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Objectives: The aim of this study was to perform a budget impact analysis (BIA) of introducing olaparib treatment for adult patients with metastatic castration-resistant prostate cancer in Argentina. Methods: A BIA model was used to estimate the cost difference between the current scenario (without olaparib) and the new scenario (incorporation of olaparib) for a third-party payer over a 5-year time horizon. The budgetary impact is estimated at the national health system level and by healthcare sectors in Argentina. Input parameters were obtained from the literature and validated by local expert opinion. Direct medical costs were obtained from both the Institute for Clinical Effectiveness and Health Policy (IECS) unit cost database and public data in Argentina. The microcosting estimation was used for key variables of the analysis. All costs are reported in US dollars (US$) as for October 2022 (1 US$ = 152.59 Argentine pesos). One-way sensitivity analyses and scenario analyses were conducted to evaluate the model robustness. Results: The incorporation of olaparib, with a wholesale price per pack of US$3176, was associated with a weighted average of the budget impact per member per month (PMPM) of US$0.0191 for the national health system, being slightly higher than the estimated budgeted high impact threshold (US$0.0153). The PMPM budget impact for a 5-year average ranged between US$0.007 (public sector) and US$0.033 (private sector). The duration of treatment with olaparib was the most influential parameter in the budget impact results. Conclusions: The introduction of olaparib for the treatment of metastatic castration-resistant prostate cancer has a high budget impact for Argentina's health system. These findings are informative to support policy decisions aimed to expand the current treatment landscape for prostate cancer. [ABSTRACT FROM AUTHOR]

Background and Objectives: Metastatic castration-sensitive prostate cancer (mCSPC) represents a critical juncture in the management of prostate cancer, where the accurate prediction of the onset of castration resistance is paramount for guiding treatment decisions. Methods: In this study, we underscore the power and efficiency of auto-ML models, specifically the Random Forest Classifier, for their low-code, user-friendly nature, making them a practical choice for complex tasks, to develop a predictive model for the occurrence of castration resistance events (CRE( . Utilizing a comprehensive dataset from MSK (Clin Cancer Res 2020), comprising clinical, genetic, and molecular features, we conducted a comprehensive analysis to discern patterns and correlations indicative of castration resistance. A random forest classifier was employed to harness the dataset's intrinsic interactions and construct a robust predictive model. Results: We used over 18 algorithms to find the best model, and our results showed a significant achievement, with the developed model demonstrating an impressive accuracy of 75% in predicting castration resistance events. Furthermore, the analysis highlights the importance of specific features such as 'Fraction Genome Altered ‘and the role of prostate specific antigen (PSA( in castration resistance prediction. Conclusion: Corroborating these findings, recent studies emphasize the correlation between high 'Fraction Genome Altered' and resistance and the predictive power of elevated PSA levels in castration resistance. This highlights the power of machine learning in improving outcome predictions vital for prostate cancer treatment. This study deepens our insights into metastatic castrationsensitive prostate cancer and provides a practical tool for clinicians to shape treatment strategies and potentially enhance patient results. [ABSTRACT FROM AUTHOR]

Background: In Retzius-sparing robot-assisted radical prostatectomy (RARP), lymphocele formation is a troublesome complication. The use of peritoneal flaps has emerged as a promising novel technique to tackle this complication. We explored this technique by suturing both the medial peritoneal flaps to each other and keeping them distracted so that the lymphadenectomy beds are left wide open. Objective: To assess the efficacy of our peritoneal distraction technique on lymphocele rates following Retzius-sparing RARP. Materials and Methods: This retrospective study included patients with localized prostate carcinoma who underwent Retzius-sparing RARP with standard pelvic lymph node dissection between May 2014 and September 2022 at Aster Medcity, Kochi, India. Based on the use of the technique, patients were divided into two groups: peritoneal distraction and closed groups. Both groups were matched using the propensity scoring method in a 1:1 ratio. Results: A total of 272 patients were included, of which 89 (32.7%) belonged to the peritoneal distraction group. Although the overall incidence of lymphocele between the two groups were comparable, none of the patients in the peritoneal distraction group required any intervention for lymphocele management, as opposed to 7 patients from the closed group (3.9%; P = 0.015). No significant association was found between lymphocele formation and serum prostate-specific antigen level, Gleason score, and the number of lymph nodes harvested. Conclusions: This study found that peritoneal distraction stitch is a simple and effective technique to reduce the incidence of symptomatic lymphocele that require intervention after Retzius-sparing RARP. [ABSTRACT FROM AUTHOR]

Background/Aim: When hormone therapy (HT) is combined with radiotherapy, understanding the recovery of testosterone levels after the end of HT becomes crucial for considering subsequent therapy. The aim of this study was to determine the factors influencing the time to recovery of testosterone levels after discontinuation of HT and the likelihood of recovery. Patients and Methods: The study included a total of 108 patients with prostate cancer who were treated with GnRH agonist in combination with radiotherapy and followed up for at least 12 months after discontinuation of the GnRH agonist. The presence of recovery of testosterone levels and the time to recovery were investigated. Univariate and multivariate analyses were performed on several factors contributing to testosterone recovery, including age at initiation of HT, and the duration of HT. Results: Testosterone levels recovered in 61 cases (56.5%). The median time to recovery was 14.8 months. There was a significant difference in the recovery of testosterone levels between patients aged ≥71 years and those aged <71 years at the start of HT (p=0.002), and between those who had been on HT for ≥34 months and those for <34 months (p=0.031). In both univariate and multivariate analyses, age at initiation of HT and duration of HT contributed to the recovery of testosterone levels. Conclusion: The rate of recovery of testosterone levels after long-term (median 34.3 months) HT was lower in patients who were older than 71 years at the start of HT. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer presents significant challenges due to its high incidence and prevalence, as it is the most common non-skin cancer in men. The timely detection of prostate cancer and its metastasis is crucial for patient outcomes. Prostate-specific membrane antigen (PSMA) emerges as a promising biomarker for its early detection, due to its specificity and membrane localization on tumor cells. Utilizing PSMA-targeting particles in conjunction with positron emission tomography (PET) scans enhances the accuracy of tumor detection compared to PET alone. This advancement has led to innovative treatment modalities such as Prostate-specific membrane antigen-targeted radionuclide therapies (PSMA-TRTs), which have shown promise in reducing or eliminating tumors, as evidenced by declines in prostate-specific antigen (PSA) levels post treatment. However, PSMA-TRT carries both benefits and adverse effects, with the long-term ones as yet unknown. The short-term adverse effects include fatigue, nausea, pain flares, and potential radiation exposure to others. Further research is needed to explore PSMA-TRT's long-term efficacy and potential applications beyond prostate cancer. Prostate cancer is one of the most challenging malignancies due to its high incidence and prevalence, as it is the most frequently diagnosed non-skin cancer in men. The timely identification of prostate cancer and its metastasis is paramount for ensuring favorable outcomes for patients. Prostate-specific membrane antigen (PSMA) emerges as a promising biomarker for its detection, due to its specificity. This makes it an ideal target for the early identification of a metastatic phenotype. Situated on the membrane of tumor cells, PSMA facilitates the attachment of PSMA-targeting particles, enabling their detection through positron emission tomography (PET) scans with relative ease. Utilizing these imaging agents in conjunction with PET scans enhances the accuracy of prostate cancer tumor detection compared to PET scans alone. The advancement in prostate cancer imaging has paved the way for innovative treatment modalities. Prostate-specific membrane antigen-targeted radionuclide therapies (PSMA-TRT) exploit PSMA imaging agents to target identified prostate cancer malignancies with precise radiation, thereby reducing or eliminating the tumor mass. PSMA-TRT exhibits significant promise in prostate cancer therapy, evident from the notable declines in prostate-specific antigen (PSA) levels post treatment. However, PSMA-TRT carries both beneficial and adverse effects. While it represents a substantial leap forward in tumor cell imaging, PSMA-based antigens, being larger particles than ligands, offer prolonged imaging capabilities. Yet, the long-term effects of PSMA-TRT remain unknown, with the short-term adverse ones including fatigue, nausea, pain flares, and potential radiation exposure to others. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer has become one of the leading causes of death in men. Cancer patients often seek alternative treatments apart from chemotherapy, radiation therapy, and surgery. The use of medicinal plants in both preventive and curative actions in healthcare has been widely recognized. One of the plants known to have anticancer activity is the soursop leaf (Annona muricata L.). Objective: This study was conducted to explore the potential of active compounds contained in A. muricata as drug candidates for the inhibition of caspase-3 in silico. Methods: The research began with the prediction of Lipinski's Rule of Five and ADMET properties for the compounds found in A. muricata. The prediction process was followed by pharmacophore modelling and molecular docking simulations on caspase-3 (PDB: 1NME) as the target protein and 2-hydroxy-5-(2-mercaptoethylsulfamoyl)- benzoic acid as the natural ligand using AutoDockTools 1.5.6. Results: Based on the molecular docking results, 22 test ligands were able to form bonds with the caspase-3 enzyme. The two best interactions were observed with the test ligands, Isolaureline and S-norcorydine, with binding energy values of -6.20 kcal/mol and -6.12 kcal/mol and inhibition constant values of 28.65 µM and 32.53 µM. In terms of receptor-target interactions, these two compounds also exhibited hydrogen bonding and van der Waals interactions similar to the natural ligand. Conclusion: The best bioactive compounds in A. muricata (Isolaureline and S-norcorydine) were predicted to have the ability to interact with caspase-3 and the potential to be used as prostate cancer drug candidates. [ABSTRACT FROM AUTHOR]

Introduction and aim. In real life, metastatic castration-resistant prostate cancer patients (mCRPC) had more complex clinical presentation than patients in the COU-AA-302 trial. This study primarily aimed to describe the overall survival of chemotherapy-naive mCRPC treated with abiraterone acetate plus prednisone (AAP). Other relevant outcomes and baseline characteristics of these patients were also evaluated. Material and methods. This retrospective, observational study collected data from chemotherapy-naive mCRPC patients treated with AAP in Vietnam. Kaplan-Meier curves were used to estimate time to treatment failure (TTF), and overall survival (OS). The impact of baseline characteristics on OS was explored using univariate and multivariate Cox proportional hazard models. Results. Data from 65 eligible patients were analyzed. The rate of PSA response was 73.8%, median PSA PFS was 10.5 months (95% CI: 7.4-13.6), median TTF was 15 months (95% CI: 11.1-18.9), and median OS was 24.9 months (95% CI: 18.9-30.9). Shorter OS was significantly associated with a higher Gleason score (≥8), shorter time from ADT start to mCRPC (<12 months), visceral metastases, and <50% PSA decline (p<0.05). Conclusion. Abiraterone acetate plus prednisone is well tolerated and effective for chemotherapy-naive mCRPC patients in clinical practice. Moreover, Gleason score, visceral metastasis, time from ADT start to mCRPC, and PSA response are the independent indicators for predicting the OS of mCRPC patients in both univariate and multivariate analyses. [ABSTRACT FROM AUTHOR]

This review provides an in-depth examination of the role that tumor-associated macrophages (TAMs) play in the progression of prostate cancer (PCa), with a particular focus on the factors influencing the polarization of M1 and M2 macrophages and the implications of targeting these cells for cancer progression. The development and prognosis of PCa are significantly influenced by the behavior of macrophages within the tumor microenvironment. M1 macrophages typically exhibit anti-tumor properties by secreting pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), thereby enhancing the immune response. Conversely, M2 macrophages contribute to tumor cell migration and invasion through the production of factors like arginase-1 (Arg1) and interleukin-10 (IL-10). This review not only explores the diverse factors that affect macrophage polarization but also delves into the potential therapeutic strategies targeting macrophage polarization, including the critical roles of non-coding RNA and exosomes in regulating this process. The polarization state of macrophages is highlighted as a key determinant in PCa progression, offering a novel perspective for clinical treatment. Future research should concentrate on gaining a deeper understanding of the molecular mechanisms underlying macrophage polarization and on developing effective targeted therapeutic strategies. The exploration of the potential of combination therapies to improve treatment efficacy is also emphasized. By emphasizing the importance of macrophages as a therapeutic target in PCa, this review aims to provide valuable insights and research directions for clinicians and researchers.

Introduction: Prostate cancer is one of the most common malignancies affecting men worldwide, which poses a serious health risk due to its high incidence and impact on quality of life. Despite advances in the diagnosis and treatment of this condition, the management of advanced and aggressive forms of the disease remains complex. Aim of the Study: The aim of this study is to review current diagnostic methods, treatment strategies and prognostic factors in prostate cancer, that a particular focus on personalized medicine and multidisciplinary approaches to improve patient outcomes. Materials and Methods: A comprehensive literature review was conducted using PubMed sources and other scientific databases, focusing on currently available publications. The literature available in the PubMed database was reviewed using the following keywords: “prostate cancer” “prostate cancer diagnosis”, “prostate cancer treatment”, “personalized medicine for prostate cancer”, “physical activity in prostate cancer”. The review included studies on prostate cancer epidemiology, pathogenesis, advances in diagnosis, treatment, physical activity and future research directions. Conclusions: Advances in diagnostic technologies and emerging new therapies have significantly improved the prognosis for patients with prostate cancer. However, continued research and commitment to personalized treatment strategies are essential to meet the challenges of advanced disease. Multidisciplinary collaboration and patient-centered care remain key to optimizing outcomes and improving quality of life for prostate cancer patients.

Simple Summary: LET-optimized pencil beam scanning (PBS) proton treatment plans have the potential to improve patient outcomes. Dose-escalated x-ray conformal therapy has improved the prostate cancer 5-year freedom from biochemical progression (FFBP) but has also increased gastrointestinal and genitourinary toxicities; toxicities can be reduced by escalating dose via a simultaneously-integrated boost (SIB) to the intraprostatic tumor (IPT). These techniques can be applied with greater precision using protons, which have shown high overall 5-year FFBP and low toxicities, although improvement in FFBP is needed for high-risk patients. Relative biological effectiveness (RBE) of 1.1 is uniformly assumed for proton treatment planning, although an increasing number of studies show that RBE increases with linear energy transfer (LETd). We show improvement with PBS LET-optimized plans over single-field optimized (SFO), or IPT-SIB plans through increased target volume LETd, RBE, and target-to-organs-at-risk (OAR) dose ratios (TODRs). This study also highlights the necessity of developing disease-specific LET-dependent RBE models. Purpose: To demonstrate the feasibility of improving prostate cancer patient outcomes with PBS proton LETd optimization. Methods: SFO, IPT-SIB, and LET-optimized plans were created for 12 patients, and generalized-tissue and disease-specific LET-dependent RBE models were applied. The mean LETd in several structures was determined and used to calculate mean RBEs. LETd- and dose–volume histograms (LVHs/DVHs) are shown. TODRs were defined based on clinical dose goals and compared between plans. The impact of robust perturbations on LETd, TODRs, and DVH spread was evaluated. Results: LETd optimization achieved statistically significant increased target volume LETd of ~4 keV/µm compared to SFO and IPT-SIB LETd of ~2 keV/µm while mitigating OAR LETd increases. A disease-specific RBE model predicted target volume RBEs > 1.5 for LET-optimized plans, up to 18% higher than for SFO plans. LET-optimized target LVHs/DVHs showed a large increase not present in OARs. All RBE models showed a statistically significant increase in TODRs from SFO to IPT-SIB to LET-optimized plans. RBE = 1.1 does not accurately represent TODRs when using LETd optimization. Robust evaluations demonstrated a trade-off between increased mean target LETd and decreased DVH spread. Conclusion: The demonstration of improved TODRs provided via LETd optimization shows potential for improved patient outcomes. [ABSTRACT FROM AUTHOR]

This article explores the impact of androgen deprivation therapy (ADT) on the quality of life, physical activity, anxiety, and depression levels of patients with intermediate- and high-risk prostate cancer. The study involved 78 patients and assessed their well-being, physical activity, and mental health using various questionnaires. The duration of ADT did not significantly affect these factors. However, the study did find a negative correlation between body mass index (BMI) and moderate physical activity, as well as a positive correlation between moderate physical activity and the functional aspect of the quality of life questionnaire. The study concludes that both short-term and long-term use of ADT result in similar side effects, and the risk level of the patients does not significantly impact these side effects. The study suggests that patient education and follow-up may play a role in improving physical activity and quality of life in prostate cancer patients. The study was conducted with ethical approval and informed consent from the participants. [Extracted from the article]

Background: Long-term treatment and associated side effects can affect a patient’s quality of life, one of which is the patient’s regret during the treatment program of prostate cancer. The decision aid (DA) program can help patients with chronic diseases to face disease treatment, but the effect on the treatment of prostate cancer patients has not been evaluated further. This study aims to assess the effect of a decision aid program on treatment regret in prostate cancer patients. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines with the search engines PubMed and Google Scholar from January–March 2023. The inclusion criteria used were randomized controlled-trial studies with full text in English, published for the last ten years, the decision regret during or after the treatment program was reported and the type of regret measurement was described. Results: Based on a literature search, 5 studies met the inclusion criteria. The relationship between decision aid and regret was not significantly lower but had a significant effect in the long-term (12 months) and minority ethnic. Studies on a wider and heterogeneous population are needed to assess the effect of decision aids on the perspective of patients with prostate cancer programs. Conclusions: Decision aid may affect the level of regret of prostate cancer patients in the treatment program. [ABSTRACT FROM AUTHOR]

Prostate cancer is a common malignant tumor in men and early diagnosis and treatment are crucial for the survival rate of patients. This study aimed to establish a machine learning-based prostate cancer prediction model to help physicians accurately identify high-risk patients. This study performed a retrospective analysis using prostate cancer patient data from the MIMIC-IV database. First, the data was cleaned and preprocessed, including imputing missing values, handling outliers, and feature selection. Then, prediction models were established using machine learning algorithms (including logistic regression, support vector machine, deep neural networks, XGBoost, LightGBM and CatBoost) and evaluated using cross-validation and ROC curve analysis. We screened out 1975 patients diagnosed with PC and 11,745 patients diagnosed with BPH based on ICD codes. However, among the BPH patients, 467 were also diagnosed with PC, so we excluded these patients. The LightGBM machine learning model outperformed the other models in distinguishing patients with PC [LightGBM vs. CatBoost vs. XGBoost vs. DNN vs. SVM vs. LR; area under the curve (AUC): 0.93 vs. 0.91 vs. 0.89 vs. 0.86 vs. 0.70 vs. 0.68, respectively]. The LightGBM model had a sensitivity of 86%, specificity of 85% at the best cut-off value. The model was capable of predicting whether a patient has prostate cancer based on their clinical features (including age, Laboratory test, etc.) and had a high level of accuracy and stability. The machine learning-based prostate cancer prediction model established in this study has some clinical application value and can help physicians accurately identify high-risk patients, providing more precise prevention and treatment plans for patients. [ABSTRACT FROM AUTHOR]

Background Radium-223 is a bone-seeking, ɑ-emitting radionuclide used to treat men with bone metastases from castration-resistant prostate cancer. Sclerotic bone lesions cannot be evaluated using Response Evaluation Criteria in Solid Tumors. Therefore, imaging response biomarkers are needed. Methods We conducted a phase 2 randomized trial to assess disease response to radium-223. Men with metastatic castration-resistant prostate cancer and bone metastases were randomly allocated to 55 or 88 kBq/kg radium-223 every 4 weeks for 6 cycles. Whole-body diffusion-weighted magnetic resonance imaging (DWI) was performed at baseline, at cycles 2 and 4, and after treatment. The primary endpoint was defined as a 30% increase in global median apparent diffusion coefficient. Results Disease response on DWI was seen in 14 of 36 evaluable patients (39%; 95% confidence interval = 23% to 56%), with marked interpatient and intrapatient heterogeneity of response. There was an association between prostate-specific antigen response and MRI response (odds ratio = 18.5, 95% confidence interval = 1.32 to 258, P  = .013). Mean administered activity of radium-223 per cycle was not associated with global MRI response (P  = .216) but was associated with DWI response using a 5-target-lesion evaluation (P  = .007). In 26 of 36 (72%) patients, new bone metastases, not present at baseline, were seen on DWI scans during radium-223 treatment. Conclusions DWI is useful for assessment of disease response in bone. Response to radium-223 is heterogeneous, both between patients and between different metastases in the same patient. New bone metastases appear during radium-223 treatment. The REASURE trial is registered under ISRCTN17805587. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second incidence of malignant tumors in men worldwide. Its incidence and mortality are increasing year by year. Enhanced expression of Cav1 in prostate cancer has been linked to both proliferation and metastasis of cancer cells, influencing disease progression. Dysregulation of the Cav1 gene shows a notable association with prostate cancer. Nevertheless, there is no systematic review to report about molecular signal mechanism of Cav1 and drug treatment in prostate cancer. This article reviews the structure, physiological and pathological functions of Cav1, the pathogenic signaling pathways involved in prostate cancer, and the current drug treatment of prostate cancer. Cav1 mainly affects the occurrence of prostate cancer through AKT/mTOR, H-RAS/PLCε, CD147/MMPs and other pathways, as well as substance metabolism including lipid metabolism and aerobic glycolysis. Baicalein, simvastatin, triptolide and other drugs can effectively inhibit the growth of prostate cancer. As a biomarker of prostate cancer, Cav1 may provide a potential therapeutic target for the treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Contemporary treatment strategies for localized prostate cancer (PCa) have been evolved over time. However, there is little data regarding survival outcomes based on initial treatment by risk group in this new era. This study aims to evaluate survival outcomes among men who underwent observation, radiotherapy, or radical prostatectomy for localized PCa using a population-based cohort. Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) prostate with watchful waiting dataset (2010– 2016) was used. We included men diagnosed with localized PCa and clinical stage T1c-2cN0M0. Other inclusion criteria were age 50–79 years, prostate-specific antigen (PSA) ≤50 ng/mL, and initial treatment with observation (active surveillance/ watchful waiting), radiotherapy, or radical prostatectomy. PCa risk was assessed using the D’Amico classification. The primary endpoint was overall survival. Secondary endpoints included PCa-specific survival. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression and competing risk analysis were performed to assess outcomes. Results: After IPTW-adjusting, pseudo-population comprised 521,656 men (observation: 170,428, radiotherapy: 175,628, radical prostatectomy: 175,600) at a median 36.5 month follow-up. Observation demonstrated the lowest 5-year overall survival rate (91.6%) after IPTW-adjusting in comparison to radiotherapy (92.4%) and radical prostatectomy (96.1%, p<0.001). Men who underwent radical prostatectomy had the lowest cumulative PCa-specific and all-cause mortality (p<0.001). Compared to observation, radiotherapy (sub-distribution hazard ratio [sHR], 0.89; 95% CI, 0.81–0.97; p=0.012) and radical prostatectomy (sHR, 0.46; 95% CI, 0.41–0.52; p<.001) had a lower risk of PCa-specific mortality in competing risk analysis after adjustment for all other factors and other-cause death. Conclusions: Intermediate-term mortality risk in men with localized PCa were lower with active treatments compared to observation - especially for intermediate- and high-risk disease. However, observation represents a safe management strategy in men within the low-risk group. [ABSTRACT FROM AUTHOR]

The introduction of novel therapeutic agents for advanced prostate cancer has led to a wide range of treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC). In the past decade, new treatment options for mCRPC, including abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, radium-223, 177Lu-PSMA-617, and Olaparib, have demonstrated a survival benefit in phase 3 trials. Bone-modifying agents have become part of the overall treatment strategy for mCRPC, in which denosumab and zoledronic acid reduce skeletal-related events. Recently, androgen receptor-signaling inhibitors (ARSIs) and docetaxel have been used upfront against metastatic castration-sensitive prostate cancer. Further, triplet therapy with ARSI, docetaxel, and androgen deprivation therapy is emerging. However, cross-resistance may occur between these treatments, and the optimal treatment sequence must be considered. The sequential administration of ARSIs, such as abiraterone and enzalutamide, is associated with limited efficacy; however, cabazitaxel is effective for patients with mCRPC who were previously treated with docetaxel and had disease progression during treatment with ARSI. Radioligand therapy with 177Lu-PSMA-617 is a new effective class of therapy for patients with advanced PSMA-positive mCRPC. Tumors with gene alterations that affect homologous recombination repair, such as BRCA1 and BRCA2 alterations, are sensitive to poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitors in mCRPC. This review sought to highlight recent advances in systemic therapy for mCRPC and strategies to support patient selection and treatment sequencing. [ABSTRACT FROM AUTHOR]

The human gut microbiota changes under the influence of environmental and genetic factors, affecting human health. Extensive studies have revealed that the gut microbiome is closely associated with many non-intestinal diseases. Among these, the influence of the gut microbiome on cancer biology and the efficacy of cancer therapy has attracted much attention. Prostate cancer cells are affected by direct contact with the microbiota of local tissues and urine, and a relationship between prostate cancer cells and the gut microbiota has been suggested. In the human gut microbiota, bacterial composition differs depending on prostate cancer characteristics, such as histological grade and castration resistance. Moreover, the involvement of several intestinal bacteria in testosterone metabolism has been demonstrated, suggesting that they may affect prostate cancer progression and treatment through this mechanism. Basic research indicates that the gut microbiome also plays an important role in the underlying biology of prostate cancer through multiple mechanisms owing to the activity of microbial-derived metabolites and components. In this review, we describe the evidence surrounding the emerging relationship between the gut microbiome and prostate cancer, termed the “gut-prostate axis.” [ABSTRACT FROM AUTHOR]

The article compares two surgical procedures, Robotic Assisted Simple Prostatectomy (RASP) and Holmium Laser Enucleation of the Prostate (HoLEP), for the treatment of huge Benign Prostatic Hyperplasia (BPH). The study finds that RASP offers advantages over HoLEP, including a wider field of view, easier access, and the ability to perform sophisticated procedures. RASP also reduces complications related to urethral stenosis and sphincter damage. However, HoLEP has shorter hospitalization and lower costs, making it more economically advantageous. The choice of surgery may depend on factors such as patient age, insurance coverage, and the size of the prostate. [Extracted from the article]

Background: Prostate cancer screening with prostate-specific antigen (PSA) can result in unnecessary biopsies and overdiagnosis. Alternately, PSA density (PSAD) calculation may help support biopsy decisions; however, evidence of its usefulness is not concrete. Objective: To evaluate the predictive value of PSAD for clinically significant prostate cancer detection by systematic and MRI-targeted biopsies. Methods: This prospective study was conducted at two tertiary hospitals in Riyadh, Saudi Arabia, between December 2018 and November 2021. Patients suspected of prostate cancer were subjected to multi-parametric MRI, and for those with positive findings, systematic and targeted biopsies were performed. Clinically non-significant and significant prostate cancer cases were classified based on histopathology-defined ISUP grade or Gleason score. The PSAD was measured using the prostate volume determined by the MRI and categorized into ≤0.15, 0.16–0.20, and >0.20 ng/ml2 subgroups. Results: Systematic and targeted biopsies were carried out for 284 patients. The discriminant ability of PSAD is higher in MRI-targeted biopsy compared with systematic biopsy (AUC: 0.77 vs. 0.73). The highest sensitivity (97%) and specificity (87%) were detected at 0.07 ng/ml2 in targeted biopsy. More than half of the clinically significant cases were detected in the >0.2 ng/ml2 PSAD category (systematic: 52.4%; targeted: 51.1%). The CHAID methodology found that the probability of having clinically significant cancer (CSC) in patients with PSAD >0.15 ng/ml2 was more than threefold than that in patients with PSAD ≤0.15 ng/ml2 (64% vs. 20.2%). When considered by age, in PSAD ≤0.15 ng/ml2 subgroup, the percentage of CSC detection rate increased from 20.2% to 24.6% in patients aged ≥60 years. Conclusion: PSAD has good discriminant power for predicting clinically significant prostate cancer. A cutoff of 0.07 ng/ml2 should be adopted, but should be interpreted with caution and by considering other parameters such as age. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to evaluate cancer-specific (CSM) and other-cause mortality (OCM) in elderly patients with prostate cancer treated with radical prostatectomy (RP) and postoperative radiotherapy (RT). Material and methods The Surveillance, Epidemiology, and End Results (SEER) database was searched for clinically non-metastatic prostate cancer (PCa) treated with RT after RP between 2010 and 2015. Patients were stratified according to age groups and underwent propensity score (PS) matching. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for survival analysis. Results In total, 5385 patients were analysed, including 738 (13.7%) elderly patients (≥70 years old) and 4647 (86.29%) younger individuals. A total of 54 (7.32%) and 69 (9.35%) patients aged ≥70 years died due to PCa and competing reasons, respectively. Among younger patients these included 275 (5.92%) and 208 (4.48%) deaths, respectively. At a median follow-up of 80 months, patients ≥70 years old had significantly shorter OCM (p <0.0001) than PS-matched younger controls without significant impairment of cancer-specific survival when compared to controls (p = 0.19). In CRR analysis older patients were at significantly higher risk of OCM (HR = 2.24, p = 0.0002 and HR = 3.3, p = 0.011 for patients aged ≥70 and ≥75 years, respectively). Simultaneously, the CRR revealed no increased risk of CSM for patients older than 70 and 75 years (HR = 1.2, p = 0.33 and HR = 1.53, p = 0.29, respectively). Conclusions Elderly patients with PCa are at high risk of dying due to competing reasons, which might prevent the survival benefit of RT after RP. Selection for salvage and adjuvant RT in these individuals should be cautious. [ABSTRACT FROM AUTHOR]

Objectives: Prostate cancer (PCa) is among the most frequently diagnosed cancers and a leading cause of cancer-related deaths in men. Although prostate-specific antigen (PSA) testing has become routine in screening and early detection, PSA has high false-positive rates and poorly correlates with disease stage. Consequently, other diagnostic and prognostic markers for PCa are urgently needed. MicroRNAs (miRNAs) modulate gene expression at the transcriptional level and are known to play key roles in various physiological events. Growing evidence indicates that miRNA dysregulation is involved in the initiation and progression of many diseases, including PCa. Various miRNAs have been associated with PCa pathogenesis, suggesting that miRNA expression profiles have potential utility in the prognosis, diagnosis, and treatment of this disease. miRNA expression levels have been investigated in prostate epithelial cells by PCa cell culture. Methods: The present study compared the expression levels of selected prognostic miRNAs targeting that have been implicated in the pathogenesis of PCa. Using cDNA obtained from the C4-2 human PCa and PNT1a normal prostate epithelial cell lines, miRNA expression levels were quantitatively analyzed via melting curve analysis using the miScript SYBR Green kit in a Rotor-Gene Q real-time polymerase chain reaction (PCR) device. Results: Reverse transcription quantitative PCR analyses have demonstrated miRNA expression levels in the C4-2 PCa cell line and PNT1a prostate epithelial cell line. MiR-125, -145, -200, and -222 were found to be overexpressed in the PCa cell line (p<0.05), while there were no statistically significant differences in miR-32 expression of miR-21, -26, Let-7, -34, or -221 between PCa cells and PNT1a cells (p>0.05). Conclusion: Considering the variation in expression level of miRNAs targeting genes responsible for the etiopathogenesis of PCa. Provides information on the use of miRNAs as prognostic markers in PCa. [ABSTRACT FROM AUTHOR]

Considering the importance of immunotoxins in the treatment of patients with prostate cancer, this study aims to summarize the findings of preclinical studies related to the types of immunotoxins used in the treatment of prostate cancer and finally, the suggestions for the treatment of any of these disease was better in the future. It seems that the important keys to success in the treatment with immunotoxins are the specificity of the target antigen and the internalization of the antigen-antibody complex to the cells that express the target antigens. Immunotherapy has long been important in advanced and treatment-resistant prostate cancer due to its anatomical location and sensitivity to immunotherapy agents. Among immunotherapy agents, satisfactory results have been obtained with monoclonal antibodies and scFv conjugated to toxins in preclinical studies. But so far, clinical trials with immunotoxins for prostate cancer have not been reported. Several antibodies that target antigens related to prostate cancer have been effective in preclinical and clinical development. Among these antibodies, anti-PSMA, PSCA, and epidermal growth factor receptor antibodies can be mentioned. Among the target antigens of prostate cancer, PSMA is known for its excessive expression and rapid internalization. It has become clear that both in active immunotherapy (vaccination) and in passive immunotherapy (monoclonal antibody), targeting multiple antigens simultaneously increases the efficacy of treatment in CRPC. Therefore, it is suggested that in future studies, several membrane-specific antigens of prostate cancer should be targeted by immunotoxins. [ABSTRACT FROM AUTHOR]

Wnt/β-catenin signaling is a pathway involved in epigenetics and cancer, regulating cell processes and malignancy in prostate cancer cells. Additionally, Wnt/β-catenin signaling is influenced by epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs. Therefore, targeting both Wnt/β-catenin signaling and epigenetics could be a promising strategy for prostate cancer therapy. Blepharis persica (B. persica) is a plant containing phenolic and flavonoid compounds known for their anti-cancer properties. However, the mechanisms behind its action remain unclear. In this study, we examined the effects of B. persica extract on Wnt/β-catenin signaling in prostate cancer cells (PC-3). To evaluate the cytotoxicity, composition, gene expression, and protein-ligand interactions of the B. persica extract on PC-3 cells, we employed the MTT assay, GC-MS, RT-qPCR, and molecular docking techniques. Our findings indicated that B. persica extract reduced the viability of PC-3 cells, down-regulated Wnt target genes ( CTNNB1 and SNAIL), and up-regulated Wnt antagonists ( APC and AXIN). Furthermore, we identified four B. persica compounds that exhibited the ability to inhibit FZD7, a Wnt receptor. Taken together, these results suggest that B. persica extract can modulate Wnt/β- catenin signaling and epigenetics in PC-3 cells, potentially offering therapeutic benefits. [ABSTRACT FROM AUTHOR]

Background/Aim: Studies have suggested that benefits of definitive radiotherapy might be limited to specific patients in clinically lymph node positive (cN1) prostate cancer (PC). However, the beneficial subgroup remains to be elucidated. This study aimed to analyze survival outcomes and prognostic factors after definitive radiotherapy and androgen deprivation therapy (definitive RT+ADT) in these patients and to define subgroups of patients who would benefit from definitive RT+ADT the most. Patients and Methods: A total of 60 patients with cN1 PC treated with definitive RT+ADT in a single tertiary hospital were accrued. Their clinicopathological variables were analyzed and a new subgroup was identified based on statistically significant variables. Results: At a median follow-up of 31 months, ADT duration ≥24 months (p=0.043, HR=0.26) and positive biopsy core ≥75% (p=0.044, HR=5.29) showed significant relationships with distant metastasis-free survival. Overall survival showed significant relationships with ADT duration ≥24 months (p=0.002, HR=0.06) and number of lymph node (LN) metastases ≥4 (p=0.019, HR=7.17). For prognostic subgroup analysis, patients were divided into three risk groups: low-risk group (LN metastases <4 and ADT ≥24 months), high-risk group (LN metastases ≥4 and ADT <24 months), and intermediaterisk group (all remaining cases). Three-year actuarial overall survival rates for the low-, intermediate-, and highrisk groups were 100%, 93.3%, and 45.7%. Conclusion: ADT duration and number of LN metastases were important prognostic factors in patients with cN1 PC receiving definitive RT+ADT, with low-risk cN1 PC patients showing better outcomes than others. [ABSTRACT FROM AUTHOR]

Background/Aim: Prostate cancer patients undergoing radiotherapy (RT) may experience distress. This study evaluated the course of distress during RT. Patients and Methods: Four distress characteristics were analyzed for change of distress in 136 patients irradiated for prostate cancer, including age, Karnofsky performance score, intent of RT, and previous RT. Results: Mean distress scores were 4.3 (±2.9) at baseline and 4.2 (±2.7) at the end of RT. Associations with increased distress were found for KPS >80 (p<0.001) and curative intent RT (p=0.072). When evaluating increased distress as binary variable (yes vs. no), KPS >80 was significant on univariable (p<0.001) and multivariable (p=0.016) analyses. In patients with baseline scores ≤5 points, KPS >80 was associated with mean change of distress (p=0.009) and increased distress (p=0.029). Conclusion: Many patients receiving RT for prostate cancer do not experience increased distress during their treatment course. Patients at higher risk of increased distress may require early psychological assistance. [ABSTRACT FROM AUTHOR]

Background/Aim: To determine the expression of long non-coding RNA urothelial cancer-associated 1 (UCA1) by performing array-based quantitative polymerase chain reaction (PCR) and to identify the clinicopathological significance of UCA1 expression in prostate cancer using in situ hybridization (ISH) of surgically resected specimens. Materials and Methods: Array-based quantitative PCR was performed using 10 pairs of fresh malignant (prostate cancer) and normal tissue samples to determine UCA1 expression. Single-color RNA ISH of surgically resected prostate cancer specimens was performed using 70 formalinfixed, paraffin-embedded tissue specimens to examine the clinicopathological significance of UCA1. Results: Prostate cancer tissues exhibited higher levels of UCA1 expression than paired benign tissues. Furthermore, a correlation between high UCA1 expression and unfavourable clinicopathological characteristics, including advanced pathologic T stage, extraprostatic extension, presence of Gleason pattern 5, and involvement of the resection margins was observed. Notably, increased UCA1 expression significantly correlated with high-or very-high-risk patients, as defined by the 2023 National Comprehensive Cancer Network guidelines. Conclusion: UCA1 could be used as a novel diagnostic and prognostic biomarker for establishing an effective treatment protocol for prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: Senescence may act as an antitumor mechanism by preventing the proliferation of cancer cells. Here we investigated the hypothesis that PC3 prostate cancer cells resistant to bortezomib respond differently to proteasomal inhibition with respect to induction of the senescence program as compared to the parental cells. Materials and Methods: The degree of senescence was measured by β-galactosidase activity and the level of senescenceassociated p16 INK4a by Western blotting after treatment of cells with varying concentrations of bortezomib. In addition, the senescence-associated secretory phenotype was analyzed by Human Cytokine Antibody Array. Results: It is reported that the basal level of senescence was lower in resistant cells compared to non-resistant cells. It was found that the basal level of the senescence marker p16 INK4a was lower in bortezomib-resistant cells than in parent non-resistant cells. Moreover, p16 INK4a was significantly reduced in both cells under conditions of 100 nM bortezomib treatment, a finding suggesting that the reduced senescence after proteasomal inhibition was likely due to the reduced levels of p16 INK4a. Finally, it is reported here for the first time that basal levels of the proteins NAP2, FGF-6, MIP-3α, and PARC are significantly increased in the resistant cells compared to the parental cells. Conclusion: Overall, the results suggest that inhibition of senescence may play an important function in the development of resistance to bortezomib. [ABSTRACT FROM AUTHOR]

Melatonin is an endogenous indoleamine that has been shown to inhibit tumor growth in laboratory models of prostate cancer. Prostate cancer risk has additionally been associated with exogenous factors that interfere with normal pineal secretory activity, including aging, poor sleep, and artificial light at night. Therefore, we aim to expand on the important epidemiological evidence, and to review how melatonin can impede prostate cancer. More specifically, we describe the currently known mechanisms of melatonin-mediated oncostasis in prostate cancer, including those that relate to the indolamine's ability to modulate metabolic activity, cell cycle progression and proliferation, androgen signaling, angiogenesis, metastasis, immunity and oxidative cell status, apoptosis, genomic stability, neuroendocrine differentiation, and the circadian rhythm. The outlined evidence underscores the need for clinical trials to determine the efficacy of supplemental, adjunct, and adjuvant melatonin therapy for the prevention and treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Background Disparities in treatment selection based on socioeconomic status for prostate cancer exist. However, the association between patient-level income with treatment selection priorities and treatment received has not been studied. Methods A population-based cohort of 1382 individuals with newly diagnosed prostate cancer was enrolled throughout North Carolina prior to treatment. Patients self-reported household income and were asked about the importance of 12 factors contributing to their treatment decision-making process. Diagnosis details and primary treatment received were abstracted from medical records and cancer registry data. Results Patients with lower income were diagnosed with more advanced disease (P  < .01). Cure was deemed to be "very important" by more than 90% of patients at all income levels. However, patients with lower vs higher household income were more likely to rate factors beyond cure as "very important" such as cost (P  < .01), effect on daily activities (P  = .01), duration of treatment (P  < .01), recovery time (P  < .01), and burden on family and friends (P  < .01). On multivariable analysis, high vs low income was associated with increased utilization of radical prostatectomy (odds ratio = 2.01, 95% confidence interval = 1.33 to 3.04; P  < .01) and decreased use of radiotherapy (odds ratio = 0.48, 95% confidence interval = 0.31 to 0.75; P  < .01). Conclusions New insights from this study on the association between income and treatment decision-making priorities provide potential avenues for future interventions to reduce disparities in cancer care. [ABSTRACT FROM AUTHOR]

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BackgroundInnovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.ObjectiveTo present the results from the APCCC 2019.Design, setting, and participantsSimilar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.Outcome measurements and statistical analysisThe panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.Results and limitationsPanellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.ConclusionsThese voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.Patient summaryThe Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.

The management of sexual complications after treatment of localized prostate cancer, such as erectile dysfunction, changes in the length of the penis, pain during sexual intercourse, and lack of orgasm, is still an unsolved problem with an important impact on patients’ quality of life. In this review, we summarize the current scientific literature about the rehabilitation of erectile dysfunction after prostate cancer treatment. The therapy for penile rehabilitation includes different types of treatments: the combination of phosphodiesterase type 5 inhibitors (PDE5-I) and the vacuum erectile device (VED) are considered first-line treatment options. When therapy begins, the duration of treatment, the dosage and the drug used all play very important roles in the treatment outcome. Intracavernous injection (ICI) therapy represents the second-line option for patients ineligible for PDE5-I therapy. Technological development has led to the emergence of devices for the stimulation of the penis without the use of drugs, such as penile vibratory stimulation (PVS) for stimulation of ejaculation in spinal cord injury and low-intensity extracorporeal shockwave therapy (LIESWT). The rapid diffusion of the latter, thanks to its easy use, attains good results without side effects. The panorama of penile rehabilitation after PC treatments is vast and many studies are needed, especially on new technologies, to find the best therapeutic regimen possible, personalized to the patient’s characteristics and the type of treatment for PC.

Background: The complexity of prostate cancer care can impact on patient understanding and participation in shared decision-making. This study used a survey-based approach to investigate patients’ recall of their prostate cancer treatment, and more broadly, to understand the perceptions of patients and the general population of prostate cancer treatment. Method: The survey was completed by 236 patients with prostate cancer (PCa cohort) and 240 participants from the general population of Australia (GenPop cohort). Free-text comments from both cohorts were analysed using content analysis. The PCa cohort reported which treatments and image-guidance related procedures they had received. These patient-reports were compared to medical records and analysed using proportion agreement, kappa statistics and regression analysis. Results: 135 (57%) PCa and 99 (41%) GenPop respondents provided at least one comment. Five major themes were identified by both cohorts: sharing experiences of treatment; preferences insights and reflections; mindsets; general commentary on the survey; and factors missing from the survey. There was overall good treatment recall amongst the PCa cohort, with proportions of correct recall ranging from 97.3% for chemotherapy to 66.8% for hormone therapy. There was a tendency for younger patients (

(1) Background: The adjustable trans-obturator male system (ATOMS) is a surgical device developed to treat post-prostatectomy incontinence (PPI) after prostate cancer treatment. We review the current literature on this anti-incontinence device with the intention of assessing the effectiveness, safety and duration of the silicone-covered scrotal port (SSP) ATOMS, the only generation of the device that is currently available. (2) Material and Methods: Non-systematic literature review is performed. Forty-eight full-text articles are assessed for eligibility. Case reports, expert opinions or commentaries without specific data reported (n = 6), studies with patients who underwent intervention before 2014 (IP or SP ATOMS; n = 10), and studies with incontinence after transurethral resection of the prostate (TUR-P; n = 2) are excluded for analysis. Thirty studies with SSP ATOMS are included in a qualitative synthesis that incorporates systematic reviews (n = 3), articles partially overlapping with other previously published studies (e.g., follow-up or series updates; n = 9), and studies focusing on specific populations (n = 8). Only articles revealing outcomes of SSP ATOMS were included in the quantitative synthesis of results (n = 10). (3) Results: the pooled data of 1515 patients from the 10 studies with SSP ATOMS confirmed very satisfactory results with this device after adjustment: dry rate: 63–82%, improved rate: 85–100%, complication rate: 7–33%, device infection rate: 2.7–6.2% and explant rate: 0–19%. The durability of the device is reassuring, with 89% of devices in place 5 years after implantation. (4) Conclusion: Despite the absence of randomized controlled studies, the literature findings confirm results of SSP ATOMS appear equivalent to those of artificial urinary sphincters (AUSs) in terms of continence, satisfaction and complications, but with a lower rate of revision in the long-term. A prospective study identified that patients with daily pad test results <900 mL and a Male Stress Incontinence Grading Scale (MSIGS) of not 4 (i.e., early and persistent stream or urine loss) are the best candidates. Future studies centered on the elder population at higher risk of impaired cognitive ability and in patients including radiation as prostate cancer treatment are needed. [ABSTRACT FROM AUTHOR]

Introduction: Tumor-homing peptides have gained great attention as tools for the development of noninvasive and targeting drug delivery systems (DDS) to minimize drug systemic toxicity and enhance bioavailability. This study aims to improve antitumor targeting in prostate cancer via uploading a drug to a DDS comprised of a cell penetrating peptide decorated with a tumor-homing peptide, PL3. Materials and Methods: The DDS was constructed via solid-phase peptide synthesis and then characterized via mass spectrum and high performance liquid chromatography. A cell viability assessment to evaluate its cytotoxicity on both tumor (prostate cancer cells) and normal cells was conducted, while a confocal laser scanning microscope and flow-cytometer were employed to investigate internalization. To inspect the effectiveness of the drug-loaded DDS, a biochemical enzyme inhibition assay on the target enzyme dihydrofolate reductase (DHFR) was performed. Results and Discussion: The findings supported the succeeded synthesis and loading of the drug into this carrier system and demonstrated its high efficacy in cytotoxic effect and inhibiting DHFR with considerable cellular uptake in prostate cancer cells. Conclusion: The drug was delivered to the target prostate cancer cells by the PL3-functionalized DDS, limiting its localization to tumor cells rather than normal cells. Therefore, the study results highlighted the significance of the DDS in tumor therapy interventions. [ABSTRACT FROM AUTHOR]

Despite the development of effective targeted therapies and a significant understanding of carcinogenesis and cancer progression, treatment resistance is a major obstacle in achieving durable long-term control in many types of cancers. Emerging evidence supports that nongenetic mechanisms could play an underappreciated role in therapy resistance. These mechanisms include phenotypic plasticity, which is recognized as a hallmark of cancer and translates to epigenetic and transcriptional control of gene expression. Alterations in the expression and activity of the epigenetic modifier enhancer of zeste homolog 2 (EZH2) support prostate cancer lineage plasticity and progression. EZH2 expression and activity is elevated in castration-resistant prostate cancer treated with androgen receptor pathway inhibitors and in treatment-resistant prostate cancer. Moreover, 17 known residues of EZH2 are phosphorylated on by multiple kinases that modulate its activity, localization, stability, and polycomb repressive complex (PRC2) assembly. In this review, we explore the contribution of EZH2 phosphorylation in regulating canonical PRC2 in a methylation-dependent manner as an epigenetic repressor and in a noncanonical manner independent of PRC2 as a transcription activator. Apart from the contribution of EZH2 phosphorylation at serine 21, threonine 350, and threonine 311 in prostate cancer progression and treatment resistance, we discuss how other EZH2 phosphorylated residues with unknown functions could contribute to prostate cancer based on their upstream regulators and potential therapeutic utility. [ABSTRACT FROM AUTHOR]

The management of sexual complications after treatment of localized prostate cancer, such as erectile dysfunction, changes in the length of the penis, pain during sexual intercourse, and lack of orgasm, is still an unsolved problem with an important impact on patients' quality of life. In this review, we summarize the current scientific literature about the rehabilitation of erectile dysfunction after prostate cancer treatment. The therapy for penile rehabilitation includes different types of treatments: the combination of phosphodiesterase type 5 inhibitors (PDE5-I) and the vacuum erectile device (VED) are considered first-line treatment options. When therapy begins, the duration of treatment, the dosage and the drug used all play very important roles in the treatment outcome. Intracavernous injection (ICI) therapy represents the second-line option for patients ineligible for PDE5-I therapy. Technological development has led to the emergence of devices for the stimulation of the penis without the use of drugs, such as penile vibratory stimulation (PVS) for stimulation of ejaculation in spinal cord injury and low-intensity extracorporeal shockwave therapy (LIESWT). The rapid diffusion of the latter, thanks to its easy use, attains good results without side effects. The panorama of penile rehabilitation after PC treatments is vast and many studies are needed, especially on new technologies, to find the best therapeutic regimen possible, personalized to the patient's characteristics and the type of treatment for PC. [ABSTRACT FROM AUTHOR]

Aims: Several studies demonstrated that folic acid (FA) supplementation had some effects on prostate cancer initiation. In this study, the effect of FA concentration was evaluated on proliferation and viability in prostate cancer cells (PCCs). Additionally, we also determined the genes dysregulated by the uptake of a certain amount of FA in prostate cancer. Methods: Changes in cell viability and proliferation were analyzed in PCC for low-dose (Group-1; 1 µM, 10 µM, 100 µM) and high-dose (Group-2; 1 mM, 10 mM) FA concentrations by Trypan blue staining and MTT assay, respectively. mRNA expression level of FOLR1, FOLR2 FOLR3, JACK1, STAT3, STAT5/A, STAT5/B, PIAS1, PTPN1, and SOCS1 were determined by quantitative real-time polymerase chain reaction. Results: Cell viability and proliferation were significantly lower than healthy prostate epithelial cells in high-dose FA-treated PCCs. mRNA expressions of FOLR1, JAK1, and STAT3 were significantly upregulated in high-dose FA-treated PCCs compared with the controls. There were no significant alterations in the expression of FOLR2-3, STAT5A/5B, PIAS1, and PTPN1 genes, however, SOCS1 mRNA expression was significantly lower than the controls. Conclusions: Low-dose FA showed no effect on cell viability and proliferation, whereas viability and proliferation were decreased by the uptake of high-dose FA that was supposed to stimulate the mRNA expression of FOLR1 in PCCs. Decreased SOCS1 and increased JAK1 and STAT3 gene expressions implicate the dosage-dependent FA effect on JAK/STAT signaling pathway in prostate cancer. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Objective: To evaluate the outcomes of conventionally-fractionated external beam radiation therapy (cEBRT) in the treatment of prostate cancer spinal metastases (PCSM). Methods: Patients who received palliative cEBRT for PCSM in our institution between 2008 and 2018 were included. Our outcomes were local progression-free survival (LPFS), overall survival (OS), pain response and toxicities graded using CTCAE version 4.03. Univariable and multivariable Cox proportional hazard regressions were performed to identify predictors for LPFS and OS. Results: A total of 100 patients with 132 sites of PCSM were identified, with a median follow-up of 54 months. Fourteen-percent of patients underwent surgical intervention before receiving cEBRT. Eighteen spinal segments (13.6%) had local progression, with a median time to local progression of 8 months. The median LPFS and OS were 7.8 and 9.0 months, respectively. The complete and partial pain response rates were 57% and 39% respectively. The incidence of grade ≥3 acute toxicities was 11%. Better ECOG performance status (0 to 1), castration-sensitive disease, spinal surgery and use of novel antiandrogen agent were identified as significant predictors for improved OS on multivariable analysis. Conclusions: In our prostate cancer cohort, cEBRT is an effective treatment modality for local palliation of spinal metastases. More aggressive treatment approach should be considered for patients with excellent performance status and castration-sensitive disease in light of their expected longer survival. Further studies are warranted to identify the predictors for radiotherapy response in this population. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer recurrence after definitive local therapy usually involves the bone and regional lymph nodes. Case Report: We present the case of a 72-yearold male patient with an isolated lung nodule, seven years after radical prostatectomy for prostate cancer, pT2bN0 and Gleason score 7(4+3), and prostatic-specific antigen (PSA) levels within normal limits. The nodule was considered as a primary lung cancer and the patient was subjected to lobectomy. The immunohistochemical staining showed that the tumor was PSA(+) and NKX3.1 (+), revealing that it was metastasis from prostatic cancer and that wedge resectomy was the proper procedure. Three years later the patient is disease-free, suggesting the importance of aggressive treatment of oligometastatic disease. Conclusion: Metastasis to the lung is present in more than 40% of men with metastatic prostate cancer; however, lung metastases without any bone or lymph node involvement are extremely rare and only a handful of cases are reported in the literature. Surgical excision of the metastatic lung site is the most common therapeutic approach associated with a good prognosis. [ABSTRACT FROM AUTHOR]

(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to systematically assess and summarize the safety, oncologic, and functional outcomes of cytoreductive prostatectomy (cRP) in mPCa. (2) Methods: Three databases were queried in September 2022 for publications that analyzed mPCa patients treated with cytoreductive prostatectomy without restrictions. The outcomes of interest were progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), perioperative complication rates, and functional outcomes following cRP. (3) Results: Overall, 26 studies were included in this systematic review. Among eight population-based studies, cRP was associated with a reduced risk of CSS and OS compared with no local therapy (NLT) after adjusting for the effects of possible confounders. Furthermore, one population-based study showed that cRP reduced the risk of CSS even when compared with radiotherapy (RT) of the prostate after adjusting for the effects of possible confounders. In addition, one randomized controlled trial (RCT) demonstrated that local therapy (comprising 85% of cRP) significantly improved the prostate-specific antigen (PSA)-PFS and OS. Overall, cRP had acceptable perioperative complication rates and functional outcomes. (4) Conclusions: Mounting evidence suggests that cRP offers promising oncological and functional outcomes and technical feasibility and that it is associated with limited complications. Well-designed RCTs that limit selection bias in patients treated with cRP are warranted. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to develop a radiomic tool for the prediction of clinically significant prostate cancer. Methods: From September 2020 to December 2021, 91 patients who underwent magnetic resonance imaging prostate fusion biopsy at our institution were selected. Prostate cancer aggressiveness was assessed by combining the three orthogonal planes-Llocal binary pattern the 3Dgray level co-occurrence matrix, and other first order statistical features with clinical (semantic) features. The 487 features were used to predict whether the Gleason score was clinically significant (≥7) in the final pathology. A feature selection algorithm was used to determine the most predictive features, and at the end of the process, nine features were chosen through a 10-fold cross validation. Results: The feature analysis revealed a detection accuracy of 83.5%, with a clinically significant precision of 84.4% and a clinically significant sensitivity of 91.5%. The resulting area under the curve was 80.4%. Conclusions: Radiomic analysis allowed us to develop a tool that was able to predict a Gleason score of ≥7. This new tool may improve the detection rate of clinically significant prostate cancer and overcome the limitations of the subjective interpretation of magnetic resonance imaging, reducing the number of useless biopsies. [ABSTRACT FROM AUTHOR]

Currently, the active surveillance of men with favorable intermediate-risk localized prostate cancer (PCa) is a longstanding controversy, in terms of their oncological outcomes, and radical prostatectomy would constitute a similar concern of overtreatment, regarding its functional outcomes. Thus, focal therapy could be considered in men belonging to favorable intermediate-risk group. Among all focal therapies, high-intensity focused ultrasound (HIFU) was the most studied methodology in clinical trials. Although HIFU provided better functional outcomes than radical prostatecomy, the oncological outcomes were inferior in men with intermediate-risk localized PCa. Two articles have been published discussing the feasibility and clinical outcomes of robot-assisted partial prostatectomy (RAPP), and both the functional and oncological outcomes were superior than those with HIFU. However, the rate of positive surgical margins (PSMs) was reported as high in the literature. Here, we present a case of favorable intermediate-risk localized PCa with an isolated tumor at the anterior apex. After reconstructing a personal three-dimensional (3D) image, we utilized it in a 3D image-guided precise excise, followed by intraoperative frozen specimen review. We found that this method may present a resolution to the high PSM rate documented in the current literature regarding RAPP. This method merits further study with a well-designed prospective study. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the variability, associated actors, and the design of nomograms for individualized testosterone recovery after cessation of androgen deprivation therapy (ADT). Materials and Methods: A longitudinal study was carried out with 208 patients in the period 2003 to 2019. Castrated and normogonadic testosterone levels were defined as 0.5 and 3.5 ng/mL, respectively. The cumulative incidence curve described the recovery of testosterone. Univariate and multivariate analyzes were performed to predict testosterone recovery with candidate prognostic factors prostate-specific antigen at diagnosis, clinical stage, Gleason score from biopsy, age at cessation of ADT, duration of ADT, primary therapy and use of LHRH (luteinizing hormone-releasing hormone) agonists. Results: The median follow-up duration in the study was 80 months (interquartile range, 49–99 mo). Twenty-five percent and 81% of patients did not recover the castrate and normogonadic levels, respectively. Duration of ADT and age at ADT cessation were significant predictors of testosterone recovery. We built two nomograms for testosterone recovery at 12, 24, 36, and 60 months. The castration recovery model had good calibration. The C-index was 0.677, with area under the receiver operating characteristic curve (AUC-ROC) of 0.736, 0.783, 0.782, and 0.780 at 12, 24, 36, and 60 months, respectively. The normogonadic recovery model overestimated the higher values of probability of recovery. The Cindex was 0.683, with AUC values of 0.812, 0.711, 0.708 and 0.693 at 12, 24, 36, and 60 months, respectively. Conclusions: Depending on the age of the patient and the length of treatment, clinicians may stop ADT and the castrated testosterone level will be maintained or, if the course of treatment has been short, we can estimate if it will return to normogonadic levels. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated prostate cancer risk associated with pioglitazone use. Materials and Methods: The Taiwan’s National Health Insurance database was used to create a propensity score-matched cohort of male patients with type 2 diabetes mellitus newly diagnosed in 1999-2005 and aged ≥25 years at baseline. The matched cohort included 20437 ever users and 20437 never users of pioglitazone. The patients were followed up for the incidence of prostate cancer until December 31, 2011. Hazard ratios (HRs) were created from Cox regression weighted on propensity score. Results: Prostate cancer was diagnosed in 121 ever users of pioglitazone (incidence: 175.84 per 100,000 person-years) and 143 never users of pioglitazone (incidence: 216.66 per 100,000 person-years). When ever users were compared to never users of pioglitazone, the HR was 0.815 (95% confidence interval [CI], 0.639–1.039; p=0.0987). When ever users were categorized into tertiles of cumulative duration of pioglitazone therapy (<6.83, 6.83–20.23, and >20.23 months), the HRs were 1.044 (95% CI, 0.741–1.471), 0.975 (95% CI, 0.690–1.377) and 0.539 (95% CI, 0.374–0.778), respectively. For the tertiles of cumulative dose of <5,040, 5,040–15,330, and >15,330 mg, the HRs were 1.008 (95% CI, 0.710–1.429), 1.090 (95% CI, 0.785–1.515) and 0.484 (95% CI, 0.330–0.711), respectively. A significantly lower risk associated with pioglitazone use could only be seen in patients aged <65 years (HR, 0.578; 95% CI, 0.360–0.927) but not in patients aged ≥65 years. Conclusions: A significantly lower risk of prostate cancer is observed after a cumulative duration of pioglitazone therapy for >20.23 months or a cumulative dose of >15,330 mg. The risk reduction is mainly observed in patients aged <65 years. [ABSTRACT FROM AUTHOR]

Purpose: To establish a prospective registry for the active surveillance (AS) of prostate cancer (PC) using the Korean Urological Oncology Society (KUOS) database and to present interim analysis. Materials and Methods: The KUOS registry of AS for PC (KUOS-AS-PC) was organized in May 2019 and comprises multiple institutions nationwide. The eligibility criteria were as follows: patients with (1) pathologically proven PC; (2) pre-biopsy prostate-specific antigen (PSA) ≤20 ng/mL; (3) International Society of Urological Pathology (ISUP) grade 1 or 2 (no cribriform pattern 4); (4) clinical T stage ≤T2c; (5) positive core ratio ≤50%; and (6) maximal cancer involvement in the core ≤50%. Detailed longitudinal clinical information, including multi-parametric magnetic resonance imaging and disease-specific outcomes, was recorded. Results: From May 2019 to June 2021, 296 patients were enrolled, and 284 were analyzed. The mean±standard deviation (SD) age at enrollment was 68.7±8.2 years. The median follow-up period was 11.2 months (5.9–16.8 mo). Majority of patients had pre-biopsy PSA ≤10 ng/mL (91.2%), PSA density <0.2 ng/mL2 (79.7%), ISUP grade group 1 (94.4%), single positive core (65.7%), maximal cancer involvement in the core ≤20% (78.1%), and clinical T stage of T1c or lower (72.9%). Fifty-two (18.3%) discontinued AS for various reasons. Interventions included radical prostatectomy (80.8%), transurethral prostatectomy (5.8%), primary androgen deprivation therapy (5.8%), radiation (5.8%), and focal therapy (1.9%). The mean±SD time to intervention was 8.9±5.2 months. The reasons for discontinuation included pathologic reclassification (59.6%), patient preference (25.0%), and radiologic reclassification (9.6%). Two (4.8%) patients with pathologic Gleason score upgraded to ISUP grade group 4, no biochemical recurrence. Conclusions: The KUOS established a successful prospective database of PC patients undergoing AS in Korea, named the KUOS-AS-PC registry [ABSTRACT FROM AUTHOR]