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We assessed the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2014 and December 2022.Considering the MACE safety profile, enzalutamide may be a better choice for prostate cancer. This needs to be further confirmed by larger prospective studies and longer follow-up periods. Background: The potential cardiovascular adverse events associated with new-generation androgen receptor pathway inhibitors (ARPI) in the treatment of prostate cancer remain unclear. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to newgeneration ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed reports of cardiovascular adverse events associated with drug therapy for prostate cancer submitted to FAERS between January 2014 and December 2022. Three primary new-generation ARPIs were identified: abiraterone acetate, enzalutamide, and apalutamide. Our primary composite endpoint was the PV of MACE caused by ARPIs in the treatment of prostate cancer, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. Results: A total of 278,031 suspected drug-adverse event pairs related to drug treatment in patients with prostate cancer were identified, of which 10,861 reports were cardiovascular events, including 5800 reports of MACE and 5061 reports of other cardiovascular events. The majority of these cardiovascular adverse event reports came from the United States (36.6%) and were mostly older men (age 76.0 ± 8.6 years). Compared with enzalutamide, the constituent ratio of MACE caused by abiraterone acetate and apalutamide was significantly increased, but the incidence of severe MACE decreased significantly. The PV signal regarding MACE was detected in abiraterone acetate and apalutamide but not in enzalutamide. Conclusion: Abiraterone acetate and apalutamide presumably are associated with a higher risk of MACE than enzalutamide in new-generation ARPI for prostate cancer. More extensive prospective studies and more extended follow-up periods need to confirm this further. [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]

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

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]

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

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]

Partial gland ablation (PGA) is an emerging treatment approach for men with intermediate-risk prostate cancer. However, the patient selection remains a challenge as pretreatment risk stratification does that always capture the true extent of disease, especially in men with intermediate-risk disease. Using nationally representative data we found that men with intermediate-risk prostate cancer who underwent radical prostatectomy had rates of adverse pathology of over 30%. This has important implication for men considering PGA as they may be undertreated. Purpose: Using nationally representative data, we determined the likelihood of adverse pathology at radical prostatectomy (RP) to better inform case selection for partial gland ablation (PGA). Materials and Methods: We identified men with clinically localized GG2 (n = 106,048) and GG3 (n = 55,488) prostate cancer on biopsy from 2010 through 2019 who subsequently underwent RP. Men with GG2 were stratified as unfavorable and favorable per NCCN guidelines. RP adverse pathology was defined as upgrading to GG4-5, pT3-4, or nodal involvement (pN1), respectively. Logistic regression determined factors associated with adverse pathology, and the Cochran-Armitage Test was used to evaluate temporal trends. Results: Men with biopsy GG3 vs. GG2 experienced significant upgrading (11.3% vs. 3.6%, P < .001), more EPE (26.9% vs. 21.1%), SVI (11.9% vs. 5.3%), and pN1 (4.3% vs. 1.6%), all P < .001. When comparing unfavorable vs. favorable GG2, men experienced more EPE (25.3% vs. 16.5%), SVI (7.2% vs. 3%), and pN1 (2.2% vs. 0.8%), all P < .001. In adjusted analysis, age, Hispanic race, PSA > 10 ng/mL, and = 50% positive biopsy cores were associated with adverse pathology (all P < .001). The likelihood of RP adverse pathology for men with biopsy GG3 increased significantly during the study period from 38.8% in 2010 to 47.3% in 2019 (P < .001). Conclusion: Approximately 40% of men with GG3 and more than 30% with unfavorable GG2 prostate cancer harbor adverse pathology that may not be curable by PGA. Given MRI often understages prostate cancer, our findings have significant implications for optimizing PGA case selection and cancer control outcomes. [ABSTRACT FROM AUTHOR]

Metastatic neuroendocrine prostate cancer (NEPC) is a rare, aggressive disease with limited data on secondline treatment. In this retrospective, multi-institutional study, clinical and treatment data were collected for 58 patients with NEPC who received second-line systemic therapy after first-line platinum. Treatments were highly varied but uniformly poor in improving survival. Further study and consensus are needed for second-line NEPC treatment. Background: De novo neuroendocrine prostate cancer (NEPC) and treatment-emergent neuroendocrine prostate cancer (T-NEPC) are rare diseases with a poor prognosis. After first-line platinum chemotherapy, there is no consensus on second-line treatments. Patients and Methods: Patients with a pathologic diagnosis of de novo NEPC or T-NEPC between 2000 and 2020 who received first-line platinum and any second-line systemic therapy were selected and standardized clinical data was collected via the electronic health record at each institution. The primary endpoint was overall survival (OS) based on second-line therapy. Secondary endpoints included objective response rate (ORR) to second-line therapy, PSA response, and time on treatment. Results: Fifty-eight patients (32 de novo NEPC, 26 TNEPC) from 8 institutions were included. At de novo NEPC or T-NEPC diagnosis, the overall cohort had a median age of 65.0 years (IQR 59.2-70.3) and median PSA of 3.0 ng/dL (IQR 0.6-17.9). Following first-line platinum chemotherapy, 21 patients (36.2%) received platinum chemotherapy, 10 (17.2%) taxane monotherapy, 11 (19.0%) immunotherapy, 10 (17.2%) other chemotherapy, and 6 (16.2%) other systemic therapy. Among 41 evaluable patients, the ORR was 23.5%. The mOS after start of second-line therapy was 7.4 months (95% CI 6.1-11.9). Conclusions: In this retrospective study, patients with de novo NEPC or T-NEPC who received second-line therapy were treated with wide variety of treatment regimens, reflecting the lack of consensus in this setting. Most patients received chemotherapy-based treatments. Overall prognosis was poor and ORR was low in the second line regardless of treatment choice. [ABSTRACT FROM AUTHOR]

Studies have suggested that intraductal carcinoma of the prostate is an aggressive disease entity. We assessed outcomes for patients in the Veterans Health Administration with intraductal carcinoma. Patients with intraductal carcinoma were at higher risk of worse disease and increased risk of biochemical recurrence and metastasis development. Intraductal status is an important prognostic indicator for patients with prostate carcinoma. Purpose: Intraductal carcinoma of the prostate (IDC-P) is a relatively unstudied feature present in some prostate cancer (PC) diagnoses with several studies suggesting associations with higher Gleason scores (GS) and earlier time to biochemical recurrence (BCR) after definitive treatment. We looked to identify cases of IDC-P in the Veterans Health Administration (VHA) database and measure associations between IDC-P and pathological stage, BCR, and metastases. Methods: Patients in the VHA database diagnosed with PC from 2000 to 2017, treated with radical prostatectomy (RP) at the VHA were included in the cohort. BCR was defined as post-RP PSA > 0.2 or administration of androgen deprivation therapy (ADT). Time to event was defined as time from RP to event or censor. Differences in cumulative incidences were assessed through Gray's test. Associations with IDC-P and pathologic features at RP, BCR and metastases were assessed through multivariable logistic and Cox regression models. Results: Of 13,913 patients meeting inclusion cr iter ia, 45 patients had IDC-P. Median follow up was 8.8 years from RP. Multivariable logistic regressions showed patients with IDC-P were more likely to have GS =8 (Odds Ratio (OR) 1.14, P = .009) and higher T stages (T3 or 4 vs. T1 or 2 OR 1.14, P < .001). In total, 4,318 patients experienced a BCR, and 1,252 patients developed metastases of whom 26 and 12, respectively, had IDC-P. On multivariable regression IDC-P was associated with higher risk of BCR (IDC-P Hazard Ratio (HR) 1.71, P = .006) and metastases (HR 2.84, P < .001). Cumulative incidence of metastases at 4 years for IDC-P and non-IDC-P were 15.9% and 5.5% (P < .001) respectively. Conclusions: In this analysis, IDC-P was associated with higher Gleason score at RP, shorter time to BCR, and higher rates of metastases. Further studies are warranted to investigate the molecular underpinnings of IDC-P to better guide treatment strategies for this aggressive disease entity. [ABSTRACT FROM AUTHOR]

This analysis of 2800 Veterans Health Administration patients found that relative to patients with PSADT > 12 months, PSADT =2, > 2-=4, > 4-=6, > 6-=8, and > 8-=10 months had significantly higher metastasis and mortality risk, and healthcare costs. This can help select patients for novel hormonal therapy and who can delay such treatments for nmCRPC. Introduction: In patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), prostate-specific antigen doubling time (PSADT) is associated with risk of metastasis and survival. This study evaluated the association of PSADT with clinical and economic outcomes in a real-world setting among patients with nmCRPC not receiving novel hormonal therapy (NHT), using 2-month PSADT thresholds. Patients and Methods: We retrospectively identified Veterans Health Administration patients with nonmetastatic prostate cancer and =2 PSA increases after medical/surgical castration (2012-2016). The third measurement was the index (CRPC) date. Patients with =3 postindex PSA measurements, including index, were followed until death or =12 months until disenrollment, study end, or death, and grouped into 2-month cohorts based on postindex PSADT. Cox regression models assessed association between PSADT, time to metastasis, and death. Healthcare resource utilization and costs were evaluated. Results: Among 2800 evaluable patients, median follow-up was 30 months and median PSADT was 17 months. Relative to the reference cohort (PSADT > 12 months), all cohorts had significantly higher metastasis risk. PSADT =10-month cohorts had significantly greater mortality risk than the reference; hazard ratios (95% confidence intervals) ranged from 12.3 (9.2, 16.4) in the PSADT =2-month cohort to 1.3 (0.9, 2.0) in the > 10 to =12-month cohort. Total costs were significantly higher for cohorts up to and including the PSADT > 8 to =10-month cohort, than for the reference cohort. Mean per patient per month all-cause medical plus pharmacy costs were $6623, $4768, and $4049 in the PSADT =2-month, > 2 to =4-month cohort, and > 4 to =6-month cohorts, respectively, versus $1911 in the PSADT > 12-month cohort (P < 0.05). Conclusion: Most patients with nmCRPC have PSADT > 12 months and a long natural history. For those with shorter PSADT, the risk of metastasis, death, and costs increased. These data can help select patients for NHT and conversely those who can safely delay NHT for nmCRPC. [ABSTRACT FROM AUTHOR]

There are complex interactions between bone and skeletal muscle. However, the prevention and treatment of treatment-induced osteosarcopenia in men with metastatic castration-resistant prostate cancer focuses predominantly on bone health. In a single-center cohort of 52 patients we demonstrate that bone-targeted Radium-223 therapy does not accelerate sarcopenia, but baseline sarcopenia is associated with poor survival in such patients. Introduction: Osteosarcopenia is the progressive loss of musculoskeletal structure and functionality, contributing to disability and mortality. Despite complex interactions between bone and muscle, osteosarcopenia prevention and treatment in men with metastatic castration-resistant prostate cancer (mCRPC) focuses predominantly on bone health. It is unknown whether Radium-223 (Ra-223) therapy affects sarcopenia. Methods: We identified 52 patients with mCRPC who had received Ra-223 and had a baseline plus =1 follow-up abdominopelvic CT scan. The total contour area (TCA) and averaged Hounsfield units (HU) of the left and right psoas muscles were obtained at the inferior L3 endplate, and the psoas muscle index (PMI) was calculated there from. Intrapatient musculoskeletal changes were analyzed across various time points. Results: TCA and PMI gradually declined over the study period (P = .002, P = .003, respectively), but Ra-223 therapy did not accelerate sarcopenia, nor the decline of HU compared to the pre-Ra-223 period. The median overall survival of patients with baseline sarcopenia was numerically worse (14.93 vs. 23.23 months, HR 0.612, P = .198). Conclusions: Ra-223 does not accelerate sarcopenia. Thus, worsening muscle parameters in men with mCRPC undergoing Ra-223 therapy are attributable to other factors. Further research is needed to determine whether baseline sarcopenia predicts poor overall survival in such patients. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer (PC) treatment causes sexual dysfunction (SD) and alters fertility, male identity, and intimate relationships with partners. In Japan, little attention has been paid to the importance of providing care for SD associated with PC treatment. This study is aimed at clarifying the care needs of Japanese men regarding SD associated with PC treatment. Methods: One-to-one semi-structured interviews were conducted with 44 PC patients to identify their care needs. Data were analyzed using thematic analysis. Results: Four core categories emerged from the analysis. (1) "Need for empathy from medical staff regarding fear of SD": patients had difficulty confiding in others about their sexual problems, and medical staff involvement in their SD issues was lacking. (2) "Need for information that provides an accurate understanding of SD and coping strategies before deciding on treatment": lack of information about SD in daily life and difficulty understanding information from medical institutions, caused men to regret their treatment. (3) "Need for professional care for individuals and couples affected by SD": men faced loss of intimacy because of their partners' unwillingness to understand their SD issues or tolerate non-sexual relationships. (4) "Need for an environment that facilitates interaction among men to resolve SD issues": men felt lonely and wanted to interact with other patients about their SD concerns. Conclusion: These findings may help form care strategies tailored to these needs and applicable to other societies with strong traditional gender norms. [ABSTRACT FROM AUTHOR]

Purpose of Review: Approximately 15% of prostate cancer patients have lymph node metastases at the time of radical prostatectomy (RP). However, there is no universally accepted standard of care for these men. The options for treatment in this subset of patients range from observation to a combination of adjuvant androgen deprivation therapy (aADT) and radiation therapy (RT). Recent Findings: A recent systematic review showed that there was no clear choice out of the options above to treat these patients. Studies have shown that patients treated with adjuvant radiation therapy have lower all-cause mortality when compared to patients treated with salvage radiation therapy. Summary: In this review, we summarize treatment options for pathologic node-positive (pN1) patients and discuss the urgent need for robust clinical trials that includes observation as the control group to help establish a standard of care for treating patients with node-positive prostate cancer after RP. [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]

Heterogeneity exists in positive nodes (pN +) preoperative negative conventional staging (cN0M0) prostate cancer (PCa) men management. We performed a survey to investigate the current opinion on this issue in the European urological community. An acceptable awareness of pN + disease and management was found. pN + PCa was considered as a multifaceted category needing a risk-adapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered. Introduction: The urological community's opinion over the management of men being found with pathologically positive nodes (pN +) following radical prostatectomy (RP) performed with curative intent after preoperative negative conventional staging (cN0M0) has never been assessed. This remains crucial, especially considering the advent of novel imaging modalities. Our aim was to investigate the current opinion on management of pN + cN0M0 prostate cancer (PCa) in the European urological community. Methods: Following validation, a 31-item survey, complying with the Cherries checklist, was distributed using a web link from December 2021 to April 2022 to 10 urological societies mailing list. Social media (Twitter, Facebook) were also used. Results: We received 253 replies. The majority were Urologists (96.8%), younger than 60 (90.5%); 5.2% did not have access to PET-scans; 78.9% believed pN + is a multifaceted category; 10-years CSS was marked as 71 to 95% by 17.5%. Gold standard management was stated not being ADT by 80.8% and being RT ±ADT by 52.3%. Early sRT ±ADT was considered an option vs. aRT ±ADT by 72.4%. In case of BCR 71% would perform and decide management based on PSMA-PET whilst 3.7% would not perform PSMA-PET. pN + management is still unclear for 77.1%. On multivariate analysis PSMAPET availability related to a lower and higher likelihood of considering aRT ±ADT as standard and of considering early salvage versus aRT respectively (P < .05). Conclusions: The Urological community has an acceptable awareness of pN + disease and management, although it may overestimate disease aggressiveness. The majority consider pN + PCa as a multifaceted category and rely on a riskadapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered. [ABSTRACT FROM AUTHOR]

In the last decade, a shift has occurred in the treatment of patients with newly diagnosed metastatic prostate cancer (ndMPC) from ADT monotherapy to early combination therapies of ADT with docetaxel or ARTAs. Although the introduction of novel systemic therapies has made more patients eligible for additional treatments, adherence to clinical practice guidelines remains suboptimal. Introduction: To describe the changes in systemic treatments (ST) of synchronous metastatic hormone-sensitive prostate cancer (mHSPC) patients in a "real-world" setting and to explore reasons why contemporary standard of care (SOC) was not administrated to the patient. Patients and methods: Since 2014, we prospectively register mHSPCpatients. Patients were grouped in 4 time periods: group 1 (Time period 1, January 2014-July 2015), group 2 after introduction of docetaxel (Time period 2, August 2015-July 2017), group 3 after introduction of abiraterone acetate (Time period 3, August 2017-February 2018) and group 4 after introduction of apalutamide (Time period 4, March 2018-October 2021). For every time period, we evaluated the initiated additional ST. In case patients received treatment that differed from contemporary SOC according to guidelines, reasons for this difference were explored. Results: In total, 243 patients were included. A progressive decline in ADT monotherapy from 85% to 29% over time was observed. The proportion of patients receiving additional STs increased from 34% to 59%. Forty percent of patients were not treated according to contemporary SOC, but this percentage varied strongly per time period (10%, 67%, 53%, and 32% from time period 1 to time period 4 respectively). Reasons for these variations were heterogenous and varied across the 4 time periods. Patients being unfit for treatment and treating physicians failing to consider additional STs were the most prevalent reasons. The proportion of patients unfit for additional ST decreased from 18% to 4% over time. Conclusion: Use of ADT monotherapy declined gradually after the introduction of additional systemic treatments. The proportion of patients unfit for additional ST declined as more treatments became available. Although compliance to SOC increased over time, these real-world data show that adherence to clinical practice guidelines remains suboptimal. Efforts should be made by clinicians to increase the adherence to practice guidelines. [ABSTRACT FROM AUTHOR]

The local treatment may not effectively improve the prognosis of mPCa patients. Patients with low level PSA underwent local treatment had better OS. Compared with RT, RP could effectively improve the prognosis of mPCa patients. Introduction: In order to identify the impact of local treatment on overall survival (OS) and cancer-specific survival(CSS) in men with mPCa. Materials and methods: Men with mPCa undergoing local treatment by radical prostatectomy (RP), radiotherapy (RT) including beam radiation and brachytherapy or no local treatment identified from Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). To evaluate local therapy impact on OS and CSS in relation to baseline character istics, univar iate and multivar iable Cox regression analysis was used to predict the prognostic value of local therapy in OS and CSS. Results: A total of 902 (25.8%) patients received local treatment and 2598 (74.2%) patients did not receive local treatment in this study. The Kaplan-Meier curves showed that there was significant difference in OS between patients underwent local treatment and patients without local treatment (P = .013) but not in CSS (P = .068). While multivariate Cox regression analysis showed that local treatment may not significantly improve OS(P = .724). In subgroup analysis, Among patients with prostate-specific antigent (PSA) < 10ng/ml, local treatment could significantly improve OS and CSS (all P < .05). Multivariate Cox regression analysis showed that local treatment could be used as an independent prognostic factor to improve OS in mPCa patients with PSA < 10ng/ml (P = .031). Another multivariate Cox regression analysis demonstrated that patients with mPCa undergoing RP had better OS and CSS (all P < .05). Conclusions: Our results showed that local salvage therapy did not seem to be an independent prognostic factor in all mPCa patients, but we found that local therapy can show a better prognosis in patients with lower PSA levels. Compared with RT, patients who had experienced RP may have better prognosis. We still need prospective research to further study the application value of local treatment in mPCa patients. [ABSTRACT FROM AUTHOR]

To characterize the impact of concomitant prostate cancer treatments with use of relugolix in advanced prostate cancer, a subgroup and pharmacokinetic/pharmacodynamic analyses of the HERO study was undertaken. Treatment with relugolix was associated with similar efficacy and safety profiles with and without concomitant enzalutamide or docetaxel. Standard-of-care use of relugolix in combination with these agents is supported by these data. Background: To characterize the impact of concomitant prostate cancer treatments with the use of relugolix, the oral GnRH receptor antagonist, in advanced prostate cancer, a subgroup and phar macokinetic/phar macodynamic analyses of the HERO study was undertaken. Patients and Methods: Overall, 934 patients were randomized 2:1 to receive relugolix 120 mg orally once daily or leuprolide injections every 12 weeks for 48 weeks. In the setting of rising PSA, patients could receive enzalutamide or docetaxel 2 months after study initiation. Assessments included sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks and safety parameters. Subgroups analyzed included patients with or without concomitant enzalutamide or docetaxel. A sensitivity analysis of the primary endpoint was performed excluding patients who received concomitant therapies that may affect testosterone. Pharmacokinetic/pharmacodynamic analyses of 20 participants in the relugolix treatment group assessed the net effect of enzalutamide on exposure to relugolix. Results: Overall, 125 patients (13.4%) took concomitant therapies that could impact testosterone levels. Enzalutamide (n = 23) was the most frequently used therapy in the relugolix (2.7%) and leuprolide groups (1.9%). Docetaxel (n = 13) was used by 1.3% and 1.6% of patients in the relugolix and leuprolide groups, respectively. All other relevant concomitant therapy were used in < 1% of population. Sensitivity analysis showed concomitant therapy did not impact the testosterone levels. Castration rates were similar with and without concomitant use of enzalutamide or docetaxel. No clinically relevant differences in adverse events were observed between subgroups in either treatment group. No differences in relugolix C trough or testosterone concentrations were observed, suggesting that any induction or inhibition properties of enzalutamide on relugolix metabolism result in a neutral net effect on relugolix exposure and testosterone suppression. Conclusion: Treatment with relugolix was associated with similar efficacy and safety profiles with and without concomitant enzalutamide or docetaxel. Standard-of-care use of relugolix in combination with these agents is supported by these data. [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]

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

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

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 (

Gay and bisexual men (GBM) with prostate cancer experience worse sexual and mental health outcomes following prostate cancer treatment than heterosexual men. Emerging evidence suggests that GBM may change their role-in-sex in response to treatment effects. The purpose of this study was to describe the impact of prostate cancer treatment on role-in-sex, to estimate the prevalence of such changes, and to determine the impact on quality of life and mental health. We conducted semi-structured interviews with 30 sexual minority prostate cancer patients. Then, we recruited 401 gay and bisexual prostate cancer patients into a study assessing the effects of rehabilitation. Qualitative data were analyzed using descriptive thematic analysis. Differences in quality of life and mental health outcomes were analyzed using multivariate analyses of variance. Prostate cancer treatment resulted in loss of role-in-sex for many patients. When changes in role-in-sex occurred, the shifts were predominantly from tops to bottoms. Those with a current top role-in-sex had significantly better sexual and mental health outcomes than either versatiles or bottoms. Clinical implications include the need for providers to ask about role-in-sex in order to address disparities in health outcomes by sexual orientation and to provide culturally appropriate care to sexual minority patients. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for 225Ac-based treatments may be limited due to low therapeutic activities. Therefore, the aim of this study was to demonstrate the feasibility of clinical quantitative low-count SPECT imaging during [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T treatment. Methods: Eight prostate cancer patients (1000 MBq/8 MBq [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T) received a single-bed quantitative 177Lu/225Ac SPECT/CT acquisition (1 h) at 24 h post treatment (high-energy collimator, 16 projections p. head à 3.5 min, 128 × 128 pixel). The gamma peak at 440 keV (width: 10%) of the progeny 213Bi was imaged along with the peak at 208 keV (width: 15%) of 177Lu. Quantification included CT-based attenuation and window-based scatter correction plus resolution modelling. Gaussian post-filtering with a full-width-half-maximum of 30 mm and 40–45 mm was employed to match the signal-to-noise ratio of 225Ac and 177Lu, respectively. Results: Kidney (r = 0.96, p < 0.01) and lesion (r = 0.94, p < 0.01) SUV for [177Lu]Lu-PSMA-I&T and [225Ac]Ac-PSMA-I&T showed a strong and significant correlation. Kidney SUV were significantly higher (p < 0.01) for [225Ac]Ac-PSMA-I&T (2.5 ± 0.8 vs. 2.1 ± 0.9), while for [177Lu]Lu-PSMA-I&T lesion SUV were significantly higher (p = 0.03; 1.8 ± 1.1 vs. 2.1 ± 1.5). For absorbed dose estimates, significant differences regarding the kidneys remained, while no significant differences for lesion dosimetry were found. Conclusion: Quantitative low-count SPECT imaging of the peak at 440 keV during [225Ac]Ac-PSMA-I&T therapy is feasible. Multi-isotope imaging for [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy indicates accumulation of free 213Bi in the kidneys. [ABSTRACT FROM AUTHOR]

Purpose: Due to limited imaging options, the visualization of a local relapse of prostate cancer used to pose a considerable challenge. However, since the integration of 18F-PSMA-1007-PET/CT into the clinic, a relapsed tumor can now easily be detected by hybrid imaging. The present study aimed to evaluate and map the allocate relapse in a large cohort of prostate cancer patients focusing on individual patient management conclusions for radiation therapy. Procedures: The current study included 135 men with prostate cancer after primary treatment who underwent 18F-PSMA-1007-PET/CT due to biochemical relapse detecting a local relapse. Imaging data were reassessed and analyzed with regard to relapse locations. For the correlation of tumor foci with clinical data, we used binary logistic regression models as well as the Kruskal–Wallis test and Mann–Whitney test. Results: In total, 69.6% of all patients (mean age: 65 years) underwent prostatectomy while 30.4% underwent radiation therapy. PET imaging detected most frequently a unifocal relapse (72.6%). There was a statistically significantly higher rate of ipsilateral cases among the relapsed tumors. Comparing both treatment approaches, tumors relapsed most commonly within the posterior region after surgery and transition/peripheral zone after radiation therapy, respectively. Conclusions: The present study confirms that 18F-PSMA-1007-PET/CT is highly suitable for the localization and allocation of a local relapse in patients with prostate cancer. The data enable further optimizing dose prescriptions and target volume delineations of radiation therapy in the future. [ABSTRACT FROM AUTHOR]

Purpose: Consistent assessment of bone metastases is crucial for patient management and clinical trials in prostate cancer (PCa). We aimed to develop a fully automated convolutional neural network (CNN)-based model for calculating PET/CT skeletal tumor burden in patients with PCa. Methods: A total of 168 patients from three centers were divided into training, validation, and test groups. Manual annotations of skeletal lesions in [18F]fluoride PET/CT scans were used to train a CNN. The AI model was evaluated in 26 patients and compared to segmentations by physicians and to a SUV 15 threshold. PET index representing the percentage of skeletal volume taken up by lesions was estimated. Results: There was no case in which all readers agreed on prevalence of lesions that the AI model failed to detect. PET index by the AI model correlated moderately strong to physician PET index (mean r = 0.69). Threshold PET index correlated fairly with physician PET index (mean r = 0.49). The sensitivity for lesion detection was 65–76% for AI, 68–91% for physicians, and 44–51% for threshold depending on which physician was considered reference. Conclusion: It was possible to develop an AI-based model for automated assessment of PET/CT skeletal tumor burden. The model's performance was superior to using a threshold and provides fully automated calculation of whole-body skeletal tumor burden. It could be further developed to apply to different radiotracers. Objective scan evaluation is a first step toward developing a PET/CT imaging biomarker for PCa skeletal metastases. [ABSTRACT FROM AUTHOR]

Purpose: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. Results: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. Conclusion: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed a cohort of 11 patients with a history of prior low dose rate brachytherapy who were treated with homogeneously dosed salvage stereotactic body radiotherapy (SBRT). Three-year progressionfree survival and overall survival were 70.1% and 100%, respectively. Late grade 2 and 3 genitourinary toxicity rates were 36.4% and 9.1%, respectively. Homogeneously dosed prostate SBRT can serve as a safe and effective salvage treatment for local recurrences following LDR brachytherapy. Introduction: We set out to evaluate the safety and efficacy of homogeneously dosed salvage stereotactic body radiation therapy (SBRT) for intraprostatic recurrences following low dose rate (LDR) brachytherapy. Patients and Methods: An institutional prostate SBRT database was interrogated for patients treated between January 2018 and December 2021 with salvage SBRT for intraprostatic recurrences who were previously treated with LDR brachytherapy. Patients received 30 to 34 Gy in 5 fractions to the prostate with a simultaneous integrated boost of 34 to 37.5 Gy to gross disease. The maximum urethral dose allowed was 34 Gy. Toxicities were graded using Common Terminology Cr iter ia for Adverse Events, version 5.0. Results: Eleven patients met our study's inclusion criteria with a median follow-up time of 37.9 months (range, 24.3-51.8 months). Median time between LDR brachytherapy and salvage SBRT was 7 years (range, 2-11 years) with a median PSA of 3.15 ng/mL (range, 0.90-9.83) at the time of salvage radiation. All 11 patients were alive at the time of last follow-up. Our 3-year Kaplan-Meier progression-free survival rate was 70.1%. Median time to recurrence was 24.1 months (range, 18.7-29.7 months). Late (=3 months) grade 1, 2, and 3 urinary toxicity rates were 27.3%, 36.4%, and 9.1%, respectively. Late (=3 months) grade 1, 2, and 3 gastrointestinal toxicity rates were 18.2%, 0%, and 9.1%, respectively. Conclusion: Homogeneous salvage SBRT to the prostate with urethral dose minimization has a favorable safety and efficacy profile for treating intra-prostatic recurrences following LDR brachytherapy. This may represent an ideal form of salvage SBRT for re-irradiation. [ABSTRACT FROM AUTHOR]

We conducted an online survey of genitourinary medical oncologists across Canada to understand how the COVID-19 pandemic has influenced treatment patterns for patients with mHSPC. We identified that there has been an increased uptake of ARATs and reduced use of docetaxel, and that this trend will likely continue beyond the pandemic. Background: In metastatic hormone sensitive prostate cancer (mHSPC), treatment intensification with either docetaxel or an androgen-receptor-axis targeted therapy (ARAT), added to androgen deprivation therapy (ADT) is the new standard of care. To better understand patterns of treatment intensification in Canada and specifically how it has been influenced by the COVID-19 pandemic, we conducted a national survey of genitourinary medical oncologists from across Canada. Methods: Using SurveyMonkey, we conducted an online survey of 119 medical oncologists in Canada from January 15 to January 27, 2021. The survey consisted of 16 questions, including demographics, and asked specifically about their approach to managing mHSPC before and during the pandemic. Results: Overall there were 50/119 (42%) respondents. Most were male (65%), from Ontario (35%), practicing in academic centers (71%), with 45% reporting their practices focused pr imar ily on genitourinary malignancies and one other tumor site. The majority were in practice 1 to 5 years (34%). Overall 65% indicated their practice patterns had changed since the pandemic, with 51% offering more ARATs and less docetaxel chemotherapy. In low volume mHSPC, the use of ARATs increased from 73% to 79%, while the use of docetaxel remained unaltered at 2%. In high volume disease, the use of ARATs increased from 63% to 84%, while the use of docetaxel decreased from 37% to 14%. Use of granulocyte colony stimulating factor (G-CSF) with docetaxel chemotherapy increased by 35%. Post-pandemic, 45% reported they intend to maintain these changes. Only 18% reported they had prostate cancer patients test positive for COVID-19, and all patients recovered. Conclusion: Management of patients with mHSPC in Canada has changed during the pandemic, with increased uptake of ARATs and reduced use of docetaxel, a trend expected to continue beyond the pandemic. How this trend will impact uptake of triplet therapy (ADT + ARAT + Docetaxel), downstream treatment choices and overall outcomes remains to be seen. [ABSTRACT FROM AUTHOR]

(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]