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In metastatic prostate cancer, 2-weekly docetaxel schedules could be preferred for frail patients. We retrospectively compared 200 patients treated with 2 or 3-weekly schedules. Patients treated with 2-weekly scheme were older and frailer and presented worse outcomes, but survival was not detrimental comparing the schedule chosen after multivariate analyses. The 2-weekly schedule produced less clinically impairing toxicities and toxic deaths. Introduction: Docetaxel 75 mg/m 2 every 3 weeks is the standard schedule for metastatic prostate cancer (mPC). Alternative dosing of 50 mg/m 2 every 2 weeks may be an option for frail patients. Our aim is to define which factors influence the choice of schedule and to compare the outcomes of both schedules in daily clinical practice. Patients and Methods: We retrospectively included patients with mPC treated with docetaxel in our institution. We compared data from patients treated with 3-weekly, 75 mg/m 2 docetaxel or 2-weekly, 50 mg/m 2 docetaxel, including basal characteristics, predefined prognostic factors, treatment received, toxicity and survival data. Results: We included 200 patients, 86% of whom presented castration resistant mPC. A total of 158 patients (79%) were treated with 3-weekly scheme. Compared with these patients, patients treated with 2-weekly scheme were significantly older, had higher Eastern Cooperative Oncology Group performance status (ECOG PS) and Charlson Comorbidity Index, presented more visceral metastases and needed opioid treatment more frequently. Patients treated with 2-weekly scheme presented shorter median overall survival; however, these differences were not shown after multivariate analysis with significant prognostic factors. Patients treated with 2-weekly scheme had more treatment delays and suspensions, but less clinically impairing toxicities such as febrile neutropenia, neuropathy and diarrhea; toxic deaths were 5 in the 3-weekly group while none in the 2-weekly group. Conclusion: Compared to docetaxel 75 mg/m 2 every 3 weeks, dosing of 50 mg/m 2 every 2 weeks may be an alternative for older, frailer and more comorbid patients. Two-weekly dosing may be used more frequently in selected patients. [ABSTRACT FROM AUTHOR]

Our retrospective analysis focuses on improving prognostication. The National Cancer Database was queried from 2010 to 2015 for men diagnosed with castration-sensitive metastatic prostate cancer. We developed and validated several prognostic phenotypes that can aid in risk stratification to potentially personalize therapy. We also performed a literature review of related works. Our nomogram (https://tinyurl.com/prostate-met) may be used to predict survival. Introduction: Castration-sensitive metastatic prostate cancer is heterogeneous. Our objective is to identify metastatic prostate cancer phenotypes and their prognostic impact on survival. Materials and Methods: The National Cancer Database was queried. The Surveillance, Epidemiology, and End Results database was used for validation. Patterns were split into: nonregional lymph node, bone only, and visceral (any brain/liver/lung). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for the univariate and multivariate Cox proportional hazards regression models, odds ratios were calculated, Kaplan-Meier curves were generated, and a nomogram of the multivariate regression model was created. Results: The training set included 13,818 men; bone only was most common (n = 11,632, 84.2%), then nonregional lymph node (n = 1388, 10.0%), and any visceral (brain/liver/lung; n = 798, 5.8%). Risk of death was increased by metastases to a visceral organ versus nonregional lymph node (HR = 2.26; 95% CI [2.00, 2.56]), bone only metastases versus nonregional lymph node (HR = 1.57; 95% CI [1.43, 1.72]), T-stage 4 versus 1 (HR = 1.27; 95% CI [1.17, 1.36]), Grade Group 5 versus 1 (HR = 1.93; 95% CI [1.61, 2.31]), PSA > 20 ng/mL versus < 10 ng/mL (HR = 1.32; 95% CI [1.23, 1.42]), and age = 80 versus < 50 (HR = 1.96; 95% CI [1.69, 2.29]). On internal validation, the model had C-indices 20.5%, 22.7%, and 14.6% higher than the current staging system for overall survival, 1-year, and 5-year survival, respectively. Conclusion: We developed and validated prognostic metastatic prostate cancer phenotypes that can assist risk stratification to potentially personalize therapy. Our nomogram (https://tinyurl.com/prostate-met) may be used to predict survival. [ABSTRACT FROM AUTHOR]

Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and alpha-emitting radiation therapy, identifying their optimal sequencing remains a challenge. Progress in the understanding of the biology of prostate cancer has provided an opportunity for a more refined and personalized treatment selection process. With the advancement of molecular sequencing techniques, genomic precision through the identification of potential treatment targets and predictive biomarkers has been rapidly evolving. In this review, we discussed biomarker-driven treatments for advanced prostate cancer. First, we presented predictive biomarkers for established, global standard treatments for advanced diseases, such as chemotherapy and androgen receptor axis-targeted agents. We also discussed targeted agents with recent approval for special populations, such as poly ADP ribose polymerase (PARP) inhibitors in patients with metastatic castrate-resistant prostate cancer with homologous recombination repair-deficient tumors, pembrolizumab in patients with high levels of microsatellite instability or high tumor mutational burden, and prostate-specific membrane antigen (PSMA) directed radioligand theragnostic treatment for PSMA expressing tumors. Additionally, we discussed evolving treatments, such as cancer vaccines, chimeric antigen receptor T-cells (CAR-T), Bispecific T-cell engagers (BiTEs), other targeted agents such as AKT inhibitors, and various combination treatments. In summary, advances in molecular genetics have begun to propel personalized medicine forward in the management of advanced prostate cancer, allowing for a more precise, biomarker-driven treatment selection with the goal of improving overall efficacy. [ABSTRACT FROM AUTHOR]

Purpose We aimed to investigate the association between androgen deprivation therapy (ADT) and the risk of dementia according to subtypes of dementia in men with prostate cancer. Materials and Methods We performed a nationwide population-based cohort study using the nationwide claims database in Korea. A total of 195,308 men with newly diagnosed prostate cancer were identified between January 2008 and December 2017, and 132,700 men were selected for analysis after applying inclusion and exclusion criteria. The patients were divided into ADT and non-ADT groups. To adjust for imbalances in relevant comorbidities between the groups, exact matching was performed. Study events included newly developed Alzheimer's disease, vascular dementia, and overall dementia. Cox proportional hazard regression models were used. Results After exact matching, 44,854 men with prostate cancer were selected for the main analysis. In age-adjusted Cox regression analysis, the ADT group was significantly associated with increased risks for overall dementia (hazard ratio [HR], 1.070; 95% confidence interval [CI], 1.009–1.134; p=0.0232) and Alzheimer's disease (HR, 1.086; 95% CI, 1.018–1.160; p=0.0127), compared to the non-ADT group. No difference in vascular dementia risk was observed between the two groups (HR, 0.990; 95% CI, 0.870–1.126; p=0.8792). Conclusions The risk of overall dementia increased in men who received ADT. According to dementia subtypes, ADT was associated with an increased risk of Alzheimer's disease, but not with vascular dementia. [ABSTRACT FROM AUTHOR]

Dietary intake selections might play a crucial role in prostate cancer (PCa) occurrence and progression. Several studies have investigated whether statin use could reduce PCa risk but with conflicting results. Nevertheless, a significantly decreased incidence of advanced PCa has been consistently noted. Statins may also reduce the risk of biochemical recurrence (BCR) in men with PCa after receiving active treatment. However, the influence of statin usage on BCR and PCa progression in men with high prostate-specific antigen levels has been found to be insignificant. In contrast, the combined use of a statin and metformin was significantly related to the survival status of PCa patients. However, some studies have revealed that the intake of long-chain omega-3 fatty acid (ω-3) from fish or fish oil supplements may elevate PCa risk. Several meta-analyses on ω-3 consumption and PCa have shown controversial results for the relationship between PCa and ω-3 consumption. However, studies with positive results for various genotypes, fatty acid intake or levels, and PCA risk are emerging. This review highlights the association among statins, ω-3, and PCa. The findings summarized here may be helpful for clinicians counseling patients related to PCa. [ABSTRACT FROM AUTHOR]

At the Advanced Prostate Cancer Consensus Conference 2021, three important areas of controversy in management of advanced prostate cancer were identified and discussed, and experts voted on 107 predefined consensus questions. The full report of the results is summarised here. Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence. To present the voting results from APCCC 2021. The experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions. The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process. The voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material. These voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identified salient questions that merit evaluation in specifically designed trials. The Advanced Prostate Cancer Consensus Conference is a forum for discussing current diagnosis and treatment options for patients with advanced prostate cancer. An expert panel votes on predefined questions focused on the most clinically relevant areas for treatment of advanced prostate cancer for which there are gaps in knowledge. The voting results provide a practical guide to help clinicians in discussing treatment options with patients as part of shared decision-making. [ABSTRACT FROM AUTHOR]

Introduction. In recent years, patient-reported outcomes have played an increasingly important role in the evaluation of the effectiveness of treatments as aspects of health-related quality of life (e.g. physical, emotional, and psychosocial), and are taken into account in the selection of treatment methods and complementary management (e.g. nursing care or physiotherapy). Objective. The aim of this pilot study was to assess changes in the health-related quality of life in a prostate cancer population before and 3 months after radical prostatectomy. The main motivation for the study is the small number of studies using validated tools to assess the quality of life of men in the Polish population suffering from prostate cancer. Materials and method. The study concerned 31 newly-diagnosed prostate cancer patients who qualified for radical prostatectomy. Quality of life assessment was performed twice - first before surgery, and then 3 months afterwards - using the EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Results. Comparison of baseline and 3-month follow-up results revealed significant deteriorations in patients' quality of life across various domains, with the clinically and statistically most significant changes being observed on the emotional, social, and role functioning scales. Conclusions. Radical prostatectomy contributed to decreased quality of life 3 months postoperatively. The psychosocial domains of the quality of life are more strongly affected than the physical domains. [ABSTRACT FROM AUTHOR]

Introduction Osteomyelitis of the pubic symphysis is a rare condition often occurring in patients with radiation therapy-related urethral strictures after prostate cancer treatment. Material and methods We retrospectively reviewed patients who presented with osteomyelitis of the pubic symphysis from November 2016 to September 2021. We investigated the factors leading to urosymphyseal fistulas, clinical presentation, radiological assessment, treatments, and outcomes. Results A total 4 cases were collected. All patients underwent surgery and adjuvant or salvage radiotherapy for prostate cancer. Subsequently, they developed stricture of the vesicourethral anastomosis which was initially treated conservatively. Symptoms of pubic bone osteomyelitis included pain in the pubic area, fever, difficulty walking, and recurrent urinary tract infections. In all cases, computed tomography and magnetic resonance imaging showed a urinary fistula arising from the vesicourethral anastomosis with the involvement of the pubic bone, and severe osteomyelitis. Due to the failure of conservative treatment, debridement of the pubic bone with cystectomy and ileal conduit was performed in 3 patients. One patient refused surgery and bilateral percutaneous nephrostomies were placed. Patients regained their original performance status 1 to 6 months after surgery. Conclusions General recommendations for the best diagnostic and therapeutic approach to osteomyelitis of the pubic symphysis due to urosymphyseal fistula still do not exist. Conservative treatment often fails and a surgical approach with definitive urinary diversion may be required. [ABSTRACT FROM AUTHOR]

Introduction Radical prostatectomy, as a prostate cancer treatment option, is associated with the presence of certain postoperative dysfunctions - physical, psychosocial, emotional and economic. However, regular and planned preoperative patient education can help and support physical and emotional wellbeing by reducing levels of anxiety, building feelings of being in control, and providing instruments for self-management by patients. Material and methods A literature search was conducted on the subject of educational interventions among cancer patients, focusing on men with prostate cancer undergoing radical prostatectomy. Results Preoperative patient education can affect key factors which have an impact on health-related quality of life such as levels of fear and anxiety, expectations and satisfaction in relation to treatment, postoperative activity, self-care management, and others. Conclusions Effective education of patients can lead to increased involvement in courses of treatment, which can in turn result in decreased postoperative complications and shorter recuperative periods. Patient education should be scheduled and organized using not only traditional methods but also modern technology, e.g. 3D printed models of organs or tumours. [ABSTRACT FROM AUTHOR]

The perineural spread could be seen in prostate cancer. In this study, we present a case of prostate cancer with bilateral lumbosacral plexopathy. A 73-year-old male patient was diagnosed with prostate adenocarcinoma on routine screening in 2005. Orchiectomy was performed, and he was followed up without any additional treatment. The patient was asymptomatic until 2014 and admitted to the hospital in 2014 due to pain, anuria, sensory and motor deficit in the lower extremities. The magnetic resonance imaging revealed bilateral lumbosacral plexopathy. Between November 16, 2015, and May 2, 2015, the patient was administered 2 Gy daily total of 50 Gy image-guided radiotherapy with tomotherapy for sacral plexus localization. Pain palliation was provided. However, the incontinence continued. The patient died 2 years later. [ABSTRACT FROM AUTHOR]

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors. [ABSTRACT FROM AUTHOR]

It is common for prostate cancer to be diagnosed by one single positive core in prostate biopsy, while the clinical significance remains unclear. In this study, we included 293 patients with single positive core prostate cancer and investigate the final pathological outcomes on radical prostatectomy. The results indicated that the single positive core prostate cancer should not be considered a low-risk disease. Background: Whether one positive core prostate cancer (PCa) is a low-risk disease remains to be determined. We investigated the pathological results of radical prostatectomy specimens diagnosed on single core positive prostate biopsy. Methods: Between January 2013 and December 2019, A total of 3441 consecutive patients treated with radical prostatectomy in our institution were examined. Among them, 293 patients were diagnosed with single positive core PCa on biopsy, and the clinical parameters and pathological findings of their radical prostatectomy specimens were analyzed. Results: Of the 293 patients, 108 (36.9%) had undergraded Gleason Scores (GS) based on the biopsy. Positive surgical margins (PSMs), perineural invasion (PNI), extracapsular extension (ECE, pT3a) and seminal vesicle invasion (SVI, pT3b) were found in 16.4%, 15.0%, 3.4% and 2.4% of patients, respectively. In the multivariate analysis, we found that preoperative PSA level predict a significant increased risk of upgraded GS and PSMs, and biopsy GS was is a strong predictor of PNI, upgraded GS, tumor stage pT3 at radical prostatectomy. Conclusions: Single positive core PCa have clinically significance in the radical prostatectomy specimens, with considerable rates of undergrading for the GS, PNI, PSMs, ECE and SVI. For patients with single positive core PCa, other prognostic factors must be considered in the treatment plan. [ABSTRACT FROM AUTHOR]

In this cohort of patients with clinically highly treatment resistant metastatic castrate sensitive prostate cancer, comprehensive genomic profiling was feasible using archival tissue and about one third of patients harbored de novo AR, DDR pathogenic and/or likely pathogenic variant prior to initiating ADT. This is a small cohort but represents patients that were likely not well represented in landmark clinical trials and are important to characterize. INTRODUCTION: While comprehensive genomic profiling (CGP) data is becoming increasingly important in the management of prostate cancer, it remains under-utilized in the setting of metastatic castrate sensitive prostate cancer (mCSPC). We aimed to explore the feasibility and potential utility of CGP in mCSPC. PATIENTS AND METHODS: Patients with mCSPC were prospectively recruited at the Princess Margaret Cancer Centre to the OCTANE trial (NCT02906943). The objective was to assess the feasibility of profiling archival standard diagnostic tumor tissue using next generation sequencing with a custom hybridization capture DNA-based or a targeted DNA/RNA amplicon-based panel. Clinical data were extracted from electronic health records. RESULTS: Among 39 mCSPC patients enrolled, 21 (54%) had sufficient archival tissue for CGP. Most had high volume (71%) or de novo (71%) mCSPC, with the majority being androgen deprivation therapy (ADT) naïve. In total, 62% of patients had a pathogenic and/or a likely pathogenic variant, many of which involved DNA damage repair (DDR, 19%), cell cycle (24%), and Androgen Receptor (AR, 10%) pathways. After median follow-up of 32.1 months, 18 of 21 patients progressed, with median time to mCRPC of 14.3 months (95% CI 10.2-21.0). Patients with AR and DDR variants seemed to have shorter median time to mCRPC; 10.2 (95% CI 9.50-NR) and 10.3 months (95% CI 6.6-14.3) respectively. CONCLUSION: In this cohort of highly treatment resistant mCSPC, most of which were ADT-naïve, CGP using archival tumor tissue was feasible for over half of patients, and 62% of patients profiled had a pathogenic and/or a likely pathogenic variant. The presence of de novo variants provides biological basis for evaluating intensification strategies of systemic therapy. This highlights the potential role of routine CGP in biomarker development and clinical trial design in the setting of mCSPC. [ABSTRACT FROM AUTHOR]

The study sought to quantify the total increase in tumor burden represented by prostate cancer working group progression criteria, and to determine the interval increase that best associates with overall survival. An absolute increase of 0.6 in aBSI from the first follow-up scan results in the highest association with survival in patients with metastatic castration resistant prostate cancer. Introduction: Radiographic progression-free survival (rPFS) by Prostate Cancer Working Group (PCWG) cr iter ia is a radiographic endpoint. The automated bone scan index (aBSI) quantifies osseous disease burden on bone scintigraphy as a percentage of total skeletal weight. Using the aBSI, we sought to quantify increase in tumor burden represented by PCWG progression criteria, and to determine the interval increase that best associates with overall survival (OS). Patient and Methods: Retrospective analysis of trials using androgen receptor axis-targeted drugs for metastatic castration resistant prostate cancer patients (mCRPC). aBSI increase in bone disease was assessed from baseline scan to time-to-progression (per PCWG cr iter ia). Threshold for time to aBSI increase were explored and the association between each time-to-threshold and OS was computed. Results: A total of 169 mCPRC patients had bone scans available for aBSI analysis. Of these, 90 (53%) had progression in bone meeting PCWG criteria. Total aBSI increase in patients meeting PCWG cr iter ia was 1.22 (interquartile range [IQR]: 0.65-2.49), with a median relative increase of 109% (IQR: 40%-377%). Median aBSI at baseline was 3.1 (IQR: 1.3-7.1). The best association between OS and time-to-progression occurred with an absolute increase in aBSI equal to 0.6 (Kendall's tau 0.52). Conclusion: An absolute increase of 0.6 or more in aBSI from the first follow-up scan results in the highest association with OS in patients with mCRPC. The rPFS by PCWG, identified progression at nearly twice this tumor burden, suggesting that aBSI may be used to further develop the PCWG cr iter ia without degrading its association with OS. [ABSTRACT FROM AUTHOR]

We investigate germline genetic mutations for prostate cancer (PCa) in Hispanic men enrolled in the SABOR cohort. From 1515 men, we identified 263 with a diagnosis of PCa or a first-degree family history. We discovered a 3.8% mutation rate with 70 variants of undetermined significance, which encourages testing of Hispanic men, and building ethnically diverse genetic references. Background: Mutations in several common hereditary cancer genes are associated with prostate cancer, but there is limited information on the prevalence of these mutations in Hispanic men. Materials and Methods: We selected men at high risk for genetic mutations from 1515 Hispanic men enrolled in the San Antonio Biomarkers of Risk for prostate cancer (SABOR) cohort. Inclusion cr iter ia included men with a diagnosis of prostate cancer or a first-degree family history of prostate cancer. We perfor med ger mline genetic testing using the Color Genomics platform, sequencing 30 genes associated with hereditary cancer risk. Additionally, we assessed ancestral informative markers to determine the admixture of the ethnically unique cohort. Results: Of the 275 subjects who met selection cr iter ia, 263 patients had sufficient samples for sequencing. We identified 3.8% of patients (10 of 263) with a pathogenic or likely pathogenic mutation in the 30 genes tested, of whom 70% would not have met established cr iter ia for genetic testing. Six of these mutations were in BRCA1/2 or ATM. There was a significant inverse association between the percentage of Native American ancestry and the risk of prostate cancer, OR 0.11 (95% CI 0.02-0.76, P = .025). Conclusion: Hispanic men with either a personal or family history of prostate cancer carry mutations in hereditary cancer genes at a significant rate, on par with non-Hispanic counterparts with similar risk factors. [ABSTRACT FROM AUTHOR]

Node-positive prostate cancer is a difficult clinical scenario without clear guidelines regarding postoperative management. We identified 336 men with node-positive prostate cancer treated at a single center with or without postoperative radiation therapy in order to develop nomograms predictive of metastasis and death. These models can discretely quantify an individual's risk of metastasis or death with and without postprostatectomy radiotherapy. Purpose/Objectives: We aimed to develop nomograms to predict the risk reduction for metastasis and death in pathologically node-positive (pN +) prostate cancer patients treated with or without radiation therapy (RT). Materials/Methods: From a prospectively gathered institutional database, we identified patients with pN + M0 prostate cancer after surgery. We evaluated several regression models of known or suspected clinical-pathologic covariates and selected the model with the highest Harrell's concordance-index (c-index) and clinical utility to prognosticate metastasis for inclusion in a nomogram. Covariates in the final, competing-risk adjusted, metastasis model included PSA nadir after surgery, pathologic T-stage, margin status, Gleason score (GS), number of positive lymph nodes, and use of postoperative radiotherapy combined with androgen deprivation therapy (RT + ADT). The overall survival model also included Charlson comorbidity score and age. Results: 336 pN + men with a mean age of 64.9 years and a median follow-up of 4.1 years who had a radical prostatectomy were included in the analysis. 83 men were recommended RT + ADT, of whom 4% refused the ADT and received RT alone. C-index was 0.85 and 0.71 for the MFS and OS models, respectively. On multivariable analysis (MVA) adjusted for competing risks, RT + ADT significantly improved MFS (HR = 0.70 P = < .01) with number of nodes positive, GS 8-10, PSA nadir > 1 ng/mL, and pT3b prognostic for metastasis. MVA for OS demonstrates RT + ADT improves survival (HR = 0.40, P = .02), with GS8-10 and PSA nadir > 1.0 prognostic for death. Conclusion: We developed predictive nomograms for patients with pN + prostate cancer following radical prostatectomy. These models can discretely quantify an individual's risk of metastasis or death with and without postprostatectomy radiotherapy. [ABSTRACT FROM AUTHOR]

We assessed the impact of MRI and PSA density on the probability to pursue an active surveillance of prostate cancer. We found that the use of these characteristics could improve selection of patients at diagnosis, stratifying the delayed treatment risk. During follow-up, some biopsies could be avoided with a reasonably risk and higher MRI lesion were at high-risk of treatment. Introduction: A greater selection of candidates for active surveillance (AS) of prostate cancer (PCa) may decrease the rate of delayed treatment. We aimed to study: 1) the impact of MRI and PSA density (PSAd) at baseline on the final status, and 2) the impact of bio-clinical features during the follow-up on pursuing AS. Materials and Methods: This retrospective, monocentric study between June 2013 and July 2020, included 99 patients in AS (median follow-up: 19 months [18-92]). All MRI were reviewed by a single radiologist. Lost to follow-up were 17 patients and 6 patients chose treatment by themselves. Treatment was proposed in case of upgrading (= GG2) or increasing PCa volume. Results: Impact of MRI and PSAd at baseline: Combining PSAd = 0.15 and PIRADS = 3, the probability to remain in AS was 72%. This rate reached 83% when PSAd = 0.10 was associated to normal MRI. During follow-up: One hundred fiftyseven prostatic biopsies (PBx) were performed and 38 (24%) found PCa upgrading. The association between negative MRI and PSAd = 0.10, during follow-up, had an excellent NPV to predict treatment (95%). This combination concerned 25% (37/151) of surveillance biopsies that could have been avoided at the cost of delaying upgrading in 3% (1/37). In multivariate analysis, only PIRADS = 4 before PBx was associated to a risk of treatment during follow-up (OR, 10.4 [95% CI, 4.2-25.8]; P < .0001). Conclusion: Using PSAd and MRI at baseline to select patients showed excellent performances to predict the maintenance in AS. During follow-up, MRI PIRADS = 4 was associated to an increased risk of treatment. [ABSTRACT FROM AUTHOR]

Biomarker panels must remain significantly associated with the outcomes across patient cohorts and add to pre-existing nomograms. We validated the prognostic ability of both IDC/C and CAPRA-S for BCR and time to BCR in over 600 patients (3 cohorts). CAPRA-S and IDC/C was significant in recurrence-free survival and an independent predictor of BCR. Background: Intraductal carcinoma and cr ibr iform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S + IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRAS low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery. [ABSTRACT FROM AUTHOR]

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Abstract Background The American Urological Association White Paper on Implementation of Shared Decision Making (SDM) into Urological Practice suggested SDM represents the state of the art in counseling for patients who are faced with difficult or uncertain medical decisions. The Michigan Urological Surgery Improvement Collaborative (MUSIC) implemented a decision aid, Personal Patient Profile-Prostate (P3P), in 2018 to help newly diagnosed prostate cancer patients make shared decisions with their clinicians. We conducted a qualitative study to assess statewide implementation of P3P throughout MUSIC. Methods We recruited urologists and staff from 17 MUSIC practices (8 implementation and 9 comparator practices) to understand how practices engaged patients on treatment discussions and to assess facilitators and barriers to implementing P3P. Interview guides were developed based on the Tailored Interventions for Chronic Disease (TICD) Framework. Interviews were transcribed for analysis and coded independently by two investigators in NVivo, PRO 12. Additionally, quantitative program data were integrated into thematic analyses. Results We interviewed 15 urologists and 11 staff from 16 practices. Thematic analysis of interview transcripts indicated three key themes including the following: (i) P3P is compatible as a SDM tool as over 80% of implementation urologists asked patients to complete the P3P questionnaire routinely and used P3P reports during treatment discussions; (ii) patient receptivity was demonstrated by 370 (50%) of newly diagnosed patients (n = 737) from 8 practices enrolled in P3P with 78% completion rate, which accounts for 39% of all newly diagnosed patients in these practices; and (iii) urologists’ attitudes towards SDM varied. Over a third of urologists stated they did not rely on a decision aid. Comparator practices indicated habit, inertia, or concerns about clinic flow as reasons for not adopting P3P and some were unconvinced a decision aid is needed in their practice. Conclusion Urologists and staff affiliated with MUSIC implementation sites indicated that P3P focuses the treatment discussion on items that are important to patients. Experiences of implementation practices indicate that once initiated, there were no negative effects on clinic flow and urologists indicated P3P saves time during patient counseling, as patients were better prepared for focused discussions. Lack of awareness, personal habits, and inertia are reasons for not implementing P3P among the comparator practices.

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. [Display omitted] • STAT Pathway: Key Regulator of Macrophage Polarization. • Non-coding RNAs: Role in Controlling Macrophage Polarization. • Dietary Supplements and Natural Compounds: Regulatory Potential. [ABSTRACT FROM AUTHOR]

Introduction: during radiotherapy, interfractional and intrafractional anatomic variations in pelvic organs may be observed. The purpose of this study is to evaluate these variations in patients with prostate cancer receiving intensity-modulated radiotherapy (IMRT). Methods: ten patients were enrolled in this study. Five weekly dosimetry scans were performed with delineation of prostate and pelvic organs (bladder and rectum). Volumetric variations of these three organs as well as prostate isocenter shift along the three axes of space (X, Y, Z) were recorded. Results: a significant mean decrease in prostate volume of 18.82% ± 3.87% (p= 0.008) was found at the end of treatment. Significant and random volumetric variations were detected in organs at risk with a higher amplitude at the level of the bladder compared to those of the rectum (-90.17 cc ± 151.56 cc and -23.90 cc ± 35.42 cc, respectively). Changes in rectal volume were correlated with prostate isocenter shift along the Y and Z axes, with an average migration of +1.90 mm ± 3,36 mm and -0.78 mm ± 1,21 mm, respectively. Conclusion: volumetric variation of the rectum in patients with prostate cancers receiving IMRT was accompanied by a significant displacement of the prostate along the Y and Z axes, which could cause partial deviation of the initially established prostate volume. [ABSTRACT FROM AUTHOR]

Background/Aim: In prostate cancer, postoperative radiotherapy timing is debated to avoid overtreatments and toxicities. This study compared acute and late rectal and bladder toxicities in the adjuvant and salvage setting. Patients and Methods: In total, 129 patients were analyzed in two groups: adjuvant radiotherapy (aRT) and salvage radiotherapy (sRT). Results: In aRT and sRT, grade 1 (G1) acute bladder toxicities were detected in 40 and 30 patients, and grade 2 (G2) in 1 and 6; G1 late bladder toxicities were described in 30 and 20, and G2 in 6 and 2, respectively. In aRT and sRT, acute G1 rectal toxicities were reported in 18 and 27 patients, and G2 in 5 and 4, respectively. Late rectal G1 toxicities were observed in 10 patients, G2 in 6 and G3 in 1 in the aRT. In sRT, 8 patients and 1 developed G1 and G2 toxicities, respectively. Regarding bladder toxicity, a higher incidence occurred in aRT; late toxicity was lower in sRT. Conclusion: Adjuvant and salvage RT in prostate cancer treatment resulted in acceptable toxicities. [ABSTRACT FROM AUTHOR]

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In the era of COVID-19, there has been a large shift toward delivering larger doses of radiation over fewer treatments using stereotactic body radiation therapy (SBRT). There is a radiobiologic basis for using SBRT, as prostate cancer cells are more sensitive to higher doses of radiation delivered over fewer treatments. Here we show that men with unfavorable intermediate-risk prostate cancer treated with SBRT lived significantly longer when treated with SBRT relative to longer courses of radiotherapy. While we await results from several ongoing clinical trials, this study lends support to the use of SBRT in men with unfavorable intermediate-risk prostate cancer. Background: Prostate stereotactic body radiotherapy (SBRT), which delivers high-dose precision treatment in =5 fractions, is a shorter, more convenient, and less expensive alternative to conventionally fractionated radiotherapy (CRFT; ~44 fractions) or moderately hypofractionated radiotherapy (MFRT; 20-28 fractions). SBRT has not been widely adopted but may have radiobiologic advantages over CFRT/MFRT. We hypothesized that SBRT would be associated with improved overall survival (OS) versus CFRT or MFRT ± androgen deprivation therapy (ADT) for unfavorable-intermediate-risk prostate cancer (UIR-PCa). Methods: Men with UIR-PCa treated with SBRT (35-40Gy in =5 fractions) or biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MRFT (=60Gy in 2.4-3.2Gy/fraction; biologically effective doses =120) were identified in the National Cancer Database (NCDB). Unweighted and propensityweighted multivariable Cox analysis (MVA) was used to compare OS hazard ratios. Results: Of 28,028 men with UIRPCa who received CFRT with (n = 12,872) or without ADT (n = 12,984); MFRT with (n = 251) or without ADT (n = 281); and SBRT with (n = 212) or without ADT (n = 1,428) were identified. Relative to CFRT without ADT, CFRT + ADT (HR 0.92, 95% CI 0.87-0.97, P = .002) and SBRT without ADT (HR 0.74, 95% CI 0.61-0.89, P = .002) were both associated with improved OS on MVA. Relative to CFRT + ADT, SBRT without ADT correlated with improved OS on MVA (HR:0.81, 95% CI 0.67-0.99, P = .04). Propensity-weighted MVA demonstrated that SBRT (HR:0.80, 95% CI 0.65-0.98, P = .036) and ADT (HR:0.91, 95% CI 0.86-0.97, P = .002) correlated with improved OS. SBRT was not associated with improved OS versus MFRT. Conclusion: SBRT, which offers a cheaper and shorter treatment course that mitigates COVID-19 exposure, was associated with improved OS versus CFRT for UIR-PCa. These results confirm guideline-based recommendations that SBRT is a viable option for UIR prostate cancer. The results from this large retrospective study require further validation in clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the experiences of Japanese men with sexual dysfunction associated with various prostate cancer treatments. Methods: We included 38 Japanese men who underwent the following initial treatments for prostate cancer: radical prostatectomy (n = 10), external beam radiotherapy (n = 12), brachytherapy (n = 5), and androgen deprivation therapy (n = 11). Semi-structured interviews were conducted regarding sexual dysfunction associated with prostate cancer treatment. Data were analyzed using a content analysis method. To obtain a unique experience for each treatment, we confirmed and organized the treatment method from which the code that constituted each category was derived. The category reliability was calculated based on Scott's formula for the matching rate of the classification by three qualitative researchers. The criterion for good reliability was set at 70%. Results: Japanese men with sexual dysfunction associated with prostate cancer treatments experienced the following: a desire to maintain sexual function and conflict in decision-making concerning the initial treatment for prostate cancer; a loss of values related to sexual dysfunction; an uncertainty regarding the consequences of sexual dysfunction; a sense of calm with fewer adverse effects of sexual dysfunction at the early treatment stage; an effort to accept sexual dysfunction; and management of their changed body at the later treatment stages. The concordance rates for the categories were 70% and 78%. Additionally, there were glimpses of experiences common to all treatments and trends in treatment-specific experiences. Conclusion: It is necessary to provide care based on the experience of Japanese men with sexual dysfunction after prostate cancer treatment. [ABSTRACT FROM AUTHOR]

The article discusses a research study on the detection and treatment of prostate cancer. Topics mentioned include the risk factors associated with prostate cancer, the common symptoms of prostate cancer, a description of various medical examinations for early detection of prostate cancer, the relation of age and the incidence of prostate cancer, and the benefit of prostate-specific antigen testing.

Objective: The aim of this study is to evaluate the effectiveness of routine additional acquisitions for lower extremity in the diagnosis and treatment of patients undergoing 68Ga prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT). Methods: The files of 59 prostate cancer patients who underwent additional acquisition of the lower extremities in addition to the vertex-upper thigh in 68Ga PSMA PET/CT studies were included in the study. In our study, patients with both lower limb acquisition on clinical suspicion and with routine lower limb acquisition were included. Along with the difference in the effectiveness of the lower limb acquisition between these two arms, the efficacy and clinical utility of the additional acquisiton were evaluated in the entire sample. Results: The rate of metastasis detected in the group with lower limb acquisiton with clinical suspicion (31.1%) is higher than in the other group (7.6%). However, metastases detected in both groups do not cause changes in the treatment. Conclusion: Considering the loss of time caused by additional acquisitons in the clinic, the radiation dose exposure of the patient and the outcomes in this study, it may be possible to say that the lower extremity acquisitons are not effective. [ABSTRACT FROM AUTHOR]

Background/Aim: The aim of this study was to evaluate the mechanical performance and the effect on dose distribution and deliverability of volumetric modulated arc therapy (VMAT) plans for prostate cancer created with the commercial knowledge-based planning (KBP) system (RapidPlan™). Materials and Methods: Three institutions, A, B, and C were enrolled in this study. Each institution established and trained a KBP model with their own cases. CT data and structures for 45 patients at institution B were utilized to validate the dose-volume parameters (D2(%), D95(%), and D98(%) for target, and V50(%), V75(%), and V90(%) for rectum and bladder), and the following mechanical performance parameters and gamma passing rates of each KBP model: leaf sequence variability (LSV), aperture area variability (AAV), total monitor unit (MU), modulation complexity score for VMAT (MCSv), MU/control point (CP), aperture area (AA)/CP, and MUxAA/CP. Results: Significant differences (p<0.01) in dosimetric parameters such as D2 and D98 for target and V50, V75, and V90 for bladder were observed among the three institutions. The means and standard deviations of MCSv were 0.31±0.03, 0.29±0.02, and 0.32±0.03, and the angles of maximum and minimum MUxAA/CP were 269° and 13°, 269° and 13°, and 273° and 153° at institutions A, B, and C, respectively. The mean gamma passing rate (1%/1 mm.) was >95% for all cases in each institution. Dose distribution and mechanical performance significantly differed between the three models. Conclusion: Each KBP model had different dose distributions and mechanical performance but could create an acceptable plan for deliverability regardless of mechanical performance. [ABSTRACT FROM AUTHOR]

Background/Aim: Heat shock proteins (HSP) play a crucial role in the cellular responses during stressful conditions. In addition, HSP are involved in the regulation of a variety of important signaling pathways and processes as well as many pathological conditions, including cancer. In prostate cancer (PC), HSP60 is associated with poor differentiation and prognostic clinical parameters, such as high Gleason score, initial serum prostate-specific antigen levels, and lower cancer-specific survival. In this study, we investigated the regulation of HSP60 protein in PC. Materials and Methods: LNCaP or PC3 cells were treated with androgens or transfected with vectors containing microRNA-1 (miR-1), HSP60, HSP60-specific short-hairpin RNA (shHSP60), or a miR-1 inhibitor. The change in HSP60 protein levels was examined using Western blot. Results: Treatment of PC cells with androgens did not alter the HSP60 protein levels. Modulation of miR-1 levels in LNCaP cells also did not affect the HSP60 protein. Furthermore, HSP60 levels could not be modified by overexpression or short hairpin RNA. Conclusion: It was found that neither physiological factors, such as androgens and the HSP60- specific miR-1, nor overexpression and knockdown systems could influence the HSP60 protein levels. These results suggest an essential role of HSP60 in PC cells, as its protein expression status is regulated very precisely. [ABSTRACT FROM AUTHOR]

We present the update of the recommendations of the French society of oncological radiotherapy on external radiotherapy of prostate cancer. External radiotherapy is intended for all localized prostate cancers, and more recently for oligometastatic prostate cancers. The irradiation techniques are detailed. Intensity-modulated radiotherapy combined with prostate image-guided radiotherapy is the recommended technique. A total dose of 74 to 80 Gy is recommended in case of standard fractionation (2 Gy per fraction). Moderate hypofractionation (total dose of 60 Gy at a rate of 3 Gy per fraction over 4 weeks) in the prostate has become a standard of therapy. Simultaneous integrated boost techniques can be used to treat lymph node areas. Extreme hypofractionation (35 to 40 Gy in five fractions) using stereotactic body radiotherapy can be considered a therapeutic option to treat exclusively the prostate. The postoperative irradiation technique, indicated mainly in case of biological recurrence and lymph node involvement, is detailed. [ABSTRACT FROM AUTHOR]

We have reported the preliminary clinical outcomes after high intensity focused ultrasound ablation for localized prostate cancer. We compared whole gland ablation and partial gland ablation and found that the partial gland ablation had favorable clinical outcomes including faster recovery of urinary incontinence and less adverse effects. Background: We compared the clinical outcomes between whole-gland ablation (WGA) and partial gland ablation (PGA) using the high-intensity focused ultrasound (HIFU) technique for localized prostate cancer (PCa). Methods: We retrospectively investigated 206 patients who underwent WGA or PGA for localized PCa. Follow-up prostatic biopsy was performed 1 year postoperatively. We performed intergroup comparison of the postoperative functional and oncological outcomes and complication rates. Results: In this study, 152 and 54 patients underwent PGA and WGA, respectively. The total operation time was significantly longer in the WGA than in the PGA group (107.5 minutes vs. 95.0 minutes, P = .004). Of the 86 patients who underwent postoperative prostate biopsy, no residual cancer was detected in 70.4% of the WGA and 72.9% of the PGA group. Incontinence-free survival was significantly shorter in the PGA than in the WGA group (P = .047); however, no significant intergroup difference was observed in erectile dysfunction-free survival (P = .317). The postoperative adverse event rate was significantly lower in the PGA than in the WGA group (37.5% vs. 66.7%, P = .023). Of the total patients investigated, 43 (20.9%) required additional endoscopic surgery for bladder outlet obstruction, and the additional endoscopic surgery rate was significantly higher in the WGA than in the PGA group (35.2% vs. 15.8%, P = .005). Conclusion: HIFU treatment was associated with acceptable oncological and fair functional outcomes in patients with localized PCa. Moreover, PGA was associated with significantly better clinical outcomes, including the faster recovery of urinary incontinence and adverse effects. [ABSTRACT FROM AUTHOR]

High risk prostate cancer (HR-PrCa) is a subset of localized PrCa with significant potential for morbidity and mortality associated with disease recurrence and metastasis. Radiotherapy combined with Androgen Deprivation Therapy has been the standard of care for many years in HR-PrCa. In recent years, dose escalation, hypo-fractionation and high precision delivery with immobilization and image-guidance have substantially changed the face of modern PrCa radiotherapy, improving treatment convenience and outcomes. Ultra-hypo-fractionated radiotherapy delivered with high precision in the form of stereotactic body radiation therapy (SBRT) combines delivery of high biologically equivalent dose radiotherapy with the convenience of a shorter treatment schedule, as well as the promise of similar efficacy and reduced toxicity compared to conventional radiotherapy. However, rigorous investigation of SBRT in HR-PrCa remains limited. Here, we review the changes in HR-PrCa radiotherapy through dose escalation, hypo- and ultra-hypo-fractionated radiotherapy boost treatments, and the radiobiological basis of these treatments. We focus on completed and on-going trials in this disease utilizing SBRT as a sole radiation modality or as boost therapy following pelvic radiation. [ABSTRACT FROM AUTHOR]

Prostate cancer (Pc) is the second most commonly diagnosed cancer in men. Survival outcome of prostate cancer depends on early detection, precise preoperative staging, grading of clinically significant cancer and therefore appropriate treatment strategy. In Georgian population preoperative histopathologic grade-Gleason score obtained from transrectal ultrasound guided (TRUS) biopsy is most common grading system for prostate cancer, despite the limitations of TRUS biopsy related to restricted visualization of small index lesions with ultrasound. Prostate imaging reporting and data system (Pi rads) as guideline with recommendations and consistent instructions for multiparametric magnetic resonance imaging (mpMRI) has ability to predict histopathological grade of prostate cancer preoperatively and noninvasively. This paper reviews major aspects of Pi rads with its components at existing literature. It describes possibility of scoring system in preoperative prostate cancer grading. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the most appropriate seed arrangement by comparing two different methods (linked seeds and loose seeds). A total of sixty-one patients (28 linked seed brachytherapy cases and 33 loose seed brachytherapy cases) with clinically localized prostate cancer were treated with I-125 permanent prostate brachytherapy. Modified peripheral loading was the method used for seed placement. The parameters evaluated were as follows: prostate D90, V100, and V150; urethral D90, D10, and D5; and rectal V100 (RV100) and D2 (RD2). Coefficient parameters (r and r2) were assessed by regression analysis. Prostate V150, urethral D90, urethral D10, urethral D5, and RD2 showed significant correlations between both methods in all patients. Urethral D90, urethral D10, urethral D5, and RD2 showed significant correlations in patients who received linked seed brachytherapy. Prostate V150, urethral D90, urethral D10, urethral D5, RV100, and RD2 showed significant correlations in patients who received loose seed brachytherapy. Urethral D90, urethral D10, urethral D5, and RD2 showed significant correlations in the linked seed and loose seed brachytherapy analyses. In contrast, prostate D90 and prostate V100 showed no correlation. Parameters of normal organ damage showed good correlations between intraplan and postplan parameters. These parameters may be useful to determine normal organ damage during guided brachytherapy with two different methods (linked seeds and loose seeds). [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common malignancy found in men and the second leading cause of cancer-related death worldwide. Castration-resistant PCa (CRPC) is defined by PCa cells that stop responding to hormone therapy. Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) plays a critical role in the biosynthesis of androgens in humans. Androgen signaling cascade is a principal survival pathway for PCa cells and androgen-deprivation therapy (ADT) remains the key treatment for patients marked with locally advanced and metastatic PCa cells. Available synthetic drugs have been reported for toxicity, drug resistance, and decreasing efficacy. Thus, the design of novel selective inhibitors of CYP17A1 lyase would help circumvent associated side effects and improve pharmacological activities. Therefore, we employed structural bioinformatics techniques via molecular docking; molecular mechanics generalized born surface area (MM-GBSA), molecular dynamics (MD) simulation, and pharmacokinetic study to identify putative CYP17A1 lyase inhibitors. The results of the computational investigation showed that the Prunus dulcis compounds exhibited higher binding energy than the clinically approved abiraterone acetate. The stability of the ligand with the highest binding affinity (quercetin-3-o-rutinoside) was observed during MD simulation for 10 ns. Quercetin-3-o-rutinoside was observed to be stable within the active site of CYP17A1Lyase throughout the simulation period. The result of the pharmacokinetic study revealed that these compounds are promising therapeutic agents. Collectively, this study proposed that bioactive compounds from P. dulcis may be potential selective inhibitors of CYP17A1Lyase in CRPC treatments. [ABSTRACT FROM AUTHOR]

Aim: In this study, utilizing the in vivo Copenhagen rat model possessing prostate cancer, we studied the possible impact of tumorigenesis on testes and liver morphology and whether riluzole (RIL) and ranolazine (RNL) treatment would have any affect or not. Method: Male Copenhagen rats were divided into four groups: 1) Control group, 2) Cancer group, 3) Cancer + 10 µM Riluzole 4), and Cancer + 2.5 µM / 5 µM Ranolazine group. The tissue samples of testes and liver were taken and processed for light microscopy, including staining with hematoxylin and eosin. Results: In the cancer group, degenerated seminiferous tubules, cell remnants in the lumen were shown in the testis, and a decrease in the spermatogenic cell line was found. The deterioration in these parameters was milder in the treatment groups and an increase in the number of normal tubules was found. In the cancer group, pyknotic nucleus, mononuclear cell infiltration, hyperemia, vacuolization, disrupted arrangement of hepatocyte plates, sinusoidal dilatations, and degenerated hepatocytes were observed in the liver. However, there was a slight damage in cancer + 10 µM RIL, cancer + 2.5 µM RNL, and cancer + 5 µM RNL groups. Properly hepatocyte arrangement and sinusoidal enlargement were observed. Conclusions: This treatment can be considered a promising protective adjuvant candidate for testes and liver tissue in prostate cancer or cancer therapy-related damage. [ABSTRACT FROM AUTHOR]

Introduction: Health state valuation and diagnostic-therapeutic pathways at the junction between nonmetastatic and metastatic castration-resistant prostate cancer (CRPC) are not well documented. We aimed at: (i) estimating the disability weights (DWs) for health states across a continuum of disease from asymptomatic non-metastatic (nmCRPC) to symptomatic metastatic state (mCRPC); (ii) mapping the diagnostic-therapeutic pathway of nmCRPC in Italy. Methods: Structured qualitative interviews were performed with clinical experts to gather information on nmCRPC clinical pathway. An online survey was administered to clinical experts to estimate DWs for four CRPC health states defined from interviews and literature review (i.e., nmCRPC, asymptomatic mCRPC, symptomatic mCRPC, mCRPC in progression during or after chemotherapy). Clinicians' preferences for health states were elicited using the Person-Trade-Off (PTO) and Visual Analogue Scale (VAS) methods. DWs associated with each health state, from 0 (best imaginable health state) and 1 (worst imaginable health state), were estimated. Results: We found that the management of nmCRPC is heterogeneous across Italian regions and hospitals, especially with respect to diagnostic imaging techniques. DWs for PTO ranged from 0.415 (95% confidence interval [CI] 0.208-0.623) in nmCRPC to 0.740 (95% CI 0.560-0.920) in mCRPC, in progression during or after chemotherapy. DWs for VAS ranged between 0.246 (95% CI 0.131-0.361) in nmCRPC to 0.689 (95% CI 0.583-0.795) in mCRPC, in progression during or after chemotherapy. Conclusions: Estimated DWs suggest that delaying transition to a metastatic state might ease the disease burden at both patient and societal levels. [ABSTRACT FROM AUTHOR]

La prise en charge de la rechute biochimique postopératoire du cancer de la prostate repose le plus souvent sur la radiothérapie de rattrapage et une hormonothérapie de durée variable en complément. Les indications de radiothérapie avec ou sans hormonothérapie deviennent mieux consensuelles pour la situation postopératoire adjuvante ou en cas de rattrapage pour élévation du PSA après une période de suivi avec une concentration de PSA indétectable. En revanche, en cas de PSA détectable immédiatement après l'opération ou en cas de rechute biochimique avec rechute macroscopique de la loge à l'imagerie du bilan classique, les options de soin sont encore en évaluation. Cet article fait le point en décrivant ces deux situations et leurs prises en charge actuelles mais aussi à venir au travers des bilans avec l'apport de l'imagerie moderne et les nouvelles options de traitement en termes de dose de radiothérapie avec ou sans hormonothérapie associée. The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (RT) and a variable duration of hormone therapy (HT) in addition. The indications for RT ± HT become more consensual for the adjuvant postoperative situation or in the event of a rising PSA level after a period where an undetectable PSA level was achieved. On the other hand, in the event of detectable PSA immediately postoperatively or in the event of a biological recurrence with macroscopic relapse in the prostate bed seen on conventional imaging assessment, the treatment options are still being evaluated. This article will describe these 2 situations and their current management but also will come through assessments with the contribution of modern imaging and new treatment options in terms of RT dose and RT ± HT combination. [ABSTRACT FROM AUTHOR]

The metabolic reprogramming of phospholipids may affect intracellular signal transduction pathways. A high-fat diet (HFD) is attributed to prostate cancer (PCa) progression, but the expression pattern and role of phospholipids in HFD-mediated PCa progression remains unclear. In this study, HFD enhanced LNCaP xenograft tumor growth by upregulating the phosphatidylinositol (PI) 3-kinase (PI3K)/AKT signaling pathway. A lipidomic analysis using xenograft tumors showed that phosphoinositides, especially PI (3,4,5)- trisphosphate (PIP3), including several species containing C38:4, C38:3, and C40:4 fatty acids, increased in the HFD group compared to control. Fatty acid synthase (FASN) was significantly upregulated in xenograft tumors under HFD in both gene and protein levels. PCa cell growth was significantly inhibited through the decreased AKT signaling pathway by treatment with cerulenin, a chemical FASN inhibitor, which also downregulated PIP, PIP2, and PIP3 but not PI. Thus, dietary fat influences PCa progression and alters phosphoinositides, especially PIP3, a critical player in the PI3K/AKT pathway. These results may offer appropriate targets, such as FASN, for dietary intervention and/or chemoprevention to reduce PCa incidence and progression. [ABSTRACT FROM AUTHOR]

Abstract Background Clinical trials have been conducted to clarify the beneficial effects of VD3 (1α,25-dihydroxy vitamin D3, also known as calcitriol) treatment in prostate cancer. However, the molecular mechanisms underlying these effects are not fully understood. Recent studies on IGFBP-3 have indicated its intracellular functions in cell growth and apoptosis. The aim of this study was to confirm the benefits of low-dose VD3 treatment and clarify the molecular mechanisms underlying these beneficial effects in prostate cancer cells. Methods The molecular effects of simultaneous treatment of LNCaP cells and their genetically modified cell lines with low concentration of docetaxel and VD3 were biologically and biochemically analyzed. To further determine the effects of VD3 treatment on IGFBP-3 induction system, cells were temporarily treated with VD3 in combination with a transcriptional inhibitor or protein synthesis inhibitor. Bcl-2 protein and its mRNA behavior were also observed in Igfbp-3 expression-modified LNCaP cells to determine the involvement of IGFBP-3 in the suppression of Bcl-2 by VD3 treatment. Results Changes in IGFBP-3 expression levels in LNCaP cells indicated that it mediated the inhibition of cell growth induced by VD3 treatment. IGFBP-3 was also found to be a mediator of the enhanced cytotoxicity of prostate cancer cells to VD3 in combination with the anti-cancer drug. We further identified the distinct property of the IGFBP-3 induction system, wherein temporal VD3 stimulation-induced prolonged IGFBP-3 expression and VD3 treatment-induced increase in IGFBP-3 expression were optimized based on the protein concentration rather than the mRNA concentration. Meanwhile, Bcl-2 expression was down-regulated by VD3 treatment in an IGFBP-3-independent manner. Conclusion These findings indicate the molecular mechanisms of IGFBP-3 induction stimulated by VD3 and IGFBP-3 independent Bcl-2 suppression by VD3 treatment in prostate cancer cells. The results could prompt a re-evaluation of VD3 usage in therapy for patients with prostate cancer.

Abstract Gold particles have been widely used in the treatment of prostate cancer due to their unique optical properties, such as their light-heat conversion in response to near-infrared radiation. Due to well-defined synthesis mechanisms and simple manufacturing methods, gold particles have been fabricated in various sizes and shapes. However, the low photothermal transduction efficiency in their present form is a major obstacle to practical and therapeutic uses of these particles. In the current work, we present a silica-coated gold nanoparticle cluster to address the therapeutic limit of single gold nanoparticles (AuNPs) and use its photothermal effect for treatment against PC-3, a typical prostate cancer. Due to its specific nanostructure, this gold nanocluster showed three times higher photothermal transduction efficiency than free single AuNPs. Moreover, while free single particles easily clump and lose optical properties, this silica-coated cluster form remained stable for a longer time in a given medium. In photothermal tests under near-infrared radiation, the excellent therapeutic efficacy of gold nanoclusters, referred to as AuNC@SiO2, was observed in a preclinical sample. Only the samples with both injected nanoclusters followed by photothermal treatment showed completely degraded tumors after 15 days. Due to the unique intrinsic biocompatibility and higher therapeutic effect of these silica-coated gold nanoclusters, they may contribute to enhancement of therapeutic efficacy against prostate cancer.

Objective: There are numerous curative treatment possibilities for prostate cancer. In patients who have undergone rectal extirpation for rectal cancer treatment, curative options are limited due to anatomic changes and previous irradiation of the pelvis. In this analysis, we validate the feasibility of CT-guided transperineal interstitial brachytherapy for this specific scenario., Patients and Methods: We analyzed the treatment procedures and outcomes of 5 patients with metachronic nonmetastatic prostate cancer. Ultrasound-guided brachytherapy was not possible in any of the patients. Of these 5 patients, 3 were treated for prostate cancer using temporary brachytherapy with Ir-192 only, and 2 were treated with external-beam radiation therapy and temporary brachytherapy as a boost. CT-guided brachytherapy was performed in all patients. We analyzed the feasibility, efficacy, treatment-related toxicity, and quality of life (EORTC-30, IEFF, IPSS, and ICIQ questionnaires) of the treatments., Results: Median follow-up was 35 months. Two out of five patients received boost irradiation (HDR 2 × 9 Gy, PDR 30 Gy). Three out of five patients were treated with PDR brachytherapy in two sessions up to a total dose of 60 Gy. Dosimetric parameters were documented as median values as follows: V100 94.7% (94.5-98.4%), D2 bladder 64.3% (50.9-78.3%), D10 urethra 131.05% (123.2%-141.2%), and D30 urethra 122.45% (116.2%-129.5%). At the time of analysis, no biochemical recurrence had been documented. Furthermore, neither early nor late side effects exceeding CTCAE grade 2 were documented., Conclusion: CT-guided transperineal brachytherapy of the prostate in patients with previous rectal surgery and radiation therapy is safe and represents a possible curative treatment option. Brachytherapy can be considered for patients with metachronic prostate cancer in this specific scenario, albeit preferably in experienced high-volume centers., (© 2024. The Author(s).)

Paclitaxel (PTX) is one of the first-line drugs for prostate cancer (PC) treatment. However, the poor water solubility, inadequate specific targeting ability, multidrug resistance, and severe neurotoxicity are far from being fully resolved, despite diverse PTX formulations in the market, such as the gold-standard PTX albumin nanoparticle (Abraxane) and polymer micelles (Genexol-PM). Some studies attempting to solve the multiple problems of chemotherapy delivery fall into the trap of an extremely complicated formulation design and sacrifice druggability. To better address these issues, this study designed an efficient, toxicity-reduced paclitaxel-ginsenoside polymeric micelle (RPM). With the aid of the inherent amphiphilic molecular structure and pharmacological effects of ginsenoside Rg5, the prepared RPM enhances the water solubility and active targeting of PTX, inhibiting chemotherapy resistance in cancer cells. Moreover, the polymeric micelles demonstrated favorable anti-inflammatory and neuroprotective effects, providing ideas for the development of new clinical anti-PC preparations.

Prostate cancer (PC) is the most frequently diagnosed cancer and second leading cause of cancer-related deaths in men. It is heterogeneous, as is evident from the wide spectrum of therapeutic approaches. Most patients with PC are initially responsive to androgen deprivation therapy; however, the majority of cases are either hormone-sensitive PC or castration-resistant PC. Current therapeutic protocols follow the evolution of PC, a continuously progressive process involving a combination of widespread genomic alterations. These genomic alterations are either hereditary germline mutations, such as mutations in BRCA2 , or specific only to tumor cells (somatic). Tumor-specific genomic spectra include genomic structural rearrangements, canonical androgen response genes, and many other specific genes such as TMPRSS2-ERG fusion, SPOP/FOXA1 , TP53/RB1/PTEN , and BRCA2 . New evidence indicates the involvement of signaling pathways including PI3K, WNT/β-catenin, SRC, and IL-6/STAT, which have been shown to promote epithelial-mesenchymal transition cancer stem cell-like features/stemness, and neuroendocrine differentiation in PC. Over the last decade, our understanding of the genotype-phenotype relationships has been enhanced considerably. The genetic background of PC related to canonical genetic alterations and signaling pathway activation genes has shed more insight into the molecular subtype and disease landscape, resulting in a more flexible role of individual therapies targeting diverse genotypes and phenotypes., Competing Interests: No conflict of interest has been declared by the author., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Objective: This study analyzed the correlation between the average segment width (ASW) and gamma passing rate according to the multi-leaf collimator (MLC) position error. Method: To evaluate the changes in the gamma passing rate according to the MLC position error, 21 volumetric modulated arc therapy (VMAT) plans were generated using pelvic lymph node metastatic prostate cancer patient's data which is sensitive to MLC position errors as they involve several long, narrow, irregular fields. The ASW for each VMAT plan was calculated using our own code developed using Visual Basic for Applications (VBA). The gamma passing rate of the VMAT plan according to the MLC position error was evaluated using ArcCHECK (Sun Nuclear, Melbourne, FL, USA) while inducing symmetric MLC position errors in 0.25 mm intervals from −1 mm to +1 mm in the infinity medical linear accelerator (Elekta AB, Stockholm, Sweden). Finally, we examined the correlation between the change in the passing rate (γ gradient) due to the MLC position error and the ASW in VMAT through linear regression analysis using the least squares method. Results: The ASW and γ gradient were found to have a linear correlation according to the MLC position error, and the coefficient of determination was 0.88. For a 1 mm position error of MLC in VMAT, the gamma passing rate improved by approximately 11.9% as the ASW increased by 10 mm. Conclusion: These results are expected to be employed as guidelines to minimize the dose uncertainty due to MLC position error in VMAT. [ABSTRACT FROM AUTHOR]

In all, 30% to 90% of prostate cancer patients undergoing radical prostatectomy (RP) recover their erectile capacity. No effective post RP erectile rehabilitation program exists to date. The aim of this exploratory qualitative study is to explore the needs of these patients and to develop a patient education program (PEP) which meets these needs. Interviews were carried out by a socio-anthropologist with prostate cancer patients treated by RP within the 6 previous months. The needs and expectations identified led to the choice of a logical model of change for the construction of the PEP. Nineteen patients were included in the study; 17 of them were living with a partner. Two categories of patients appeared during the interviews: informed patients resigned to lose their sexuality and patients misinformed about the consequences of the surgery. The tailored program was built on the Health Belief Model and provides six individual sessions, including one with the partner, to meet the needs identified. This study designed the first program to target comprehensively the overall sexuality of the patient and his partner, and not only erection issues. To demonstrate the effectiveness of this program, a controlled, multicentric clinical trial is currently ongoing. [ABSTRACT FROM AUTHOR]