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Background: Prostate cancer is well known as the commonest cancer in men and the second leading cause of cancer-related death. CT, MRI and bone scintigraphy are considered the commonly widely used imaging diagnostic tools for detection, staging and follow-up of prostate cancer. Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, that can be concentrated in prostate cancer cells up to 100 times higher than in normal cells. PSMA-targeted imaging modalities have now proven their efficacy in diagnosis, staging and follow-up of prostate cancer. The use of 68Ga PSMA PET-CT has efficiently improved the detection of loco-regional and metastatic disease. 68Ga PSMA PET-CT also has an effective role in the primary diagnosis, staging, and detecting biochemical recurrence after curative treatment and in metastasis-targeted therapy. This work aims to review the role of 68Ga PSMA PET-CT in anatomical staging of prostate cancer in correlation with histopathological staging. Results: Zonal correlation between 68Ga PSMA findings and biopsy results showed sensitivity ranging between 76.9 and 90.6% and specificity ranging from 85.7 to 100%. There was high significant correlation between the SUVmax uptake and the biopsy results, between the SUVmax uptake and the local staging as well as between the Gleason score and 68Ga PSMA PET/CT findings. Conclusions: 68Ga PSMA PET/CT is a highly promising imaging modality with an effective role in detection of prostate cancer showing high sensitivity and specificity in prediction of zonal histopathological results and loco-regional Gleason score staging with significant positive correlation between the SUV uptake results, Gleason score and the PSA levels. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and validate a predictive model for clinically significant prostate cancer (csPCa) using prostate MRI and patient risk factors. In total, 960 men who underwent MRI from 2015 to 2019 and biopsy either 6 months before or 6 months after MRI were identified. Men diagnosed with csPCa were identified, and csPCa risk was modeled using known patient factors (age, race, and prostate-specific antigen [PSA] level) and prostate MRI findings (location, Prostate Imaging Reporting and Data System score, extraprostatic extension, dominant lesion size, and PSA density). csPCa was defined as Gleason score sum ≥ 7. Using a derivation cohort, a multivariable logistic regression model and a point-based scoring system were developed to predict csPCa. Discrimination and calibration were assessed in a separate independent validation cohort. Among 960 MRI reports, 552 (57.5%) were from men diagnosed with csPCa. Using the derivation cohort (n = 632), variables that predicted csPCa were Prostate Imaging Reporting and Data System scores of 4 and 5, the presence of extraprostatic extension, and elevated PSA density. Evaluation using the validation cohort (n = 328) resulted in an area under the curve of 0.77, with adequate calibration (Hosmer-Lemeshow P =.58). At a risk threshold of >2 points, the model identified csPCa with sensitivity of 98.4% and negative predictive value of 78.6% but prevented only 4.3% potential biopsies (0-2 points; 14 of 328). At a higher threshold of >5 points, the model identified csPCa with sensitivity of 89.5% and negative predictive value of 70.1% and avoided 20.4% of biopsies (0-5 points; 67 of 328). The point-based model reported here can potentially identify a vast majority of men at risk for csPCa, while avoiding biopsy in about 1 in 5 men with elevated PSA levels. [Display omitted] [ABSTRACT FROM AUTHOR]

Variability in prostate MRI quality is an increasingly recognized problem that negatively affects patient care. This report aims to describe the results and key learnings of the first cohort of the ACR Learning Network Prostate MR Image Quality Improvement Collaborative. Teams from five organizations in the United States were trained on a structured improvement method. After reaching a consensus on image quality and auditing their images using the Prostate Imaging Quality (PI-QUAL) system, teams conducted a current state analysis to identify barriers to obtaining high-quality images. Through plan-do-study-act cycles involving frontline staff, each site designed and tested interventions targeting image quality key drivers. The percentage of examinations meeting quality criteria (ie, PI-QUAL score ≥4) was plotted on a run chart, and project progress was reviewed in weekly meetings. At the collaborative level, the goal was to increase the percentage of examinations with PI-QUAL ≥4 to at least 85%. Across 2,380 examinations audited, the mean weekly rates of prostate MR examinations meeting image quality criteria increased from 67% (range: 60%-74%) at baseline to 87% (range: 80%-97%) upon program completion. The most commonly employed interventions were MR protocol adjustments, development and implementation of patient preparation instructions, personnel training, and development of an auditing process mechanism. A learning network model, in which organizations share knowledge and work together toward a common goal, can improve prostate MR image quality at multiple sites simultaneously. The inaugural cohort's key learnings provide a road map for improvement on a broader scale. [ABSTRACT FROM AUTHOR]

The construction and results of a multiple-reader multiple-case prostate MRI study are described and reported to illustrate recommendations for how to standardize artificial intelligence (AI) prostate studies per the review constituting Part I 1. Our previously reported approach was applied to review and report an IRB approved, HIPAA compliant multiple-reader multiple-case clinical study of 150 bi-parametric prostate MRI studies across 9 readers, measuring physician performance both with and without the use of the recently FDA cleared CADe/CADx software ProstatID. Unassisted reader AUC values ranged from 0.418 – 0.759, with AI assisted AUC values ranging from 0.507 – 0.787. This represented a statistically significant AUC improvement of 0.045 (α = 0.05). A free-response ROC (FROC) analysis similarly demonstrated a statistically significant increase in θ from 0.405 to 0.453 (α = 0.05). The standalone performance of ProstatID performed across all prostate tissues demonstrated an AUC of 0.929, while the standalone lesion level performance of ProstatID at all biopsied locations achieved an AUC of 0.710. This study applies and illustrates suggested reporting and standardization methods for prostate AI studies that will make it easier to understand, evaluate and compare between AI studies. Providing radiologists with the ProstatID CADe/CADx software significantly increased diagnostic performance as assessed by both ROC and free-response ROC metrics. Such algorithms have the potential to improve radiologist performance in the detection and localization of clinically significant prostate cancer. [ABSTRACT FROM AUTHOR]

MRI has firmly established itself as a mainstay for the detection, staging and surveillance of prostate cancer. Despite its success, prostate MRI continues to suffer from poor inter-reader variability and a low positive predictive value. The recent emergence of Artificial Intelligence (AI) to potentially improve diagnostic performance shows great potential. Understanding and interpreting the AI landscape as well as ever-increasing research literature, however, is difficult. This is in part due to widely varying study design and reporting techniques. This paper aims to address this need by first outlining the different types of AI used for the detection and diagnosis of prostate cancer, next deciphering how data collection methods, statistical analysis metrics (such as ROC and FROC analysis) and end points/outcomes (lesion detection vs. case diagnosis) affect the performance and limit the ability to compare between studies. Finally, this work explores the need for appropriately enriched investigational datasets and proper ground truth, and provides guidance on how to best conduct AI prostate MRI studies. Published in parallel, a clinical study applying this suggested study design was applied to review and report a multiple-reader multiple-case clinical study of 150 bi-parametric prostate MRI studies across nine readers, measuring physician performance both with and without the use of a recently FDA cleared Artificial Intelligence software. 1 [ABSTRACT FROM AUTHOR]

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Second‐generation androgen receptor (AR) signaling inhibitors (ARSIs), such as abiraterone and enzalutamide, prolong the life of patients with castration‐resistant prostate cancer (CRPC). However, patients receiving ARSIs ultimately develop resistance through various complex mechanisms, including AR mutations, constitutively active AR‐splice variants (AR‐Vs), and AR overexpression. Here, we characterized a novel AR pure antagonist, TAS3681, which inhibits AR transcriptional activity and downregulates AR‐full length (AR‐FL) and AR‐Vs. TAS3681 reduced the protein levels of AR‐FL and AR‐Vs including AR‐V7 in enzalutamide‐resistant cells (SAS MDV No. 3‐14), in vitro and in vivo, showing strong antitumor efficacy in an AR‐V7‐positive xenograft model. In AR‐overexpressing VCaP (prostate cancer) cells, conversely to enzalutamide, TAS3681 effectively suppressed cell proliferation and downregulated AR expression. Importantly, TAS3681 blocked the transcriptional activity of various mutant ARs, including mutations F877L/T878A and H875Y/T878A, which confer resistance to enzalutamide, and V716M and H875Y mutations, which confer resistance to darolutamide. Our results demonstrate that TAS3681 suppresses the reactivation of AR signaling, which causes resistance to ARSIs, via a newly identified mechanism of action. Therefore, TAS3681 could be a new therapeutic option for CRPC treatment. [ABSTRACT FROM AUTHOR]

The androgen receptor (AR) is the main driver in the development of castration‐resistant prostate cancer, where the emergence of AR splice variants leads to treatment‐resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs. MA suppressed the full‐length AR (AR‐FL), its spliced variant AR‐V7, and the AR‐regulated prostate‐specific antigen (PSA; also known as KLK3) and human kallikrein 2 (hK2; also known as KLK2) genes. RNA sequencing (RNA‐seq) analysis and protein modeling studies revealed E2F8 interactions with DNA as a potential novel target of MA, suppressing AR transcription and its synthesis. This novel mechanism of blocking AR biogenesis via E2F8 may provide an opportunity to control therapy‐resistant prostate cancer over the currently used AR antagonists designed to target different parts of the AR gene. [ABSTRACT FROM AUTHOR]

Background: Mucinous adenocarcinoma of the prostate (MACP) is one of the rarest variants of prostatic neoplasm, with more aggressive behavior than non-mucinous prostatic cancer. Previous studies suggested that these tumors exhibit different imaging magnetic resonance imaging (MRI) features compared with those of non-mucinous adenocarcinoma of the prostate upon which the conventional PIRADS v2.1 is based. To the best of our knowledge, this case series is the first to describe the multiparametric magnetic resonance imaging features of the MACP. Results: We presented two cases of biopsy proven mucinous adenocarcinoma of the prostate studied with multiparametric MRI. In both cases, diagnosis was late because of the different MRI features of MACP than those of the more common adenocarcinoma of the prostate. In both mpMRI, MACP appears to be hyperintense on T2WI, there was not a significant decrease in diffusivity in ADC maps and it exhibits early enhancement in DCE-MRI; the septa resulted in hypointense on T2WI compared to the PZ Conclusions: According to our experience, the conventional PIRADS v2.1 score is not suitable for mucinous prostate adenocarcinoma. MACP appears to be hyperintense on T2WI, has a lower ADC value, and exhibits early enhancement in DCE-MRI; the septa are usually hypointense on T2WI compared to the PZ. It is imperative for radiologists and urologists to be cognizant of this rare variant of prostate cancer to promptly identify and diagnose it, thereby preventing any diagnostic delays. [ABSTRACT FROM AUTHOR]

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. Highlights: EAF2 is associated with the progression of prostate cancer. EAF2 is correlated with Gleason score of prostate cancer. EAF2 is closely related to macrophages recruitment and polarition. EAF2 recruits M2 macrophages through upregulation of MIF. [ABSTRACT FROM AUTHOR]

Background/Objectives: In the current era, abiraterone acetate is mainstay of the treatment strategies of castration-resistant prostate cancer and proven to prolong overall survival. We aimed to prospectively identify factors associated with duration of response to abiraterone. Patients and methods: All metastatic castration-resistant prostate cancer patients eligible for abiraterone were included in the study from February 2019 till March 2020. All baseline data and potential factors associated recorded and follow-up with prostate-specific antigen (PSA), and required investigations were done at 1 month interval. Duration of PSA response was recorded, and patients were divided in five groups on the basis of duration of response. Univariate and multivariate analyses of potential factors were done, and data analysis was done with SPSS (Statistical Package for the Social Sciences) version 21.0. Results: In this study, after univariate analysis, seven factors were associated with longer duration of response to abiraterone. These were PSA at diagnosis (hazard ratio (HR) = −1.011 (95% confidence interval (CI) = 1.003–1.020), p -value = 0.008), PSA at start of abiraterone (HR = −1.018 (95% CI = 1.011–1.025), p -value = 0.0001), nadir PSA (HR = −1.063 (95% CI = 1.024–1.104), p -value = 0.001), prostate-specific antigen doubling (PSAD) time (HR = −0.745 (95% CI = 0.672–0.827), p -value = 0.001), raised alkaline phosphatase (ALP) (HR = −1.002 (95% CI = 1.001–1.003), p -value = 0.001), neutrophil/lymphocyte ratio (NLR) (HR = −2.16 (95% CI = 1.672–2.81), p -value = 0.001) and <5 bone metastasis (HR = −0.235 (95% CI = 0.130–0.422), p -value = 0.01). But after multivariate analysis, nadir PSA achieved, PSAD, NLR and ⩽5 bone metastasis were predictors of better response to abiraterone. Conclusion: This study had identified that less nadir PSA achieved, long PSAD time, low NLR and limited number of skeletal metastases were potential factors for better PSA response to abiraterone. Level of evidence: 1 [ABSTRACT FROM AUTHOR]

Objective: Currently the National Institute for Health and Care Excellence (NICE) recommends an abnormal digital rectal examination (DRE) as a standalone referral criterion for suspected prostate cancer. Unlike referrals for a raised prostate-specific antigen (PSA) which are triaged directly to magnetic resonance imaging (MRI), an abnormal DRE requires re-examination in a secondary clinic first. Here, we investigated the ongoing value of the abnormal DRE as a referral criterion. Methods: This study is a retrospective review of patients referred to secondary care for suspected prostate cancer based on an abnormal DRE over a 15-month period at a single UK hospital (n = 158). Age, PSA, primary and repeat DRE findings and eventual diagnosis were collated. Results: A concurrent raised PSA was present in 65/158 (41%). Concordance between primary and secondary care DRE was only 72/158 (46%). The overall and significant cancer detection rate was 26/158 (16%) and 22/158 (14%), respectively. Among men with a concurrent raised PSA, 19/65 (29%) had significant cancer found, whereas with an abnormal primary care DRE and normal PSA (n = 93), only 3/93 (3%) had a significant cancer. Mandating a PSA before referral for an abnormal DRE would have redirected 65/158 (41%) of men to MRI first, negating the need for a repeat DRE (p < 0.0001). This finding was recapitulated in a second prospective validation cohort (n = 30) with 9/30 (30%) redirected to MRI first. Conclusions: This is one of the first studies to investigate the value of the DRE in contemporary practice. We propose that PSA is used to triage men with an abnormal DRE to MRI without needing a repeat DRE. If the PSA is normal, the diagnostic yield is low but may still warrant a repeat DRE to assess the need for further investigations. Additional multi-centre studies are required to further validate our findings. Level of evidence: 4 [ABSTRACT FROM AUTHOR]

Objective: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most common urologic diseases in aging males. The negative association between prostate/BPH size and incidence of PCa is well documented in the literature. However, the exact mechanism is not well understood. This study aims to further investigate the possible effect of prostate volume on prostate capsule thickness and glandular cell density in the prostatic peripheral zone (PZ). Materials and Methods: A total of 100 patients were selected that had undergone radical prostatectomy with prostate sizes ranging from 20 to 160 mL. Quantitative measurements of capsule thickness and density of epithelial glands within the peripheral zone not affected by cancer were analysed and calculated on histo-anatomical slides using computer-based imaging software. Associations between the different variables were calculated using Spearman correlation with 95% confidence intervals (CIs). Results: In the non-cancerous areas of the PZ, prostate volume and average capsule thickness are positively associated (rs = +0.6526, 95% CI +0.5233 to +0.7526, p < 0.0001), while prostate volume and average glandular epithelial cell density of the PZ are negatively associated (rs = −0.6011, 95% CI −0.7133 to −0.4589, p < 0.0001). These associations remain consistent on subgroup analysis. Conclusion: The findings of this study support the hypothesis that transition zone (TZ) growth in large BPH prostates may cause pressure on the outer PZ, leading to fibrosis and atrophy of the glandular tissue. This may provide a protective effect against PCa, as most PCa originates in the PZ of the prostate. Level of evidence: Not applicable [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the therapeutic value of pelvic lymph node dissection (PLND) in high-grade margin-negative prostate cancer without and with lymph node metastases. Methods: We retrospectively reviewed cases in the Western Australian radical prostatectomy (RP) database between January 1, 2010, and December 31, 2017. We identified men who had RP only (no PLND) and those had RP with PLND. Further, a subset of high-grade (Gleason score (GS) ⩾8) margin-negative cancers were identified. We assessed the therapeutic impact of PLND in this high-risk but potentially curable subset. Results: A total of 5648 prostatectomies were performed, and 1209 of these had concurrent PLND, negative surgical margins, and follow-up prostate-specific antigen (PSA) data. Of 558 men with high-grade margin-negative prostate cancer, 395 men had PLND, while 163 did not. There were significantly more patients with T3/T4 disease in the PLND group compared to those without PLND. Preoperative PSA did not differ significantly between the two groups. However, when stage matched, PLND had no impact on the numbers of men who were cured compared to those who failed surgical intervention. Conclusion: PLND has value in staging high-grade prostate cancer but has limited impact on producing a durable PSA cure or avoiding adjuvant therapy. Level of evidence: Not applicable for this multicenter audit. [ABSTRACT FROM AUTHOR]

To investigate the predictors of Gleason Grading Group (GGG) upgrading in low-risk prostate cancer (Gleason score = 3 + 3) from transperineal biopsy after radical prostatectomy (RP). The clinical data of 160 patients who underwent transperineal biopsy and RP from January 2017 to December 2022 were retrospectively analyzed. First, univariate and multivariate logistic regression analysis were used to obtain independent predictors of postoperative GGG upgrading. Then receiver operating characteristic curve was used to evaluate the diagnostic efficacy of predictors. Finally, Linear-by-Linear Association test was used to analyze the risk trends of patients in different predictor groups in the postoperative GGG. In this study, there were 81 cases (50.6%) in the GGG concordance group and 79 cases (49.4%) in the GGG upgrading group. Univariate analysis showed age, free/total prostate-specific antigen (f/tPSA), proportion of positive biopsies, positive target of magnetic-resonance imaging (MRI) and positive target of contrast-enhanced ultrasound had significant effects on GGG upgrading (all P <.05). In multivariate logistic regression analysis, age (odds ratio [OR] = 1.066, 95%CI = 1.007-1.127, P =.027), f/tPSA (OR = 0.001, 95%CI = 0-0.146, P =.001) and positive target of MRI (OR = 3.005, 95%CI = 1.353-76.674, P =.007) were independent predictors. The prediction model (area under curve = 0.751 P <.001) had higher predictive efficacy than all independent predictors. The proportion of patients in exposed group of different GGG increased with the level of GGG, but decreased in nonexposed group, and the linear trend was significantly different (all P <.001). Age, f/tPSA, and positive target of MRI were independent predictors of postoperative GGG upgrading. The predictive model constructed had the best diagnostic efficacy. [ABSTRACT FROM AUTHOR]

Efficiently detecting and characterizing metastatic bone lesions on staging CT is crucial for prostate cancer (PCa) care. However, it demands significant expert time and additional imaging such as PET/CT. We aimed to develop an ensemble of two automated deep learning AI models for 1) bone lesion detection and segmentation and 2) benign vs. metastatic lesion classification on staging CTs and to compare its performance with radiologists. This retrospective study developed two AI models using 297 staging CT scans (81 metastatic) with 4601 benign and 1911 metastatic lesions in PCa patients. Metastases were validated by follow-up scans, bone biopsy, or PET/CT. Segmentation AI (3DAISeg) was developed using the lesion contours delineated by a radiologist. 3DAISeg performance was evaluated with the Dice similarity coefficient, and classification AI (3DAIClass) performance on AI and radiologist contours was assessed with F1-score and accuracy. Training/validation/testing data partitions of 70:15:15 were used. A multi-reader study was performed with two junior and two senior radiologists within a subset of the testing dataset (n = 36). In 45 unseen staging CT scans (12 metastatic PCa) with 669 benign and 364 metastatic lesions, 3DAISeg detected 73.1% of metastatic (266/364) and 72.4% of benign lesions (484/669). Each scan averaged 12 extra segmentations (range: 1–31). All metastatic scans had at least one detected metastatic lesion, achieving a 100% patient-level detection. The mean Dice score for 3DAISeg was 0.53 (median: 0.59, range: 0–0.87). The F1 for 3DAIClass was 94.8% (radiologist contours) and 92.4% (3DAISeg contours), with a median false positive of 0 (range: 0–3). Using radiologist contours, 3DAIClass had PPV and NPV rates comparable to junior and senior radiologists: PPV (semi-automated approach AI 40.0% vs. Juniors 32.0% vs. Seniors 50.0%) and NPV (AI 96.2% vs. Juniors 95.7% vs. Seniors 91.9%). When using 3DAISeg, 3DAIClass mimicked junior radiologists in PPV (pure-AI 20.0% vs. Juniors 32.0% vs. Seniors 50.0%) but surpassed seniors in NPV (pure-AI 93.8% vs. Juniors 95.7% vs. Seniors 91.9%). Our lesion detection and classification AI model performs on par with junior and senior radiologists in discerning benign and metastatic lesions on staging CTs obtained for PCa. [ABSTRACT FROM AUTHOR]

Copyright of Konuralp Medical Journal / Konuralp Tip Dergisi is the property of Duzce University Medical School and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT‐driven LIF/LIFR signaling induces brain‐derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration‐resistant PCa (CRPC) and a positive correlation with programmed death‐ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to determine changes in patient-reported hematuria and urinary symptoms after hyperbaric oxygen (HBO2) treatment for radiation cystitis (RC). Materials and Methods: We analyzed prospectively collected data from the Multicenter Registry for Hyperbaric Oxygen Therapy Consortium accumulated within a week of beginning and ending HBO2. Measures included the modified Radiation Therapy Oncology Group (RTOG) Hematuria Scale, Urinary Distress Inventory Short Form, and EuroQol Five Dimension Five Level instrument. RTOG hematuria and Urinary Distress Inventory Short Form scores were compared using the sign test. Logistic regression was used to evaluate characteristics associated with hematuria improvement. Results: A total of 470 registry patients had RC. The median age, number of HBO2 sessions, and years after radiation were 73 (IQR 12) years, 39 (IQR 10) sessions, and 5 (IQR 8) years, respectively. Eighty-four percent of patients (393/470) had prostate cancer--related radiation. EuroQol Five Dimension Five Level scores improved from 0.83 (IQR 0.14) to 0.85 (IQR 0.22; P < .001. Three hundred seventy patients had complete RTOG hematuria scores that improved from 2 (IQR 2) to 0 (IQR 2; P < .001. Two hundred forty-six patients had complete Urinary Distress Inventory Short Form ratings that decreased from 33.3 (IQR 44) to 22.2 (IQR 33; P < .001). Regression analysis of those with visible hematuria before HBO2 showed lower improvement odds associated with higher HBO2 hematuria scores (odds ratio [OR] 0.44, 95% CI 0.26-0.73; P < .01), a smoking history (OR 0.44, 95% CI 0.21-0.92; P [ .03), or a nonprostate cancer history (OR 0.32, 95% CI 0.10-0.99; P [ .05). Conclusions: HBO2 for RC improved reported hematuria, urinary function, and quality of life. Higher baseline hematuria scores, smoking, and nonprostate cancer history were associated with lower odds of hematuria improvement. [ABSTRACT FROM AUTHOR]

Purpose: Family history and germline genetic risk single nucleotide polymorphisms (SNPs) have been separately shown to stratify lifetime risk of prostate cancer. Here, we evaluate the combined prognostic value of family history of prostate and other related cancers and germline risk SNPs among patients with favorable-risk prostate cancer. Materials and Methods: A total of 1367 participants from the prospective Health Professionals Follow-up Study diagnosed with low- or favorable intermediaterisk prostate cancer from 1986 to 2017 underwent genome-wide SNP genotyping. Multivariable Cox regression was used to estimate the association between family history, specific germline risk variants, and a 269 SNP polygenic risk score with prostate cancer--specific death. Results: Family history of prostate, breast, and/or pancreatic cancer was observed in 489 (36%) participants. With median follow-up from diagnosis of 14.9 years, participants with favorable-risk prostate cancer with a positive family history had a significantly higher risk of prostate cancer--specific death (HR 1.95, 95% CI 1.15-3.32, P [ .014) compared to those without any family history. The rs2735839 (19q13) risk allele was associated with prostate cancer--specific death (HR 1.81 per risk allele, 95% CI 1.04-3.17, P [ .037), whereas the polygenic risk score was not. Combined family history and rs2735839 risk allele were each associated with an additive risk of prostate cancer--specific death (HR 1.78 per risk factor, 95% CI 1.25-2.53, P [ .001). Conclusions: Family history of prostate, breast, or pancreatic cancer and/or a 19q13 germline risk allele are associated with an elevated risk of prostate cancer--specific death among favorable-risk patients. These findings have implications for how family history and germline genetic risk SNPs should be factored into clinical decision-making around favorable-risk prostate cancer. [ABSTRACT FROM AUTHOR]

To investigate the predictive value of the pre-treatment diffusion parameters of diffusion-weighted magnetic resonance imaging (DW-MRI) using artificial intelligence (AI) for prostate-specific antigen (PSA) response in patients with low- and intermediate-risk prostate cancer (PCa) treated with stereotactic ablative radiotherapy (SABR). Retrospective evaluation was performed for 30 patients using pre-treatment multi-parametric MR image datasets between 2017 and 2021. MR-based mean- and minimum apparent diffusion coefficients (ADC mean , ADC min) were calculated for the intraprostatic dominant lesion. Therapeutic response was assessed using PSA levels. Predictive performance was assessed by the receiver operating characteristic (ROC) analysis. Statistics performed with a significance level of p ≤ 0.05. No biochemical relapse was detected after a median follow-up of twenty-three months (range: 3–50), with a median PSA of 0.01 ng/ml (range: 0.006–2.8) at the last examination. Significant differences were observed between the pre-treatment ADC mean , ADC min parameters, and the group averages of patients with low and high 1-year-PSA measurements (p < 0.0001, p < 0.0001). In prediction, the random forest (RF) model outperformed the decision tree (DT) and support vector machine (SVM) models by yielding area under the curves (AUC), with 0.722, 0.685, and 0.5, respectively. Our findings suggest that pre-treatment MR diffusion data may predict therapeutic response using the novel approach of machine learning in PCa patients treated with SABR. Clinicians shall measure and implement the evaluation of the suggested parameters (ADC min , ADC mean) to provide the most accurate therapy for the patient. [ABSTRACT FROM AUTHOR]

Objective: Infection is one of the common complications of post-prostate biopsy. Therefore, prophylaxis with fluoroquinolones and/or cephalosporins is recommended. We aimed to evaluate the prevalence of antibiotic-resistant bacteria isolated from rectal swabs in candidates for transrectal ultrasound-guided (TRUS) biopsy. The possible patient's related risk factors attributing to resistance to antibiotics were also assessed. Methods: This cross-sectional study was performed on 126 male patients who were candidates for TRUS biopsy. Rectal swabs were collected and the samples were transferred to the laboratory in Amies transport medium during 2 hours and cultured on MacConkey agar with ciprofloxacin 1 mg/L and ciprofloxacin-resistant strains were identified. Kirby-Bauer disc diffusion method was used to determine the antibiotic susceptibility of the isolates. Results: In total, 59 bacterial isolates were obtained, which were Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, respectively, in terms of frequency. They showed the lowest resistance to levofloxacin. Smoking was associated with positive culture results. Age was a factor with a significant effect on carrying ciprofloxacin-resistant strains. Conclusion: Ciprofloxacin resistance was high in almost all strains, but post-biopsy infectious complications were very low. Level of evidence: Not applicable [ABSTRACT FROM AUTHOR]

Objective: This study examines the diagnostic accuracy of multi-parametric magnetic resonance imaging (mpMRI) in a high-volume centre to potentially stratify patients prior to prostate biopsy. Methods: All biopsy naïve patients who had mpMRI prostate and transperineal biopsy of prostate (TPBx) in 2017 and 2018 were included. There were no exclusion criteria. All patients, regardless of the mpMRI result, underwent systematic template biopsy under general anaesthesia with cognitive target biopsy if indicated. Clinicopathological data were extracted from medical records. The primary outcome was the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of mpMRI prostate in the detection of prostate cancer (PCa) compared with template TPBx. Results: In total, 140 patients were included. Overall, 57.1% had a positive biopsy. A higher Prostate Imaging-Reporting and Data Systems (PI-RADS) score was associated with a higher risk of diagnosing clinically significant PCa (International Society of Urological Pathology (ISUP) ⩾ 2) (p < 0.001). The sensitivity, specificity, NPV, and PPV of mpMRI in detecting clinically significant PCa with a PI-RADS ⩾ 3 lesion, was 95% (95% confidence interval (CI) 83.0–99.3%), 41% (95% CI 31.3–51.3%), 95.3% (95% CI 84.2–99.4%) and 39.2% (95% CI 29.4–49.6%), respectively. Combining this with prostate-specific antigen density (PSAD) of <0.15 further improved the NPV to 100% (86.3–100). Binomial logistic regression to understand the effects of PSA, DRE and PI-RADS score on predicting clinically significant PCa (ISUP ⩾ 2) found increasing PSA (odds ratio (OR) 1.06, (95% CI 1.00–1.11, p = 0.022)) and PI-RADS (OR 3.17, (95% CI 1.94–5.18, p < 0.001)) to be significant predictors. Malignant DRE was not a significant predictor (p = 0.087). Conclusion: This study demonstrates that the high sensitivity and NPV of mpMRI combined with PSAD may play a pivotal role in stratifying men for prostate biopsy and help avoid biopsy and its associated morbidity in select patients. Level of Evidence: 2b (Oxford Centre for Evidence-Based Medicine: Levels of Evidence) [ABSTRACT FROM AUTHOR]

Bien que la thérapie par la testostérone (TRT) soit recommandée chez les hommes hypogonadiques, cette thérapie est toujours théoriquement contre-indiquée chez les hommes ayant des antécédents de cancer de la prostate. Des données plus récentes suggèrent que la croissance ou l'évolution du cancer de la prostate est minime ou inexistante en cas d'administration de testostérone chez les hommes traités pour un cancer de la prostate localisé. Une revue de la littérature de la base de données PubMed a été effectuée pour identifier les études évaluant le risque de cancer de la prostate sous TRT mais également la sécurité et l'efficacité du TRT chez les patients ayant des antécédents de cancer de la prostate. La littérature disponible fournit des preuves de la sécurité de l'application de la TRT chez les patients hypogonadiques à risque de développer un cancer de la prostate en surveillance active ou précédemment traités pour un cancer de la prostate localisé que ce soit par prostatectomie ou par radiothérapie. Maintenant, il existe même des preuves que des taux bas de testostérone peuvent conduire à des résultats oncologiques plus défavorables. Par ailleurs, la TRT a probablement un rôle majeur à jouer dans la récupération ou le maintien de la fonction érectile et d'autres aspects de la qualité de vie, voire de survie chez les patients ayant un déficit en testostérone après avoir été traités pour un cancer de la prostate. La TRT devrait être proposée à certains patients hypogonadiques ayant un cancer de la prostate traité localisé ou un cancer de la prostate à bas risque surveillé. Cependant, le niveau de preuve reste faible et des essais contrôlés randomisés sont encore nécessaires pour confirmer avec certitude l'innocuité et l'efficacité du TRT dans cette population. Although testosterone therapy (TRT) is recommended in hypogonadal men, it is still theoretically contraindicated in men with a history of prostate cancer. More recent data suggest that prostate cancer growth or progression is minimal or non-existent with testosterone administration in men treated for localized prostate cancer. A literature review of the PubMed database was carried out to identify studies evaluating the risk of prostate cancer under TRT but also the safety and efficacy of TRT in patients with a history of prostate cancer. The available literature provides evidence of the safety of applying TRT in hypogonadal patients at risk of developing prostate cancer under active surveillance or previously treated for localized prostate cancer either by prostatectomy or radiotherapy. Now, there's even evidence that low testosterone levels can lead to worse oncological outcomes. Furthermore, TRT probably has a major role to play in the recovery or maintenance of erectile function and other aspects of quality of life, and even survival in patients with testosterone deficiency after treatment for prostate cancer. TRT should be offered to selected hypogonadal patients with localized treated prostate cancer or monitored low-risk prostate cancer. However, the level of evidence remains low, and randomized controlled trials are still needed to confirm with certainty the safety and efficacy of TRT in this population. [ABSTRACT FROM AUTHOR]

L'objectif était de rapporter une mise au point sur les modalités de la surveillance active (SA) dans le cancer de la prostate (CaP) à risque intermédiaire. Une recherche sur la base de données PubMed et un examen narratif des articles en français ou en anglais ont été effectués en février 2024 afin de proposer une revue compréhensive de la littérature sur le sujet. Dans l'essai ProtecT qui incluait 34 % de patients à risque intermédiaire ou élevé, en utilisant un protocole de SA allégé, la surveillance a démontré sa capacité à maintenir une survie similaire en comparaison aux traitements radicaux. Dans une récente méta-analyse incluant 29 673 patients à risque intermédiaire non sélectionnés (incluant les ISUP 3), le risque de traitement définitif et de métastase était augmenté en comparaison aux patients à faible risque, mais était similaire en analyse en sous-groupe lorsque les patients ISUP 3 étaient exclus. Les patients avec une maladie ISUP 2 sont candidats à la SA si la maladie présente par ailleurs des critères favorables (PSA < 10 ng/mL, stade ≤ T2a), une faible charge tumorale à la biopsie (< 3 biopsies positives et < 50 % d'envahissement par biopsie) et une faible proportion de grade 4 (< 10 %). Les modalités de surveillance les plus communément admis ont été énumérées dans les recommandations du CCAFU et dans le consensus DETECTIVE et incluent un toucher rectal annuel, un contrôle régulier du PSA (tous les 6 mois), et la réalisation d'IRM et de biopsies de suivi. La SA est une option pour certains patients sélectionnés à risque intermédiaire. Les patients doivent néanmoins être informés du faible niveau de preuve disponible et s'astreindre à une surveillance rigoureuse. To report an update on the modalities of active surveillance (AS) in intermediate-risk prostate cancer (PCa). A search of the PubMed database and a narrative review of articles in French or English were carried out in February 2024 to provide a comprehensive review of the literature. In the ProtecT trial, which included 34% of intermediate- or high-risk patients, using a mild AS protocol, monitoring demonstrated its ability to maintain a survival rate similar to that of radical treatments. In a recent meta-analysis including 29,673 unselected intermediate-risk patients (including ISUP 3), the risk of definitive treatment and metastasis was increased compared with low-risk patients but was similar in subgroup analysis when ISUP 3 patients were excluded. Patients with ISUP 2 disease are candidates for AS if the disease otherwise has favorable criteria (PSA < 10 ng/mL, stage ≤ T2a), a low biopsy tumor burden (< 3 positive biopsies and < 50% biopsy core involvement) and a low proportion of grade 4 (< 10%). The most commonly accepted surveillance modalities were listed in the CCAFU guidelines and the DETECTIVE study and include an annual digital rectal examination, regular PSA monitoring (every 6 months), and MRI + biopsies during follow-up. AS is an option for selected intermediate-risk patients. However, patients should be informed of the low level of evidence available and undertake rigorous monitoring. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Due to infectious complications of transrectal prostate biopsy (TRBx), the transperineal prostate biopsy (TPBx) technique is gaining popularity and is the first-line method in many institutions. We share our experience of the first 100 patients with TPBx, performed using the coaxial needle technique under local anesthesia. PATIENTS AND METHODS: We retrospectively reviewed the records of the first 100 patients who had undergone TPBx between December 2022 and September 2023. Complication rates, cancer detection rates, patient tolerance, and pain response to the TPBx under local anesthesia at different steps of the procedure were collected. RESULTS: The mean age, total prostate-specific antigen (PSA), prostate volume, and PSA density were 64.5±7.5 years, 8.82±12 ng/mL, 58.4±26.4 mL, and 0.17±0.18 ng/mL2. Prostate cancer (PCa) was detected at histopathological evaluation in 51 patients. The mean positive core number and percentage of cancer involvement per core in patients who have PCa were 5.4±3.2 and 68.5±29.1, respectively. The mean pain score during the entire procedure was 2.85±1.48. When the steps are evaluated separately, the mean pain score during the probe placement step, local anesthetic, and sampling steps were 3.35±1.65, 2.54±1.45, and 0.9±0.82, respectively. CONCLUSIONS: Transperineal prostate biopsy with coaxial needle technique under local anesthesia is a well-tolerated procedure with feasible complication rates and patient discomfort. [ABSTRACT FROM AUTHOR]