)-polymerase (PARPi) as systemic therapy for metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Of all HRR-screened patients with metastatic prostate cancer, baseline characteristics were sampled. Kaplan-Meier estimates and multivariable Cox regression models predicted the effect of HRR/BRCA1/2 alterations on OS. RESULTS: Of 196 eligible patients, 61 (31%) harboured any HRR and 40 (20%) BRCA1/2 alterations. Of HRR alterations, 40 (66%) vs six (10%) vs five (8.2%) vs four (6.6%) vs two (3.3%) vs four (6.6%) were BRCA1/2 vs Ataxia-telangiectasia mutated kinase (ATM) vs checkpoint kinase 2 (CHEK2) vs cyclin-dependent kinase 12 (CDK12) vs Fanconi anaemia complementation Group A (FANCA) vs positive for other mutations. Of these, 30% received a PARPi. OS differed significantly between HRR-positive vs -negative patients. Specifically in hormone-sensitive prostate cancer, the median OS was 63 (HRR positive) vs 57 (BRCA1/2 positive) vs 113 months (HRR negative) (P ≤ 0.01). In mCRPC, OS was 42 (HRR positive) vs 41 (BRCA1/2 positive) vs 70 months (HRR negative) (P ≤ 0.01). HRR and BRCA1/2 alterations were associated with worse OS after multivariable adjustment. Finally, patients with mCRPC with BRCA1/2 mutation treated without PARPi harboured worse OS than patients with BRCA1/2 mutation and PARPi therapy (median OS: 33 vs 48 months, P < 0.03). CONCLUSION: Incidence of HRR alteration in a clinical real-world setting is high when using blood- and tissue-based tests. Patients with HRR/BRCA alterations have worse outcomes resulting in significant OS differences between HRR/BRCA-positive patients with mCRPC with and without PARPi usage vs HRR/BRCA-negative patients.

Health Literacy, Individual and Community Engagement, and Cardiovascular Risks and Disparities: JACC: CardioOncology State-of-the-Art Review.

Cardiovascular and cancer outcomes intersect within the realm of cardio-oncology survivorship care, marked by disparities across ethnic, racial, social, and geographical landscapes. Although the clinical community is increasingly aware of this complex issue, effective solutions are trailing. To attain substantial public health impact, examinations of cancer types and cardiovascular risk mitigation require complementary approaches that elicit the patient's perspective, scale it to a population level, and focus on actionable population health interventions. Adopting such a multidisciplinary approach will deepen our understanding of patient awareness, motivation, health literacy, and community resources for addressing the unique challenges of cardio-oncology. Geospatial analysis aids in identifying key communities in need within both granular and broader contexts. In this review, we delineate a pathway that navigates barriers from individual to community levels. Data gleaned from these perspectives are critical in informing interventions that empower individuals within diverse communities and improve cardio-oncology survivorship.

Social Determinants of Health Mediate Racial Disparities in Cardiovascular Disease in Men With Prostate Cancer.

Background: Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in men with prostate cancer; however, data on racial disparities in CVD outcomes are limited. Objectives: We quantified the disparities in CVD according to self-identified race and the role of the structural social determinants of health in mediating disparities in prostate cancer patients. Methods: A retrospective cohort study of 3,543 prostate cancer patients treated with systemic androgen deprivation therapy (ADT) between 2008 and 2021 at a quaternary, multisite health care system was performed. The multivariable adjusted association between self-reported race (Black vs White) and incident major adverse cardiovascular events (MACE) after ADT initiation was evaluated using cause-specific proportional hazards. Mediation analysis determined the role of theme-specific and overall social vulnerability index (SVI) in explaining the racial disparities in CVD outcomes. Results: Black race was associated with an increased hazard of MACE (HR: 1.38; 95% CI: 1.16-1.65; P < 0.001). The association with Black race was strongest for incident heart failure (HR: 1.79; 95% CI: 1.32-2.43), cerebrovascular disease (HR: 1.98; 95% CI: 1.37-2.87), and peripheral artery disease (HR: 1.76; 95% CI: 1.26-2.45) (P < 0.001). SVI, specifically the socioeconomic status theme, mediated 98% of the disparity in MACE risk between Black and White patients. Conclusions: Black patients are significantly more likely to experience adverse CVD outcomes after systemic ADT compared with their White counterparts. These disparities are mediated by socioeconomic status and other structural determinants of health as captured by census tract SVI. Our findings motivate multilevel interventions focused on addressing socioeconomic vulnerability.

Internal urethral sphincter reconstruction with anterior bladder neck tube for robotic and laparoscopic radical prostatectomy: improving early return of continence.

Background: In recent years, despite several surgical techniques having been applied, the early incontinence rate after radical prostatectomy (RP) remains high. In this study, we reconstructed an internal urethral sphincter (IUS) with anterior bladder neck tube (ABNT) to improve early return of continence and find a more effective technique for early urinary incontinence after RP. Methods: In this study, 96 previous patients who did not receive an ABNT between October 2018 and May 2020 were compared as historical controls (the control group). A total of 210 consecutive patients underwent robotic or laparoscopic RP with ABNT between May 2020 and February 2023 (the ABNT group). The inclusion criteria included Eastern Cooperative Oncology Group (ECOG) score 0-1 and localized prostate cancer (clinical stages cT1-3, cN0, cM0). The exclusion criteria included patients with diabetes, neurologic diseases, previous pelvic operations, symptoms of urinary incontinence, prior radiation, focal therapy, or androgen deprivation therapy for prostate cancer. ABNT was reconducted with a U-shaped flap from the anterior wall of the bladder neck, and was then anastomosed with the urethra. In the control group, the bladder outlet was directly anastomosed with the urethra. Continence, as defined if 0 pads were used per day and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score ≤6, was assessed at 1, 4, 8, 12, and 24 weeks after catheter removal. At 2 weeks after catheter removal, urethral pressure profilometry (UPP) and upright urethrography were performed to evaluate the function of ABNT in the ABNT group. Results: More patients in the ABNT group were continent than those in the control group at 1 week (85.2% vs. 22.9%, P<0.001), 4 weeks (91.4% vs. 27.1%, P<0.001), 8 weeks (95.2% vs. 40.6%, P<0.001), 12 weeks (100% vs. 71.9%, P<0.001), and at 24 weeks (100% vs. 87.5%, P<0.001) after catheter removal. Stricture was presented in 5.2% and 2.1% (P=0.34) in the ABNT group and control group, respectively. UPP showed that a functional IUS was reconstructed with ABNT. Upright urethrography showed that the ABNT was filled with contrast medium in the urination period and with no contrast medium during the storage period and interruption of urination. Conclusions: The ABNT technique significantly improved early return of continence in comparison with the no ABNT technique, especially the immediate continence. The ABNT technique reconstructed the functional IUS with acceptable urethral stricture. The limitations of the present study include that the comparison was conducted retrospectively with a historical cohort and lack of randomization, and the single center setting. A prospective, randomized, and multicenter evaluation is expected.

The Growth Inhibitory Effect of Resveratrol and Gallic Acid on Prostate Cancer Cell Lines through the Alteration of Oxidative Stress Balance: the Interplay between Nrf2, HO-1, and BACH1 Genes.

BACKGROUND: The association between oxidative stress and prostate cancer (PC) has been demonstrated both epidemiologically and experimentally. Balance in reactive oxygen species (ROS) levels depends on multiple factors, such as the expression of Nrf2, HO-1, and BACH1 genes. Natural polyphenols, such as resveratrol (RSV) and gallic acid (GA), affect cellular oxidative profiles. OBJECTIVE: The present study investigated the possible effects of GA and RSV on the oxidative profiles of PC3 and DU145 cells, as well as Nrf2, HO-1, and BACH1 gene expression to achieve an understanding of the mechanisms involved. METHODS: PC3 and DU145 cells were treated with ascending concentrations of RSV and GA for 72h. Then cell growth and mRNA expression of Nrf2, HO-1, and BACH1 genes were analyzed by real-time PCR. Various spectrophotometric analyses were performed to measure oxidative stress markers. RESULTS: RSV and GA significantly decreased the growth of PC3 and DU145 cells compared to the control group in a concentration-dependent manner. RSV and GA also decreased ROS production in PC3 cells, but in DU145 cells, only the latter polyphenol significantly decreased ROS content. In addition, RSV and GA had ameliorating effects on SOD, GR, GPX, and CAT activities and GSH levels in both cell lines. Also, RSV and GA induced HO- 1 and Nrf2 gene expression in both cell lines. BACH1 gene expression was induced by RSV only at lower concentrations, in contrast to GA in both cell lines. CONCLUSION: Our data suggest that RSV and GA can prevent the growth of prostate cancer cells by disrupting oxidative stress-related pathways, such as changes in Nrf2, HO-1, and BACH1 gene expression.

Non-invasively identifying candidates of active surveillance for prostate cancer using magnetic resonance imaging radiomics.

Active surveillance (AS) is the primary strategy for managing patients with low or favorable-intermediate risk prostate cancer (PCa). Identifying patients who may benefit from AS relies on unpleasant prostate biopsies, which entail the risk of bleeding and infection. In the current study, we aimed to develop a radiomics model based on prostate magnetic resonance images to identify AS candidates non-invasively. A total of 956 PCa patients with complete biopsy reports from six hospitals were included in the current multicenter retrospective study. The National Comprehensive Cancer Network (NCCN) guidelines were used as reference standards to determine the AS candidacy. To discriminate between AS and non-AS candidates, five radiomics models (i.e., eXtreme Gradient Boosting (XGBoost) AS classifier (XGB-AS), logistic regression (LR) AS classifier, random forest (RF) AS classifier, adaptive boosting (AdaBoost) AS classifier, and decision tree (DT) AS classifier) were developed and externally validated using a three-fold cross-center validation based on five classifiers: XGBoost, LR, RF, AdaBoost, and DT. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE) were calculated to evaluate the performance of these models. XGB-AS exhibited an average of AUC of 0.803, ACC of 0.693, SEN of 0.668, and SPE of 0.841, showing a better comprehensive performance than those of the other included radiomic models. Additionally, the XGB-AS model also presented a promising performance for identifying AS candidates from the intermediate-risk cases and the ambiguous cases with diagnostic discordance between the NCCN guidelines and the Prostate Imaging-Reporting and Data System assessment. These results suggest that the XGB-AS model has the potential to help identify patients who are suitable for AS and allow non-invasive monitoring of patients on AS, thereby reducing the number of annual biopsies and the associated risks of bleeding and infection.

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

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

EAF2 Downregulation Recruits Tumor-associated Macrophages in Prostate Cancer through Upregulation of MIF.

BACKGROUND: The role of tumor inflammatory microenvironment in the advancement of cancer, particularly prostate cancer, is widely acknowledged. ELL-associated factor 2 (EAF2), a tumor suppressor that has been identified in the prostate, is often downregulated in prostate cancer. Earlier investigations have shown that mice with EAF2 gene knockout exhibited a substantial infiltration of inflammatory cells into the prostatic stroma. METHODS: A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization. RESULTS: Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout. CONCLUSIONS: Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF.

Anti-EGFR immunoliposomes for cabazitaxel delivery: From formulation development to in vivo evaluation in prostate cancer xenograft model.

Liposomes functionalized with monoclonal antibodies offer targeted therapy for cancer, boasting advantages like sustained drug release, enhanced stability, passive accumulation in tumors, and interaction with overexpressed receptors on cancer cells. This study aimed to develop and characterize anti-EGFR immunoliposomes loaded with cabazitaxel and assess their properties against prostate cancer in vitro and in vivo. Using a Box-Behnken design, a formulation with soy phosphatidylcholine, 10% cholesterol, and a 1:20 drug-lipid ratio yielded nanometric particle size, low polydispersity and high drug encapsulation. Immunoliposomes were conjugated with cetuximab through DSPE-PEG-Maleimide lipid anchor. Characterization confirmed intact antibody structure and interaction with EGFR receptor following conjugation. Cabazitaxel was dispersed within the liposomes in the amorphous state, confirmed by solid-state analyses. In vitro release studies showed slower cabazitaxel release from immunoliposomes. Immunoliposomes had enhanced cabazitaxel cytotoxicity in EGFR-overexpressing DU145 cells without affecting non-tumor L929 cells. Cetuximab played an important role to improve cellular uptake in a time-dependent fashion in EGFR-overexpressing prostate cancer cells. In vivo, immunoliposomes led to significant tumor regression, improved survival, and reduced weight loss in xenograft mice. While cabazitaxel induced leukopenia, consistent with clinical findings, histological analysis revealed no evident toxicity. In conclusion, the immunoliposomes displayed suitable physicochemical properties for cabazitaxel delivery, exhibited cytotoxicity against EGFR-expressing prostate cancer cells, with high cell uptake, and induced significant tumor regression in vivo, with manageable systemic toxicity.

Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study.

BACKGROUND AND OBJECTIVE: Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions. METHODS: A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes. KEY FINDINGS AND LIMITATIONS: A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p < 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a "day-case" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue. PATIENT SUMMARY: We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were willing to accept additional treatments for survival benefits, in particular treatments that preserved urinary function and reduced fatigue.

Evaluating recommendation-based dietary and physical activity strategies for prostate cancer prevention: a target trial emulation in the Health Professionals Follow-up Study.

The 2018 World Cancer Research Fund/American Institute for Cancer Research recommends sustained strategies of physical activity and diet for cancer prevention, but evidence for long-term prostate cancer risk is limited. Using observational data from 27,859 men in the Health Professionals Follow-up Study, we emulated a target trial of recommendation-based physical activity and dietary strategies and 26-year risks of prostate cancer, adjusting for risk factors via the parametric g-formula. Compared with no intervention, limiting sugar-sweetened beverages showed a 0.4% (0.0-0.9%) lower risk of lethal (metastatic or fatal) disease and 0.5% (0.1-0.9%) lower risk of fatal disease. Restricting consumption of processed foods showed a 0.4-0.9% higher risk of all prostate cancer outcomes. Estimated risk differences for clinically significant disease were close to null for strategies involving fruits and non-starchy vegetables, whole grains and legumes, red meat, and processed meat, as well as under a joint strategy of physical activity and diet. Compared with a "low adherence" strategy, maintaining recommended physical activity levels showed a 0.4% (0.1-0.8%) lower risk of lethal and 0.5% (0.2-0.8%) lower risk of fatal disease. Adhering to specific components of current physical activity and dietary recommendations may help to prevent lethal and fatal prostate cancer over 26 years.