The real-world outcomes of patients with metastatic prostate cancer (mPCa) are largely unexplored. We investigated the improvements in overall survival (OS) and cancer-specific survival (CSS) in patients with de novo mPCa in latest years. The USA SEER Research Data (2000-2017) were analyzed using the SEER*Stat software. The Kaplan-Meier method and Cox regression were used. Patients with de novo mPCa were allocated to 3 cohorts based on year of diagnosis: A (2000-2003), B (2004-2010), C (2011-2014). Maximum follow-up was fixed to 5 years. Overall, 26434 patients were included. Age, race and metastatic stage significantly affected OS and CSS. After adjustment for age and race, patients in cohort C showed 9% reduced risk of death (HR:0.91 [95% CI, 0.87-0.95], p<0.001) and 8% reduced risk of cancer-specific death (HR:0.91 [95% CI, 0.87-0.95], p<0.001) compared to those in cohort A. After adjustment for age, race and metastatic stage, patients in cohort C showed an improvement in OS and CSS compared to cohort B (HR:0.94 [95% CI, 0.91-0.97], p=0.001 and HR:0.89 [95% CI, 0.85-0.92], p<0.001). Patients with M1c disease had a more pronounced improvement in OS and CSS compared with the other stages. No differences were found between cohort B and C. In conclusion, the prognosis of de novo mPCa remains poor with a median OS of 30 months and a median CSS of 35 months. Limited OS and CSS improvements were observed in latest years.

Lower urinary tract symptoms (LUTS) and hematuria are common symptoms in men with benign prostatic hyperplasia (BPH) and prostate cancer (PCa) mainly affecting the elderly population. Prostatic arterial embolization (PAE) is a minimally invasive pro-cedure that has shown promising results in managing massive intractable prostatic he-maturia in patients with BPH and PCa. A few studies, however, have provided valuable insights into the durability and efficacy of PAE focusing on the long-term effectiveness, quality of life, and cancer-specific control of hemostasis and urinary symptoms. As a result of concomitant cardiovascular conditions, these patients often take anticoagulants or antithrombotics, which can worsen their hematuria and clinical status. Transurethral resection of the prostate (TURP) is considered a very high-risk procedure even without massive bleeding, and requires discontinuation of Vitamin K antagonists and antiplate-let therapies. Such patients usually have their surgery postponed, and PAE should be considered a safe alternative treatment. We aimed to report a narrative review from 1976 to June 2023 of the current state of PAE for massive and intractable hematuria highlighting recent developments in this technique, including prospective cohort stud-ies and focusing on long-term outcome, safety, and complication management in PCa patients with significant hemorrhagic symptoms. As an additional contribution, we propose a simple algorithm for treating intractable bleeding associated with prostate cancer in a 92-year-old man with LUTS.

This study aimed to investigate Coll-I, III, IV and elastin in canine normal prostate and PC, using Picrosirius red (PSR) and Immunohistochemical (IHC) analysis. Eight normal prostates and 10 PC from formalin-fixed, paraffin-embedded samples were used. Collagen fibers area was analyzed with ImageJ software. The distribution of Coll-I and Coll-III was approximately 80% around prostatic ducts and acini, 15% among smooth muscle and 5% surrounding blood vessels, in both normal prostate and PC. There was a higher median area of Coll-III in PC, when compared to normal prostatic tissue (p=0.001 for PSR and p= 0.05 for IHC). Immunostaining for Coll-IV was observed in the basal membrane of prostate acini, smooth muscle, blood vessels, and nerve fibers of normal and PC samples. Although there was no difference in Coll-IV area between normal tissue and PC, tumors with Gleason score 10 showed absence of Coll-IV, when compared to scores 6 and 8 (p=0.0095). Elastic fibers were found in the septa dividing the lobules and around the prostatic acini of normal samples, and was statistically higher in PC, compared to normal tissue (p=0.00229). Investigation of ECM components brings new information and should be correlated with prognosis in future studies.

We present a case of neglected atypical high grade prostatic stromal sarcoma (PSS) at the transitional zone , invading the peripheral zone, prostatic capsule & peri prostatic fat reaching to pelvic side wall, it showed T2WI hyperintense signal (compared to typical cases of PSS showing T2WI hypointense signal) corresponding to developing on top of pre-existing nodular hyperplasia. Careful reviewing of prostatic central / transitional zone lesions is mandatory especially at T2WI, diffusion & contrast images to exclude malignancy which can be easily missed due to multiple signal patterns described. Most common tumors at transitional zone is stromal sarcoma which could be typical showing T2 hypointense signal or atypical showing T2 hyperintense signal intensity.

Background: Prostate cancer is a complex condition, in which both genetic and environmental factors concomitantly contribute to the tumor initiation and progression. Recently, HOXB13 has been proposed as a susceptibility gene for prostate cancer. Objective: So the current study was conducted to test the existence of potential variations in HOXB13 gene in Iranian men with prostate cancer (PCa) compared to benign prostatic hyperplasia (BPH) cases. Methods: The HOXB13 genetic status was screened in 51 samples, including 21 blood and tissue of PCa cases compared to 30 cases affected by BPH using PCR/sequencing. Then potential association between genomic DNA alterations in blood and tissue PCa specimens was investigated Results: Analysis of BPH tissues showed single nucleotide variations c.366C > T (rs) or c.513T > C (rs9900627) in exon 1, but not in exon 2. Evaluation of PCa tissues revealed two cases with both synonymous c.366C > T and c.513T > C variants and two cases with the synonymous c.366C > T variant in exon 1. The variants c.366C > T and c.513T > C simultaneously or separately were found blood samples of PCa patients. The novel variant c.127A > G in the exon 2 was detected in 1 PCa blood sample. Our analysis indicated a significant reciprocal correlation between HOXB13 mutation in tissue and blood in PCa cases (P=0.02). Conclusion: The variants in exon 2 of HOXB13 may influence the risk of prostate cancer. Also, evaluation of HOXB13 mutation may be considered as a novel marker for screening of PCa. Further investigations are warranted to evaluate the clinical significance of HOXB13 in Iranian population.

Introduction: Lowered thiol or sulfhydryl (-SH) groups and glutathione (GSH) metabolism may be associated with prostate cancer (PCa) and benign prostatic hyperplasia (BPH). The main objectives of this study were to systematically review and meta-analyze the evidence on the associations among -SH groups, GSH, GSH peroxidase (GPx), GSH reductase (GR) and GSH transferase (GST) and PCa/BPH. Methods: Four electronic databases were searched for studies that reported -SH and GSH variables in PCa/BPH and healthy controls (HC) and the data were meta-analyzed by calculating Hedges’s g with 95% confidence intervals. Results: Twenty studies were included in this meta-analysis including 800 PCa and 791 BPH patients and 592 HC. Total -SH (g=-1.750, -2.341/-1.159), GPx (g=-0.789, -1.234/-0.344), GSH (g=-2.219, -4.132/-0.305), and the combination of -SH, GPx, and GSH (g=-1.271, -1.271/-0.800) were significantly lower in PCa patients than in HC. -SH (g=-1.752, -3.123/-0.381) and the combination of -SH, GPx, and GSH (g=-0.813, -1.298/-0.327) were significantly lower in BPH patients than in HC. GPx was significantly lower in PCa than in BPH patients (g=-0.455, -0.896/-0.014). Heterogeneity levels were very high, but Egger’s test showed that none of the biomarkers showed significant publication bias. Conclusion: Thiol/GPx antioxidant defenses are significantly attenuated in patients with PCa while patients with BPH occupy an intermediate risk group position between PCa patients and HC. Those results suggest that reduced thiol-related antioxidant mechanisms play a crucial role in prostatic disorders, especially in PCa. Future research should examine whether thiols/GPx antioxidants are associated with the onset of PCa/BHP.

The changes in body composition during androgen deprivation therapy (ADT) in patients suffer from prostate cancer (PCa) are recognized by professionals more often as key for effective treatment. The aim of this study was to investigate the impact of ADT on the sarcopenia development in PCa. The following databases were used: PubMed, Embase, Web of Science and Scopus databases. Out of 2183 studies, 7 were included in this review. The fixed-effect model was used in the meta-analysis. Significant increase in SATI: 0.32 (95%CI: 0.13-0.51) p= 0.001, de-crease in SMI: -0.38 (95% CI: -0.57 to -0.19) p < 0.0001 and SMD: -0.46 (95% CI: -0.69 to -0.24) p < 0.0001 was observed. No statistical association was visible between ADT and changes in BMI: 0.05 (95%CI: -0.18-0.28), p= 0.686 and VATI: 0.17 (95% CI: -0.02 to 0.37), p=0.074. In conclusion, the ADT significantly contributes to the body composition changes and sarcopenia development.

According to the guidelines of the European Association of Urology (EAU), it is recommended to exclude PSA testing when the expected remaining lifespan is less than 10 years. In this study, we provide a comprehensive analysis of the impact of prostate-specific antigen (PSA) testing on the quality of life of elderly men who are frail. We conducted a comprehensive literature review to identify publications that examine the use of PSA as a screening and prognostic tool for prostatic illnesses in frail men. Our search included the following keywords: Prostate-specific antigen, Frailty, Prostate cancer screening, Hypogonadism, and Benign Prostatic Obstruction (BPO). Prostate-specific antigen (PSA) testing can be used to identify prostate cancer in its early and treatable stages in fragile men with a life expectancy of over 15 years. Additionally, PSA testing allows for the evaluation of the effectiveness of various prostate cancer treatments and the monitoring of testosterone replacement therapy for hypogonadism. PSA is also indicative of the clinical development of patients with benign prostatic obstruction (BPO). Nevertheless, PSA is being extensively provided without individualised patient assessment, contributing to the economic strain on healthcare systems. Conducting a frailty evaluation on men to determine the potential advantages of PSA tests on their quality of life will help minimise avoidable expenses.

Biochemical recurrence (BCR) after primary treatments for prostate cancer (PC) is an extremely heterogeneous phase and at least a stratification in low and high-risk cases for early progression in metastatic disease is necessary. At now PSA-DT represents the best parameter to define low and high risk BCR PC, but a real precision medicine is strongly suggested to define a tailored management of patients with BCR. Before defining management, it is necessary to exclude the presence of low volume metastasis associated with PSA progression using new generation imaging preferably with PSMA PET/CT. Low risk BCR cases should be actively observed without early systemic therapies. Early treatment of low risk BCR with continuous androgen deprivation therapy (ADT) can produce disadvantages such the development of castration resistance before the appearance of metastases (non-metastatic castration resistant PC). Patients with high risk BCR benefit from early systemic therapy. The primary end point must be metastasis-free survival (MFS), even with the same overall survival (OS). The EMBARK study is able to impact on the management of high risk BCR, by introducing the concept of anticipation and intensification through the use of androgen receptor signaling inhibitors (ARSI) and ADT combination therapy. In high risk (PSA-DT ≤ 9 months) BCR cases, the combination of enzalutamide with leuprolide significantly improves MFS when compared to leuprolide alone, maintaining the quality of life unchanged in an asymptomatic phase of the disease. The possibility of using ARSI alone in this early disease setting is suggested by the EMBARK study (arm with enzalutamide alone) with less evidence than the intensification of the combination therapy. Continued use versus discontinuation upon reaching undetectable PSA levels of enzalutamide plus leuprolide intensified therapy needs to be better defined with further analysis. Real world analysis must verify the significant results obtained in the context of a phase 3 study.

Obesity represents a worldwide epidemic disorder, increasing the overall morbidity and mortality rate. In this study we investigated the impact of obesity on peri-operative and long-term functional outcomes of Robotic assisted simple prostatectomy (RASP). Baseline flowmetry parameters and validated questionnaires’ scores were prospectively recorded. Follow-up assessments included Flowmetry and validated questionnaires. Composite outcomes (Trifecta) was defined as combination of: post-operative Q-max>15 ml/sec, IPSS score<8 and absence of complications. Pentafecta included also post-operative ejaculation persistence (MSHQ score>0) and the Erectile function maintenance (∆IEEF<6). Data were stratified by BMI (<30 or ≥30). 81 patients underwent RASP in our Institution. Baseline demographics and clinical features, questionnaires score and baseline flowmetry results were comparable between obese and non-obese cohorts. At follow-up, obese patients reported lower subjective improvement in IPSS (p=0.02) and OABQ scores (p<0.001) and higher incidence of stress incontinence requiring Duloxetin (p<0.001). Flowmetry outcomes, were also worse in this cohort (p=0.02 and p=0.03, respectively). At comprehensive outcomes assessment, obese patients had comparable Trifecta (67% vs 54%, p=0.39) and pentafecta achievement rate (p=0.76). Our prelimirary results proved that obesity is associated with worse functional outcomes (storage LUTS and incontinence rate) after RASP, but doesn’t affect trifecta and pentafecta achievement rate.

Background: The currently advised follow-up scheme of PSA-testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. Methods: All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had &lt;1 year of PSA follow-up. Postoperative PSA-values were collected. Biochemical persistence (BCP) was defined as PSA-level &gt;0.10 ng/mL at 0-4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA-level &gt;0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time-points after surgery. Results: Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥0.2 ng/mL. BCR further developed in 51 (4.7%), and 37 (3.4%) patients at 5-8 and 9-12 months after RARP, respectively. In 12 patients, BCR was found at 5-8 months after RARP in absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA-level at 0-4 months after RARP also had unmeasurable PSA-level 5-8 months after surgery. Limitations are the retrospective design and incomplete follow-up. Conclusions: Patients with an unmeasurable PSA-level at 3-4 months after RARP may not need to be retested until 12 months of follow-up as almost 100% of patients will not have biochemically recurrent disease at 5-8 months of follow-up. This will reduce PSA-testing substantially at the costs of hardly any missed patients with recurrent disease.

Simple cysts (SCs) within the testes are rare in adults. The testicular SC lining comprises mesothelial cells. This report presents a case involving the accidental discovery of a castration-worthy SC in the right testis of a Japanese man in his 90s who was diagnosed with prostatic adenocarcinoma. Microscopic analysis revealed that the cystic wall was covered with flat to cuboidal mesothelial cells. Immunohistochemistry demonstrated mesothelial cell positivity for calretinin, Wilms tumor 1 (WT-1), Hector Battifora mesothelial epitope-1 (HBME-1), and cyclin-dependent kinase inhibitor p16 (p16INK4a). Notably, no human papillomavirus (HPV) in situ hybridization was detected. This report outlines an exceptionally rare instance of a simple cyst within the testis, suggesting the possibility of its origin from ectopic rete testis epithelium. This marks the inaugural documentation in the English literature of an SC within the testis found incidentally during castration for prostatic cancer.

Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine ε-nitrogen atom, a dipeptide as peptide fragment of the linker, including two phenylalanine residues in the L-configuration, and 3- or 4-(tributylstannyl)benzoic acid as prosthetic group in their structures for radiolabeling. The standard compounds ([127I]PSMA-m-IB and [127I]PSMA-p-IB) for comparative and characterization studies were firstly synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence, followed by replacement of the Sn(Bu)3 group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [123I]PSMA-p-IB was higher than those of [123I]PSMA-m-IB, which were 74.9± 1.0% and 49.4 ± 1.2%, respectively. The radiochemical purity of [123I]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [123I]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [123I]PSMA-p-IB showed less accumulation than [177Lu]Lu-PSMA-617 in several normal organs (liver, kidney and bone). These results warrants further preclinical development including toxicology evaluation and experiments in tumor-bearing mice.

The accuracy of multi-parametric MRI (mpMRI) in pre-operative staging of prostate cancer (PCa) remains controversial. Objective: To evaluate the ability of mpMRI to accurately predict PCa extra-prostatic extension (EPE) on a side-specific basis using a risk-stratified 5-point Likert scale. This study also aimed to assess the influence of mpMRI scan quality on diagnostic accuracy. Patients and Methods: We included 124 men who underwent robot-assisted RP (RARP) as part of the NeuroSAFE PROOF study at our centre. Three radiologists retrospectively reviewed mpMRI blinded to RP pathology and assigned a Likert score (1-5) for EPE on each side of the prostate. Each scan was also ascribed a Prostate Imaging Quality (PI-QUAL) score for assessing the quality of the mpMRI scan, where 1 represents poorest and 5 represents best diagnostic quality. Outcome measurements and statistical analyses: Diagnostic performance is presented for binary classification of EPE including 95% confidence intervals and area under the receiver operating characteristic curve (AUC). Results: A total of 231 lobes from 121 men (mean age 56.9 years) were evaluated. 39 men (32.2%), or 43 lobes (18.6%) had EPE. Likert score ≥3 had sensitivity (SE), specificity (SP), NPV, PPV of 90.4%, 52.3%, 96%, 29.9%, respectively, and AUC was 0.82 (95% CI: 0.77-0.86). AUC was 0.63 (95% CI: 0.37-0.9), 0.77 (0.71-0.84) and 0.92 (0.88-0.96) for biparametric scans, PI-QUAL 1-3 and PI-QUAL 4-5 scans, respectively. Conclusions: MRI can be used effectively by genitourinary radiologists to rule out EPE and help inform surgical planning for men undergoing RARP. EPE prediction was more reliable when the MRI scan was a) multi-parametric and b) of a higher image quality according to the PI-QUAL scoring system.

Objective To assess the quality and readability of online information on holmium laser enucleation of the prostate in management of benign prostate hyperplasia using the most used search engine worldwide, google. Methods The google search term “Holmium laser surgery” and “enlarged prostate” was used and the initial 150 webpages were reviewed. Webpages that were paywall, scientific literature, and/or promoted advertisements were excluded. Quality assessment tools - DISCERN, QUEST, and JAMA criteria were used, while readability tools like FKG, GFI, SMOG, and FRE score were used. Two authors independently reviewed the included sites for further analysis; for any discrepancy, a third author would be involved. Results 107 webpages were included in the data analysis. The median DISCERN score was 42 out of 80 (IQR 35-49). The median JAMA score was 0 out of 4 (IQR 0-1). The median QUEST score was 9 out of 28 (IQR 9-12). Using the non-parametric ANOVA and post-hoc test, significant differences were identified between rankings of webpages. Sponsorship had no influence on quality of webpages. Overall readability level required a minimum reading level of grade 11. Linear regression analysis showed a higher rank webpage is a positive predictor for all three quality assessment tools. Conclusion The overall quality of online information regarding HoLEP is poor. We identify that top ranked google searches have a higher DISCERN score and is a positive predictor for DISCERN/QUEST/JAMA. Quality online information can be used to benefit patients but should be used in conjunction with consultation from a medical professional.

Parts I and II of this 3-part series indicated how a global review of both English-language and non-English language papers plus a focus on a lipidosterolic extract of Serenoa repens (LSESr) having a standardized fatty acid profile have together engendered new insights about the biological activity of LSESr vs. LUTS. In this last of a 3-part series, data from the world literature is presented that confirms that LSESr efficacy is the predominant finding in clinical trials. Despite two placebo-controlled clinical trials performed in the U.S. that failed to confirm a benefit of LSESr vs. placebo in LUTS, the global body of the peer-reviewed literature attests not only to efficacy but also to safety. Results will be presented of important trials that compare LSESr to alpha-blockers such as tamsulosin (Flomax®) as well as to 5α-reductase inhibitors such as finasteride (Proscar®) that demonstrate consistent findings of near equivalency between LSESr and these pharmacologic agents. Studies relating data indicative of an additive effect or synergy between LSESr and tamsulosin will be presented as well. The heightened effectiveness of LSESr in men with severe LUTS vs. moderate LUTS expands the importance of our scrutinization of the global literature concerning LSESr. Of great consequence are the contributions of non-English language peer-reviewed publications that have consistently provided evidence of LSESr efficacy in treating LUTS/BPH. These peer-reviewed articles have shown that the effect of LSESr is not that of a placebo. Finally, a comparison of the LSESr extraction products used in the treatment of LUTS, and a discussion of the milieu factors that affect the natural history of LUTS and influence the outcome of clinical trials complete this sedulous analysis of LSESr vs. LUTS.

Given the extent of this global analysis, this report will be presented in three sections. Part I will introduce LUTS. What are the demographics of LUTS? What symptoms are assessed by LUTS and how do we quantify LUTS? Why would a non-prescription item be a valuable consideration in LUTS treatment versus other treatment options? What is basic information about Serenoa repens and what defines a standardized LSESr product? What are the published trials that have affected the acceptability of Serenoa repens in the treatment of LUTS? Finally, a major portion of Part I will discuss the four major reviews of Serenoa repens versus LUTS that have influenced how it is accepted in the USA, in Europe, and other parts of the world. Part I, therefore, lays the groundwork and is foundational for the important findings relating to LUTS and Serenoa repens that will be presented in Parts II and III.

Part I of this 3-part series provided the groundwork for understanding the role of a standardized lipidosterolic extract of Serenoa repens (LSESr) in the treatment of LUTS. It documented that a treatment having a high therapeutic index (i.e., a ratio of benefit to adverse reactions) is a critical need in the demographic context of a rapidly growing elder population. Part I described the clinical symptomatology of LUTS and how it is quantified. A critique of the reports from four authoritative bodies: the European Scientific Cooperative on Phytotherapy (ESCOP), Cochrane 2012, the European Medicines Agency (EMA), and the AUA (American Urological Association) was presented. The foundation above then fine-tuned our search to require (a) consistent evaluability criteria, (b) the quantification of clinical findings, (c) the need to focus on studies employing a standardized LSESr product meeting the fatty acid profile set forth by the European Medicines Agency (EMA) and the US Pharmacopeia and (d) a global assessment of scientific investigations published in all languages and not limited to only English. Part II details the following “new” findings when LSESr vs. LUTS is examined with the above constraints.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.