Prostate Cancer Patients Research Articles

Cellular and Molecular Evidence of the Synergistic Antitumour Effects of Hydroxytyrosol and Metformin in Prostate Cancer

Prostate cancer (PCa) is the tumour pathology with the second highest incidence among men worldwide. PCa is strongly influenced by obesity (OB), which increases its aggressiveness. Hence, some metabolic drugs like metformin have emerged as potential anti-tumour agents against several endocrine-related cancers. Likewise, a high adherence to the Mediterranean diet has been associated with lower rates of OB and a reduction in PCa aggressiveness since this diet contains phenolic bioactive compounds such as hydroxytyrosol (HT) that is mainly present in extra virgin olive oil. Thus, we decided to analyse the therapeutic potential of the combination of HT + metformin in different PCa cell models. Specifically, combinations of different doses of HT and metformin were evaluated by analysing the proliferation rate of LNCaP, 22Rv1, DU-145, and PC−3 cells using the SynergicFinder method. The results revealed a synergistic effect of HT + metformin in significantly reducing proliferation, especially in LNCaP cells. This anti-tumour effect of HT + metformin was also confirmed in migration and tumoursphere formation assays in LNCaP. The effects on the cell cycle and apoptosis were also assessed by flow-cytometry, and a cycle arrest in the G1 phase and an increase in late apoptosis were observed with the combination of HT + metformin. The phosphorylation levels of critical components of different oncogenic pathways were measured which revealed that the combination of HT + metformin significantly reduced the activity of multiple components of the MAPK, AKT, and TGF-β pathways. Overall, the combination of HT + metformin might represent a new therapeutic avenue for the management of PCa patients, an observation that certainly warrants further investigation through a well-designed clinical trial.

The correlation between the expression of androgen receptor splice variant-7 (AR-V7) protein with the time of occurrence of castration-resistant prostate cancer and overall survival in prostate cancer in Indonesian population

IntroductionProstate cancer follows a natural trajectory characterized by genetic alterations that transform initially hormone-sensitive cancer cells into castration-resistant prostate cancer (CRPC), which is associated with high mortality. This study endeavours to elucidate the predictive role of androgen receptor splice variant 7 (AR-V7) protein expression in determining the time to CRPC onset and overall survival in prostate cancer patients.MethodsThis retrospective cohort study utilized paraffin-embedded tissue block samples collected from prostate cancer patients undergoing Androgen Deprivation Therapy at Dr. Sardjito General Hospital between 2016 and 2022 (n = 47). AR-V7 protein expression was assessed via immunohistochemistry. Time to CRPC and overall survival were subjected to Log- Rank analysis and Cox regression.ResultsPatients exhibiting AR-V7 + protein expression experienced a considerably shorter time to CRPC onset compared to those with AR-V7-expression (21.13 vs. 40.05 months; p-value = 0.020). In the assessment of overall survival, patients with AR-V7 + protein expression demonstrated significantly poorer overall survival rates in contrast to those with AR-V7-expression (17.00 vs. 22.00 months; p = 0.00).ConclusionsDiminished AR-V7 + protein expression emerges as a predictive indicator for a shortened time to CRPC onset. Moreover, AR-V7 protein expression holds prognostic value in predicting overall survival among prostate cancer patients.

Identification of selective SWI/SNF dependencies in enzalutamide-resistant prostate cancer

Enzalutamide is a potent second-generation antiandrogen commonly used to treat hormone-sensitive and castration-resistant prostate cancer (CRPC) patients. While initially effective, the disease almost always develops resistance. Given that many enzalutamide-resistant tumors lack specific somatic mutations, there is strong evidence that epigenetic factors can cause enzalutamide resistance. To explore how resistance arises, we systematically test all epigenetic modifiers in several models of castration-resistant and enzalutamide-resistant prostate cancer with a custom epigenetic CRISPR library. From this, we identify and validate SMARCC2, a core component of the SWI/SNF complex, that is selectivity essential in enzalutamide-resistant models. We show that the chromatin occupancy of SMARCC2 and BRG1 is expanded in enzalutamide resistance at regions that overlap with CRPC-associated transcription factors that are accessible in CRPC clinical samples. Overall, our study reveals a regulatory role for SMARCC2 in enzalutamide-resistant prostate cancer and supports the feasibility of targeting the SWI/SNF complex in late-stage PCa.

Prognostic value of systemic immune-inflammation index for patients undergoing radical prostatectomy: a systematic review and meta-analysis

ObjectiveThe prognostic value of the systemic immune-inflammation index (SII) for prostate cancer (PCa) patients receiving different treatments remains unclear. This research examined the relevance of SII in individuals undergoing radical prostatectomy (RP).MethodsPubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI) dat3 abases were used to search literature up to May 2024. The quality was evaluated with Newcastle-Ottawa Scale. Outcomes examined were associations between SII and overall survival (OS), biochemical recurrence-free survival (BFS), and cancer-specific survival (CSS). Pooled analysis, Egger’s test, and sensitivity analysis were conducted using Review Manager 5.4.1 and Stata 15.1. The GRADE system was employed to evaluate and grade the evidence for each outcome. Subgroup analyses were performed for outcomes with significant heterogeneity to evaluate the possible confounders, if data were sufficient.ResultsOut of 101 identified studies, eight studies involving 8,267 individuals were included. Patients with higher SII had shorter overall survival (HR: 1.89; 95% CI: 1.31-2.71; P = 0.0006), biochemical recurrence-free survival (HR: 1.55; 95% CI: 1.08-2.22; P = 0.02), and cancer-specific survival (HR: 3.63; 95% CI: 1.66-7.94; P = 0.001). The evidence for OS and CSS was rated very low-quality due to serious heterogeneity and/or imprecision. The prognostic value of SII for BFS was rated as low-quality evidence, given no serious risk observed. Subgroup analysis showed that, except for the subgroup aged >65 years (HR: 3.70; 95%CI: 0.91, 15.06, P=0.07), the prognostic value of SII for OS was not significant, but the prognostic value of SII for OS in other subgroups was still significant.ConclusionsHigh SII was linked to shorter OS, BFS, and CSS in patients undergoing RP. However, the quality of the evidence provided by this study was low.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024558431.

Prevalence of Somatic BReast CAncer Gene (BRCA) 1 and 2 Pathogenic Variants in Portuguese Metastatic Prostate Cancer Patients

Prevalence of Somatic BReast CAncer Gene (BRCA) 1 and 2 Pathogenic Variants in Portuguese Metastatic Prostate Cancer Patients

The association between the interval from biopsy to radical prostatectomy and biochemical recurrence in patients with intermediate- and high-risk prostate cancer

ObjectiveTo investigate the association between the interval from biopsy to radical prostatectomy (RP) and biochemical recurrence (BCR) in prostate cancer patients.MethodsWithin a tertiary-care database (01/2014 to 06/2023), D’Amico intermediate- and high-risk prostate cancer patients were stratified according to interval from biopsy to RP (≤3 vs. >3-≤6 months). Kaplan-Meier survival analyses and Cox regression models addressed BCR.ResultsOf 680 patients, 328 vs. 153 exhibited intermediate-risk prostate cancer and had interval from biopsy to RP ≤3 vs. >3-≤6 months. Similarly, 158 vs. 41 exhibited high-risk prostate cancer and had interval from biopsy to RP ≤3 vs. >3-≤6 months. Median interval from biopsy to RP was 59 vs. 113 days in intermediate- and 55 vs. 117 days in high-risk patients, respectively. In both intermediate- and high-risk patients, rates of adverse histopathological outcomes, namely pT3/pT4, pN1, and R1 status, did not differ according to interval from biopsy to RP. In survival analyses, three-year BCR-free survival rates were 82 vs. 88% in intermediate-risk (p=0.5) and 76 vs. 75% in high-risk patients (p=1). In multivariable Cox regression models, BCR did not significantly differ according to interval from biopsy to RP in intermediate- (hazard ratio 0.85, 95% confidence interval 0.49-1.46; p=0.5) and high-risk patients (hazard ratio 1.05, 95% confidence interval 0.50-2.22; p=0.9).ConclusionsBoth intermediate- and high-risk prostate cancer patients with an interval from biopsy to RP >3-≤6 months did not differ from those treated with RP ≤3 months after biopsy, regarding adverse histopathological outcomes and BCR rates. Therefore, it might be safe to postpone RP up to six months.

JMJD6 Rewires ATF4-Dependent Glutathione Metabolism to Confer Ferroptosis Resistance in SPOP-Mutated Prostate Cancer.

Ferroptosis inducers have shown therapeutic potential in prostate cancer (PCa), but tumor heterogeneity poses a barrier to their efficacy. Distinguishing the regulators orchestrating metabolic crosstalk between cancer cells could shed light on therapeutic strategies to more robustly activate ferroptosis. Here, we found that aberrant accumulation of jumonji domain containing 6 (JMJD6) proteins correlated with poorer prognosis of PCa patients. Mechanistically, PCa-associated speckle type BTB/POZ protein (SPOP) mutants impaired the proteasomal degradation of JMJD6 proteins. Elevated JMJD6 and ATF4 coordinated enhancer-promoter loop interactions to stimulate the glutathione biosynthesis pathway. Independent of androgen receptor, JMJD6 recruited mediator subunits (Med1/14) to assemble de novo enhancers mapping to pivotal genes associated with glutathione metabolism, including SLC7A11, GCLM, ME1, and others. SPOP mutations thus induced intrinsic resistance to ferroptosis, dependent on enhanced JMJD6-ATF4 activity. Consequently, targeting JMJD6 rendered SPOP-mutated PCa selectively sensitive to ferroptosis. The JMJD6 antagonist SKLB325 synergized with erastin in multiple pre-clinical PCa models. Together, this study identifies JMJD6 as a druggable vulnerability in SPOP-mutated PCa to increase sensitivity to ferroptosis inducers.

The effectiveness of dyadic interventions for health outcomes of prostate cancer patients and informal caregivers: a systematic review and meta-analysis

BackgroundProstate cancer is a worldwide health issue, and current prostate cancer care extends to the patient‒caregiver dyadic setting, where individuals are interdependent and interact with each other as well as possible negative psychological and behavioural outcomes. However, the impact of dyadic care interventions on health outcome indicators for prostate cancer patients and their informal caregivers has yet to be examined.AimTo describe the characteristics of dyadic interventions involving patients with prostate cancer and their informal caregivers and investigate their effects on psychosocial health, sexual health, and dyadic relationships.MethodsTen electronic databases (Web of Science, Cochrane Library, PsycINFO, PubMed, Embase, CINAHL, CNKI, Wanfang, VIP, and SinoMed) were thoroughly searched for related publications published between the database’s founding and April 2024. The risk of bias for the included studies was evaluated using the Cochrane risk-of-bias tool, and a meta-analysis was performed using RevMan 5.4.ResultsThis study identified and evaluated 19 RCTs reporting 22 different interventions, as well as outcome indicators for the three aspects of psychosocial health, sexual health, and dyadic relationships in prostate cancer patients and informal caregivers. A meta-analysis of pooled data revealed that for prostate cancer patients, the intervention improved dyadic coping (SMD95% CI [95% CI] = 0.22 [0.01;0.42], p = 0.04), and for informal caregivers the dyadic care intervention reduced anxiety (SMD95% CI [95% CI] = -0.35 [-0.65;-0.06], p = 0.02), enhanced self-efficacy (SMD [95% CI] = 0.22 [0.01;0.43], p = 0.04), and improved sexual functioning (SMD [95% CI] = 0.29 [0.05;0.54], p = 0.02). No statistically significant overall effects were observed for the other outcome indicators.ConclusionThe results of this review indicate that dyadic care interventions benefit prostate cancer patients and informal caregivers. However, given features such as research quality and sample size, further randomized controlled trials with excellent study designs are needed in the future to evaluate and validate the efficacy of dyadic care treatments for patients with prostate cancer.Trial registrationThe protocol for this study is registered in PROSPERO with registration number (CRD42024567542).

Elevated serum levels of GPX4, NDUFS4, PRDX5, and TXNRD2 as predictive biomarkers for castration resistance in prostate cancer patients: an exploratory study.

Prostate cancer (PCa) is a heterogeneous disease affecting over 14% of the male population worldwide. Although patients often respond positively to initial treatments within the first 2-3 years, many eventually develop a more lethal form of the disease known as castration-resistant PCa (CRPC). At present, no biomarkers that predict the onset of CRPC are available. This study aims to provide insights into the diagnosis and prediction of CRPC emergence. Protein expression dynamics were analysed in drug (androgen receptor inhibitor)-tolerant persister (DTP) and drug withdrawal cells using proteomics to identify potential biomarkers. These biomarkers were subsequently validated using a mouse model, 180-paired carcinoma/benign tissues, and 482 serum samples. Five machine learning algorithms were employed to build clinical prediction models, wherein the SHapley Additive exPlanation (SHAP) framework was used to interpret the best-performing model. Moreover, three regression models were developed to determine the Time from initial PCa diagnosis to CRPC development (TPC) in patients. We identified that the protein expression levels of GPX4, NDUFS4, PRDX5, and TXNRD2 were significantly upregulated in PCa patients, particularly in those with CRPC. Among the tested machine learning models, the random forest and extreme gradient boosting models performed best on tissue and serum cohorts, achieving AUCs of 0.958 and 0.988, respectively. In addition, a significant inverse correlation was observed between TPC and serum levels of these four biomarkers. This correlation was formulated in three regression models, which achieved the smallest mean absolute error of 1.903 on independent datasets for predicting CRPC emergence. Our study provides new insights into the role of DTP cells in CRPC development. The quad protein panel identified in our study, along with the post hoc and intrinsically explainable prediction models, may serve as a convenient and real-time prognostic tool, addressing the current lack of clinical biomarkers for CRPC.

Personalized metronomic radiopharmaceutical therapy through injection profile optimization via physiologically based pharmacokinetic (PBPK) modeling

Each treatment cycle of radiopharmaceutical therapy (RPT) is administered as a single dose. We aimed to investigate a personalized metronomic RPT paradigm, employing multiple lower-dose administrations, to evaluate its effect on delivering radiopharmaceuticals to tumors. We developed a physiologically-based pharmacokinetic (PBPK) model applied to metastatic castration-resistant prostate cancer patients to analyze the impact of metronomic framework and various infusion durations (1–4 h) on absorbed doses (ADs) in tumors and organ-at-risk (OAR). We designed a treatment algorithm to select optimal regimens with high AD, while investigating what we term radiopharmaceutical delivery payload (RDP). This metric evaluates the efficiency of radiopharmaceutical delivery by quantifying the proportion of the administered dose that successfully reaches the target tissue. The goal is to optimize trade-offs between RDP and tumors-AD among injection profiles, amongst varying radioactivity (1-22GBq), total radiopharmaceutical mass (25-210nmol), number of injections (2–6), and time intervals (12–36 h) between injections. Our framework applied to five patients led to increased AD between 2 and 358 Gy (between 2 and 146%) higher than normally administered to patients, safeguarding OARs. Using single-dose scenarios to match ADs in metronomic approach, led to significant increase in injected activities, requiring injection of 0 to 9GBq additional activity (reducing RDP by 3–75%). Maintaining total administered radioactivity within clinically therapeutic levels, increasing frequency, time interval, and infusion duration increases tumors and OARs AD by 0.05-73%, while it decreased tumors-to-OARs AD ratios by 0.1–30%. Based on the PBPK modeling approach, metronomic RPT appears to improve efficacy (RDP) in delivered doses to tumors for a given total injected radioactivity.

Association Between the Aromatase rs2414096 Polymorphism and Prostate Cancer

Abstract Objectives The purpose of this study was to investigate association between the aromatase (CYP19A1) rs2414096 polymorphism and the risk of prostate cancer development, progression and aggressiveness in the Slovak population. Background Aromatase catalyses the final reaction of androgens aromatization to estrogens, irreversible conversion of androstenedione to estrone and testosterone to estradiol. Methods The study population consisted of 721 prostate cancer patients and 660 men in the control group. Genotyping was performed via restriction fragment length polymorphism analysis. The expression levels of CYP19A1 in prostate cancer tissues were compared with those in benign prostatic hyperplasia tissues. Results The CYP19A1 rs2414096 AA genotype and A allele were significantly associated with an increased risk of prostate cancer development. The significant association between this genotype and PSA level ≥ 10 ng/ml, Gleason score ≥ 7 and with the presence of metastases was observed. Significantly decreased relative expression of CYP19A1 was detected in prostate cancer tissues. Patients with the AA genotype presented higher relative CYP19A1 expression than did those with the GG genotype. Significantly lower circulating testosterone levels and higher serum PSA levels were detected in patients with the AA genotype. Conclusion The CYP19A1 rs2414096 polymorphism was significantly associated with prostate cancer development and aggressiveness in Slovak patients.

Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint report by SIPMO AND SIOMMMS

Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint report by SIPMO AND SIOMMMS

592 Weight gain with leuprolide therapy in prostate cancer patients: a retrospective study

592 Weight gain with leuprolide therapy in prostate cancer patients: a retrospective study

Impact of delayed pelvic imaging on the staging of biochemical recurrence in prostate cancer patients using [18F]DCFPYL PET/CT: a retrospective evaluation.

The aim of this study was to evaluate the added diagnostic value of additional second stage pelvic scanning as part of the [18F]DCFPYL PET/CT procedure in patients treated for prostate cancer (PCa) who have biochemical recurrence (BR). Consecutive patients with a diagnosis of PCa who underwent a dual-phase PSMA-PET scan between September 2022 and December 2023, were retrospectively included. We analyzed the number and maximum SUV (SUVmax) of lesions only in the pelvic region (prostate, locoregional lymph nodes and bone), based on PSMA-RADS version 2.0 and miTNM criteria. To assess the potential diagnostic benefit of additional delayed pelvic PET/CT imaging as part of the PSMA-PET procedure, the change in molecular TNM classification was evaluated after the procedure. Additional delayed pelvic PET/CT imaging as part of the PSMA-PET procedure resulted in a change in molecular TNM classification in 22 out of 136 patients (16.2%). The highest percentage change was obtained in the miN classification (14/22 patients), followed by the miT classification (7/22) and lastly miM (1/22). Moreover, we found that patients in whom delayed pelvic imaging resulted in a change in molecular TNM classification were significantly older and had a higher PSA level than those in whom delayed imaging did not provide additional information. Pelvic delayed imaging in patients with biochemical recurrence of prostate cancer undergoing PET/CT with [18F]DCFPYL shows a non-negligible influence on patient staging, modifying the miTNM classification in 16.2% of cases, with pelvic lymphatic involvement benefiting the most from the dual study.

Detection and Quantification of Polymorphic MICA and MICB Molecules in Immunoassays: Initial Insights.

The MICA and MICB molecules, expressed on the cell membrane in response to cellular stress or cancer transformation, pose significant challenges for immunoassays. They exhibit high sequence and structural similarity, alongside considerable allelic polymorphism, with 291 and 53 known protein sequences, respectively. Some researchers treat MICA and MICB as a unified target because of their structural and functional similarities, while others distinguish between them. However, which approach is superior and under what circumstances remains unknown. Moreover, information about assays' reactivity with MICA and MICB allelic variants is often missing. In this study, we developed 10 monoclonal antibodies (mAbs) and two sandwich ELISAs for the detection and quantification of these molecules. We assembled a panel of recombinant proteins representing the diversity of MICA and MICB in the European population and profiled the reactivities of the mAbs and ELISAs. The performance of these sandwich ELISAs was evaluated using samples from prostate cancer patients and pregnant women experiencing premature rupture of membranes. Our study assessed the impact of MICA and MICB polymorphism on their detection and quantification by immunological methods, providing evidence to support differential or non-differential approaches for their detection.

MiRNA Signatures as Predictors of Therapy Response in Castration-Resistant Prostate Cancer: Insights from Clinical Liquid Biopsies and 3D Culture Models

Background/Objectives: Prostate cancer (PCa) patients who do not respond to androgen deprivation therapy (ADT), referred to as castration-resistant prostate cancer (CRPC), remain a clinical challenge due to confirm the aggressive nature of CRPC and its resistance to conventional therapies. This study aims to investigate the potential of microRNAs (miRNAs) as biomarkers for predicting therapeutic response in CRPC patients. Methods: We performed miRNA and mRNA expression analyses using publicly available datasets and applied 3D cell culture models to replicate more physiologically relevant tumor conditions. Genetic analysis techniques were employed on publicly available data, and expression profiles from 3D cell culture models were examined. Results: Eighteen miRNAs with differential expression were identified between patients who responded favorably to abiraterone therapy (responders) and those with advanced CRPC (non-responders). Specifically, miRNAs such as hsa-miR-152-3p and hsa-miR-34a-3p were found to be associated with critical pathways, including TGF-β signaling and P53, which are linked to therapeutic resistance. Several miRNAs were identified as potential predictors of treatment efficacy, including therapies like abiraterone. Conclusions: These results indicate that miRNAs could serve as non-invasive biomarkers for predicting therapeutic outcomes, facilitating a more personalized approach to CRPC treatment. This study provides a novel perspective on treatment strategies for CRPC, emphasizing the role of miRNAs in improving therapeutic precision and efficacy in this complex disease.

Prognostic Stratification Using Early Prostate-specific Antigen Kinetics in Men With Metastatic Hormone-sensitive Prostate Cancer.

The prognostic significance of prostate-specific antigen (PSA) kinetics in metastatic castration-sensitive prostate cancer (mCSPC) patients treated with upfront therapy remains unclear. This study investigated the correlation between early PSA response and clinical outcomes in patients with mCSPC who received upfront therapy. We analyzed 106 patients with mCSPC who received upfront therapies [abiraterone acetate (ABI), enzalutamide (ENZ), apalutamide (APA), and docetaxel (DOC)] at Kurume University Hospital and its affiliated hospitals. Thirty-nine, 15, 38, and 14 patients were treated with ABI, DOC, ENZ, and APA, respectively. Among the total number of patients, 67 met the criteria for high-volume disease. Additionally, 83 patients were categorized as high risk. Patients with a PSA decline rate of ≥90% at 4 and 12 weeks post-upfront therapies had a significantly longer time to develop CRPC than those with a PSA decline of <90%. PSA cutoff values >26 ng/ml at 4 weeks post-upfront therapies and a PSA decline rate of ≥90% at 12 weeks post-upfront therapies were independent predictors of poor prognosis. Furthermore, patients were stratified into three groups based on PSA levels at 4 weeks and PSA decline rate at 12 weeks. A larger PSA decline within three months of initiating upfront therapy is significantly associated with a longer time to CRPC in patients with mCSPC treated with upfront therapy. A combination of early PSA kinetics can be used to stratify the risk of CRPC progression in patients with mCSPC treated with upfront therapies.

Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment.

Prostate cancer is prevalent among men aged 65 and older. Bone metastasis occurs in up to 90% of advanced prostate cancer patients, metastatic prostate cancer is generally considered a non-curative condition which can impact quality of life. The tumor microenvironment, comprising diverse cellular and non-cellular elements, interacts with prostate cancer cells to affect tumor growth and bone metastasis. Within the bone microenvironment, different cell types, including osteoblasts, osteoclasts, adipocytes, endothelial cells, hematopoietic stem cells, and immune cells, engage with tumor cells. Some cells alter tumor behavior, while others are impacted or overpowered by tumor cells, leading to different phases of tumor cell movement, dormancy, latency, resistance to treatment, and advancement to visible bone metastasis. This review summarizes recent research on the tumor microenvironment and bone microenvironment in prostate cancer bone metastasis, exploring underlying mechanisms and the potential value of targeting these environments for treatment.

Clinical, Diagnostic and Therapeutic Framework of mHSPC and nmCRPC: A Multidisciplinary Consensus Project of the Italian Society for Uro-Oncology (SIUrO).

The recent evidences provided in metastatic hormone sensitive prostate cancer (nmHSPC) and in nonmetastatic castration resistant (nmCRPC) introduced the possibility to adopt Androgen Receptor Signaling inhibitor (ARSi) alone (both settings) or with chemotherapy (in mHSPC). In daily clinical practice there are some opening questions regarding the inclusion of next generation imaging, mainly PSMA-PET, how integrate local treatment as radiotherapy, how to select patients or drugs in a multiple-choice scenario, and how to manage patients with comorbidities and polypharmacy. These issues led the Italian Society for Uro-Oncology (SIUrO) to develop a consensus project involving all of the most important Italian scientific societies engaged in the multidisciplinary and multiprofessional management of the disease. This paper describes the items and statements approved, with the aim to support clinicians in managing metastatic hormone sensitive and nonmetastatic castration resistant prostate cancer patients.

Implementing and Optimizing Universal Germline Genetic Testing for Patients with Prostate Cancer in Clinical Practice Consider.

To advocate for universal germline genetic testing (UGGT) in prostate cancer and provide practical recommendations for its implementation. Although guidelines for germline genetic testing (GGT) in prostate cancer have progressed, usage remains limited and inconsistent due to barriers including access, cost, and variable guideline adherence. These issues prevent some patients with germline pathogenic/likely pathogenic variants from benefiting from risk assessment, precision therapies (e.g., PARP inhibitors, PD-1 inhibitors) and potential clinical trials. Despite these benefits, studies indicate that GGT use remains low, especially in prostate cancer care. The PROCLAIM trial (Shore et al., 2023) highlighted that nearly half of patients with pathogenic variants are missed under NCCN guidelines, particularly impacting non-white patients and those with incomplete family history data. Additional racial and socioeconomic disparities further hinder access and variant interpretation accuracy. Given these challenges, UGGT for all prostate cancer patients has been proposed to improve care equity and decision-making. In March 2024, prostate cancer experts convened to discuss strategies for UGGT implementation. The outcome of that meeting includes recommendations for integrating UGGT into oncology and urology practices and have been outlined in this paper. To maximize the benefits while mitigating the potential risks of UGGT, it is essential to address implementation details, including careful gene panel selection, VUS reporting and management, appropriate genetics follow-up, and seamless integration of test reports into EMRs for accessibility by patients and providers.