The most important prognostic factors in curatively treated prostate cancer at the initial diagnosis are T and N stage, histological subtype, Gleason score, initial PSA, PSA density and percentage of core biopsy positivity. Newer, but non-standard prognostic factors are urine PCA3 and genetic markers of prostate cancer. A simple, but seemingly underestimated standard test is serum Calcium (Ca) level, which has been shown by a previous study group to be a good predictor of lethal prostate cancer, but there is scarce evidence regarding the prognostic value of calcium levels at diagnosis. We aimed to determine whether a Ca level in the upper part of normal values has a prognostic value in curatively treated prostate cancer. We have retrospectively included 84 consecutive patients with prostate cancer, who underwent curative radiotherapy (primary or adjuvant; external beam RT with or without brachytherapy). We have performed statistical analysis of available prognostic factors. Ca level at diagnosis was found to be a statistically significant predictor of disease-free survival.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium thus most commonly found in a gastrointestinal tract, however not exclusively. Primary signet ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical case: In June of 2023 a 54-year-old Caucasian male came to the hospital complaining of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma st. IV. Unfortunately, the patient with the disease this advanced, PE, and third-degree thrombocytopenia was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results which may contribute to its late diagnosis which together with inconsistent immunohistochemical findings and unpredictable response to hormonal treatment pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusion: The study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease which may positively influence the prognosis.

Prostate cancer lung metastasis represents a clinical conundrum due to their implication of advanced disease progression and the complexities they introduce in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, the review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, the review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

The purpose of this study was to determine the maximum tolerated dose (MTD) for stereotactic body radiation therapy (SBRT) in the treatment of non-metastatic prostate cancer. This study was a phase 1 dose escalation trial conducted in Japan. Patients with histologically proven prostate cancer without lymph node or distant metastasis were enrolled. The prescribed doses were 42.5, 45, or 47.5 Gy in five fractions. Dose-limiting toxicity (DLT) was defined as grade (G) 3+ gastrointestinal or genitourinary toxicity within 180 days after SBRT completion and a 6 plus 6 design was used as the method of dose escalation. A total of 16 patients were enrolled, with 6 in the 42.5 Gy group and 10 in the 45 Gy group. No DLT was observed in the 42.5 Gy group. In the 45 Gy group, one patient experienced G3 rectal hemorrhage, and another had G4 rectal perforation, leading to the determination of 42.5 Gy as the MTD. None of the patients experienced biochemical recurrence or death during the follow-up period. We concluded that SBRT for non-metastatic prostate cancer at 42.5 Gy in 5 fractions could be safely performed, but a total dose of 45 Gy increased severe toxicity.

Recently intraductal carcinoma of the prostate (IDCP) has attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced accessibility to immune cells, which reflect the pathological characteristics of IDCP, may influence the aggressiveness of high-grade prostate cancer.

Auger electrons (AEs) represent an intriguing topic in the field of radionuclide therapy. They are emitted by several radionuclides commonly used in nuclear medicine (indium-111, iodine-123, iodine-125), allowing for highly localized energy deposition and thus exerting a radiotoxic effect on specific cellular and sub-cellular targets. However, due to their short range in matter, AEs have had limited use in therapeutic applications so far. In recent years, the synthesis of various radiopharmaceuticals capable of binding to the enzyme poly(ADP-ribose) polymerase 1 has reignited interest in this type of therapy, laying the groundwork for a theranostic approach based on radionuclides emitting AEs. The enzyme PARP-1 operates enzymatically in close proximity to DNA that represents the prime target of radionuclide therapies. Following this trend, several PARP-targeted radiopharmaceuticals for AE-based theranostics have been developed. We provide an updated overview of preclinical studies focused on the applications of this new theranostic approach in glioblastoma, breast, prostate and ovarian carcinoma, and pancreatic adenocarcinoma.

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.

Introduction: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph-nodes, instead para-aortic lymph-nodes are considered as distant metastases. Aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Material/methods: This is a retrospective analysis. De-novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; pattern of recurrence was evaluated too. A propensity score matching (PSM) was applied to create comparable cohorts. Primary end-point was the progression-free survival (PFS). Secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS) and pattern of relapse. Results: 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. Median PFS was 20 and 11 months in pelvic and para-aortic patients respectively (p=0.042). The difference was not confirmed at the multivariate analysis (p=0.06). Median BRFS was 16 and 9 months respectively in pelvic and para-aortic group (p=0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-years LPFS was 90.5%. At PSM no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have PFS comparable to pelvic disease; local control is high in both cohorts. Our results support the use of SBRT also to para-aortic metastases.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR>MTYR>>TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

Background: this interventional pilot study aimed to evaluate the short-term (3 years) efficacy of focal laser ablation (FLA) in treating the index lesion of low-intermediate risk prostate cancer, along with assessing the safety of the procedure (ClinicalTrials.gov ID NCT04045756). Methods: forty patients aged between 46 and 86 with histologically proven organ-confined prostate cancer and low to intermediate progression risk were included. FLA was performed under percutaneous fusion magnetic resonance/ultrasound guidance in a Day Hospital setting under local anesthesia. Patients underwent regular clinical assessments, PSA measurements, post-procedure MRI scans, and biopsies at 36 months or if positive findings were detected earlier. Statistical analyses were conducted to assess trends in PSA levels and cavity dimensions over time. Results: forty patients were initially included, with 15 lost to follow-up. At 36 months, a mean PSA reduction of 60% was observed, and 80% of MRI scans showed no signs of in-field clinically significant residual/recurrent cancer. Biopsies at 36 months revealed no malignant findings in 20 patients. No deterioration in sexual function or urinary symptoms was recorded. Conclusions: FLA appears to be safe, feasible and effective in the index lesion treatment of low-intermediate risk prostate cancer, with a high rate of tumor eradication and preservation of quality of life.

Prostate cancer is the second most frequent malignancy (after lung cancer) in men worldwide. Prostate tissue biopsies are usually graded using scores according to the Gleason grading system. This Gleason score is the most popular prognostic marker that reveals the potential aggressiveness of the disease. However, inter-observer variability in rating by human assessors is a major limiting factor. Such variability could lead to missing a severe case or suggesting unnecessary treatments. This study explores the discriminative ability of artificial intelligence (deep learning models) for Gleason score assessment. The study was designed to use whole-slide images of digitized H&E-stained biopsies of prostate tissues to automate the grading process and provide a remotely accessible clinical decision support system. Custom convolutional neural network architectures were trained on 10,616 images of prostate tissues. Gaussian filters were applied to pre-process the images and improve model performance. Transfer learning was applied to train eight machine learning architectures namely: Xception, VGG16 & 19, ResNet101, MobileNet, DenseNet121, EfficientNetB5 & B7. Efficient NetB7 had the best performance 85.2% compared with ground-truth classification by experts. Performance improves as more data is available. The model was deployed and hosted as a web application API on Google cloud service to ensure remote access. Tissue biopsy images can be uploaded and the corresponding Gleason score recovered immediately. This system reduces diagnostics turnaround time, increase throughput, and compensate for limited skills, especially in low resource settings.

Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration-resistance is often developed during the course of treatment, though its influences require further understanding. This study explores the human microbiome for its implications in castration-resistance and metastasis in prostate cancer. RNA sequencing data was downloaded for bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These sequences were mapped to bacterial sequences to yield species-level abundance approximations. Numerous species were found to correlate to the expression of known markers of castration-resistance, including AR, PI3K, and AKT. Castration-resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for relation to these species. EGFR and SLC3A2 were widely downregulated with greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration-resistance and stemness in prostate cancer. By considering the microbiome’s importance in these factors, we may better understand the highly aggressive and highly invasive nature of prostate cancer, allowing for needed improvement in the treatment of this disease.

Human papillomavirus (HPV) infections, primarily transmitted through sexual contact, have been linked to various cancers, including cervical, penile, anal, oropharynx, breast, and prostate cancers. This study presents a unique case of concurrent high-risk HPV35, HPV45, and HPV59 infections in both prostate and bladder cancer tissues from a single patient, representing the first documented instance worldwide with identical HPV types detected in two adjacent organs of the same individual. Employing a multiplex-PCR approach, gel electrophoresis, and Sanger sequencing, we confirmed the presence of these high-risk HPV types. Additionally, Western blot analysis using an HPV E7 antibody demonstrated the active expression of HPV oncoproteins in both cancer types. This discovery underscores the potential for HPV intra-organ transmission and necessitates further exploration of alternative transmission routes. The implications of our results offer new insights into the complex dynamics of HPV transmission in cancer pathogenesis.

This study employs molecular docking simulations using Autodock Vina with the Pyrx program to investigate the binding interactions between Human prostate-specific antigen (PSA) and natural compounds, namely Amentoflavone, Ginketin, Rutin, and Hypericin. The evaluation reveals excellent binding energy values, averaging around -10 kcal/mol, suggesting robust and favorable interactions between the selected compounds and PSA. The results provide valuable insights into the potential therapeutic applications of these natural compounds in the context of prostate cancer treatment or management. Further experimental validation is warranted to confirm these findings and explore the viability of these compounds as promising candidates for innovative therapeutic strategies. This research contributes to the growing body of knowledge in the field of molecular docking and its applications in drug discovery and bioinformatics.

Background: MRI-guided prostate biopsies from visible tumor-specific lesions (TBx) can be used to diagnose clinically significant carcinomas (csPCa) requiring treatment more selectively than conventional systematic biopsies (SBx). Ex vivo fluorescence confocal microscopy (FCM) is a novel technique that can be used to examine TBx prior to conventional histologic workup. Methods: TBx from 150 patients were examined with FCM on the day of collection. Preliminary findings were reported within 2 hours of collection. The results were statistically compared with the final histology. Results: 27/40 (68%) of the csPCa were already recognized in the intraday FCM in accordance with the results of conventional histology. Even non-significant carcinomas (cisPCa) of the intermediate and high-risk groups (PSA > 10 or 20 ng/ml) according to conventional risk stratifications were reliably detectable. In contrast, small foci of cisPCa were often not detected or were difficult to distinguish from reactive changes. Conclusion: The rapid reporting of preliminary FCM findings helps reduce the psychological stress on patients an can improve the clinical management of csPCa. Additional SBx can be avoided in individual cases, leading to lower rates of complications and scaring in the future surgical area. Additional staging examinations can be arranged without losing time. FCM represents a promising basis for future AI-based diagnostic algorithms.

Nerve-sparing vs. non nerve sparing surgery (NSS vs. non-NSS) is associated with improved functional outcomes in prostatectomy patients. The aim of the present study is to compare the oncological outcomes of patients with high-risk localized prostate cancer undergoing nerve-sparing and non nerve-sparing robot-assisted radical prostatectomy (RARP). Between November 2002 and December 2018, we prospectively recorded data of patients undergoing RARP for high-risk localized prostate cancer (PCa). NSS (nerve-sparing surgery) was offered based on preoperative clinical characteristics of patients and intraoperative assessment. Patients were stratified into 2 groups according to NSS. The primary outcome was biochemical recurrence (BCR), while positive surgical margin (PSM) and cancer-specific survival (CSS) were secondary outcomes. Logistic regression was used to investigate predictive factors. A total of 779 patients were included in the study, 429 (55.1%) underwent NSS while 350 (44.9%) underwent a non-NSS. After a mean (±SD) follow-up of 192 (±14) months, 328 (42.1%) patients developed BCR, no significant difference was found between NSS and non-NSS group (156 vs. 172; p=0.09). Both univariable and multivariable analysis found that nerve-sparing approach was not a predictor of BCR (p>0.05). NSS vs. non-NSS was not associated with worse oncological outcomes in patients with high-risk PCa

Endocrine-disrupting chemicals (EDCs) may impact the development of Prostate Cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential Oils or their metabolites like lavender oil and tea tree oil have been reported to act as potential EDCs and contribute towards sex steroid imbalance in case of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of Essential oils with CYP17A1 and CYP19A1, and functional assays were done using the radiolabeled substrates or Liquid Chromatography high‑resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone & (-)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these Essential oils in various beauty and hygiene products is common, but only a limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output, ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for the novel compounds against hyperandrogenic disorders such as PCa and PCOS.

The classification of tumors in subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when tumor responds to a therapy. In all these cases, cancer cells acquire the ability to trans-differentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma and pancreatic adenocarcinoma.

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.

Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH). Blood serum samples from mCRPC patients (n=51) and BPH patients (n=48) underwent metabolome analysis through 1H-NMR spectroscopy. The expression levels of serum exosomal miRs in mCRPC and BPH patients were evaluated using quantitative real-time polymerase chain reaction (qRT‒PCR). The 1H-NMR metabolomics analysis revealed significant alterations in lactate, acetate, citrate, 3-hydroxybutyrate, and branched-chain amino acids (BCAAs, including valine, leucine, and isoleucine) in mCRPC patients compared to BPH patients. MiR-15a, miR-16, miR-19a-3p, and miR-21 exhibited a down-regulation of more than twofold in the mCRPC group. Significant correlations were predominantly observed between lactate, citrate, acetate, and miR-15a, miR-16, miR-19a-3p, and miR-21. The importance of integrating metabolome analysis of serum with selected serum exosomal miRs in mCRPC patients has been confirmed, suggesting their potential utility as clinical diagnostic markers.

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.

Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP) and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.

This article describes a novel electrochemical on-chip biosensor that utilizes anti-PSA antibody (Ab) and silver nanoparticles (AgNPs) to enhance the sensing and detection capability of prostate specific antigen (PSA) in the blood. The AgNPs are prepared, characterized, and applied onto a silicon photonic on-chip biosensing receptor platform designed to enhance the accurate detection of PSA. The AgNPs were synthesized by a chemical reduction method using silver nitrate (AgNO₃) as the precursor. Transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersion X-ray spectroscopy (EDS), small angle X-ray scattering (SAXS), X-ray diffraction (XRD), and light microscopy were among the methods used in the characterization and analysis of the AgNPs. Each stage of the immunosensor fabrication was characterized using cyclic voltammetry. The proposed immunosensor was applied in the detection of PSA, a prostate cancer biomarker, with a high sensitivity and a limit of detection of 0.17 ng/mL over a linear concentration range of 2.5 to 11.0 ng/mL. The immunosensor displayed good stability and was selective in the presence of interfering species like immunoglobulin (Ig) in human serum, ascorbic acid (AA), and diclofenac (Dic). The detectivity and sensitivity are significantly higher than previous reports on similar or related technologies.

Enzalutamide is a second-generation androgen-receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker after enzalutamide administration. A retrospective subgroup analysis and prognostic survey of 43 patients with mCRPC and bone metastases, treated in Juntendo University-affiliated hospitals from 2015–2022, were conducted. Patients were treated with 160 mg enzalutamide daily. CTC analyses on blood samples were performed regularly before and every three months post-treatment. Relationship between the patients' clinical factors and the OS rate was analyzed using the log-rank test; the median OS was 37 months. Patients with no detected CTCs at baseline showed significantly longer OS than those with CTCs at baseline. Furthermore, patients showing negative reversion of CTCs during enzalutamide treatment had significantly longer OS than patients with CTC-positive continuation. Two biomarkers–higher hemoglobin at baseline and achieving negative-reversion of CTCs–were significantly associated with prolonged OS. This study suggests that patients achieving CTC-negative reversion during treatment for mCRPC with bone metastases exhibit improved long-term OS. Chronological measurement of CTC status might be clinically useful in treatment of mCRPC.

Prostate cancer (PC) is the second most diagnosed cancer among men. It was observed that early diagnosis of disease is highly beneficial for survival of cancer patients. Therefore, extension and increasing quality of life of PC patients can be achieved by broadening the Cancer Screening programs that are aimed at the identification of cancer manifestation in patients at earlier stages before they demonstrate well-understood signs of the disease. Therefore, there is an urgent need in standard, sensitive, robust, and commonly available screening and diagnosis tools for identification of early signs of cancer pathologies. In this respect, “Holy Grail” of cancer researchers and bioengineers for decades have been molecular sensing probes that would allow diagnosis, prognosis, and monitoring of cancer diseases by their interaction with cell-secreted and cellassociated PC biomarkers, e.g. PSA and PSMA correspondinly. At present, most PSA tests are performed at centralized laboratories using high throughput Total PSA immune analyzers which are suitable for dedicated laboratories and are not readily available for the broad health screening. Therefore, the current trend in detection of PC is developments of the portable biosensors for mobile laboratories and individual use. Phage display since its conception by George Smith in 1985 has emerged as a premier tool in molecular biology with widespread applications. This review describes how the paradigm of molecular evolution and phage display revolutionized the methods of early diagnosis and monitoring of PC.

Introduction: Depending on the kind of cancer and neurological disorders, there might be a direct or inverse link between neurodegeneration and cancer. The inverse interaction between cancer and Alzheimer's pathology has garnered substantial interest in medical research. While this inverse interaction between Alzheimer's pathology and cancer presents a fascinating scientific puzzle, there is still limited information and studies on the potential mechanisms involved in this inverse rela-tionship. Aim: This study aims to identify potential genes from Alzheimer's disease that may protect against cancer. Method: The Gene Expression Omnibus (GEO) database provided the Alzheimer's pathology dataset, and GEO 2R was utilized to examine genes that were differentially expressed. The expression of upregulated Alzheimer's pathology genes in breast, colorectal, and prostate cancer was compared using VENN 2.1, colorectal, and prostate cancer was compared using VENN 2.1, and colorectal and prostate cancers were compared using VENN 2.1. Results: Among the upregulated genes associated with Alzheimer's disease, 25 genes are shared among breast cancer, colorectal cancer, and prostate cancer, while 28 of these genes were exclusive to Alzheimer's dis-ease. Gene expression profiling interactive analysis among the shared genes revealed that AQP1, C4A, CSRP2, CRYAB, MACF1, HSPB2, and NEAT1 were downregulated in breast, colorectal, and prostate cancers. These genes have varying roles in cancer progression and suppression. Functional analysis of Alzheimer's disease-related upregulated genes revealed that C1orf56 and HIST1H2AC control cell proliferation, with HIST1H2AC playing a role in necroptosis. Additionally, C1orf56 worked as an oncogenic modifier to support DNMT3B's tumor suppressor properties. Conclusion: Given the role of HIST1H2AC and C1orf56 in the negative control of cell proliferation and their upregulation in Alzheimer's disease, there is a need to further investigate HIST1H2AC and C1orf56 as potential tumor suppressors responsible for Alzheimer's disease and cancer inverse association.

We developed a novel machine learning algorithm to augment clinical diagnosis of prostate cancer utilizing first and second-order texture analysis metrics and novel application of machine learning radiomics analysis. We successfully discriminated between significant prostate cancers versus non-tumor regions and provided accurate prediction between Gleason score cohorts with statistical sensitivity of greater than 0.91 sensitivity across three separate cohorts. Tumor heterogeneity and prediction between GS cohorts were quantified using two feature selection approaches and two classifiers with tuned hyperparameters (including grid search and randomized search). There was a total of 71 patients analyzed in this study. Multiparametric MRI, incorporating T2WI and the ADC maps, were used to derive radiomics features. Recursive feature elimination (RFE), the least absolute shrinkage and selection operator (LASSO), and two classification approaches, including a support vector machine (SVM) (with grid search) and random forest (RF) (with randomized search), were utilized to differentiate between non-tumor regions versus significant cancer and prediction among Gleason score groups. In T2WI images, the RFE feature selection approach combined with RF and SVM classifiers outperformed LASSO with SVM and RF classifiers regarding performance. The detection precision of the radiomics framework depending on multiple imaging modalities was lower than the diagnostic accuracy of single imaging modality model with every machine learning approach assessed. The best performance was achieved by combining LASSO and SVM into a model that used both T2WI and ADC. This model had an area under the curve (AUC) of 0.91. Radiomic features computed from ADC and T2WI images were used to predict three groups of Gleason score using two kinds of feature selection methods (RFE and LASSO), RF and SVM classifier models with tuned hyperparameters. Using combined sequences (T2WI and ADC map images) and combined radiomics (1st and GLCM features), LASSO, with a feature selection method with RF, was able to predict G3 with the highest sensitivity at a level AUC of 0.92. To predict G3 for single sequence (T2WI images) using GLCM features, LASSO with SVM achieved the highest sensitivity with an AUC of 0.92.

The use of ARPIs has led to an increase in the proportion of AR-null prostate cancer, including NEPC and DNPC, but the mechanism underlying this lineage transition has not been elucidated. We found that ID2 expression was increased in AR-null prostate cancer. In vitro and in vivo studies confirmed that ID2 promotes PCa malignancy and can confer resistance to enzalutamide in PCa cells. We generated a ID2 UP50 signature, which is capable to determine resistance to enzalutamide and also valuable for predicting patient prognosis. Functional experiments showed that ID2 could activate the stemness-associated JAK/STAT and FGFR signaling while inhibiting the AR signaling pathway. Our study indicates that ID2 promotes the acquisition of a stem-like phenotype in adenocarcinoma cells, leading to resistance to ADT and next-generation ARPIs in prostate cancer.

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.

Prostate cancer (PCa) is characterised by androgen-dependency. Unfortunately, under anti-androgen treatment pressure, castration-resistant prostate cancer (CRPC) emerges, characterised by heterogeneous cell populations that, over time, lead to the development of different androgen-dependent or -independent phenotypes. Despite important advances in therapeutic strategies, CRPC remains incurable. Context-specific essential genes represent valuable candidates for targeted anti-cancer therapies. Through the investigation of gene and protein annotations and the integration of several published transcriptomic data, we identified two consensus lists to stratify PCa patients' risk and discriminate CRPC phenotypes based on androgen receptor activity. ROC and Kaplan-Meier survival analyses were used for gene set validation in independent datasets. We further evaluated these genes for their association with cancer dependency. The deregulated expression of the PCa-related genes was associated with overall and disease-specific survival, metastasis and/or high recurrence risk, while the CRPC-related genes clearly discriminated between adeno and neuroendocrine phenotypes. Some of the genes showed context-specific essentiality. We further identified candidate drugs through a computational repositioning approach for targeting these genes and treating lethal variants of PCa. This work provides a proof-of-concept for the use of an integrative approach to identify candidate biomarkers involved in PCa progression and CRPC pathogenesis within the goal of precision medicine.

Background：Increasingly, epidemiological surveys and experimental research findings indicate the involvement of immune cells in the onset and progression of prostate cancer. However, it remains unclear whether the relationship between specific immune cell types and prostate cancer is causal or influenced by bias. Through a two-sample Mendelian randomization design, our study aims to uncover the association between different immune cells and the risk of prostate cancer.Methods：A comprehensive study was conducted to investigate the association between immunophenotypes and prostate cancer risk. The study included a total of 731 immunophenotypes as potential exposure factors and analyzed data from 182,625 individuals of European ancestry from the UK Biobank. A screening of 12,097,504 single nucleotide polymorphisms (SNPs) was performed. The main analysis utilized the two-sample Mendelian randomization method with inverse variance weighting (IVW). Additionally, multiple analysis methods were combined, and various tests were conducted to assess heterogeneity and pleiotropy.Results：The resulting study showed a causal relationship between a total of 34 immune phenotypes and prostate cancer. Among them, the four immune phenotypes of CD62L- DC AC, CD19 on sw mem, FSC-A on plasmacytoid DC and HLA DR on monocyte simultaneously meet three or more statistical methods, suggesting a significant causal relationship with prostate cancer. Additionally, among the 34 immunophenotypes, CD28-CD8dim AC was shown to be positive in reverse Mendelian randomization. Most of these cell phenotypes have been reported to be potentially associated with prostate cancer.Conclusions：Our study demonstrates a causal link between immune cells and prostate cancer risk. Filled in the possible roles of all current immune cell pathways in the development and progression of prostate cancer. The next step is to verify the content and influencing mechanism of these immune phenotypes in cancer cells and adjacent cells through experiments, so as to provide new ideas and methods for the prevention and treatment of prostate cancer.

Some bispecific radiotracers have been developed to overcome the limitations of monospecific tracers and improve detection sensitivity for heterogeneous tumor lesions. Here we aim to synthesize two bispecific tracers targeting prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are key markers expressed in prostate cancer. A pyridine-based FAP-targeted ligand was synthesized through multi-step organic synthesis, and then connected to the 2-Nal-containing PSMA-targeted motif. Ki(PSMA) values of Ga-complexed bispecific ligands, Ga-AV01084 and Ga-AV01088, were 11.6 ± 3.25 and 28.7 ± 6.05 nM, respectively, and the IC50(FAP) values of Ga-AV01084 and Ga-AV01088 were 10.9 ± 0.67 and 16.7 ± 1.53 nM, respectively. The uptake values for PSMA-expressing LNCaP tumor xenografts were 9.05 ± 1.54 and 8.85 ± 1.25 %ID/g for [68Ga]Ga-AV010184 and [68Ga]Ga-AV01088, respectively, which were lower than the monospecific PSMA-targeted tracer [68Ga]Ga-PSMA-617 (16.7 ± 2.30 %ID/g). The uptake values for FAP-expressing HEK293T:hFAP tumor xenografts were 1.90 ± 0.41 and 1.20 ± 0.25 %ID/g for [68Ga]Ga-AV01084 and [68Ga]Ga-AV01088, respectively, which were also lower than the monospecific FAP-targeted tracer, [68Ga]Ga-AV02070 (7.93 ± 1.88 %ID/g). Further investigations are needed to optimize the selection of linkers and targeted pharmacophores to improve the tumor uptake of PSMA/FAP bispecific tracers for prostate cancer imaging.

Background: We aimed to evaluate the impact of two different phytotherapeutic agents on the decision making regarding prostate biopsy in patients with higher-than-normal prostate-specific antigen (PSA) levels. Methods: From June 2022 to May 2023, all patients attending two urological institutions due to higher-than-normal PSA levels were randomized to receive either oral capsules of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica (Group A) or Serenoa Repens 320 mg (Group B), for 3 months. At the follow-up visit after 3 months all patients underwent PSA test and multiparametric magnetic resonance imaging (mpMRI). Results: In the per-protocol analysis, data from 66 patients in Group A and 76 in Group B were analyzed. Fifty patients in Group A (75.7%) showed a significant reduction of total PSA compared to 49 in Group B (64.4%) (p<0.001). Twenty-eight patients had PI-RADS III or higher at mpMRI: 12 in Group A and 14 in Group B. Twenty-three patients (34.8%) in Group A underwent prostate biopsy based on mpMRI findings and PSA values and 59 (77.6%) in Group B (p<0.001). Three patients in Group A showed a significant reduction of total PSA value while having positive findings at mpMRI (6%) compared with 9 in Group B (19.5%) (p<0.001). On the contrary, 7 patients in Group A did not show a significant reduction of total PSA value and had negative findings at mpMRI (43%) compared to 22 in Group B (81.4%) (p&lt;0.001). Conclusions: In conclusion, a three-month course of a combination of Curcuma Longa, Boswellia, Pinus pinaster, and Urtica dioica seems an interesting tool to avoid unnecessary prostate biopsies in men with higher-than-normal PSA levels.

Background: Mosaic cancers are composed of two or several genetically different cell populations. Mosaicism has been considered to be rare among malignancies, with the exception of the germ cell tumours. Although it has been described that neuroendocrine foci might be present within adenocarcinomas of the prostate, this was meant for advanced stage diseases and the clinical relevance of the histological finding has not been clarified. Patients and methods: We recall a single centre cohort of patients with neuroendocrine cancer of the prostate. We show for the first time histological images of a primary mosaic neuroendocrine/adenocarcinoma of the prostate. Results: Contrarily to the general assumption of a rare disease with poor prognosis, the clinical incidence was found to be 2%, being 50 fold higher than the earlier data. During the follow-up the overall survival of some metastatic patients reached several years. The particularity of patients with favourable outcome was the parallel elevation of PSA and NSE. They received anticancer treatments in an alternating way directed according to the tumour marker that was actually in rise. Histological images of primary mosaic prostate cancers are shown. A model explaining the development of mosaic cancers is presented. Conclusion: Mosaic neuroendocrine-/adenocarcinoma of the prostate is underdiagnosed and its prognosis is underestimated.

Purpose: Prostate cancer is the most common male prevalent malignancy in Europe. Biological recurrence occurs in 20-40% of patients within 10 years following treatment. [18F]F-Choline PET/CT is the most used technique for detecting recurrent disease but is rarely positive for low PSA levels. [18F]PSMA-1007 PET/CT allows early detection of recurrence sites. Methods: We conducted a prospective multicenter study. Each patient had access to a [18F]F-Choline and [18F]PSMA PET/CT. The primary endpoint was to determine the therapeutic impact of the [18F]PSMA comparative to [18F]F-Choline PET/CT. Secondary endpoints were the diagnostic performance and the correlation between PET/CT parameters and prognostic factors of prostate disease. Results: 47 patients were included. A therapeutic modification was observed in 36% of them between what the clinicians expected after the [18F]F-Choline PET/CT and what they finally decided after the [18F]PSMA PET/CT. Diagnostic performance of [18F]F-Choline was 28% versus 70% for [18F]PSMA with a significant difference. With [18F]PSMA PET/CT, there was a significative correlation between PSA level of biological recurrence and SUVmax but not between ISUP score and SUVmax of the selected lesion. Conclusion: This study found a modification in therapeutic management following [18F]PSMA PET/CT in one third of patients. This change could result in earlier and better management with detection of lesions at a lower PSA level than is possible with [18F]F-Choline.

Prostate cancer (PCa) used to be one of the most common nondermatologic cancers in men that can be treated only with surgery. However, a revolutionary breakthrough came in the 1980s with the introduction of long-acting luteinizing hormone-releasing hormone (LHRH) agonists for the cu-rative treatment of PCa. This paradigm shift contributed to the combined use of androgen depri-vation therapy (ADT), chemotherapy, and radiotherapy for the treatment. The latest data high-light the use of treatment intensification (TI), i.e., combined use of radiotherapy (RT) and hormo-nal or drug treatments, for localized or locally advanced PCa. Indeed, the results of combined modality treatments have shown a reduction in disease-specific mortality and improved overall survival. Although TI seems promising, more research studies are warranted to confirm its effi-cacy. This review summarizes the latest available outcome results of pivotal trials and clinical studies on the efficacy of TI.

This study focused on the precise detection and concordant analysis of circulating tumor cells (CTCs) to verify the usefulness of CTCs as promising clinical markers. CTCs are traditionally achieved using immune-fluorescence and morphological techniques. By combining two prostate cancer-specific genes (PSA and PSMA) and two epithelial-specific genes (EpCAM and KRT19), the CTC detection efficiency can be enhanced. The detection rates of localized prostate cancer (LPC), locally advanced prostate cancer (LAPC), metastatic hormone-sensitive prostate cancer (mHSPC), and metastatic castration-resistive prostate cancer (mCRPC) were 63.04 % (29/46), 70.59% (34/51), 94.34% (50/53), and 90% (126/140), respectively. Subsequent correlation analysis between the four genes, baseline PSA, and CTC count revealed that only the CTC count correlated with baseline PSA in the localized stages of prostate cancer, whereas all four genes were correlated with baseline PSA and CTC count in the metastatic stages of prostate cancer. The precise detection of CTCs using both numerical and transcriptomic analyses can improve the accuracy of biomarker investigations. This study provides valuable insights into the limitations of serum PSA testing and offers a promising alternative to diagnose and manage prostate cancer via the CTC number and specific genes for prostate cancer.

Prostate cancer is a highly heterogeneous disease, and mortality is mainly due to metastases, but the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM) from 43 patients enrolled in clinical trial. We present evidence that while there are some cases of clonally independent primary tumor foci, 87% of primary tumor foci and metastases are descended from a common ancestor. We demonstrate that genes related to oxidative phosphorylation are upregulated in LNM and in African-American patients relative to White patients. We further show that mutations in TP53, FLT4, EYA1, NCOR2, CSMD3, and PCDH15 are enriched in prostate cancer metastases. These findings were validated in a meta-analysis of 3,929 primary tumors and 2,721 metastases and reveal a pattern of molecular alterations underlying the pathology of metastatic prostate cancer. We show that LNM contain multiple subclones that are already present in primary tumor foci. We observed enrichment of mutations in several genes including understudied genes such as EYA1, CSMD3, FLT4, NCOR2, and PCDH15 and find that mutations in EYA1 and CSMD3 are associated with poor outcome in prostate cancer.

Prostate cancer (PCa) is a complex disease and the cause of one of the highest cancer-related mortalities in men worldwide. Annually, more than 1.2 million new cases are diagnosed globally, accounting for 7% of newly diagnosed cancers in men. Programmed cell death (PCD) plays an essential role in removing infected, functionally dispensable or potentially neoplastic cells. Apoptosis is the canonical form of PCD with no inflammatory responses elicited, and the close relationship between apoptosis and PCa has been well studied. Necroptosis and pyroptosis are two lytic forms of PCD resulting in the release of intracellular contents, which induces inflammatory responses. An increasing number of studies have confirmed that necroptosis and pyroptosis are also closely related to the occurrence and progression of PCa. Recently, a novel form of PCD named PANoptosis, which is a combination of apoptosis, necroptosis, and pyroptosis, revealed the attached connection among them and may be a promising target for PCa. Apoptosis, necroptosis, pyroptosis and PANoptosis are good examples to better understand the mechanism underlying PCD in PCa. This review aims to summarize the emerging roles and therapeutic potential of apoptosis, necroptosis, pyroptosis and PANoptosis in PCa.

Background: Prostate cancer remains a significant global health concern, and understanding the molecular drivers of this disease is crucial for developing effective diagnostic and therapeutic strategies. Steroid Receptor Coactivator-3 (SRC-3), a member of the SRC family, has emerged as a key player in prostate cancer pathogenesis. This review comprehensively examine the role of SRC-3 in prostate cancer, encompassing molecular mechanisms, clinical implications, and therapeutic opportunities. Methods: A systematic literature search following PRISMA guidelines was conducted in PubMed, PMC, and other relevant databases to identify studies that investigate SRC-3 in prostate cancer. A total of 67 articles were selected based on predetermined inclusion criteria. Results: 785 articles were retrieved from databases using specific keywords and MeSH terms related to SRC-3 and Prostate Cancer. After removing 461 duplicates, 260 articles were excluded based on title and abstract review. Subsequently, a comprehensive screening by three researchers resulted in 47 relevant articles for this systematic review. We summarize its contributions to AR-mediated transcriptional regulation, tumor growth, and metastasis. Evidence suggests that SRC-3 expression correlates with prostate cancer aggressiveness, disease recurrence, and poor patient outcomes. Its potential as a diagnostic biomarker and therapeutic target is explored, offering insights into personalized medicine approaches. Conclusions: SRC-3 plays a pivotal role in prostate cancer, influencing disease progression and clinical outcomes. Understanding the molecular intricacies of SRC-3 in prostate cancer offers new opportunities for precision medicine and innovative therapeutic approaches. This review provides a comprehensive overview of SRC-3's involvement in prostate cancer, emphasizing its clinical relevance and potential as a therapeutic target, ultimately contributing to improved patient care in the era of personalized oncology.

Background: Prostate cancer is a global health concern, necessitating ongoing research to enhance our comprehension of its molecular foundations and develop more efficacious therapeutic approaches. Among the emerging protagonists in this arena is Speckle-type POZ (pox virus and zinc finger protein) (SPOP), an E3 ubiquitin ligase substrate adaptor protein. SPOP's recent ascent to prominence in prostate cancer research is attributed to its crucial role in regulating the Androgen Receptor (AR) signaling pathway. This systematic review aims to provide a comprehensive synthesis of existing knowledge concerning SPOP mutations in prostate cancer. It seeks to elucidate their significance in characterizing the disease and their potential as therapeutic targets. Methods: A systematic literature search was conducted in multiple databases, including PubMed, Web of science, Scopus and google scholar to identify relevant studies published up to September 2023. Eligible studies included investigations of SPOP mutations in prostate cancer and their implications. Data extraction, quality assessment, and synthesis were performed in conformity to the PRISMA guidelines. Results: The review revealed that SPOP mutations are recurrent events in prostate cancer, with a notable prevalence in specific molecular subtypes. These mutations primarily affect the MATH domain of SPOP, disrupting its substrate recognition function. Notably, SPOP mutations have profound consequences on the AR signaling pathway, leading to increased AR protein stability and transcriptional activity. The clinical implications of SPOP mutations remain diverse, with varying associations with prognostic outcomes. Conclusion: SPOP mutations represent a significant facet of prostate cancer biology, influencing disease heterogeneity and clinical behavior. While their precise prognostic significance is evolving, their functional impact on the AR pathway highlights their potential as therapeutic targets. This systematic review provides a comprehensive overview of SPOP mutations in prostate cancer, contributing to our understanding of the disease's molecular landscape and therapeutic avenues.

Objectives: This study aimed to assess the impact of a predictive model for detecting extracapsular extension on pathology (pECE+) on biochemical recurrence-free survival (BCRFS) within 4 years after robotic-assisted radical prostatectomy (RARP). Methods: Retrospective data analysis from a single center between 2015 to 2022. Variables under consideration included prostate-specific antigen (PSA) levels, patient age, prostate volume, MRI semantic features and Gleason score (GS). We also assessed the influence of pECE+ and positive surgical margins on BCRFS. using the Kaplan-Meier survival function and Cox regression model were assessed. Additionally, we analyzed the MRI features on BCR (biochemical recurrence) in low/intermediate risk patients. Results: 177 participants with a follow-up exceeding 6 months post-RARP were included. The 1-year, 2-year, and 4-year risks of BCR after curative prostatectomy were 5%, 13%, and 21%, respectively. The survival analysis showed that adverse MRI features as macroscopic ECE on MRI (mECE+), capsular disruption, high tumor capsular contact length (TCCL), GS≥8, positive surgical margins (PSM), and pECE+ on pathology were risk factors for BCR. In low/intermediate-risk patients (pECE- and GS &lt;(4+4)) the presence of adverse MRI features, has been shown to increase the risk of BCR. Conclusions: The study highlights the importance of incorporating predictive MRI features for detecting extracapsular extension pre-surgery in influencing early outcomes and clinical decision-making; mECE+, TCCL, capsular disruption, and GS≥8 based on pre-surgical biopsy were independent prognostic factors for early BCR. The presence of adverse features on MRI can assist in identifying low/intermediate-risk patients who would benefit from closer monitoring.

U-Net, based on a deep convolutional neural network (CNN), has been clinically used to au-to-segment normal organs and potentially target volumes. However, CNNs with local geometric dependencies may limit the accuracy of segmentation. Additionally, the performance of CNNs can vary depending on the selection of network hyper-parameters, which was mitigated by the proposition of nnU-Net. We chose a vision transformer architecture called VT U-Net, which features a self-attention excluding the convolution layer, to overcome the limitations of CNNs by utilizing global geometric information of images. The VT U-Net v.2 became more powerful thanks to the adaptive hyper-parameter optimizer embedded in nnU-Net. However, despite leveraging the benefits of nnU-Net, VT U-Net v.2 still had additional network hyper-parameters that needed to be optimally chosen. Accordingly, among various hyper-parameters, this study attempted to find the optimal combination of the patch size and the embedded dimension regarding the transformer. From the 4-fold cross-validation, the modified VT U-Net v.2 showed the highest average performance for planning target volume (PTV) segmentation among the investigated networks. Though nnU-Net was based on convolution layers, the adaptive hyper-parameter optimizers turned out to enhance the performance. It was also confirmed that network hyper-parameters affected the segmentation accuracy of vision transformers.

Prostate cancer (PCa) is a major cause of cancer-related mortality worldwide, with a rising incidence observed over the years. The androgen receptor (AR) signaling pathway plays a pivotal role in male development and maintaining masculine characteristics. Dysregulation of AR signaling in prostate cancer can lead to disease progression and resistance to standard therapies. Understanding the intricate regulation and function of AR in both healthy and diseased states is crucial for developing effective treatment strategies. This review comprehensively explores the role of androgen receptors in prostate cancer susceptibility, disease progression, and treatment response by analyzing recent literature. An extensive search of peer-reviewed publications in major databases, including PubMed, Scopus, and Web of Science, was conducted using specific keywords related to androgen receptor, prostate cancer, disease progression, and treatment resistance. Relevant conference abstracts and clinical trial reports were also included. The review presents an overview of the role of androgen receptors in prostate cancer initiation, progression, and treatment resistance. It highlights emerging biomarkers associated with AR signaling dysregulation and their potential utility for early detection and personalized treatment approaches. Additionally, recent advances in targeting the AR pathway for novel therapeutic strategies to improve patient outcomes and overcome treatment resistance in advanced prostate cancer are discussed. The findings contribute to a comprehensive understanding of the AR signaling pathway in prostate cancer and offer insights into its multifaceted role in disease development and treatment response. They may pave the way for innovative therapeutic interventions and precision medicine approaches based on specific AR signaling profiles, enhancing patient care and reducing the burden of this lethal disease.

Since decades, oxybutynin hydrochloride is prescribed to improve bladder control in cases of incontinence and excessive urination frequency. This review summarizes synthetic methods enabling preparation of the racemic drug and, in a detailed manner, preparation of (S)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid, a key intermediate in the synthesis of (S)-oxybutynin. Mode of action and metabolism are briefly commented in order to explain the main adverse effects associated with its use and to justify the evolution observed in the diverse commercial formulations. Repositioning opportunities are discussed in terms of clinical trials for the management of hyperhidrosis, hot flashes, and obstructive sleep apnea.

The microbiome, once considered peripheral, is emerging as a relevant player in the intricate web of factors contributing to cancer development and progression. These often overlooked microorganisms, in the context of urological malignancies, have been investigated primarily focusing on the gut microbiome, while exploration of urogenital microorganisms remains limited. In light of this, our systematic review delves into the complex role of these understudied actors in various neoplastic conditions, including prostate, bladder, kidney, penile, and testicular cancers. Our analysis found a total of 37 studies, with prostate cancer-12, bladder cancer-20, kidney cancer-4, penile/testicular cancer-1, which reveals distinct associations specific to each condition, hinting at potential therapeutic avenues and future biomarker discoveries. It becomes evident that further research is imperative to unravel the complexities of this domain and provide a more comprehensive understanding.

Background: Mosaic cancers are composed of two or several genetically different cell populations. Mosaicism has been considered to be rare among malignancies, with the exception of the germ cell tumours. Although it has been described that neuroendocrine foci may be present within an adenocarcinoma of the prostate, this was ment for advanced stage disease and the clinical relevance of the histological finding has not been clarified. Patients and methods: We recently published the analysis of a small cohort of patients who had neuroendocrine cancer of the prostate. Contrarily to the general assumption of a rare disease with poor prognosis, the incidence was found to be 2%, being 50 fold higher than the earlier data. During the follow-up the overall survival of some metastatic patients reached several years. The particularity of patients with favourable outcome was the parallel elevation of PSA and NSE. They received anticancer treatments in an alternating way directed according to the tumour marker that was in rise. The aim of this paper is to show the pathological background of our clinical observations. Results: Histological images of de novo mosaic prostate cancers are shown. A model explaining the development of mosaic prostate cancers is presented. The hypothesis of mosaicism within adenocarcinomas is formulated in addition. Conclusion: Mosaic neuroendocrine-/adenocarcinoma of the prostate is underestimated regarding its incidence as well as its prognosis.

Cancer theragnostics is a novel approach that combines diagnostic imaging and radionuclide therapy. It is based on the use of a pair of radiopharmaceuticals, one optimized for positron emission tomography imaging, through linkage to a proper radionuclide, and the other bearing a beta-emitter isotope that can induce significant damage to cancer cells. In recent years, the use of theragnostics in nuclear medicine clinical practice has increased considerably, and thus investigation has focused on the identification of novel radionuclides that can bind to molecular targets which are typically dysregulated in different cancers. The major advantages of the theragnostic approach include elimination of multi-step procedures, reduced adverse effects to normal tissues, early diagnosis, better predicting responses and personalized patient care. This review aims to discuss emerging theragnostic molecules that have been investigated in a series of human malignancies, including gliomas, thyroid cancer, neuroendocrine tumors, cholangiocarcinoma and prostate cancer, as well as potent and recently introduced molecular targets, like cell-surface receptors, kinases, and cell adhesion proteins. Furthermore, special reference has been made to copper radionuclides as theragnostic agents, and their radiopharmaceutical applications since they present promising alternatives to the well-studied gallium-68 and lutetium-177.

The cancer stem cell hypothesis suggests that neoplastic cells with stem characteristics hierarchically regulate tumor generation and its high cellular heterogeneity. These cells have been detected in all cancer types, and specific signaling pathways give the regulation of self-renewal and differentiation. In prostate cancer, androgen receptor signaling has been extensively studied, and in non-stem cells, it promotes cell proliferation and tumor progression, but in the cancer stem cell population, it negatively regulates processes such as self-renewal. However, in other types of cancer, such as breast and glioblastoma, the androgen receptor seems to favor the maintenance of cancer stem cells, suggesting that androgen signaling has different effects depending on the tumor context. This review discusses the role of androgen receptor in maintaining cancer stem cells by regulating proliferation, self-renewal, and differentiation, as well as the possible signaling pathways involved in these processes.

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities in de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have changed the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road towards a personalized treatment for de novo mHSPC is still long considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as predictive biomarker requires further validation, as well as it remains to ascertain how the genomic alterations detected in mHSPC, that are considered predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachythera-py has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision-making regarding radiological parameters by radiation oncologists. Combined use of LDR brachytherapy with other therapeutical modalities, such as external beam radiation and androgen deprivation therapy, for clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology depart-ments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PC) that commonly emerges through a transdifferentiation process from prostate adenocarcinoma and evades conventional therapies. Extensive molecular research has revealed factors that drive lineage plasticity, uncovering novel therapeutic targets to be explored. A diverse array of targeting agents is currently under evaluation in pre-clinical and clinical studies with promising results in suppressing or reversing the neuroendocrine phenotype and inhibiting tumor growth and metastasis. This new knowledge has the potential to contribute to development of novel therapeutic approaches that may enhance clinical management and prognosis of this lethal disease.

Introduction: Prostate cancer (PCa) is one of the deadliest and most common causes of malignancy and death in men worldwide, more specifically with higher prevalence and mortality in developing countries. Factors such as age, family history, race and certain genetic mutations are some of the factors contributing to the occurrence of PCa in men. The recent advances in technology and algorithms gave rise to the computer-aided diagnosis (CAD) of PCa. With the availability of medical image datasets and emerging trends in state-of-the-art machine and deep learning techniques, there is a growth in recent related publications. Materials and Methods: In this study, we present a systematic review of PCa diagnosis with medical images using machine learning and deep learning techniques. We conducted a thorough review through relevant studies indexed in four databases (IEEE, PubMed, Springer and ScienceDirect) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. With well-defined search terms, a total of 608 articles were identified and 77 met the final inclusion criteria. Key elements in the included papers were presented and conclusions were drawn from them. Results: Findings showed that the United States has the most research in PCa diagnosis with machine learning, Magnetic Resonance Images are the most used datasets and transfer learning is the most used method of diagnosing PCa in recent times. In addition, some available PCa datasets and some key considerations for choice of loss function in the deep learning models were presented. The limitations and lessons learnt were discussed and some key recommendations were made. Conclusion: The discoveries and the conclusions of this work have been organized so as to enable researchers in the same domain to use this work and make crucial implementation decisions.

Background: The level of food processing has gained interest for a potential determinant of human health. The aim of this study was to assess the relation between level of food processing and prostate cancer severity. Methods: A sample of 120 consecutive patients were examined for their dietary habits assessed through validated food frequency questionnaires, their dietary intake of food groups categorized according to the NOVA classification, and the severity of prostate cancer according to the European Association of Urology (EAU) guidelines groups risk. Uni- and multivariate logistic regression analyses were performed to test the association between the variables of interest. Results: Individuals reporting higher consumption of unprocessed/minimally processed foods were less likely to have worse prostate cancer severity than lower consumers in the energy-adjusted model [odds ratio (OR) = 0.38, 95% confidence interval (CI): 1.17-0.84, P = 0.017 and OR = 0.33, 95% CI: 0.12-0.91, P = 0.032 for medium/high vs. low grade and high vs. medium/low grade prostate cancers, respectively); however, after adjusted for potential confounding factors, the association was no more significant (Table 4). A borderline association was also found between higher consumption of UPF and worse prostate cancer severity in the energy-adjusted model (OR = 2.11, 95% CI: 0.998-4.44; P = 0.051), but again the association was no more significant after adjusting for the other covariates. Conclusions: The level of food processing seems not to be independently associated with prostate cancer severity, while potentially related to other factors that need further investigation.

Prostate cancer is a common cancer among men and typically progresses slowly for several decades before becoming aggressive and spreading to other organs, leaving few treatment options. While large animals have been studied, the dog's prostate is anatomically similar to humans and has been used to study spontaneous prostate cancer. However, most research currently focuses on the mouse as a model organism due to the ability to genetically modify their prostatic tissues for molecular analysis. One hallmark in this research was the identification of the prostate-specific promoter Probasin, allowing for prostate-specific expression of transgenes. This has led to generations of mice with aggressive prostatic tumors through overexpression of the SV40 oncogene. The Probasin promoter is also used to drive Cre expression and allow researcher to generated prostate specific loss-of-function studies. Another landmark in the process of modeling prostate cancer in mice was orthoptic delivery of viral particles. This technology allows selective overexpression of oncogenes from lentivirus or the use of CRISPR to generate complex loss of function studies. These genetic modified models are complemented by classical xenografts of human prostate tumor cells in immune deficient mice. Overall, pre-clinical models have provided a portfolio of model systems to study and address complex mechanisms in prostate cancer for improved treatment options. This review will focus on the advances of each technique.

Prostate cancer is the most common cancer among men in Poland. A significant proportion of prostate cancers can be cured, providing longer survival. Patients have the opportunity to undergo minimally invasive treatment methods like brachytherapy, while maintaining their previous quality of life. The disease itself, as well as treatment complications, primarily affect the functioning of the urinary and digestive systems and impact the sexual sphere. Aim: This study aims to assess the quality of life of patients after prostate brachytherapy. Methods: The research was conducted at the Lower Silesian Oncology Centre in Wroclaw. The study included fifty men aged between 51 and 85 years. The following questionnaires were used: EORTC QLQ-C30, QLQ-PR25. Scales: Katz, Mini-MAC, PSS-10. Moreover, the study used a self-designed survey covering socio-demographical factors. Results: Prostate brachytherapy has a significant impact on the degree of sexual dysfunction. Compared to sexually inactive individuals, sexually active individuals exhibit fewer negative psychological symptoms. Choosing a destructive coping strategy intensifies the occurrence of symptoms, lowers patients' level of independence, and negatively affects their quality of life. Conclusions: Brachytherapy contributes to worsening sexual function and temporarily affects urinary system function, which may lower the overall quality of life in patients.

Background: The incidence of prostate cancer (PC) has been risen annually. Despite the diagnosis is made mainly with non-metastatic PC, mortality is explained by the metastatic disease (mPC). Without a doubt there is an intermediate scenario in which patients have no mPC but will have initiated a metastatic cascade through an epithelial-mesenchymal transition. There is indeed a need for more and better tools to predict what patients will progress in the future to non-localized clinical disease or already have micrometastatic disease, and therefore, will clinically progress after primary treatment. Biomarkers for predicting mPC are still under development; there are few studies and not much evidence of their usefulness. Summary: This review is focused on tissue-based genomic biomarkers (TBGB) for predicting metastatic disease. We developed four main research questions that will attempt to answer according to the current evidence. Why is important to predict metastatic disease? Which tests are available to predict metastatic disease? What impact should there be on clinical guidelines and clinical practice in predicting metastatic disease? What are current prostate cancer treatments? Key Messages: Knowing useful predict tools could help determine which patients may need multimodal or adjuvant treatment even with a localized disease, and in consequence, what patients do not need more than a single modality of treatment. The importance of predicting metastasis is fundamental, given that once metastasis is diagnosed, the quality of life (QoL) and survival drop dramatically.

Prostate cancer is the most occurred malignant disease in the male population in over one-half of the countries and still constitutes the fifth leading cause of death in 2020, worldwide. Metastatic prostate cancer is a lethal malignancy that mostly is terminated within several years through the patient's death. Researchers should focus on the phenomenon which is rigorously appertaining to metastatic cascade and operating as an initiator of metastases to provide the knowledge needed to solve the problem of diagnostics and treatment of advanced prostate cancer patients. The epithelial-mesenchymal transition is one such phenomenon. The current review is based mainly on three papers published in 2021, which describe the most important tissue-specific factors managing epithelial-mesenchymal transition and are discussed with scientific papers published in acknowledged journals. The effect of the current review is the specification of profiles of precise tissue factors predicting the progression of the prostate neoplasm to its metastatic stage in a new edition.

Enzalutamide is a drug used to treat PC. Docetaxel is a drug for chemotherapy for different cancers including prostate cancer (PC). The effectiveness of these drugs in treating castration-resistant prostate cancer (CRPC) is not consistent and thus, CRPC is still an incurable disease. Recent evidence showed that the bio-inhibitor of FABP5, dmrFABP5, suppressed the tumorigenicity and metastasis of the CRPC cells. In this work, we studied the possible synergic effect of dmrFABP5 combined with either Enzalutamide or Docetaxel on suppressing tumorigenicity of the PC cells. A highly significant synergic effect was observed when dmrFABP5 was used in combination with Enzalutamide on the androgen-responsive PC cells 22RV1. A highly significant synergic effect was also observed when dmrFABP5 was combined with Docetaxel on 22RV1 cells and on the highly malignant, androgen-receptor (AR)-negative DU145 cells. These combined applications exhibited a highly significant inhibitory action on the viability, migration, invasion and colony formation abilities of both 22RV1and DU145 cells. However, dmrFABP5 did not produce any suppression effect when used on FABP5-negative cell line LNCaP, although Enzalutamide can significantly suppress LNCaP cells as a single agent. Further investigations suggested that these synergistic effects were produced by interrupting the FABP5-related signal transduction pathway in PC cells.

Oncological changes in the prostate are a common cause of death among elderly men. Malignant cells are difficult to identify at early stages, which are asymptomatic. The patient often seeks medical assistance when the disease has already progressed, and the treatment is less effective. Early diagnosis of prostate cancer (PC) is thus one of the priority tasks of modern urology and healthcare in general. The aim of this study is the detection of microRNAs (miRNAs), which are known to be associated with PC. The detection of the target miRNAs in human plasma samples has been performed with a nanoribbon biosensor system, which was based on "silicon-on-insulator" structures (SOI-NR biosensor). In order to provide biospecific detection of the target miRNAs, the surface of individual nanoribbons has been modified with DNA oligonucleotide probes (oDNA probes), whose nucleotide sequences were complementary to those of the target miRNAs. The high detection sensitivity has been demonstrated with the use of model oDNAs, which are complementary to nanoribbon-immobilized oDNA probes, in buffer solutions. The sensitivity threshold was 1.1 × 10^-17 M. The successful detection of target miRNAs, isolated from real plasma samples of PC patients, has also been demonstrated. We believe that the development of highly sensitive nanotechnology-based biosensors for PC markers is a step towards personalized medicine.

Abstract: A recent approach to radiotherapy for prostate cancer is the administration of high doses of radiation to the prostate while minimizing the risk of side effects. Thus, image-guided radiotherapy utilizes advanced imaging techniques and is a feasible strategy for increasing the radiation dose. New radioactive particles are another approach to achieving high doses and safe procedures. Prostate brachytherapy is currently considered as a combination therapy. Spacers are useful to protect adjacent organs, specifically the rectum, from excessive radiation exposure.

Accurately distinguishing between indolent and aggressive tumors is a crucial unmet need in the clinical management of prostate cancer (PCa). The traditional Gleason grading system has been utilized for this purpose; however, there is often ambiguity in classifying tumors with a Gleason grade of 7. Clinicians commonly resort to using secondary Gleason grades, such as 3+4 or 4+3, to classify these tumors as indolent or aggressive, respectively. Unfortunately, such classifications are prone to misinterpretation, leading to erroneous diagnoses and prognoses. To address this challenge, we investigated the application of Machine Learning (ML) techniques to classify PCa patients based on gene expression data sourced from The Cancer Genome Atlas. By comparing gene expression levels between indolent and aggressive tumors, we sought to identify distinctive features for developing and validating a range of ML algorithms and stacking techniques. The stacking based model achieved an impressive accuracy of 96% for all samples encompassing primary Gleason grades 6 to 10. Notably, when excluding Gleason grade 7 from the analysis, the accuracy further improved to 97%. This study underscores the effectiveness of the stacked ML algorithm for accurately classifying indolent versus aggressive PCa. Leveraging gene expression data and employing a combination of classifiers, this approach offers a powerful solution to address the unmet need in robustly distinguishing between different types of PCa tumors. Future implementation of this methodology may significantly impact clinical decision-making and patient outcomes in the management of prostate cancer.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol® modified citrus pectin (P-MCP) is a food supplement generally recognized as safe (GRAS) by the Food and Drug Administration (FDA) and is a competitive inhibitor of galectin-3 protein, involved in cancer pathogenesis. P-MCP treatment of BRPC-M0 patients for 6 months led to a 75% prostate-specific antigen doubling time (PSADT) improvement. To determine the longer-term effects of P-MCP we investigated an additional 12 months of treatment (phase II) with oral P-MCP at 4.8 grams X 3/day in patients with no disease progression in the previous 6 months. Of the 46 patients that entered the second phase, 7 patients withdrew consent and continued therapy independently, and 39 received another 12 months of therapy. After a total of 18 months P-MCP treatment, 62% (n=24) had a decreased/stable PSA, 90% (n=35) had improved PSADT, and 85% (n=33) had a durable long-term response, with a decreased/stable PSA, and/or improvement of PSADT, and negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long term durable efficacy, and is safe, in BRPC-M0.

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.

Backgound: Exosomes are extracellular nanovesicles, carriers of different biomolecules such as lipids, proteins, nucleic acids. Their composition and the fact that their release dramatically increases in case of tumorigenesis, opens different scenarios on the possible application in the research for new biomarkers.Methods: The most widely applied methodologies include ultracentrifugation techniques, size-based techniques, immunoaffinity capture-based techniques (mainly ELISA) and precipitation. To optimize the acquisition of exosomes from the reference sample, more techniques can be applied in sequence for a single extraction, determining an increase in labor time and costs. Results: The analysis of PSA-expressing exosomes provides an incredibly accurate way to discriminate between healthy patients and those with prostate disease. Specifically, IC-ELISA alone method achieved 98.57% sensitivity and 80.28% specificity in discriminating prostate cancer (PC) from benign prostatic hyperplasia (BPH).An immunocapture-based ELISA assay was performed to quantify and characterize carbonic anhydrase (CA) IX expression in exosomes. The results revealed that CA IX positive exosomes were 25-fold higher in plasma samples from PC patients than in those from healthy control. Conclusions: The analysis of PC-linked exosomes represents a promising diagnostic model that can effectively distinguish patients with PC from those with non-malignant prostatic disease, However, the use of exosome analysis in clinical practice is currently limited by several issues, including a lack of standardization in the analytical process and high costs, which are still too high for a large-scale use.

Prostate cancer (PCa) is the most diagnosed non-cutaneous cancer in men. Despite therapies such as radical prostatectomy, which is considered curative, distant metastases may form resulting in biochemical recurrence (BCR). This study used radiomic features calculated from multi-parametric magnetic resonance imaging (MP-MRI) to evaluate their ability to predict BCR and PCa presence. Data from a total of 279 patients, of which 46 experienced BCR, undergoing MP-MRI prior to surgery were assessed for this study. After surgery, the prostate was sectioned using patient-specific 3D-printed slicing jigs modeled using the T2-weighted imaging (T2WI). Sectioned tissue was stained, digitized, and annotated by a GU-fellowship trained pathologist for cancer presence. Digitized slides and annotations were co-registered to the T2WI and radiomic features were calculated across the whole prostate and cancerous lesions. A tree regression model was fitted to assess the ability of radiomic features to predict BCR, and a tree classification model was fitted with the same radiomic features to classify regions of cancer. We found that 10 radiomic features predict eventual BCR with an AUC of 0.97 and classifying cancer at an accuracy of 89.9%. This study showcases the application for a radiomics-based tool to screen for the presence of prostate cancer and assess patient prognosis, as determined by biochemical recurrence.

This article presents a comparative analysis of three Machine Learning models, namely Logistic Regression, Decision Tree Classifier, and Random Forest Classifier, for prostate cancer detection. The models were trained and evaluated using clinical data, and their performance was assessed using various evaluation metrics. The results show that Logistic Regression achieved the highest accuracy (90%) among the three models, followed by Random Forest Classifier (76.67%) and Decision Tree Classifier (73.33%). Similarly, Logistic Regression demonstrated superior precision (95.65%) and F1 Score (93.62%), indicating its effectiveness in identifying true positive cases. However, the Decision Tree Classifier exhibited higher recall for the negative class (83.33%) compared to the positive class (70.83%), while Random Forest Classifier showed balanced recall for both classes (66.67% for negative and 79.17% for positive). These findings suggest that Logistic Regression outperforms the other models in terms of accuracy and precision, while the Decision Tree Classifier and Random Forest Classifier provide better recall for certain classes. The results highlight the potential of Machine Learning in prostate cancer detection and provide insights for further research and improvement of the models.

The possibility of treating more patients for a longer time, has exploded the concept of anticipation in the systemic treatment of metastatic prostate cancer (mPC). The genetic analysis of Damage DNA Repair (DDR) mutations in pathogenetic variants (PV) and the development of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors led to the first valid precision medicine option tailored for mPC. PARP inhibitors are repeating the same evolutionary path experienced for androgen receptor signaling inhibitors (ARSI), starting from the late stage of second line mCRPC in a limited population and time frame. Inevitably also PARP inhibitors will be absorbed by the concept of anticipation and intensification of care. The anticipation of PARP inhibitors in the first line mCRPC therapy is already underway and further one in mHSPC will soon be verified. According to the crosstalk between androgen receptors (AR) and DNA repair, the new message that is emerging is that the combination of PARP inhibitors with ARSI, disconnects PARP from the genetic analysis. Most of the recent trials analyzing PARP inhibitors plus abiraterone or enzalutamide, enrolled first line mCRPC irrespectively to gene PV. The conclusion of the PROPEL trial was that the advantage was independent to PV status, however the highest advantage was reported in BRCA1/2 mutated subgroup. The conclusion of the MAGNITUDE trial was different, with a significant advantage only in the DDR mutated subgroup and the DDR non-mutated was closed for further enrollment. The combination of PARP inhibitors with ARSI represents a significant strategy in the concept of anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR.

Prostate cancer (PCa) Lung metastases are rarely resected, therefore PCa lung metastases are insufficiently molecularly characterized. We recently identified carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as a potential driver of pulmonary metastatic spread. Here, we show the biological significance of CEACAM6 in PCa cell proliferation, apoptosis and migration. CEACAM6 was silenced by siRNA in PC3 cells. Functional assessment of apoptosis, cell viability, proliferation and migration were performed in siRNA-CEACAM6 PC3 cells. Non-treated and scrambled (scr) RNA PC3 cells were used as control. Following a specific knockdown of CEACAM6 in PC3 cells, the expression of CEACAM6 protein was significantly decreased in comparison to controls. Cell viability and cell counts decreased in CEACAM6 silent PC3 cells. In contrast, caspase-3 activity was highly elevated in siRNA-CEACAM6 PC3. Furthermore, by performing a cell scratch assay, the migration ratio in siRNA-CEACAM6 PC3 cells were significantly diminished compared with the control group after 48 hours of post transfection incubation. CEACAM6 as a cell adhesion molecule has been implicated in promoting metastatic disease in several solid tumours such as colorectal or gastric cancer. We could show that silencing of CEACAM6 has a significant functional effect on PCa cells. CEACAM6 might play an important role in fostering metastatic spread to the lung of PCa patients via enhancing proliferation and suppressing apoptosis. CEACAM6 might therefore pose an attractive therapeutic target to prevent metastatic disease.

Background: Optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of the moderately hypofractionated post-prostatectomy radiotherapy in 16 daily fractions delivered with IMRT/VMAT. The treatment schedule selection was motivated by limited technology resources. Methods: One hundred consecutive M0 patients with post-prostatectomy radiotherapy were evaluated. Radiotherapy indication was adjuvant (ART) in 19%, early salvage (eSRT) in 46% and salvage (SRT) in 35%. The dose prescription for prostate bed PTV was 52.8 Gy in 16 fractions of 3.3 Gy. The Common Terminology Criteria v.4 for Adverse Events scale was used for toxicity grading. Results: The median follow-up was 61 months. Five-year biochemical recurrence-free survival (bRFS) was 78.6%, distant metastases-free survival was 95.7% and overall survival was 98.8%. Treatment indication was the only significant factor for 5-year bRFS in multivariate analysis which was 84.6% vs. 67.6% for ART or eSRT vs. SRT respectively (HR 0.15, 95% CI 0.05–0.47, p=0.001). Acute GI toxicity grade 2 was recorded in 24%, grade 3 in 2% and acute GU toxicity grade 2 in 10% and no grade 3. Cumulative rate of late GI toxicity grade ≥2 was observed in 9% and late GU toxicity grade ≥2 in 16%. Conclusion: Observed results confirmed efficacy and acceptable toxicity of post-prostatectomy hypofractionated radiotherapy in 16 daily fractions.

Within the oligometastatic state, oligo-recurrent lymph node disease in prostate cancer represents an interesting clinical entity characterized by a relatively indolent biology that makes it unique: it can be treated radically, and its treatment is usually associated with a long period of control and excellent survival. Additionally it is an emergent situation that we are facing more frequently, mainly due to: a) the incorporation into clinical practice of the PSMA PET that provides strikingly increase superior images in comparison to conventional imaging, with higher sensitivity and specificity; b) the higher detection rates of bone and node disease with extremely low levels of PSA; and c) the availability of high-precision technology in radiotherapy treatments with the incorporation of stereotaxic body radiotherapy (SBRT) or stereotaxic ablative radiotherapy (SABR) technology that allows the safe administration of high doses of radiation in a very limited number of fractions with low toxicity and excellent tolerance. This approach of new image-guided patient management is compelling for doctors and patients since it can potentially contribute to improve the clinical outcome. In this work we discuss the available evidence, areas of debate, and potential future directions concerning the utilization of new imaging guided SBRT for the treatment of nodal recurrence in prostate cancer.

Prostate cancer (PCa) is most commonly observed in male patients. Although PCa progresses relatively slowly, high-risk PCa is associated with an increased risk of lymph nodes, distant metastases, and PCa-related death. Several guidelines recommend radiation therapy (RT) of the prostate combined with long-term androgen deprivation therapy for high-risk PCa. A comparison of clinical outcomes between radical prostatectomy (RP) and RT for high-risk PCa by propensity score-matched analysis showed that RP had a significantly higher risk of biochemical recurrence than RT. However, the combination of neoadjuvant chemohormonal therapy followed by RP may be more likely to achieve a cure when overall survival is considered the primary endpoint. In this review, we aimed to confirm the oncological outcomes of RP and RT for high-risk PCa and highlight the importance of neoadjuvant therapy followed by RP for high-risk PCa.

Epidemiological data highlight prostate cancer as a significant global health issue, with high incidence and substantial impact on patients' quality of life. The prevalence of this disease is associated with various factors, including age, heredity, and race. Recent research in prostate cancer genetics has identified several genetic variants that may be associated with an increased risk of developing the disease. However, despite the significance of these findings, genetic markers for prostate cancer are not currently utilized in clinical practice as reliable indicators of the disease. In addition to genetics, epigenetic alterations also play a crucial role in prostate cancer development. Aberrant DNA methylation, changes in chromatin structure, and microRNA (miRNA) expression are major epigenetic events that influence oncogenesis. Existing markers for prostate cancer, such as prostate-specific antigen (PSA), have limitations in terms of sensitivity and specificity. The cost of testing, follow-up procedures, and treatment for false-positive results and overdiagnosis contributes to the overall healthcare expenditure. Improving the effectiveness of prostate cancer diagnosis and prognosis requires either narrowing the risk group by identifying new genetic factors or enhancing the sensitivity and specificity of existing markers. Immunological biomarkers (both circulating and intra-tumoral), including markers of immune response and immune dysfunction, represent a potentially useful area of research for enhancing the diagnosis and prognosis of prostate cancer. Our review emphasizes the need for developing novel immunological biomarkers to improve the diagnosis, prognosis, and management of prostate cancer. We highlight the most recent achievements in the identification of biomarkers provided by circulating monocytes and tumor-associated macrophages (TAMs). We highlight that monocytes-derived and TAMs-derived biomarkers can enable to establish the missing links between genetic predisposition, hormonal metabolism and immune responses in prostate cancer.

Prostate-specific membrane antigen (PSMA) is a well validated prostate cancer marker, but reported PSMA-targeted tracers derived from the Lys-urea-Glu pharmacophore including the clinically validated [99mTc]Tc-EDDA/HYNIC-iPSMA have high off-target uptake in kidneys, spleen and salivary glands. In this study, we synthesized and evaluated three novel 99mTc-labeled PSMA-targeted tracers and investigated if the tracers derived from the Lys-urea-Aad pharmacophore could have minimized uptake in off-target organs/tissues. In vitro competition binding assays showed that compared with HYNIC-iPSMA, the three novel ligands had slightly weaker PSMA binding affinity (average Ki = 3.11 vs 8.96 - 11.6 nM). Imaging and ex vivo biodistribution studies in LNCaP tumor-bearing mice showed that [99mTc]Tc-EDDA/HYNIC-iPSMA and the three novel tracers successfully visualized LNCaP tumor xenografts in SPECT images and were excreted mainly via the renal pathway. The average tumor uptake at 1 h post-injection varied from 5.40 to 18.8 %ID/g, and the tracers derived from the Lys-urea-Aad pharmacophore had much lower uptake in spleen and salivary glands. Compared with the clinical tracer [99mTc]Tc-EDDA/HYNIC-iPSMA, the Lys-urea-Aad derived [99mTc]Tc-EDDA-KL01127 had lower background uptake and superior tumor-to-background contrast ratios, and is therefore promising for clinical translation to detect prostate cancer lesions with SPECT.

Prostate cancer contributes to cancer-related deaths globally, and the etiology of this disease is not yet fully understood. While Human Papillomavirus (HPV) has been associated with several types of cancer, including cervical, anal, and oropharyngeal cancer, studies investigating the relationship between HPV and prostate cancer have shown mixed results. This systematic review aimed to evaluate the causative association between HPV and prostate cancer using Bradford Hill's criteria. A comprehensive search of PubMed was conducted, and 60 out of 482 studies were included in the review. The included studies were evaluated based on nine Bradford Hill criteria, and information on the identification and transmission of the virus and potential oncogenic mechanisms was also extracted. The strength of association criterion was not met, and other criteria, such as consistency and coherence, were not fulfilled. However, biological plausibility was supported, and potential oncogenic mechanisms were identified. While some studies have reported the presence of HPV in prostate cancer tissues, the overall quality of evidence remains low, and the association between HPV and prostate cancer is weak. Nevertheless, the prostate is a potential reservoir for the transmission of HPV, and the HPV E6 and E7 oncoproteins and inflammation are likely to be involved in any oncogenic mechanisms. Further studies with a higher level of evidence are needed to establish a definitive link between HPV and prostate cancer.

The methyltransferase, KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis we have performed a microarray study in a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and Gene Ontology analysis revealed apoptosis and DNA damage signaling are up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase dependent manner to modulate both histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilized as a biomarker for effective therapeutic targeting.

Background: Micro-RNAs (miRNA) are emerging as biomarkers in the detection and prognosis of cancers due to their inherent stability and resilience. Methods: To summarize evidence regarding urinary miRNA (umiRNAs) role in the detection, prognosis and therapeutic management of urological cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary mir-na)AND(prostate cancer); (urinary mirna)AND(bladder cancer); (urinary mirna)AND(renal cancer); (urinary mirna)AND(testicular cancer); (urinary mirna)AND(urothelial cancer). Results: Of all, 1364 articles were initially selected. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. Urinary miRNA (UmiRNAs) are downregulated in prostate cancers and may serve as potential non-invasive molecular biomarkers. Several umiR-NAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BCa), allowing to discriminate malignant from non-malignant forms of haematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle invasive BCa and could predict the aggressivity and prognosis of muscle-invasive BCa. In renal cell carcinoma, miRNAs have been identified as predictors of tumour detection, aggressiveness, and progression to metastasis. Conclusion: umiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.

Euphorbia ingens is traditionally used to treat and manage cancer in Ambeere community of Embu County in Kenya. Whilst research has demonstrated the bioactivities of E. ingens including antimicrobial, antitubercular and antifungal activities, scientific validation of its anticancer properties is limited. This study evaluated the antiproliferative potentials of E. ingens on human prostate cancer cell line (DU-145). The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay was used to assess the antiproliferative activity, chemical constituents were analysed by qualitative colour method and Gas Chromatography-Mass Spectrometry analysis. At the same time, the investigation of putative molecular targets and mechanisms of action of E. ingens was done through network pharmacological analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was carried out to validate the network predictions of putative targets. Our result showed E. ingens ethyl acetate inhibited DU-145 growth (IC50 of 9.71 ± 0.4 µg/ml) with a high selectivity index of 8.26. There was the presence of phenols, terpenoids, flavonoids, tannins, sterols, and saponins; additional 18 compounds were identified by the GC-MS approach. ESR1, IL6, MMP9, CDK2, MAP2K1, AR, PRKCD, CDK1, CDC25B, and JAK2 were indicated as key targets of E. ingens against prostate cancer with the PI3K-AKT, MAPK, and p53 signalling pathways identified as the most probable mechanisms of action. There was significant downregulation of AR and BCL2, and upregulation of p53 and caspase-3 in E. ingens-treated DU-145 cells compared to 0.2 % DMSO negative control. Our results suggest that E. ingens has phytochemical compounds efficacious at inhibiting the proliferation of DU-145 cells; therefore, the plant can be considered a potential source of compounds that may be used to manage and treat prostate cancer; however, further in vivo evaluations are needed.

Prostate cancer is driven by acquired genetic alterations, including those impacting the epigenetic machinery. With African ancestry a significant risk factor for aggressive disease, we hypothesize that dysregulation among the roughly 656 epigenetic genes may contribute to prostate cancer health disparities. Interrogating prostate tumor genomic data from 109 men of southern African and 56 men of European Australian ancestry, we found African-derived tumors to present with a longer tail of epigenetic driver gene candidates (72 versus 10). Biased towards African-specific drivers (63 versus 9 shared), many are novel to prostate cancer (18/63) including several putative therapeutic targets (CHD7, DPF3, POLR1B, SETD1B, UBTF and VPS72). Through clustering of all variant types and copy number alterations, we describe two epigenetic PCa taxonomies capable of differentiating patients by ancestry and predicted clinical outcomes. We identified top genes in African and European-derived tumors that represent a multifunctional “generic machinery”, alteration to which may be instrumental in epigenetic dysregulation and prostate tumorigenesis. In conclusion, numerous somatic alterations in the epigenetic machinery drive prostate carcinogenesis but African-derived tumors appear to achieve this with greater diversity amongst such alterations. The greater novelty observed in African-derived tumors illustrates the significant clinical benefit to be derived from a much needed African tailored approach to prostate cancer healthcare aimed at reducing prostate cancer health disparities.

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second most common cause of death due to cancer. About 30% of patients with PCa who have been castrated develop a castration-resistant form of the disease (CRPC), which is incurable. In the last decade, new treatments that control the disease have emerged, slowing progression and spread, and prolonging survival while maintaining the quality of life. These include immunotherapies; however, we do not yet know the optimal combination and sequence of these therapies with the standard ones. All therapies are not always suitable for every patient due to co-morbidities or adverse effects of therapies or both, so there is an urgent need for further work on new therapeutic options. Advances in cancer immunotherapy with an immune checkpoint inhibition mechanism (e.g., ipilimumab, an anti-CTLA-4 inhibitor) have not shown a survival benefit in patients with CRPC. Other immunological approaches have also not given clear results, which has indirectly prevented breakthrough for this type of therapeutic strategy into clinical use. Currently, the only approved form of immunotherapy for patients with CRPC is a cell-based medicine, but it is only available to patients in some parts of the world. Based on the experience gained from recently completed clinical research on immunotherapy with dendritic cell-based immunohybridomas, the aHyC dendritic cell vaccine, for patients with CRPC, we highlight the current status, and possible alternatives that should be considered in the future.

Background: In this paper, it was aimed to evaluate the biomarker potential as well as the effect of the prognostic nutritional index (PNI), which is calculated using the albumin level reflecting nutritional status and lymphocyte count reflecting immune status, in determining the prognosis of metastatic castration-sensitive prostate cancer (mCSPC). Methods: This retrospective observational study included the complete data of 108 patients with mCPSC who were treated for at least three months between January 1, 2010, and June 1, 2021. The relationship between cancer specific survival (CSS), overall survival (OS), progression free survival (PFS) and PNI was evaluated. Kaplan-Meier method for OS, PFS, and CSS, as well as univariate and multivariate Cox regression models were used in statistical analyses. Results: The median age of 108 patients included in the study was 68.54 (61.05-74.19) years. While 71.3% (n = 77) of the patient population were high-volume according to CHAARTED, 52.8% (n = 57) were high-risk based on LATITUDE. 49.75 was determined as the best cut-off point for the PNI. OS (months) was found to be significantly lower in patients with low PNI (median: 34.93, 95% CI: 21.52–48.34) compared to patients with high PNI (median: 65.60, 95% CI: 39.36–91.83) (p=0.016). Patients with high PNI (median: 48.20, 95% CI: 34.66–61.73) had significantly better CSS (months) than patients with low PNI (median: 27.86, 95% CI: 24.16–31.57) (p=0.001). Conclusions: PNI calculated at the time of diagnosis strongly predicts OS and CSS but not PFS in patients with mCSPC.

To examine the association of clinical, treatment, and dose parameters with late urinary toxicity after low-dose-rate brachytherapy (LDR-BT) for prostate cancer, we retrospectively studied patients with prostate cancer who underwent LDR-BT from January 2007 through December 2016. Urinary toxicity was assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder (OAB) Symptom Score (OABSS). Severe and moderate lower urinary tract symptoms (LUTS) were defined as IPSS ≥ 20 and ≥ 8, respectively; OAB was defined as a nocturnal frequency of ≥ 2 and a total OABSS of ≥ 3. In total, 203 patients (median age, 66 years) were included, with a mean follow-up of 8.4 years after treatment. The IPSS and OABSS worsened after 3 months of treatment; these scores improved to pretreatment levels after 18–36 months in most patients. Patients with a higher baseline IPSS and OABSS had a lower frequency of moderate and severe LUTS and OAB at 24 and 60 months, respectively. LUTS and OAB at 24 and 60 months were not correlated with the dosimetric factors of LDR-BT. Although the rate of long-term urinary toxicities assessed using IPSS and OABSS was low, the baseline scores were related to long-term function. Refining patient selection may further reduce long-term urinary toxicity.

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.

Aim of the study: To draw inferences from a retrospective evaluation of PSMA PET CT scans performed for the evaluation of biochemical recurrence. Material and Methods: Retrospective analysis of 295 PSMA PET CT scans spanning 3 years between 2020 and 2022 was undertaken. Results: Of 295 PET CT scans, 179 were positive, 66 negative and 50 had indeterminate findings. In positive group, 67 had radical prostatectomy and PSMA avid lesions were seen most commonly in pelvic lymph nodes. Remaining 112 positive scans, in non-radical prostatectomy group; 25 had recurrence only in prostate, 17 had recurrence involving prostate bed; 28 had no recurrence in prostate gland, while 42 had recurrence in prostate as well as extra prostatic sites. Overall, in non-prostatectomy group, 75 % population was harbouring a PSMA avid lesion in prostate gland while in remaining 25% population recurrence did not involve prostate gland. Majority of indeterminate findings were seen in small pelvic or retroperitoneal lymph nodes or skeletal regions (ribs/others) and in 9 patients indeterminate focus was seen in the prostate bed only. Follow up PSMA PET CT was helpful in prior indeterminate findings and unexplained PSA rise. Conclusion: A higher recurrence in prostate bed while evaluating biochemical recurrence prompts us to think; whether prostatectomy should be offered more proactively? Follow up PSMA PET CT is helpful for indeterminate findings; a PSA rise of 0.7 ng/ml in 6 months can result in positive PSMA PET CT while negative scan can be seen upto 2ng/ml PSA rise in 6 months.

Radical prostatectomy (RP) is one of the recommended treatments to achieve oncological outcomes in localized prostate cancer. However, radical prostatectomy is a major abdominopelvic surgery. Venous thromboembolism (VTE) is a well-known complication associated with surgical procedures including RP. There is a lack of consensus regarding VTE prophylaxis in urological procedures. The aim of this systematic review was to investigate different aspects of VTE in post-Radical Prostatectomy patients. A comprehensive literature search was performed, and relevant data were extracted. The primary aim was to perform a systematic review and meta-analysis (wherever possible) of VTE occurrence in post-RP patients in relation to surgical approach, pelvic lymph node dissection, and type of prophylaxis (mechanical or combined prophylaxis). The secondary aim was to investigate- the incidence and other risk factors of VTE in post-RP patients. A total of 16 studies were included for quantitative analysis. Statistical methods for analysis included the DerSimonian-Laird random effects. We were able to conclude that the overall incidence of VTE in post-radical prostatectomy is 1% and minimally invasive procedures (MIS), including laparoscopic as well as robotic procedures for radical prostatectomy and RP without pelvic lymph node dissection (PLND) are associated with less risk of developing VTE. Additional pharmacological prophylaxis to mechanical methods may not be necessary in all cases and should be considered in high-risk patients only.

Background: Current prostate cancer evaluation can be inaccurate and burdensome. Quantitative evaluation of MRI sequences non-invasively helps prostate tumor assessment. However, including Dynamic Contrast Enhancement in the examined MRI sequence set can add complications, inducing possible side effects from the IV placement or injected contrast material, and prolongs scanning time. Purpose: Predict the risk of developing Clinically Significant (Insignificant) prostate cancer CsPCa (CiPCa) and International Society of Urologic Pathology (ISUP) grade using processed Signal to Clutter Ratio (SCR) derived from spatially registered bi-parametric MRI (SRBP-MRI) and thereby enhance non-invasively management of prostate cancer. Methods: This pilot study retrospectively analyzed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRI (Apparent Diffusion Coefficient, High B-value, T2) were resized, translated, cropped, and stitched to form spatially registered SRBP-MRI. Efficacy of noise reduction was tested by regularizing, eliminating principal components (PC), and minimizing elliptical volume from the covariance matrix to optimize the SCR. MRI guided biopsy (MRBx), Systematic Biopsy (SysBx), combination (MRBx+SysBx), or radical prostatectomy determined the ISUP grade for each patient. ISUP grade >=2 (<2) was judged as CsPCa (CiPCa). Linear and Logistic regression were fitted to ISUP grade and CsPCa/CiPCa SCR. Correlation Coefficients (R) and Area Under the Curves (AUC) for Receiver Operator Curves (ROC) evaluated the performance. Results: High correlation coefficients (R) (>0.55) and high AUC (=1.0) for linear and/or logistic fit from processed SCR and z-score for SRBP-MRI greatly exceed fits using prostate serum antigen, prostate volume, and patient age (R~0.17). Patients assessed with combined MRBx+SysBx and from individual MRI scanners achieved higher R (R=0.207+/-0.118) than using all patients in the fits. Conclusions: In the first study to date to apply and test hyperspectral approaches for assessing tumor aggressiveness on SRBP-MRI, high values of R and exceptional AUC to fit the ISUP grade and CsPCA/CiPCA were comparable or better than those from artificial intelligence in other studies.

Erectile dysfunction (ED) is a common and feared complication of radical prostatectomy (RP) for prostate cancer. Recently, tissue engineering is being attempted for post-prostatectomy ED, with controlled interactions between cells, growth factors, and extracellular matrix (ECM) being important for nerve regeneration's structural integrity. In this study, we evaluated the effects of biomechanical ECM patch on human bone marrow-derived mesenchymal stem cells (hBMSCs) morphology and behavior in bilateral cavernous nerve injury (BCNI) rat model. The ECM patch, made of decellularized human fibroblast-derived ECM (hFDM) and a biocompatible polyvinyl alcohol (PVA) hydrogel, was tested with human bone marrow-derived mesenchymal stem cells (hBMSCs) on a bilateral cavernous nerve injury (BCNI) rat model. In vitro analysis showed that the hFDM/PVA + hBMSCs patches significantly increased neural development markers. In vivo experiments demonstrated that the rats treated with the hFDM/PVA patch had higher ICP/MAP ratio, a higher ratio of smooth muscle to collagen, increased content of nNOS, higher levels of eNOS protein expression, and a higher cGMP level compared to the BCNI group. These results indicate that the hFDM/PVA patch is effective in promoting angiogenesis, smooth muscle regeneration, and nitrergic nerve regeneration, which could contribute to improved erectile function in post-prostatectomy ED.

Longer operating time in radical prostatectomy may escalate the risk of perioperative complications. Various factors like cancer extent, procedure’s level of difficulty, habitus and previous surgeries may lengthen robotic assisted radical prostatectomy (RARP) and therefor compromise outcomes. Objective: this study investigates the influence of operating time on outcomes after RARP in real life settings in a monocentric single surgeon study. Methods: 500 consecutive patients who underwent RARP between April 2019 and August 2022 were included. Patients were divided in three groups. Short (n=157; 31.4%) under or equal to 120 minutes, average (n=255; 51%) between 121 and 180 minutes, long (n=88; 17,6%) above 180 minutes console-time. Demographic, baseline and perioperative data were analyzed and compared between groups. Univariate logistic regression was completed to investigate the association between console-time and outcomes and to predict factors which may prolong surgery. Results: hospital stay and catheter days were significantly longer in group 3 with medians 6 and 7 days (p<0.001 and <0.001, respectively). Those findings were confirmed in univariate analysis, p=0.012 for Catheter days and p<0.001 for Hospital stay. Moreover, major complications were higher in patients with longer procedures p=0.008. Prostate volume was the only predictor for prolonged console time (p=0.005). Conclusion: RARP is a safe procedure and most patients will be discharged uneventfully. Yet longer console-time is associated with longer hospital stay, catheter days and major complications. Caution has to be taken in large prostate to avoid longer procedures, which may prevent postoperative advert events.

Introduction Prostate Cancer (PCa) exhibits one of the widest racial and socioeconomic disparities. PCa disparities have also been widely linked to location as living in more deprived regions was associated with lower healthcare access and worse outcomes. This study aims to examine PCa survival across various US counties in function of different socioeconomic profiles and discuss the role of potential intermediary factors. Methods The SEER database linked to county-level SES was utilized. Five-year PCa-specific survival using the Kaplan Meier method was performed for 5 racial/ethnic categories in function of SES quintiles. Multilevel Cox proportional hazards regression was performed to assess the relationship between county-level SES and PCa survival. Multivariate regression analysis was performed to examine the role of healthcare utilization and severity. Results 279,000 PCa records were extracted, 5-year PCa-specific survival was 94%. Overall, living in counties with worst poverty/income quintile and highest proportions of foreign-born/language-isolated increased PCa mortality by 23% each. No association was observed with county-level High-School education, while Bachelor’s-level education decreased mortality risk by 23%. Associations varied considerably upon racial/ethnic stratification. Multilevel analyses showed varying contributions of individual and area-level factors to survival within minorities. The relationship between SES and PCa survival appeared to be influenced by healthcare utilization and disease stage/grade. Discussion Racial/ethnic categories responded differently under similar county-level SES and individual-level factors to the point where disparities reversed in Hispanics. The inclusion of Healthcare utilization and severity factors may provide partial early support for their role as intermediaries. Healthcare access (insurance) might not necessarily be associated with better PCa survival, through performing biopsy and or/surgery. County-level education plays an important role in PCa decision-making as it might elucidate discussions of other non-invasive management options. Conclusion Findings of this study demonstrate that interventions need to be tailored according to each group's needs. This potentially informs the focus of public health efforts in terms of planning and prioritizing. This study could also direct further research delving into pathways between area-level characteristics with PCa survival.

Growing evidence indicates the involvement of a genetic component for CaP susceptibility and clinical severity. Somatic mutations of TP53 have been associated with 50% of diverse human cancers. Studies have also reported the role of germ line mutations and single nucleotide poly-morphisms (SNPs) of TP53 as possible risk factors for cancer development. In this single De-partment of Defense institutional retrospective study, we identified common SNPs in the TP53 gene in AA and CA men and performed association analyses for functional TP53 SNPs with clinico-pathological features of CaP. The CPDR Oncoarray database on blood derived genomic DNA from 321 men treated by radical prostatectomy at WRNMMC were used to examine clini-co-pathological associations with TP53 SNPs. The SNP genotyping analysis on the final cohort of 308 patients (212 AA; 95 CA) identified 74 SNPs in the TP53 gene region with a minor allele fre-quency (MAF) of at least 1%. Two SNPs were non-synonymous in the exonic region of TP53: rs1800371 (Pro47Ser) and rs1042522 (Arg72Pro). The Pro47Ser variant, had a minor allele frequency of 0.01 in AA, however, was not detected in CA. Arg72Pro was the most common SNP with a minor allele frequency of 0.50 (0.41 in AA; 0.68 in CA). Additionally, Arg72Pro was associated with time to biochemical recurrence (BCR) after statistical adjustment for patient age at diagnosis, self-reported race, and Gleason score (p= 0.046; HR = 1.52). The present study demonstrated ancestral differences in allele frequencies of TP53 Arg72Pro and Pro47Ser SNPs in AA and CA CaP, providing a valuable framework for the interrogating CaP disparity among AA and CA men.

The androgen/androgen receptor (AR)-signaling axis plays a central role in the development and growth of prostate cancer (PCa) cells. Upon androgen-binding the AR dimerizes with another AR, translocates into the nucleus where the AR-dimer activates/inactivates androgen-dependent genes. In consequence treatments for locally advanced or metastatic PCa are commonly based on androgen deprivation therapies (ADT). Unfortunately, the clinical benefits of ADT are only transitory and most tumors develop mechanisms allowing the AR to bypass its need for physiological levels of circulating androgens. In the clinic failure of ADT is often characterized by the synthesis of a C-terminally truncated, constitutively active AR splice variant, termed AR-V7. In contrast to AR, the constitutively active AR-V7 does no longer need androgenic stimuli for nuclear entry and/or dimerization. The goal of the present study was to mechanistically decipher the interaction between full-length AR (AR-FL) and AR-V7 in AR-null HEK-293 cells using the NanoLuc Binary Technology (NanoBiT) structural complementation assay under androgen stimulation and deprivation conditions. Our data point toward a hypothesis that AR-FL/AR-FL homodimers form in the cytoplasm, whereas AR-V7/AR-V7 localize in the nucleus. However, after 15 min of androgen stimulation, all AR-FL/AR-FL, AR-FL/AR-V7 and AR-V7/AR-V7 dimers localized in the nucleus. In this way, we can show an androgen-regulated interaction between AR-FL and AR-V7 at forming heterodimers that localize in the nucleus, whereas AR-V7/AR-V7 dimers were found to localize in the absence of androgens in the nucleus. Treatment with enzalutamide diminished the luminescence of AR-FL homodimers and AR-FL/AR-V7 heterodimers but not AR-V7/AR-V7 homodimers.

This study was performed to synthesize multimodal radiopharmaceutical designed for the diagnosis and treatment of prostate cancer. To achieve this goal, Super Paramagnetic Iron Oxide (SPIO) nanoparticles were used as a platform for targeting molecule (PSMA-617) and for complexation of two scandium radionuclides, 44Sc for PET imaging and 47Sc for radionuclide therapy. TEM and XPS images showed that the Fe3O4 NPs have a uniform cubic shape and a diameter from 38 to 50 nm. The Fe3O4 core are surrounded by SiO2 and an organic layer. The saturation magnetization of the SPION core was 60 emu/g. However, coating the SPIONs with silica and polyglycerol reduces the magnetization significantly. The obtained bioconjugates were labeled with 44Sc and 47Sc, with a yield higher than 97%. The radiobioconjugate exhibited high affinity and cytotoxicity towards the human prostate cancer LNCaP (PSMA+) cell line, much higher than for PC-3 (PSMA-) cells. High cytotoxicity of the radiobioconjugate was confirmed by radiotoxicity studies on LNCaP 3D-spheroids. In addition, the magnetic properties of the radiobioconjugate should allow for its use in guide drug delivery driven by magnetic field gradient.

Prostate cancer (PC) is the most frequently diagnosed non-skin cancer in the world. Previous studies showed that genomic alterations represent the most common mechanism for molecular alterations that cause the development and progression of PC. Great efforts have been done to identify common protein-coding genetic variations; however, the impact of non-coding variations including regulatory genetic variants is not still well understood. To gain an understanding of the functional impact of genetic variants, particularly, regulatory variants in PC, we developed an integrative pipeline (AGV) that used whole genome/exome sequences, GWAS SNPs, chromosome conformation capture data, and ChIP-Seq signals to investigate the potential impact of genomic variants on the underlying target genes in PC. We identified 646 putative regulatory variants, of which 30 of them significantly altered the expression of at least one protein-coding gene. Our analysis of chromatin interactions data (Hi-C) revealed that the 30 putative regulatory variants may affect 131 coding and non-coding genes. Interestingly, our study showed the 131 protein-coding genes are involved in disease-related pathways including Reactome and MSigDB in which for most of them targeted treatment options are currently available. Together, our results provide a comprehensive map of genomic variants in PC and revealed their potential contribution to prostate cancer progression and development.

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.

Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with the genetics, genomics, and the environmental influence in causality of PCa, not many studies employing the next generation sequencing (NGS) approaches of PCa have been carried out. In our previous study, we have identified some causal genes and mutations specific to Indian PCa using Whole-Exome Sequencing (WES). In the recent past, with the help of different cancer consortiums such as The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), along with differentially expressed genes (DEGs), many cancer-associated novel non-coding RNAs have been identified as biomarkers. In this work, we attempt to identify DEGs as well as long non-coding RNAs (lncRNAs) associated with signature pathways from an Indian PCa cohort using RNA-sequencing (RNA-seq) approach. From a cohort of 60, we screened 6 patients who underwent prostatectomy; we performed a whole transcriptome shotgun sequencing (WTSS)/RNA-sequencing to decipher the DEGs. We further normalized the read counts using fragments per kilobase of transcript per million mapped reads (FPKM) and analyzed the DEGs using a cohort of downstream regulatory tools, viz. GeneMANIA Stringdb, Cytoscape-Cytohubba, cbioportal to map the inherent signatures associated with PCa. By comparing the RNA-seq data obtained from the pairs of normal and PCa tissue samples using our benchmarked in-house cuffdiff pipeline, we observed some important genes specific to PCa such as STEAP2, APP, PMEPA1, PABPC1, NFE2L2, HN1L and some other important genes known to be involved in different cancer pathways such as, COL6A1, DOK5, STX6, BCAS1, BACE1, BACE2, LMOD1, SNX9, CTNND1 etc. We also identified a few novel lncRNAs such as LINC01440, SOX2OT, ENSG00000232855, and ENST00000647843.1 that need to be characterized further. Deregulation of SOX2OT is observed in various tumors, including lung cancer, gastric cancer, esophageal cancer, breast cancer, hepatocellular carcinoma, ovarian cancer, pancreatic, laryngeal squamous cell carcinoma, osteosarcoma, nasopharyngeal carcinoma, and glioblastoma. It would be interesting to characterize its function in PCa as well. In comparison with publicly available datasets, we have identified characteristic DEGs and novel lncRNAs implicated in signature PCa pathways in an Indian PCa cohort which have perhaps not been reported. As a pilot study, this has set a precedent for us to validate further experimentally, and we firmly believe this will pave a way towards discovery of biomarkers and development of novel therapies.

Prostate Cancer (PCa) is still ranked as the first cancer in male population and evidences have suggested an alteration of glycemic and lipidic metabolism that are related to its progression and prognosis. Aim of the study is to investigate associations between enzymes’ expression, especially involved in the lipidic pathway, and PCa aggressiveness. We retrospectively analyzed data from 390 patients with PCa or benign prostatic hyperplasia (BPH) at the Department of Urology, University of Catania. Immunohistochemical slides were evaluated for the expression of proteins related to glucose and lipidic metabolism. A total of 286 were affected by PCa while 104 by BPH. We demonstrated that ATP-lyase (odds ratio [OR]: 1.71; p&lt;0.01), fatty acide sinthase (OR: 4.82; p&lt;0.01), carnitine palmitoyl transferase-1a (OR: 2.27; p&lt;0.05) were associated with androgen receptor (AR) expression. We found that steaoryl Co-A desaturase expression in PCa patients with total cholesterol ≥ 200 mg/dl was independently associated with ISUP ≥4 (OR: 4.22; p=0.049). We found that CPT-1a+ was associated with biochemical recurrence (hazard ratio: 1.94; p=0.03]). Our results support the evidences that the manipulation of lipidic metabolism could serve in the future to contrast PCa progression.

Introduction: A dual malignancy with both Ewing Sarcoma and Prostate Adenocarcinoma has not been reported in the English literature. We report a case of simultaneous diagnosis of Ewing sarcoma and prostate adenocarcinoma with profound clinical manifestation. Case presentation: A 53-year-old male with advanced metastatic prostate cancer (Gleason-9) admitted with classical presentation of cauda equina syndrome including incontinence, back pain, and paresis following bilateral nephrostomy insertion for the treatment of bilateral renal hy-dronephrosis. The patient was diagnosed with an epidural abscess at the level of L5-S1 and an emergency surgical spine decompression was performed. No abscess was found, and pathology results showed a concomitant primary Ewing sarcoma in the spine. Conclusions: Very rare occurrences of a dual primary malignancy, in this case, Ewing sarcoma and prostate adenocarcinoma, should be kept in mind in patients suffering from complex clinical course of malignancies.

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, 68Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of 68Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: 68Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those 2/17 had NePC. Semiquantitative analysis with standardized uptake values (SUV) (e.g. SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. 68Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastic lesion with identifiable 68Ga-DOTATATE uptake. Marked 68Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. 3 patients had mild 68Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after 68Ga-DOTATATE imaging. Conclusions: 68Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with 68Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.

Introduction: The aim of our study was to evaluate the efficacy and toxicity of a daily-adaptive MR-guided SBRT on 1.5 T MR-linac in patients affected by lymphnode oligometastases from PCa. Materials and Methods: The present study is a prospective observational study conducted in a single institution (protocol n°: MRI / LINAC n. 23748). Patients with oligometastatic lymphnodes from PCa treated with daily-adaptive MR-guided SBRT on 1.5T MR-linac were included in the study. Minimum required follow-up of 3 months after SBRT. Primary end-point was local progression-free survival (LPFS). Secondary end-points were: nodal progression-free survival (NPFS), and progression-free survival (PFS), and toxicity. Results: 118 lymphnode oligometastases from PCa were treated with daily-adaptive 1.5T MR-guided SBRT in 63 oligometastatic patients. 63.5% patients were oligoprogressive and 36.5% oligoprogressive. Two-year LPFS was 94.5%. Median NPFS was 22.3 months, and the 2-year NPFS was 46.5%. Having received hormone therapy before SBRT was correlated with lower NPFS at the multivariate analysis (1-y NPFS 87.1% versus 42.8%; p= 0.002 - HR 0.199, 95% CI 0.073-0.549). Furthermore, the oligorecurrent state during ADT was correlated with a lower NPFS than the oligoprogressive state. Median PFS was 10.3 months, the 2-year PFS was 32.4%. Patients treated with hormone therapy before SBRT had a significantly lower 1-year PFS the others (28% versus 70.4%; p= 0.01 - HR 0.259, 95% CI 0.117-0.574). No acute and late toxicities occurred during treatment. Conclusion: the present is the largest prospective study of 1.5T lymphnode SBRT on MR-linac in patients with PCa. Lymphnode SBRT by 1.5T MR-linac provides high local control rates with an excellent toxicity profile.

The prognostic value of inflammatory indices such as absolute monocyte count (AMC) has been a subject of interest in recent prostate cancer (PCa) literature, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized disease. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data was available for all cases based on the National Cancer Registry with a median observation time of 120 months (IQR 80.9-144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox proportional hazards regression model was used for analysis. The median age was 68.8 years (IQR 63.3-73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0-19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, ISUP Grade Group, clinical T stage and maximum PSA concentration. The study demonstrated that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa.