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.

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.

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.

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.

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.

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.

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 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: 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.

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.

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.

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.

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.

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.

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) 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.

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.

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.

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 &lt; 0.0001 and SMD: -0.46 (95% CI: -0.69 to -0.24) p &lt; 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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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&gt;MTYR&gt;&gt;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: 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 &gt; 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.

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.

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.

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, according to the World Health Organization (WHO), ranks as the fourth most prevalent type in the population, even though it is highly frequent when detected early and promptly treated, resulting in a low mortality rate. However, in some cases, despite adherence to proper clinical protocols, there is a progression to castration-resistant prostate cancer (CRPC). In these cases, as outlined in clinical guidelines such as those developed by the National Comprehensive Cancer Network (NCCN), one approach involves the utilization of the pharmaceutical agent abiraterone to implement androgen deprivation therapy (ADT), aimed at suppressing the production of hormones directly implicated in disease progression. Another noteworthy aspect is the limited literature on clinical protocols and their efficacy concerning the Amazonian indigenous population, which often exhibits unique genomic profiles, with descriptions of variants not yet documented in the literature. Building upon these considerations, this study aims to survey the variants identified in genes associated with the abiraterone signaling pathway, their frequencies in the Amazonian indigenous population, and the correlation of these frequencies with those observed in other global populations. The objective is to contribute to the refinement of clinical practices in the treatment of prostate cancer within this population.

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.