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Androgen deprivation therapy (ADT) forms the cornerstone in the treatment of advanced prostate cancer. However, by suppressing testosterone ADT results in a decrease of skeletal muscle mass. In this narrative review, we explore the magnitude and mechanisms of ADT-induced muscle mass loss and the consequences for muscle strength and physical performance. Subsequently, we elucidate the effectiveness of supervised resistance exercise training as a means to mitigate these adverse effects. Literature shows that resistance exercise training can effectively counteract ADT-induced loss of appendicular lean body mass and decline in muscle strength, while the effect on physical performances is inconclusive. As resistance exercise training is feasible and can be safely implemented during ADT (with special attention for patients with bone metastases), it should be incorporated in standard clinical care for prostate cancer patients (starting) with ADT. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer. Methods: IONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP). Results and Discussion: The MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging. [ABSTRACT FROM AUTHOR]

Prostate gland segmentation is the primary step to estimate gland volume, which aids in the prostate disease management. In this study, we present a 2D-3D convolutional neural network (CNN) ensemble that automatically segments the whole prostate gland along with the peripheral zone (PZ) (PPZ-SegNet) using a T2-weighted sequence (T2W) of Magnetic Resonance Imaging (MRI). The study used 4 different public data sets organized as Train #1 and Test #1 (independently derived from the same cohort), Test #2, Test #3 and Test #4. The prostate gland and the peripheral zone (PZ) anatomy were manually delineated with consensus read by a radiologist, except for Test #4 cohorts that had pre-marked glandular anatomy. A Bayesian hyperparameter optimization method was applied to construct the network model (PPZ-SegNet) with a training cohort (Train #1, n = 150) using a five-fold cross validation. The model evaluation was performed on an independent cohort of 283 T2W MRI prostate cases (Test #1 to #4) without any additional tuning. The data cohorts were derived from The Cancer Imaging Archives (TCIA): PROSTATEx Challenge, Prostatectomy, Repeatability studies and PROMISE12-Challenge. The segmentation performance was evaluated by computing the Dice similarity coefficient and Hausdorff distance between the estimated-deep-network identified regions and the radiologist-drawn annotations. The deep network architecture was able to segment the prostate gland anatomy with an average Dice score of 0.86 in Test #1 (n = 192), 0.79 in Test #2 (n = 26), 0.81 in Test #3 (n = 15), and 0.62 in Test #4 (n = 50). We also found the Dice coefficient improved with larger prostate volumes in 3 of the 4 test cohorts. The variation of the Dice scores from different cohorts of test images suggests the necessity of more diverse models that are inclusive of dependencies such as the gland sizes and others, which will enable us to develop a universal network for prostate and PZ segmentation. Our training and evaluation code can be accessed through the link: https://github.com/ mariabaldeon/PPZ-SegNet.git. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) have been implicated as a tumor microenvironment (TME) cell population, which may be playing a vital role in the inhibition of effective T cell responses in the prostate TME. In this manuscript, we leverage a novel microscale cell culture platform, known as Stacks, to investigate mono-, co-, and tri-culture TME models comprised of prostate tumor cell lines, primary macrophages, and autologous T cells from patients with prostate cancer. Through multiplexed analysis of these multi-cellular prostate tumor models, we capture a dynamic interaction between primary TAMs and activated T cells that resulted in reciprocal proinflammatory activation of both cell populations upon interaction. These findings suggest that activated T cells are capable of reprogramming immunosuppressive TAMs in the context of prostate tumor models and that TAM reprogramming may play a key supportive role in restoring proinflammatory T cell tumor responses in the prostate TME. [ABSTRACT FROM AUTHOR]

Background: The characteristics of a tumor are largely determined by its interaction with the surrounding micro-environment (TME). TME consists of both cellular and non-cellular components. Cancer-associated fibroblasts (CAFs) are a major component of the TME. They are a source of many secreted factors that influence the survival and progression of tumors as well as their response to drugs. Identification of markers either overexpressed in CAFs or unique to CAFs would pave the way for novel therapeutic strategies that in combination with conventional chemotherapy are likely to have better patient outcome. Methods: Fibroblasts have been derived from Benign Prostatic Hyperplasia (BPH) and prostate cancer. RNA from these has been used to perform a transcriptome analysis in order to get a comparative profile of normal and cancer-associated fibroblasts. Results: The study has identified 818 differentially expressed mRNAs and 17 lincRNAs between normal and cancer-associated fibroblasts. Also, 15 potential lincRNA-miRNA-mRNA combinations have been identified which may be potential biomarkers. Conclusions: This study identified differentially expressed markers between normal and cancer-associated fibroblasts that would help in targeted therapy against CAFs/derived factors, in combination with conventional therapy. However, this would in future need more experimental validation. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is an epithelial malignancy occurring in the prostate. PC ranks second in incidence among all male malignancies globally by the latest statistics from the World Health Organization. Notably, China has seen a more rapid increase in PC incidence compared to developed European and American nations. By 2022, the newly reported cases and deaths due to PC in China increased to 134,200 and 47,500, respectively. Thus, early diagnosis and standardized treatment for prostate cancer in China remain far-reaching objectives. Burgeoning research on advanced PC and castration-resistant prostate cancer in recent years have paved the way for a new era of integrated treatment methods including novel endocrine drugs, chemotherapy, targeted therapy, and immunotherapy. Future therapies involve precision treatment guided by genetic testing and individualized integrated treatment as part of a multidisciplinary integrated diagnosis and treatment model for PC. The Genitourinary Oncology Committee of the China Anti-Cancer Association (CACA-GU) has invited multidisciplinary experts across fields including surgery, oncology, pathology, radiology, herbal medicine, physiatry, and psychology to collaboratively write, discuss, and revise guidelines on managing PC. The CACA Guidelines for Holistic Integrative Management of Prostate Cancer includes epidemiology, screening and diagnosis, treatment for localized PC, diagnosis and treatment of PC recurrence after radical prostatectomy, management of metastatic PC, traditional Chinese medicine diagnosis and treatment of PC, and rehabilitation from PC. This guideline aims to standardize the clinical diagnosis and treatment management of PC in China. It is more aligned with China's clinical practice, highlights Chinese characteristics, and bears significant clinical importance. [ABSTRACT FROM AUTHOR]

Background: Patients in palliative care are often treated with antithrombotics, even in the late stages of disease. Clear guidelines regarding deprescribing are lacking. Objective: The aims of this study were to investigate bleeding as a side effect of antithrombotic treatments the last year in life and map the timing of deprescribing. Methods: A retrospective cohort study was performed. All medical records were screened for deceased patients admitted to a palliative care unit in Stockholm, Sweden, over a 3-year period. Patients with antithrombotics were identified; data on bleeding, and on side effects due to deprescribing, were extracted from the medical records. Log-binomial models were used to explore factors associated with bleeding. Results: Of 1501 patients, 897 were treated with antithrombotics during the last year of life (mean age 75 years, 41% women). Of these, 56% continued treatment up until the last 3 days of life. Of the 897 patients, 144 (16%) had at least one bleeding during the treatment. The risk for bleeding was significantly higher for men with prostate cancer compared to other cancer forms, adjusted relative risk 1.9 (95% CI 1.1–3.2). No difference in risk for bleeding was found between sex, age groups, type of antithrombotics, or indication. Two patients (0.2%) developed strokes after antithrombotics were deprescribed. Conclusions: Treatment with antithrombotics during the last year of life is associated with a high risk of bleeding. In this cohort, men with prostate cancer seemed to have more side effects of bleeding than other groups. Few experienced side effects from deprescribing. [ABSTRACT FROM AUTHOR]

Background: The co-treatment of androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) with the fetal estrogen estetrol (E4) may further inhibit endocrine PCa tumor stimulators. We previously reported the suppression of follicle-stimulating hormone (FSH), total and free testosterone, and prostate-specific antigen by ADT+E4. Here, we provide more detailed data on FSH suppression by E4 and present new findings on the effect of ADT+E4 on insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study (the PCombi study) was conducted in advanced PCa patients treated with ADT. The study assessed the effect of E4 co-treatment with LHRH agonist ADT on tumor stimulators, including FSH and IGF-1. Patients starting ADT were randomized 2:1 to receive either 40 mg E4 (n = 41) or placebo (n = 21) for 24 weeks. Non-parametric analyses were performed on the per-protocol population (PP) and individual changes were visualized. Results: The PP included 57 patients (37 ADT+E4; 20 ADT+placebo). ADT+E4 almost completely suppressed FSH in all patients (98% versus 37%; p < 0.0001). IGF-1 levels decreased by 41% with ADT+E4 versus an increase of 10% with ADT+placebo (p < 0.0001). Conclusions: The almost complete suppression of the tumor stimulator FSH using ADT plus E4 observed in all individual patients in this study, along with the augmented suppression of IGF-1 versus an increase by ADT only, may be clinically relevant and suggest the enhanced anti-cancer treatment efficacy of E4 in addition to the previously reported additional suppression of total and free T and PSA. [ABSTRACT FROM AUTHOR]

Simple Summary: In the radio-oncological treatment of patients with prostate cancer, there are significant differences in therapy tolerance due to risk factors, previous illnesses, and pre-treatment of the prostate. Patients with previous prostate surgery (TURP or ThuLEP) are a significant risk group in prostate cancer treatment and differ from non-operated patients in terms of quality of life. Patients who underwent transurethral prostate resection (TURP) exhibited greater overall quality of life impairment immediately after radiotherapy compared to those who had transurethral laser enucleation (ThuLEP) or no surgery. Operation time and radiation technique are important factors regarding therapy tolerance. In our study, the post-radiotherapy quality of life of prostate cancer patients who previously underwent transurethral resection of the prostate (TURP) is compared to those who had thulium laser enucleation of the prostate (ThuLEP) and those who had no prior surgery. It also aims to identify and assess risk factors affecting therapy tolerance in this patient group. We analyzed 132 patients with localized prostate cancer treated with definitive radiotherapy (RT), including 23 who had prior TURP and 19 who previously underwent ThuLEP. A total of 62% of patients underwent irradiation within 12 months after surgery. We included only patients treated with radiotherapy using the IMRT technique. Changes in patient-reported urinary toxicity were evaluated using the International Prostate Syndrome Score (IPSS) and the quality of life index of the World Health Organization (QoL/WHO-PSS) over a three-year post-radiotherapy period. Patients with prior TURP experienced significant deterioration in QoL and IPSS immediately after irradiation (p < 0.001), whereas those without previous surgery showed both less significant differences in IPSS and QoL scores. In conclusion, patients with previous TURP/ThuLEP differ from those without previous surgery in urinary quality of life and acute and chronic urinary symptom profiles after RT. The surgical technique (ThuLEP vs. TURP) and the time interval to irradiation are crucial factors affecting RT tolerance in acute and late settings. The previously operated patient group reported a significantly longer period of increased symptom burden. [ABSTRACT FROM AUTHOR]

Simple Summary: Limited knowledge exists on the effects of the COVID-19 pandemic and the pandemic lockdown on cancer detection and diagnoses in Switzerland. Population-based Swiss cantonal cancer registry data of the cantons of Zurich and Zug from 2018/19 to 2021 were used. Differences in cancer diagnoses were analyzed descriptively and using multivariate regression models. A decrease in all-cancer incidence was observed in 2020 compared to 2018/19, mainly during the lockdown phase in April. Meanwhile, higher all-cancer incidence rates were observed in 2021 compared to 2018/19. The impact in Switzerland was less severe than in other countries. Our findings may inform the decisions of policymakers and the public health system during future pandemics. Background/Objectives: This study aims to investigate differences in cancer diagnosis based on absolute case numbers and age-standardized incidence rate ratios (IRRs) in the pre-Coronavirus disease 2019 (COVID-19) years (2018/19) and the first two years of the COVID-19 pandemic (2020, 2021) in two Swiss cantons. Methods: Data of the Swiss cantonal cancer registry of the cantons of Zurich (ZH) and Zug (ZG) were used to descriptively investigate differences in annual and monthly absolute numbers regarding all-cancer and the five most common cancer types. Directly age-standardized monthly incidence rates (IRs) were calculated. Multivariate Quasipoisson regression models were fitted to determine the IRRs with 95% confidence intervals (95% CI). Results: Annual absolute numbers of all investigated cancers were similar in 2018/19, 2020, and 2021, except for prostate cancer (increase of 20.8% in 2021 compared to 2018/19). In 2020, there were generally more cancer diagnoses in January and February followed by a decrease in April and May. Compared to the pre-COVID-19 period, lower IRs were observed in 2020 for all-cancer (IRR = 0.96 [95% CI 0.96, 0.97]) and female breast cancer (0.92 [0.89, 0.96]), whereas higher IRs were observed in 2021 for all-cancer (1.02 [1.02, 1.02]) and prostate cancer (1.23 [1.18, 1.28]). Conclusions: Cancer detection and diagnoses decreased during the first year of the pandemic, especially during the most stringent lockdown phase in April. The findings of this study may inform the decisions of policymakers and public health system during future pandemics. [ABSTRACT FROM AUTHOR]

Simple Summary: Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma have potential to serve as an alternative for non-invasive Gleason score characterization, for the prediction of biochemical recurrence and to differentiate benign from malignant increased tracer uptake. However, prior to their implementation in clinical practice, additional, clinically relevant studies performed according to recently published guidelines and checklists, offering full transparency, including large enough datasets as well as external validation, are mandatory. Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize the available literature data on radiomics and machine learning using these imaging agents in prostate carcinoma. Gleason scores derived from biopsy and after resection are discordant in a large number of prostate carcinoma patients. Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma might be better performing than biopsy-based Gleason-scoring and could serve as an alternative for non-invasive GS characterization. Furthermore, it may allow for the prediction of biochemical recurrence with a net benefit for clinical utilization. Machine learning based on PET/CT radiomics features was also shown to be able to differentiate benign from malignant increased tracer uptake on PSMA-targeting radioligand PET/CT examinations, thus paving the way for a fully automated image reading in nuclear medicine. As for prediction to treatment outcome following 177Lu-PSMA therapy and overall survival, a limited number of studies have reported promising results on radiomics and machine learning applied to PSMA-targeting radioligand PET/CT images for this purpose. Its added value to clinical parameters warrants further exploration in larger datasets of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is most commonly diagnosed in males after the age of 55 years. These patients are also at risk for cardiovascular disease and venous thromboembolism requiring antithrombotic therapy. Prostate cancer treatments, such as androgen receptor axis-targeted therapies (ARATs, i.e., abiraterone acetate, apalutamide, darolutamide, and enzalutamide), may interact with common antithrombotic medications like warfarin, clopidogrel, and the direct oral anticoagulants. However, the data detailing the clinical outcomes of patients treated with these combinations are limited. We undertook a comprehensive review of the literature and modified Delphi process to enable development of an evidence-based consensus document for the co-prescribing of ARATs with antithrombotic medications. Our assessments relied heavily on pharmacokinetic data and extrapolation from drug interaction studies of similarly metabolized drugs, highlighting the need for more research into the clinical impact of drug interactions in prostate cancer patients. Nonetheless, we provide a practical framework to support clinicians in day-to-day therapeutic decision making. Background/Objectives: Abiraterone acetate, apalutamide, darolutamide, and enzalutamide, which make up the androgen receptor axis-targeted therapies (ARATs) drug class, are commonly used in the management of prostate cancer. Many patients on ARATs also receive oral antithrombotic therapy (i.e., anticoagulants or antiplatelets). The concomitant use of ARATs and antithrombotic therapies creates the potential for clinically relevant drug–drug interactions, but the literature regarding the actual consequences of these interactions, and guidance for co-prescribing, is limited. We assembled a multidisciplinary panel of experts and provided them with clinical information derived from a comprehensive literature review regarding the drug–drug interactions between ARATs and antithrombotic therapies. Methods: A three-stage modified electronic Delphi process was used to gather and consolidate opinions from the panel. Each stage consisted of up to three rounds of voting to achieve consensus on which ARAT/antithrombotic therapy drug pairs warrant attention, the possible clinical consequences of drug–drug interactions, and suggested actions for management. Results: The panel achieved consensus to avoid 11 ARAT/antithrombotic therapy drug pairs and modify therapy for eight pairs. Assessments relied heavily on pharmacokinetic data and extrapolation from drug–drug interaction studies of similarly metabolized drugs. Conclusions: This e-Delphi process highlights the need for further research into the clinical impact of ARAT/antithrombotic drug interactions. Nonetheless, the suggested actions aim to provide clinicians with a practical framework for therapeutic decision making. [ABSTRACT FROM AUTHOR]

Simple Summary: HER2 is a well-known driver of worse outcomes for many types of cancer, including prostate cancer. While HER2 has been previously evaluated in prostate cancer bench studies and clinical trials, there has been a lack of diversity in the experimental designs and protocols. For this reason, it has only recently been reported that Black men with prostate cancer may have a higher prevalence of HER2 overexpression. To thoroughly address health inequities that exist for Black men with prostate cancer, it is critical to utilize diverse biospecimens and enroll diverse study participants into studies that evaluate genetic and molecular contributors to worse prognosis for high-risk populations. In this review, we reconsider the role of HER2 in prostate cancer with an approach that incorporates the effects of race and genetic ancestry. Human epidermal growth factor receptor 2 (HER2) is a major driver of disease progression, treatment resistance, and worse survival for patients with various types of cancers, including prostate cancer. However, key bench studies and clinical trials have failed to evaluate the role of HER2 in prostate cancer using racially diverse experimental designs and protocols. This lack of diversity represents what has been the status quo of cancer research in the United States for decades. In the case of prostate cancer, homogenic study designs are problematic as Black men are much more likely to be diagnosed and die from aggressive and incurable forms of the disease. Therefore, the strategic inclusion of biospecimens collected from Black patients as well as the recruitment and enrollment of Black men into prostate cancer clinical trials is necessary to comprehensively evaluate genetic and molecular factors that contribute to variable outcomes in this high-risk population. Additionally, a higher prevalence of HER2 expression in Black men was recently reported in a small cohort of prostate cancer patients and may contribute to worsened prognosis. In this review, we carefully consider the role of HER2 in prostate cancer while, for the first time, taking into account the influences of race and genetic ancestry. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent advancements in anticancer drug treatments face significant challenges due to drug resistance, often leading to only partial or short-term responses in patients. Our previous in vitro studies indicated that autophagy is linked to drug resistance in prostate cancer (PCa). Consequently, combination therapies targeting multiple pathways could help overcome resistance and extend treatment efficacy. To validate our earlier findings, we conducted in vivo experiments. Our data demonstrated that combining Abiraterone (Abi) with an autophagy inhibitor such as Chloroquine (Chl) not only reduces autophagy but also suppresses tumors more effectively than Abi alone. Thus, the combination of Abi with autophagy inhibitors represents a promising therapeutic strategy that could potentially offer a novel approach for patients. Objective: Abi, when used in conjunction with prednisone, is an established treatment for advanced PCa. Our goal was to explore the level of autophagy induced by Abi treatment, both alone and in combination with the autophagy inhibitor Chl, in a castrated mouse xenograft model. Methods: LNCaP cells were injected into the left and right sides of the back of nude mice that had been previously castrated. Mice were divided into four groups and treated daily with intraperitoneal injections of vehicle (control), Abi (10 mg/kg), Abi (10 mg/kg) combined with Chl (10 mg/kg), or Chl (10 mg/kg), and were monitored for periods of 2 and 3 weeks. Results: A significant reduction in tumor weight was observed in mice treated with the combination therapy, as opposed to those receiving vehicle control, Abi, or Chl alone. Mice receiving Abi + Chl exhibited reduced expression of ATG5, Beclin 1, and LC3 punctuations, along with an increase in P62, as determined by immunofluorescence and WES analysis. AR expression decreased significantly in all treatment groups compared to the control. PSMA expression was highest in the vehicle and combined treatment groups after 3 weeks, with a significant reduction observed with Chl treatment. Conclusions: These findings demonstrate that Abi + Chl treatment lowers autophagy levels and suppresses tumors more effectively than Abi alone. [ABSTRACT FROM AUTHOR]

Background The role of Th17 cells in prostate cancer is not fully understood. The transcription factor BATF controls the differentiation of Th17 cells. Mice deficient in Batf do not produce Th17 cells. Methods In this study, we aimed to characterize the role of Batf -dependent Th17 cells in prostate cancer by crossbreeding Batf knockout mice with mice conditionally mutant for Pten. Results We found that Batf knockout mice had changes in the morphology of prostate epithelial cells compared with normal mice, and Batf knockout mice deficient in Pten (called Batf-) had smaller prostate size and developed fewer invasive prostate adenocarcinomas than Pten -deficient mice with Batf expression (called Batf+). The prostate tumors in Batf- mice showed reduced proliferation, increased apoptosis, decreased angiogenesis and inflammatory cell infiltration, and activation of nuclear factor–κB signaling. Moreover, Batf- mice showed significantly reduced interleukin 23 (IL-23)-IL-23R signaling. In the prostate stroma of Batf- mice, IL-23R–positive cells were decreased considerably compared with Batf + mice. Splenocytes and prostate tissues from Batf- mice cultured under Th17 differentiation conditions expressed reduced IL-23/IL-23R than cultured cells from Batf + mice. Anti–IL-23p19 antibody treatment of Pten -deficient mice reduced prostate tumors and angiogenesis compared with control immunoglobulin G–treated mice. In human prostate tumors, BATF messenger RNA level was positively correlated with IL-23A and IL-23R but not RORC. Conclusion Our novel findings underscore the crucial role of IL-23-IL-23R signaling in mediating the function of Batf -dependent Th17 cells, thereby promoting prostate cancer initiation and progression. This finding highlights the BATF–IL-23R axis as a promising target for the development of innovative strategies for prostate cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Objective: To assess whether prostate biopsy rates have altered with the July 2018 change in Australian Medicare Benefits Schedule (MBS) rebates supporting multiparametric magnetic resonance imaging (mpMRI) for diagnosing prostate cancer. Methods: Biopsy data (both trans-rectal and trans-perineal) were obtained from the Victorian Agency for Health Information from July 2016 to June 2022. The data were stratified by financial year, age group and hospital type (public vs private). Comparison was made between rates pre and post the mpMRI MBS code change. Results: There was an 11.9% increase in the number of biopsies performed per year compared to the pre-MBS change period. There is a significant decreasing trend (P < 0.001–4) in number of biopsies in the 40–49, 50–59 and 60–69-year-old age groups with a significant increasing trend (P < 0.001) in the 70–79 and 80–89-year-old age groups. There was a 32.9% reduction in the mean number of biopsies performed per year in public hospitals, compared with an 18.3% increase in private. Conclusion: Contrary to expectations, and proposed funding, there has been an increase in the number of prostate biopsies since MRI became more easily available. This change will put increased pressure on the health budget and the large increase in biopsies in elderly patients was not anticipated when the changes were proposed. A review of the criteria is suggested. What is known about the topic? Multiparametric magnetic resonance imaging (mpMRI) is increasingly used in the diagnosis of prostate cancer. In 2018, it was included in the Medicare Benefits Schedule with the expectation that the number of prostate biopsies performed would decrease. What does this paper add? By 2022, biopsies increased nearly 12% with over a 50% increase in the 80–89 age group – those least likely to benefit from curative treatment. What are the implications for practitioners? The criteria for funding mpMRI and the performance of prostate biopsies should be altered to enable better use of resources. [ABSTRACT FROM AUTHOR]

To present the final results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumors in different extracranial sites. The DESTROY-2 trial, planned as a prospective dose escalation study in oligometastatic (one to five lesions) cancer patients relied on the delivery of a single high dose of radiation utilizing high-precision technology. The primary study endpoint was the definition of the maximum tolerated dose (MTD) of SRS-VMAT. The secondary objectives of the study were the evaluation of safety, efficacy, and long-term outcomes. All patients consecutively observed at our radiotherapy unit matching the inclusion criteria were enrolled. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, other), and sequentially assigned to a particular dose level. Two hundred twenty seven lesions in 164 consecutive patients (male/female: 97/67, median age: 68 years; range: 29–92) were treated. The main primary tumors were: prostate cancer (60 patients), colorectal cancer (47 patients), and breast cancer (39 patients). The maximum planned dose level was achieved in all study arms, and the MTD was not exceeded. 34 Gy, 32 Gy, 24 Gy, and 24 Gy were established as the single-fraction doses for treating lung, liver, bone, and other extracranial lesions, respectively. The prescribed BED 2Gy α/β:10 to the planning target volume ranged from 26.4 Gy to 149.6 Gy. Twenty-seven patients (16.5%) experienced grade 1–2 and only one grade 3 acute toxicity, which was a pulmonary one. In terms of late toxicity, we registered only 5 toxicity>G2: a G3 gastro-intestinal one, three G3 bone toxicity, and a G3 laryngeal toxicity. The overall response was available for 199 lesions: 107 complete response (53.8%), 50 partial response (25.1%), and 31 stable disease (15.6%), leading to an overall response rate of 94.5%. Progression was registered only in 11 cases (5.5%). The overall response rate in each arm ranged from 88.6% to 96.4%. The overall two-year local control, distant metastasis free survival, disease free survival, and overall survival were 81.7%, 33.0%, 25.4%, and 78.7% respectively. In conclusion, the planned doses of 34 Gy, 32 Gy, 24 Gy, and 24 Gy were successfully administered as single-fractions for the treatment of lung, liver, bone, and other extracranial lesions, respectively, in a prospective SRS dose-escalation trial. No dose-limiting toxicities were registered, and minimal acute and late toxicity were reported. New indications for SRS are currently being studied in oligoprogressive patients receiving targeted drugs or in combination with immunotherapy. The DESTROY-2 trial represents, in our opinion, a credible starting point for future modern radiosurgery trials. • One of the few prospective SRS studies exploring MTD across different clinical settings. • 34 Gy, 32 Gy, and 24 Gy single fraction were safely delivered to lung, liver, bone. • The highest dose level was reached in all the settings, not exceeding the MTD. • The toxicity profile was low with one acute and five late toxicities >G2. • High LC rates and encouraging long-term outcomes were observed. [ABSTRACT FROM AUTHOR]

Background The coronavirus disease 2019 (COVID-19) pandemic impacted cancer services worldwide. We examined the effect of the first three pandemic waves on the number of electronic (e)-referrals to rapid access clinics (RACs) for breast, lung and prostate cancer in Ireland. Methods This study used a retrospective, repeated cross-sectional design. The predicted weekly number of e-referrals by suspected cancer types from March 2020 to May 2021 was calculated using the Holt-Winters seasonal smoothing method, based on the observed numbers from a representative pre-pandemic period (01 January 2019 to 01 March 2020) and compared this with the observed number across the first three pandemic waves (02 March 2020 to 09 May 2021). Percentage differences were calculated between observed and predicted numbers of e-referrals for the three RACs and patterns were examined in each wave. Results Observed e-referrals were lower than predicted for all three RACs in the first wave of the pandemic (15.7% lower for breast, 39.5% lower for lung and 28.1% lower for prostate) with varying levels of recovery in the second and third waves for the three e-referral types. Conclusions The COVID-19 pandemic impacted patterns of e-referrals to RACs in the first three pandemic waves in Ireland. Early identification of changes in engagement with health services, such as a decrease in primary care presentations with a resultant decrease in e-referrals to RACs can allow for a rapid response from cancer control programmes. Continued surveillance of the impact of service disruption on cancer services allows policy makers and strategic leaders in cancer control programmes to respond rapidly to mitigate the impact on cancer outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of herbal products, one component of the growing field of integrative cancer care, is a common yet controversial practice. OBJECTIVES: This article distinguishes nursing issues specific to patient safety when herbal products are used during cancer treatment and identifies available evidence-based resources to enhance patient and professional comprehension. METHODS: PubMed®, CINAHL®, and Google Scholar™ databases were searched for literature published between 2018 and 2024 specific to the clinical sequelae of the use of herbal products and their interactions with antineoplastic drugs, as well as patient and healthcare providers' perceptions of efficacy and safety. METHODS: PubMed®, CINAHL®, and Google Scholar™ databases were searched for literature published between 2018 and 2024 specific to the clinical sequelae of the use of herbal products and their interactions with antineoplastic drugs, as well as patient and healthcare providers' perceptions of efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: This study aims to determine the effect of virtual reality glasses application on pain, anxiety, and patient satisfaction during a transrectal prostate biopsy. Materials and Methods: The study was conducted with pre-tests, post-tests, and a control group, using a randomized controlled experimental research design. A total of 70 patients (35 in the intervention group and 35 in the control group) were included in the study. The intervention group watched a video with virtual reality glasses during the biopsy process. A Descriptive Information Form, State-Trait Anxiety Inventory (STAI-I, STAI-II), Scale of Patient Perception of Hospital Experience with Nursing Care (PPHEN), and Visual Analog Scale for Pain (VAS) were used for data collection. To evaluate the data, numbers, percentages, mean, standard deviation, chi-square, paired sample t test, independent samples t test, regression analysis, and Cronbach's alpha Reliability Coefficient were used. Results: There was no significant difference between the groups in terms of descriptive and clinical characteristics (p >.05). The mean VAS and STAI post-test scores of the patients in the intervention group were lower than the control group, and the difference between them was statistically significant (p <.05). The mean PPHEN post-test scores of the patients in the intervention group were significantly higher than those in the control group (p <.05). Conclusion: The application of virtual reality glasses during a transrectal prostate biopsy significantly reduced the level of pain and anxiety and increased patient satisfaction. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging (PAI) is an emerging modality in biomedical imaging with superior imaging depth and specificity. However, PAI still has significant limitations, such as the background noise from endogenous chromophores. To overcome these limitations, we developed a covalent activity‐based PAI probe, NOx‐JS013, targeting NCEH1. NCEH1, a highly expressed and activated serine hydrolase in aggressive cancers, has the potential to be employed for the diagnosis of cancers. We show that NOx‐JS013 labels active NCEH1 in live cells with high selectivity relative to other serine hydrolases. NOx‐JS013 also presents its efficacy as a hypoxia‐responsive imaging probe in live cells. Finally, NOx‐JS013 successfully visualizes aggressive prostate cancer tumors in mouse models of PC3, while being negligibly detected in tumors of non‐aggressive LNCaP mouse models. These findings show that NOx‐JS013 has the potential to be used to develop precision PAI reagents for detecting metastatic progression in various cancers. [ABSTRACT FROM AUTHOR]

Prostate-specific antigen (PSA)-based prostate cancer screening is a preference-sensitive decision for which experts recommend a shared decision making (SDM) approach. This study aimed to examine PSA screening SDM in primary care. Methods included qualitative analysis of audio-recorded patient-provider interactions supplemented by quantitative description. Participants included 5 clinic providers and 13 patients who were: (1) 40–69 years old, (2) Black, (3) male, and (4) attending clinic for routine primary care. Main measures were SDM element themes and "observing patient involvement in decision making" (OPTION) scoring. Some discussions addressed advantages, disadvantages, and/or scientific uncertainty of screening, however, few patients received all SDM elements. Nearly all providers recommended screening, however, only 3 patients were directly asked about screening preferences. Few patients were asked about prostate cancer knowledge (2), urological symptoms (3), or family history (6). Most providers discussed disadvantages (80%) and advantages (80%) of PSA screening. Average OPTION score was 25/100 (range 0–67) per provider. Our study found limited SDM during PSA screening consultations. The counseling that did take place utilized components of SDM but inconsistently and incompletely. We must improve SDM for PSA screening for diverse patient populations to promote health equity. This study highlights the need to improve SDM for PSA screening. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common cancer in over 50% of countries and the third most common malignancy worldwide. The tumor microenvironment includes the non‐cancerous cells and components present in the tumor, including the molecules they produce and release. Prostate cancer proliferation, angiogenesis, metastasis, and drug resistance are closely associated with the tumor microenvironment. With the continuous development of in vitro tumor models, they have gradually become important tools for recapitulating in vivo parental tumors and studying the reciprocal interactions between tumors and their microenvironment. In this perspective, we describe the significant in vitro models of prostate cancer, analyze the research results on incorporating the tumor microenvironment into these models, and compare their advantages and disadvantages. Furthermore, we highlight the future developmental direction of in vitro prostate cancer model research according to the hotspots of in vitro model research in other cancer types to facilitate precision medicine in prostate cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives: Effective communication between patients and healthcare providers is essential for informed decision making in cancer care. Communication aids that can help prostate cancer patients optimize their involvement in treatment care planning are not widely used in the U.S. This research details the adaptation and validation process of a patient prompt list for localized prostate cancer patients undergoing treatment decisions. Methods: This process occurred in three steps: Step 1 involved gathering usable questions from the literature; in Step 2, we evaluated the tool's content via expert (N = 6) feedback; and in Step 3, we assessed the usefulness of the prompt list with patients (N = 30). Results: Sixty percent of candidate questions (20/33) were retained for inclusion after achieving acceptable item-level content validity index (range: 0.83–1.00) and scale-level content validity index (S-CVI = 0.96) scores. The final 20 questions were classified into 5 domains (1: Treatment Options and Information, 2: Side Effects, Risks, and Recovery, 3: Emotional and Social Support, 4: Logistical and Practical Concerns, and 5: Future Health Considerations) through a card sorting exercise with a subset of patients (N = 3) and providers (N = 2). Most patients rated the prompt list as "useful or very useful" both to themselves (80%, N = 24) and to other men presenting with prostate cancer (83%, N = 25). Conclusions: The participatory process used to develop and validate the prompt list offers insights for the development of similar tools. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy has been crucial in prostate cancer treatment. However, manual segmentation is labor intensive and highly variable among radiation oncologists. In this study, a deep learning based automated contouring model is constructed for clinical target volumes (CTVs) of intact and postoperative prostate cancer. Methods: Computed tomography (CT) data sets of 197 prostate cancer patients were collected. Two auto‐delineation models were built for radical radiotherapy and postoperative radiotherapy of prostate cancer respectively, and each model included CTVn for pelvic lymph nodes and CTVp for prostate tumors or prostate tumor beds. Results: In the radical radiotherapy model, the volumetric dice (VD) coefficient of CTVn calculated by AI, was higher than that of the one delineated by the junior physicians (0.85 vs. 0.82, p = 0.018); In the postoperative radiotherapy model, the quantitative parameter of CTVn and CTVp, counted by AI, was better than that of the junior physicians. The median delineation time for AI was 0.23 min in the postoperative model and 0.26 min in the radical model, which were significantly shorter than those of the physicians (50.40 and 45.43 min, respectively, p < 0.001). The correction time of the senior physician for AI was much shorter compared with that for the junior physicians in both models (p < 0.001). Conclusion: Using deep learning and attention mechanism, a highly consistent and time‐saving contouring model was built for CTVs of pelvic lymph nodes and prostate tumors or prostate tumor beds for prostate cancer, which also might be a good approach to train junior radiation oncologists. [ABSTRACT FROM AUTHOR]

Background: Gallstones are a common health concern, particularly in women. Estrogen is suspected to play a role, potentially altering bile composition and promoting gallstone development. This review explores the link between estrogen exposure and gallstone formation in various contexts, including pregnancy, postmenopausal hormone replacement therapy (HRT), and gender-affirming hormone therapy (GAHT). Methods: Two independent authors systematically searched PubMed, Cochrane, and Embase for literature relevant to estrogen-induced gallstones. Studies were included if they discussed the role of estrogen in the induction of gallstones by different conditions such as HRT, GAHT, prostatic carcinoma, and pregnancy. A scoping review identified 18 studies (1979–2021) encompassing over 211,000 patients and healthy controls. We investigated the risk of gallstones in postmenopausal HT users, pregnant women, oral contraceptive users, men receiving estrogen therapy for prostate cancer, and individuals on GAHT. Results: Our findings suggest an increased risk of gallstones with prolonged HT use (> 45 years). Estrogen therapy elevated biliary cholesterol saturation in both men and women taking oral contraceptives. A low incidence (2%) of gallstones was observed in the third trimester of pregnancy. Interestingly, a case of GAHT-associated gallstone development in a transgender woman emerged. Conclusions: Estrogen exposure, both natural and through various therapies, appears to be associated with an increased risk of gallstones. Further research is needed to elucidate the specific mechanisms in different contexts. Notably, estrogen therapy for specific conditions like hypogonadism or surgical menopause seems unrelated to gallstone formation. [ABSTRACT FROM AUTHOR]

Glomus tumor (GT) is a neoplastic lesion of mesenchymal origin arising from the neuromyoarterial canal or glomus body. Although most GT occur in the peripheral soft tissue and extremities, these tumors can grow anywhere in the body. Here, we describe an uncommon case of GT involving the prostate. [ABSTRACT FROM AUTHOR]

Background: Current prostate cancer treatments are associated with life-threatening side effects, prompting the search for effective and safer alternatives. Aspilia pluriseta Schweinf. ex Engl. has previously shown anticancer activity in lung and liver cancer cell lines. This study investigated its potential for prostate cancer. Methods: A crude extract of A. pluriseta root was prepared using dichloromethane/methanol (1:1 v/v) and partitioned into hexane, ethyl acetate, and water fractions. The MTT assay was used to assess the antiproliferative activity of the fractions. The active fractions were tested at 6.25–200 µg/ml on human prostate cancer DU-145 cells and non-cancerous Vero E6 cells. Qualitative phytochemical and gas chromatography-mass spectrometry (GC-MS) analyses were conducted to identify chemical compounds. Network pharmacology was employed to predict molecular targets and modes of action of the identified chemical compounds, with subsequent validation through molecular docking and real-time PCR. Results: Active extracts included crude dichloromethane/methanol, hexane, and ethyl acetate fractions, inhibiting DU-145 cell proliferation with IC50 values of 16.94, 20.06, and 24.14 µg/ml, respectively. Selectivity indices were determined to be 6.04 (crude), 3.62 (hexane), and 6.68 (ethyl acetate). Identified phytochemicals comprised phenols, terpenoids, flavonoids, tannins, sterols, and saponins. GC-MS analysis revealed seventy-nine (79) compounds, with seven (7) meeting ideal drug candidate parameters; their hub gene targets included MAPK3, MAPK1, IL6, TP53, ESR1, PTGS2, MMP9, MDM2, AR, and MAP2K1, implicating regulation of PI3K/Akt, MAPK, and p53 signaling pathways as potential modes of action. Core compounds such as 1-heneicosanol, lanosterol, andrographolide, and retinoic acid exhibited strong binding activities, particularly lanosterol with MAPK21 (-9.7 kcal/mol), ESR1 (-8.9 kcal/mol), and MAPK3 (-8.8 kcal/mol). Treatment with A. pluriseta downregulated AR expression and upregulated p53, while also downregulating CDK1 and BCL-2 and upregulating caspase-3. Conclusions: A. pluriseta extracts inhibited DU-145 cell growth without causing cellular toxicity, suggesting great potential for development as an anti-prostate cancer agent. However, further in vitro and in vivo experiments are recommended. [ABSTRACT FROM AUTHOR]

Simple Summary: The majority of newly diagnosed prostate cancer patients are eligible for active surveillance, and those at moderate to high risk frequently receive definitive treatments such as radiotherapy or radical prostatectomy. A considerable proportion of patients will experience biochemical recurrence, as well as localized and distant metastatic recurrence following definitive treatment. Salvage cryotherapy has emerged as a safe and effective alternative for treating localized recurrence. This review examines the oncologic and functional outcomes of whole-gland and focal salvage cryotherapy, as well as the crucial role of multiparametric prostate MRI and PSMA-targeted PET imaging. The outcomes of cryotherapy compared to those of other salvage ablation techniques like high-intensity focused ultrasound (HIFU) are also explored. Prostate cancer is the most common non-cutaneous malignancy in men, with the majority of newly diagnosed patients eligible for active surveillance. Despite definitive treatment, a considerable percentage of men will experience biochemical recurrence and even regional and distant metastatic recurrence after radiation therapy or radical prostatectomy. Salvage prostatectomy, while oncologically effective, poses significant morbidity with poor functional outcomes. Salvage cryotherapy has emerged as a promising alternative for localized recurrence, demonstrating safety and efficacy. This review examines the oncologic and functional outcomes of whole-gland and focal salvage cryotherapy, including disease-free survival, cancer-specific survival, and overall survival. The crucial role of multiparametric prostate MRI and evolving role of next-generation PSMA-targeted PET imaging are also examined. The comparison of outcomes of cryotherapy to other salvage ablation modalities, such as high-intensity focused ultrasound (HIFU), is also explored. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PCa) is among the most common cancers. While PCa is frequently diagnosed in elderly men as a slow-growing, low-risk disease, in about 10–15% of cases, it can become a life-threatening danger. Unfortunately, biomarkers able to discriminate indolent prostatic tumors from aggressive forms are lacking, and watchful waiting remains one of the best options. However, available data support the hypothesis that distinctive biological characteristics of PCa stroma can contribute to cancer progression in a clinically relevant way. According to the current view, tissue alterations induced by tumor growth affect both metabolism of resident normal cells and composition of the extracellular matrix and are able also to recruit cells from circulation. Here, we seek to respond to the challenge of identifying stroma-associated biomarkers that may be relevant to assist prognostic decisions in PCa patients. Prostate cancer (PCa), the most commonly diagnosed cancer in men worldwide, is particularly challenging for oncologists when a precise prognosis needs to be established. Indeed, the entire clinical management in PCa has important drawbacks, generating an intense debate concerning the possibility to individuate molecular biomarkers able to avoid overtreatment in patients with pathological indolent cancers. To date, the paradigmatic change in the view of cancer pathogenesis prompts to look for prognostic biomarkers not only in cancer epithelial cells but also in the tumor microenvironment. PCa ecology has been defined with increasing details in the last few years, and a number of promising key markers associated with the reactive stroma are now available. Here, we provide an updated description of the most biologically significant and cited prognosis-oriented microenvironment biomarkers derived from the main reactive processes during PCa pathogenesis: tissue adaptations, inflammatory response and metabolic reprogramming. Proposed biomarkers include factors involved in stromal cell differentiation, cancer-normal cell crosstalk, angiogenesis, extracellular matrix remodeling and energy metabolism. [ABSTRACT FROM AUTHOR]

Simple Summary: Drugs work by binding to a specific 3D structure on a protein. Drug discovery has historically been driven by prior knowledge of function, either of a protein or chemical. This knowledge of function then drives investigations to probe chemical/protein interactions. We undertook a different approach. We first identified unique 3D structures, agnostic of function, and investigated whether they could lead us to innovative therapeutics. Using a synchrotron-based X-ray source, we first determined high-resolution structures of hundreds of proteins. With a supercomputer running analytical programs created by us, we identified novel 3D structures and screened for chemicals binding them. We then tested their ability to inhibit cancer growth without damaging normal cells. We identified a potent inhibitor of a deadly cancer, melanoma. It was not toxic to normal cells even at 2100-fold higher doses. It worked by inducing anoikis, a fundamental process of known importance for cancer. Therapeutics that selectively induce anoikis are needed. In summary, we demonstrate the power of using a 3D protein structure as the starting point to discover new biology and drugs. Drug discovery historically starts with an established function, either that of compounds or proteins. This can hamper discovery of novel therapeutics. As structure determines function, we hypothesized that unique 3D protein structures constitute primary data that can inform novel discovery. Using a computationally intensive physics-based analytical platform operating at supercomputing speeds, we probed a high-resolution protein X-ray crystallographic library developed by us. For each of the eight identified novel 3D structures, we analyzed binding of sixty million compounds. Top-ranking compounds were acquired and screened for efficacy against breast, prostate, colon, or lung cancer, and for toxicity on normal human bone marrow stem cells, both using eight-day colony formation assays. Effective and non-toxic compounds segregated to two pockets. One compound, Dxr2-017, exhibited selective anti-melanoma activity in the NCI-60 cell line screen. In eight-day assays, Dxr2-017 had an IC50 of 12 nM against melanoma cells, while concentrations over 2100-fold higher had minimal stem cell toxicity. Dxr2-017 induced anoikis, a unique form of programmed cell death in need of targeted therapeutics. Our findings demonstrate proof-of-concept that protein structures represent high-value primary data to support the discovery of novel acting therapeutics. This approach is widely applicable. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the optimal timing and effectiveness of radiotherapy in treating oligometastatic prostate cancer (OMPC), which is characterized by limited metastatic spread. We evaluated the impact of early intervention with radiotherapy, targeting both the primary tumor and metastatic sites, on patient survival. Our results show that early radiotherapy to oligometastatic sites, particularly when combined with primary tumor treatment, significantly enhances survival outcomes. These findings underscore the critical importance of timely and personalized treatment strategies in improving the management and care of patients with OMPC. Background/Objectives: Oligometastatic prostate cancer (OMPC) represents an early stage of metastatic disease characterized by a limited number of lesions. Recent advancements in imaging and treatment have revived interest in personalized therapies, including metastasis-directed radiotherapy (OMDRT) and primary prostate radiotherapy (PPR). This study evaluates the impact of OMDRT timing and the role of PPR on survival outcomes in OMPC patients; Methods: In this retrospective cohort study, 82 patients with OMPC who underwent OMDRT between 2010 and 2019 were analyzed. Patients were classified based on OMDRT timing (early vs. late) and disease type (synchronous vs. metachronous). Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, assessed via Kaplan-Meier analysis and Cox proportional hazards models; Results: Among the patients, 36 (43.9%) had synchronous and 46 (56.1%) had metachronous OMD. With a median follow-up of 32 months, the 5-year PFS and OS rates were 77.5% and 88.5%, respectively. Early OMDRT significantly improved PFS (HR 0.461, 95% CI: 0.257–0.826, p = 0.009) and OS (HR 0.219, 95% CI: 0.080–0.603, p = 0.003). Subgroup analysis showed the most favorable outcomes for synchronous OMD patients receiving early OMDRT, with a median PFS of 22.2 months and a 5-year survival rate of 42.1%. The treatment of the primary prostate provided a survival benefit in the OS of synchronous OMD patients (5-year 83.1% vs. 50%, p = 0.025), and there was a further improvement in OS after PPR (5-year 87.7% vs. 50%, p = 0.015). Conclusions: Early OMDRT significantly enhances survival outcomes in OMPC, in both synchronous and metachronous cases. The integration of PPR can further improve results, emphasizing the importance of early intervention and personalized treatment strategies. To more definitively clarify our findings across various clinical situations, further studies with larger cohorts or prospective designs are necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: This research highlights the differences in genetic mutations between primary tumors and their subsequent spine metastases. These distinctions are relevant to neurosurgeons because effective surgical planning and goals rely on factors such as patient prognosis, which is impacted by tumor genetic markers. Certain genetic markers may be more or less favorable, thus impacting the predicted patient treatment course and prognosis. The authors aim to present an overview of these complex molecular characteristics for neurosurgical oncology providers. The content of this review is intended to assist neurosurgeons' decision-making when caring for spinal oncology patients and to illustrate the importance of multidisciplinary management of this complex patient population. For many spine surgeons, patients with metastatic cancer are often present in an emergent situation with rapidly progressive neurological dysfunction. Since the Patchell trial, scoring systems such as NOMS and SINS have emerged to guide the extent of surgical excision and fusion in the context of chemotherapy and radiation therapy. Yet, while multidisciplinary decision-making is the gold standard of cancer care, in the middle of the night, when a patient needs spinal surgery, the wealth of chemotherapy data, clinical trials, and other medical advances can feel overwhelming. The goal of this review is to provide an overview of the relevant molecular biomarkers and therapies driving patient survival in lung, breast, prostate, and renal cell cancer. We highlight the molecular differences between primary tumors (i.e., the patient's original lung cancer) and the subsequent spinal metastasis. This distinction is crucial, as there are limited data investigating how metastases respond to their primary tumor's targeted molecular therapies. Integrating information from primary and metastatic markers allows for a more comprehensive and personalized approach to cancer treatment. [ABSTRACT FROM AUTHOR]

Background: The ASCAPE project aims to improve the health-related quality of life of cancer patients using artificial intelligence (AI)-driven solutions. The current study employs a comprehensive dataset to evaluate sleep and urinary incontinence, thus enabling the development of personalized interventions. Methods: This study focuses on prostate cancer patients eligible for curative treatment with surgery. Forty-two participants were enrolled following their diagnosis and were followed up at baseline and 3, 6, 9, and 12 months after surgical treatment. The data collection process involved a combination of standardized questionnaires and wearable devices, providing a holistic view of patients' QoL and health outcomes. The dataset is systematically organized and stored in a centralized database, with advanced statistical and AI techniques being employed to reveal correlations, patterns, and predictive markers that can ultimately lead to implementing personalized intervention strategies, ultimately enhancing patient QoL outcomes. Results: The correlation analysis between sleep quality and urinary symptoms post-surgery revealed a moderate positive correlation between baseline insomnia and baseline urinary symptoms (r = 0.407, p = 0.011), a positive correlation between baseline insomnia and urinary symptoms at 3 months (r = 0.321, p = 0.049), and significant correlations between insomnia at 12 months and urinary symptoms at 3 months (r = 0.396, p = 0.014) and at 6 months (r = 0.384, p = 0.017). Furthermore, modeling the relationship between baseline insomnia and baseline urinary symptoms showed that baseline insomnia is significantly associated with baseline urinary symptoms (coef = 0.222, p = 0.036). Conclusions: The investigation of sleep quality and urinary incontinence via data analysis through the ASCAPE project suggests that better sleep quality could improve urinary disorders. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the difference in the diagnostic efficacy of 18F-PSMA-1007 PET/CT and pelvic MRI in primary prostate cancer, as well as the correlation between the two methods and histopathological parameters and serum PSA levels. Methods: A total of 41 patients with suspected prostate cancer who underwent 18F-PSMA-1007 PET/CT imaging in our department from 2018 to 2023 were retrospectively collected. All patients underwent 18F-PSMA-1007 PET/CT and MRI scans. The sensitivity, PPV and diagnostic accuracy of MRI and 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were calculated after comparing the results of MRI and 18F-PSMA-1007 PET/CT with biopsy. The Spearman test was used to calculate the correlation between 18F-PSMA-1007 PET/CT, MRI parameters, histopathological indicators, and serum PSA levels. Results: Compared with histopathological results, the sensitivity, PPV and diagnostic accuracy of 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were 95.1%, 100.0% and 95.1%, respectively. The sensitivity, PPV and diagnostic accuracy of MRI in the diagnosis of prostate cancer were 82.9%, 100.0% and 82.9%, respectively. There was a mild to moderately positive correlation between Gleason (Gs) score, Ki-67 index, serum PSA level and 18F-PSMA-1007 PET/CT parameters (p < 0.05). There was a moderately negative correlation between the expression of AMACR (P504S) and 18F-PSMA-1007 PET/CT parameters (p < 0.05). The serum PSA level and the Gs score were moderately positively correlated with the MRI parameters (p < 0.05). There was no correlation between histopathological parameters and MRI parameters (p > 0.05). Conclusion: Compared with MRI, 18F-PSMA-1007 PET/CT has higher sensitivity and diagnostic accuracy in the detection of malignant prostate tumors. In addition, the Ki-67 index and AMACR (P504S) expression were only correlated with 18F-PSMA-1007 PET/CT parameters. Gs score and serum PSA level were correlated with 18F-PSMA-1007 PET/CT and MRI parameters. 18F-PSMA-1007 PET/CT examination can provide certain reference values for the clinical diagnosis, evaluation, and treatment of malignant prostate tumors. [ABSTRACT FROM AUTHOR]

Background: Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells. Methods: We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures. Results: We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro. Conclusions: Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). Methods: PCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis. Results: TOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients. Conclusions: In this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is well known as the commonest cancer in men and the second leading cause of cancer-related death. CT, MRI and bone scintigraphy are considered the commonly widely used imaging diagnostic tools for detection, staging and follow-up of prostate cancer. Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, that can be concentrated in prostate cancer cells up to 100 times higher than in normal cells. PSMA-targeted imaging modalities have now proven their efficacy in diagnosis, staging and follow-up of prostate cancer. The use of 68Ga PSMA PET-CT has efficiently improved the detection of loco-regional and metastatic disease. 68Ga PSMA PET-CT also has an effective role in the primary diagnosis, staging, and detecting biochemical recurrence after curative treatment and in metastasis-targeted therapy. This work aims to review the role of 68Ga PSMA PET-CT in anatomical staging of prostate cancer in correlation with histopathological staging. Results: Zonal correlation between 68Ga PSMA findings and biopsy results showed sensitivity ranging between 76.9 and 90.6% and specificity ranging from 85.7 to 100%. There was high significant correlation between the SUVmax uptake and the biopsy results, between the SUVmax uptake and the local staging as well as between the Gleason score and 68Ga PSMA PET/CT findings. Conclusions: 68Ga PSMA PET/CT is a highly promising imaging modality with an effective role in detection of prostate cancer showing high sensitivity and specificity in prediction of zonal histopathological results and loco-regional Gleason score staging with significant positive correlation between the SUV uptake results, Gleason score and the PSA levels. [ABSTRACT FROM AUTHOR]

We present a novel tool designed for the semiautomatic detection and assessment of prostate cancer during recurrence diagnostics using PET-CT with prostate-specific membrane antigen (PSMA). The tool automatically generates a structured report, which is enhanced by 3D images and ensures the reproducibility of the findings. Moreover, the area of the findings is automatically determined and can be corrected manually. Image data from 50 patients following radical prostatectomy was used. Our approach and its user interface were qualitatively evaluated by a nuclear medicine specialist. The segmentation analysis revealed a requirement for further automation. The resulting report was deemed highly beneficial, particularly in terms of the resulting reproducibility and the presentation of 3D images depicting the findings. The presented tool has great potential for much-needed support in everyday clinical practice, as it facilitates the communication of the diagnostic results to colleagues and patients and thus prevents misunderstandings. [ABSTRACT FROM AUTHOR]

Higher levels of aneuploidy, characterized by imbalanced chromosome numbers, are associated with lethal progression in prostate cancer. However, how aneuploidy contributes to prostate cancer aggressiveness remains poorly understood. In this study, we assessed in patients which genes on chromosome 8q, one of the most frequently gained chromosome arms in prostate tumors, were most strongly associated with long-term risk of cancer progression to metastases and death from prostate cancer (lethal disease) in 403 patients and found the strongest candidate was cohesin subunit gene, RAD21, with an odds ratio of 3.7 (95% CI 1.8, 7.6) comparing the highest vs. lowest tertiles of mRNA expression and adjusting for overall aneuploidy burden and Gleason score, both strong prognostic factors in primary prostate cancer. Studying prostate cancer driven by the TMPRSS2-ERG oncogenic fusion, found in about half of all prostate tumors, we found that increased RAD21 alleviated toxic oncogenic stress and DNA damage caused by oncogene expression. Data from both organoids and patients indicate that increased RAD21 thereby enables aggressive tumors to sustain tumor proliferation, and more broadly suggests one path through which tumors benefit from aneuploidy. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is regarded as one of the most common forms of cancer and has recorded high mortality globally. However, lower mortality rates are reported in advanced countries due to early PCa detection and treatment. In developing countries such as Ghana, most PCa victims are diagnosed in the late stage of the disease with poor prognosis. Using a quantitative approach, this study assessed PCa awareness, knowledge, and screening practices considering 423 men aged at least 30 years. We found that the majority of respondents (85.8%) were aware of PCa. About half (52.5%) of the respondents interviewed were deemed to have adequate knowledge of PCa considering our at least 4/8 criterion. Highest educational level and occupation of respondents were found to be significantly associated with awareness and knowledge of PCa. Only, 10.2% of the respondents had ever screened for PCa. Participants with adequate knowledge on PCa had 4.99 times (95% CI = 1.78–13.97) the odds of screening for PCa compared to those with inadequate knowledge. Lack of education on PCa and fear of the unknown were the most reported barriers to prostate cancer screening. There is the need for deliberate and well-tailored dissemination of male reproductive health information regarding PCa from formal sources such as health professionals most especially health educators and promotors through the mass media. [ABSTRACT FROM AUTHOR]

Objective: The objective of this review is to provide an overview of common drug-drug interactions (DDIs) associated with prostate cancer treatments and outline recommendations for managing polypharmacy. Data sources: A literature search of PubMed, Embase, and CINAHL was carried out to identify pharmacokinetic and pharmacodynamic changes caused by DDIs that are relevant for prostate cancer patients, DDIs between prostate cancer therapies and co-administered medications (both prescription and over-the-counter), and measures to prevent DDIs. Medication package inserts were used to identify the impact of DDI on the prostate cancer therapy and suggested interventions. Data summary: No DDIs are expected for the LHRH agonists leuprolide acetate, histrelin, goserelin, or leuprolide mesylate. However, DDIs have been reported for GnRH antagonists, anti-androgens, PARP inhibitors, and taxanes. Although there are no confirmed DDIs for sipuleucel-T to date, it is not generally recommended to use sipuleucel-T concurrently with immunosuppressive medications. Interventions to prevent DDIs include the use of software that can detect clinically significant DDIs, up-to-date medication reconciliation, the inclusion of dedicated clinical pharmacists in cancer treatment teams, and patient/caregiver education. Conclusions: Prostate cancer patients have a high risk of potential DDIs due to numerous new anti-cancer therapies, the increased use of treatment combinations, and the likelihood of comorbid conditions also requiring drug therapy. Drug-drug interaction screening software, up-to-date medication reconciliation, inclusion of oncology pharmacists on healthcare teams, and patient/caregiver education will aid the development of treatment plans that focus on achieving an optimal risk-benefit profile whilst reducing the risk of DDIs. [ABSTRACT FROM AUTHOR]

Background: Clinicians make clinical decisions using the dual process theory. The dual process theory comprises two approaches, System 1, based on heuristics, and System 2, involving an analytical and effortful thought process. However, there are inherent limitations to the dual process theory, such as relying on inaccurate memory or misinterpreting cues leading to inappropriate clinical management. As a result, clinicians may utilize mental shortcuts, termed heuristics, and be susceptible to clinical errors and biases that may lead to flawed decision making and diagnosis. Methods: This case series describes four clinical cases whereby the clinicians use distinct strategies to assess and manage complex clinical presentations. Discussion: Through the use of self-reflection and acknowledging diagnostic uncertainty, the clinicians were able to reduce common cognitive biases and provide effective and timely patient care. We discuss strategies that clinicians can implement in their daily practice to improve clinical decision-making processes and deliver quality care. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer remainsa leading cause of cancer-related deaths in men worldwide. This review focuses on the transformative role of prostate-specific membrane antigen (PSMA) in the diagnosis and treatment of prostate cancer. PSMA is highly expressed in prostate cancer cells, making it a valuable target for both imaging and therapy. The integration of PSMA-targeted imaging with radioligand therapy, known as theranostics, has significantly improved the detection and management of advanced prostate cancer. Recent clinical trials, including the VISION trial, have demonstrated the effectiveness of PSMA-targeted therapies, such as 177Lu-PSMA-617. These advancements highlight the potential of theranostics in offering personalized and more effective treatment options for prostate cancer patients. Prostate cancer, a leading cause of cancer-related mortality among men, is characterized by complex genetic and epigenetic alterations, dysregulation of oncogenic pathways, and a dynamic tumor microenvironment. Advances in molecular diagnostics and targeted therapies have significantly transformed the management of this disease. Prostate-specific membrane antigen (PSMA) has emerged as a critical biomarker, enhancing the precision of prostate cancer diagnosis and treatment. Theranostics, which integrates PSMA-targeted imaging with radioligand therapies, has shown remarkable efficacy in detecting and treating advanced prostate cancer. By leveraging the dual capabilities of PSMA-based diagnostics and therapeutic agents, theranostics offers a personalized approach that improves patient outcomes. This comprehensive review explores the latest developments in PSMA-targeted theranostics and their impact on the future of prostate cancer management, highlighting key clinical trials and emerging therapeutic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases from systemic cancer are the most common tumors of the central nervous system. For prostate metastases to the brain, the clinical progression is poorly understood. This retrospective study aims to elucidate clinical risk factors associated with overall survival (OS; months post-diagnosis) in prostate metastases to the brain, and then develop a nomogram to aid in clinical decision making for this vulnerable population. We identified several factors associated with survival, including race, tumor size, and the presence of additional metastases. This study should serve as a clinical framework for prognostication in metastatic prostate cancer to the brain. Brain metastases are an uncommon yet life-limiting manifestation of prostate cancer. However, there is limited insight into the natural progression, therapeutics, and patient outcomes for prostate cancer once metastasized to the brain. This is a retrospective study of 461 patients with metastatic prostate cancer to the brain with a primary outcome of median overall survival (OS). The Surveillance, Epidemiology, and End Results (SEER) database was examined using Cox regression univariate and multivariable analyses, and a corresponding nomogram was developed. The median overall survival was 15 months. In the multivariable analysis, Hispanic patients had significantly increased OS (median OS 17 months, p = 0.005). Patients with tumor sizes greater than three centimeters exhibited significantly reduced OS (median OS 19 months, p = 0.014). Patients with additional metastases to the liver exhibited significantly reduced OS (median OS 3.5 months, p < 0.001). Increased survival was demonstrated in patients treated with chemotherapy or systemic treatment (median OS 19 months, p = 0.039), in addition to radiation and chemotherapy (median OS 25 months, p = 0.002). The nomogram had a C-index of 0.641. For patients with prostate metastases to the brain, median OS is influenced by race, tumor size, presence of additional metastases, and treatment. The lack of an association between traditional prostate cancer prognosis metrics, including Gleason and ISUP grading, and mortality highlights the need for individualized, metastasis-specific prognosis metrics. This prognostic nomogram for prostate metastases to the brain can be used to guide the management of affected patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PCa) is a major health issue among men, with risk factors such as age, family history, genetics, and race being well known. However, the impact of lifestyle choices has often been overlooked. This study aimed to understand health professionals' perceptions of PCa risk factors to design a questionnaire applicable to the male population. Three focus groups were conducted to discuss topics, such as the impact of diet, physical activity, alcohol consumption, smoking, sexual health, and screening and treatment methods. Although healthy lifestyles can generally improve PCa outcomes, no specific lifestyle change has been identified as a preventive measure, particularly for older adults. Lycopene, present in tomatoes, was highlighted for its antioxidant benefits. This study demonstrates the necessity for additional research on how lifestyle affects PCa and emphasizes the importance of health professionals in encouraging the adoption of healthier habits. It also suggests exploring non-invasive screening through urine and innovative treatment methods to reduce false positives and side effects, respectively. Prostate cancer (PCa) accounts for 20% of new cancer cases and 10.5% of cancer-associated mortality in Portugal. Associated risk factors include advanced age, family history, genetic alterations, and race/ethnicity. However, the role of lifestyle factors is often underestimated. To explore health professionals' perceptions of PCa risk factors, a qualitative study with three focus groups (FG), with a total of twenty-one general practitioners and urologists, was conducted via videoconference between February and April 2023. Seven themes emerged, including general perceptions of PCa; PCa risk factors; nutritional impact; the role of physical activity; alcohol consumption and smoking; sexual activity and sexually transmitted diseases roles in PCa; and screening, diagnosis, and treatment methods. Despite agreeing that healthy lifestyles could promote better PCa outcomes and quality of life, participants did not specify any lifestyle factors that could promote or prevent this disease, posing challenges to lifestyle changes, particularly among older adults. Non-invasive screening methods, such as biomarkers and alternative treatments, are crucial for future research. This study underscores the need for further investigation into the correlation of lifestyle factors with PCa and highlights the necessity of health professionals in encouraging their patients to adopt healthier lifestyles, while offering important insights into awareness, prevention, and alternative screening, diagnosis, and treatment methods, which could help reduce false positives and treatment side effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Following its introduction, the innovative purpose-built Single Port (SP) robotic platform has been utilized for various urological surgical procedures, including for the management of clinically significant prostate cancer. This study sought to compare the different cancer-related and postoperative functional outcomes between the novel SP Extraperitoneal robotic radical prostatectomy (RARP) and the gold-standard Transperitoneal multi-port RARP approaches. The findings from this study can be beneficial to assist clinicians to determine best surgical approach based on the individual patient's characteristics to ensure the favorable outcomes following RARP. (1) Background: Since the introduction of the purpose-built Single Port (SP) robotic platform, there has been an ongoing debate regarding its advantages compared to the established multi-port (MP) system. The goal of this present study is to compare the perioperative, oncological, and functional outcomes of SP Extraperitoneal robotic radical prostatectomy (RARP) versus that of MP Transperitoneal RARP approach at a high-volume tertiary center. (2) Methods: Based on a retrospective review of the prospectively maintained IRB-approved database, 925 patients successfully underwent RARP by a single experienced robotic surgeon. A 4:1 propensity-matched analysis based on the baseline prostate cancer International Society of Urological Pathology (ISUP) Grade Group, clinical stage, and preoperative Prostate Specific Antigen (PSA) was performed, which yielded a cohort of 606 patients—485 in the SP EP and 121 in the MP TP approaches. Of note, the SP EP approach also included the traditional Extraperitoneal (n = 259, 53.4%) and the novel Transvesical (TV) approaches (n = 226, 46.6%). (3) Results: The overall operative time was slightly longer in the SP cohort, with a mean of 198.9 min compared to 181.5 min for the MP group (p < 0.001). There were no intraoperative complications with the MP approach and only one during the SP approach. The SP EP technique demonstrated significant benefits, encompassing reduced intraoperative blood loss (SP 125.1 vs. MP 215.9 mL), shorter length of hospital stay (SP 12.6 vs. MP 31.9 h), reduced opioid use at the time of discharge (SP 14.4% vs. MP 85.1%), and an earlier Foley catheter removal (SP 6 vs. MP 8 days). From an oncological perspective, the rate of positive surgical margins remained comparable across both groups (p = 0.84). Regarding functional outcomes, the mean continence rates and Sexual Health Inventory for Men (SHIM) scores were identical between the two groups at 6 weeks, 3 months, and 6 months respectively. (4) Conclusion: SP EP RARP demonstrates similar performance to MP TP RARP in terms of oncologic and functional outcomes. However, SP EP RARP offers several advantages in reducing the overall hospital stay, decreasing postoperative pain and hence the overall opioid use, as well as shortening the time to catheter removal, all of which translates to reduced morbidity and facilitates the transition to outpatient surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Nonlinear curve fitting of the pharmacokinetic model to DCE-MRI concentration curves is highly time-consuming. The estimation of highly non-linear dispersion-related parameter in MR dispersion imaging (MRDI) makes the process even more tedious. The fast MRDI (fMRDI) model is proposed to simplify and accelerate the MRDI model by representing the dispersion-applied arterial input function (AIF) as the weighted-sum of a fast and a slow population-based AIFs. A deep learning-based two-stage inference method is proposed to accelerate quantitative MRDI. The deep learning model makes a initial estimation of the parameters directly from the concentration curves and the parameters is then refined by a number of iterative optimization. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measures microvascular perfusion by capturing the temporal changes of an MRI contrast agent in a target tissue, and it provides valuable information for the diagnosis and prognosis of a wide range of tumors. Quantitative DCE-MRI analysis commonly relies on the nonlinear least square (NLLS) fitting of a pharmacokinetic (PK) model to concentration curves. However, the voxel-wise application of such nonlinear curve fitting is highly time-consuming. The arterial input function (AIF) needs to be utilized in quantitative DCE-MRI analysis. and in practice, a population-based arterial AIF is often used in PK modeling. The contribution of intravascular dispersion to the measured signal enhancement is assumed to be negligible. The MR dispersion imaging (MRDI) model was recently proposed to account for intravascular dispersion, enabling more accurate PK modeling. However, the complexity of the MRDI hinders its practical usability and makes quantitative PK modeling even more time-consuming. In this paper, we propose fast MR dispersion imaging (fMRDI) to effectively represent the intravascular dispersion and highly accelerated PK parameter estimation. We also propose a deep learning-based, two-stage framework to accelerate PK parameter estimation. We used a deep neural network (NN) to estimate PK parameters directly from enhancement curves. The estimation from NN was further refined using several steps of NLLS, which is significantly faster than performing NLLS from random initializations. A data synthesis module is proposed to generate synthetic training data for the NN. Two data-processing modules were introduced to improve the model's stability against noise and variations. Experiments on our in-house clinical prostate MRI dataset demonstrated that our method significantly reduces the processing time, produces a better distinction between normal and clinically significant prostate cancer (csPCa) lesions, and is more robust against noise than conventional DCE-MRI analysis methods. [ABSTRACT FROM AUTHOR]

Simple Summary: Placental allograft tissue has been extensively used in wound healing. It can also be placed along the neurovascular bundles during radical prostatectomy to improve post-operative continence and erectile function recovery. The existing literature shows how placental allografts lead to improved functional recovery after radical prostatectomy. It is unknown whether these allografts have an impact on biochemical recurrence (BCR). Our study was a single surgeon retrospective review of 362 radical prostatectomy cases. The subgroups were the negative control group and two brands of cryopreserved amniotic membrane (CAM). Our data show improved continence recovery using CAM allografts. At a median follow-up of 41 months, there was no observed impact of BCR. Interestingly, in vitro analysis also revealed decreased cell viability of prostate cancer cell lines when incubated with the CAM allograft. Although further investigation is required, our data do not support a need for oncologic concern while using CAM allografts during radical prostatectomy. Background: Human placental allografts are widely used to promote wound healing. Placental (or amniotic membrane/umbilical cord) allografts are placed along the neurovascular bundles during radical prostatectomy to improve continence and erectile function recovery. It is unknown whether placental allografts impact biochemical recurrence (BCR). Methods: This was a single-surgeon retrospective study of 566 robotic radical prostatectomies performed from April 2015 to March 2021. The patients were divided into three groups: the negative control, Brand A, and Brand B. Brand A and Brand B were both cryopreserved amniotic membrane (CAM) allografts. A total of 324 cases were included for BCR Kaplan–Meier and risk-adjusted multivariate analyses (362 for continence analysis). In vitro analyses were performed to determine the effect of CAM allografts on prostate cancer (PCa) cell line growth. Results: For propensity score-matched analysis (adjusting for pre-operative PSA, tumor stage, Gleason Grade, and margin status), (1) the allograft groups did not show differences in time to BCR vs. the negative control group (p = 0.7), and (2) combined allograft treatment groups showed better continence recovery vs. the negative controls (p = 0.01). In vitro, placental allografts reduced PCa cell line growth in co-culture assays. Conclusions: cryopreserved AM allografts (combined or individual brands) did not show a significant effect on BCR but improved continence recovery for PCa patients. [ABSTRACT FROM AUTHOR]