Characteristics Of Prostate Cancer Patients Research Articles

Mainstream Model of Genetic Testing for Prostate Cancer at a Large Tertiary Cancer Centre

BackgroundAn estimated 20% to 30% of men with advanced prostate cancer carry a mutation in DNA damage repair genes, of which half are estimated to be germline. Eligibility criteria for germline genetic testing expanded significantly for Ontario patients in May 2021 and many centers adopted a “mainstream” model, defined as oncologist-initiated genetic testing. MethodsWe conducted a retrospective chart review to report on the first-year mainstream experience of a large tertiary oncologic center, the Sunnybrook Odette Cancer Centre. All patients who underwent mainstream at the discretion of their treating physician were included. A subset underwent somatic profiling as part of clinical trial screening. Descriptive statistics were used to report baseline clinicopathologic characteristics and treatments received. ResultsBetween May 1, 2021, and May 30, 2022, 174 patients with prostate cancer underwent mainstream germline genetic testing with a 19-gene panel. Median age was 75 (IQR 68-80), and 82% of patients were diagnosed with either de novo metastatic or high-risk localized prostate adenocarcinoma. Fourteen patients (8%; 95% CI 4%-12%) were found to have a deleterious germline mutation, including pathogenic or likely pathogenic variants in BRCA1/2, ATM, CHEK2, PMS2, RAD51C, HOXB13, and BRIP1. Forty-nine patients (28%; 95% CI 21%-35%) were found to have a variant of uncertain significance. Thirty-four patients also had next-generation sequencing (NGS) of their somatic tissue. Among this subset, 8 of 34 (23%) had an alteration in homologous recombination repair (HRR) genes. Of the 14 patients with a germline mutation, none had a prior personal history of malignancy and 6 (43%) did not have any first- or second-degree relatives with history of prostate, pancreatic, breast, or ovarian cancer. ConclusionWe report on the real-world characteristics of prostate cancer patients who underwent mainstream germline genetic testing. Personal history and family history of cancer cannot reliably stratify patients for the presence of pathogenic germline variants.

UP48 - The correlation of microRNA-21 and microRNA-221 expression levels in prostate tumor tissue with the clinicopathological characteristics of prostate cancer patients

UP48 - The correlation of microRNA-21 and microRNA-221 expression levels in prostate tumor tissue with the clinicopathological characteristics of prostate cancer patients

Characteristics of prostate cancer patients captured by facility-based versus geography-based cancer registries.

We determined differences in demographics, tumor factors, and treatment patterns of prostate cancer patients in a geographic-based cancer registry based on eligibility for a facility-based cancer registry system. We identified prostate cancer patients captured by the Surveillance, Epidemiology, and End Results (SEER) database from 2018 to 2019. Our exposure was receipt of cancer care at a facility accredited by the American College of Surgeons' Commission on Cancer (CoC) providing eligibility for inclusion in the National Cancer Database (NCDB). Outcomes included patient demographics, tumor factors (e.g., biopsy grade), and treatment with radical prostatectomy. We identified 113,733 prostate cancer patients of whom 65,708 (57%) were NCDB-eligible with an analytic abstract, and 11,010 (10%) were NCDB-eligible without an analytic abstract. NCDB-eligible men were younger (67.0 vs. 68.1 years, P < 0.001), less likely to be Hispanic/Latino (8.7% vs. 13.2%, P < 0.001), and more likely in a county with median income over $75,000 (40.9% vs. 30.0%, P < 0.001). NCDB eligibility varied widely by registry, from 95.9% in Connecticut to 42.6% in Utah. NCDB-ineligible patients were more likely to have unknown stage (17.2% vs. 2.9% NCDB-eligible) and missing PSA (22.9% vs 9.3% NCDB-eligible). NCDB-eligible men were less likely to have Grade Group 1 cancer on biopsy (28.2% vs. 39.2%, P < 0.001). Treatment with prostatectomy was more common among NCDB-eligible patients for low-risk (19.6% vs. 8.8%, adjusted OR 2.30, 95% CI 1.72-6.66) and high-risk tumors (43.5% vs. 26.0%, adjusted OR 1.95, 95% CI 1.33-2.86). Compared NCDB-ineligible patients, those eligible for inclusion in the NCDB have important differences in demographics, eligibility for active surveillance, and treatment patterns. Generalizations related to epidemiologic trends, practice patterns, and outcomes for this select population should be interpreted with caution.

Sexual characteristics of patients with prostate cancer seen for radiation treatment.

Prostate cancer was estimated to be the second most diagnosed cancer and the fifth leading cause of cancer mortality among men, with an estimated 1.4 million new cases and 375,000 deaths globally in 2020. There are significant changes in sexual activities and subsequent changes in quality of life associated with the diagnosis and treatment of prostate cancer. Sexual problems experienced by prostate cancer patients include erectile dysfunction, reduced sexual desire, reduced sexual function, problems with ejaculation, as well as problems with orgasm, and these could occur before and/or after treatment. This study aims to highlight the sexual characteristics of prostate cancer patients, which would help identify altered sexuality that might require intervention by healthcare providers. All patients who presented with pathologically diagnosed, organ-confined prostate cancer referred for high-dose-rate brachytherapy were approached for participation in the study. An interviewer-administered questionnaire was administered to the consenting patients. A total of 56 patients gave consent for the study out of 60. All the patients were married, with 5 (8.9%) having multiple wives. Only ten respondents (17.9%) reported having other sexual partners besides their wives. More than half of the patients (34) (60.7%) started having sexual intercourse between the ages of 18 and 20. Many patients claimed that the diagnosis of prostate cancer had affected their sexual lives. About half of the respondents (44.6%) believed that their partners were less satisfied with their sexual performance, as evidenced by the loss of partners (5.4%), partners refusing sexual advances (14.3%), partners complaints (10.7%), and partners' reduced inclination to ask for sex (33.9%). One patient expressed fears of passing the disease to their partners. The management of prostate cancer should include sex therapy and rehabilitation in couples from the point of diagnosis to maintain sexual function as close as possible to that in the general population in order to maintain an improved quality of life.

Longitudinal Changes and Predictive Value of Multiparametric MRI Features for Prostate Cancer Patients Treated with MRI-Guided Lattice Extreme Ablative Dose (LEAD) Boost Radiotherapy.

Simple SummaryIn this study, we investigated the longitudinal changes and predictive value of multiparametric MRI (mpMRI) features of prostate cancer patients receiving Lattice Extreme Ablative Dose (LEAD) boost radiotherapy (RT). Ninety-five mpMRI from 25 patients, acquired pre-RT and at 3 time points following RT were analyzed. Five regions of interest were analyzed, related to tumor, peritumoral, and normally-appearing tissues. We identified significant changes in the imaging parameters following RT in all regions. By using selected features at the four scan points and their differences (Δ radiomics), we were able to build viable predictive models for endpoint biopsy positivity. Our study demonstrates that RT causes significant changes to quantitative imaging features in both tumorous and normally-appearing tissues. Because of the noninvasive nature of the mpMRI, acquiring multiple exams post-RT is feasible to monitor treatment response. Several quantitative imaging features are promising predictors of treatment failure based on post-treatment positive biopsy, a strong marker for clinically relevant endpoints.We investigated the longitudinal changes in multiparametric MRI (mpMRI) (T2-weighted, Apparent Diffusion Coefficient (ADC), and Dynamic Contrast Enhanced (DCE-)MRI) of prostate cancer patients receiving Lattice Extreme Ablative Dose (LEAD) radiotherapy (RT) and the capability of their imaging features to predict RT outcome based on endpoint biopsies. Ninety-five mpMRI exams from 25 patients, acquired pre-RT and at 3-, 9-, and 24-months post-RT were analyzed. MRI/Ultrasound-fused biopsies were acquired pre- and at two-years post-RT (endpoint). Five regions of interest (ROIs) were analyzed: Gross tumor volume (GTV), normally-appearing tissue (NAT) and peritumoral volume in both peripheral (PZ) and transition (TZ) zones. Diffusion and perfusion radiomics features were extracted from mpMRI and compared before and after RT using two-tailed Student t-tests. Selected features at the four scan points and their differences (Δ radiomics) were used in multivariate logistic regression models to predict the endpoint biopsy positivity. Baseline ADC values were significantly different between GTV, NAT-PZ, and NAT-TZ (p-values < 0.005). Pharmaco-kinetic features changed significantly in the GTV at 3-month post-RT compared to baseline. Several radiomics features at baseline and three-months post-RT were significantly associated with endpoint biopsy positivity and were used to build models with high predictive power of this endpoint (AUC = 0.98 and 0.89, respectively). Our study characterized the RT-induced changes in perfusion and diffusion. Quantitative imaging features from mpMRI show promise as being predictive of endpoint biopsy positivity.

CORRELATION OF TMPRSS2-ERG GENE FUSION STATUS WITH CLINICOPATHOLOGICAL CHARACTERISTICS IN PROSTATE CANCER OF IRAQI PATIENTS

The aim of this study was to establish the existence and interaction of TMPRSS2 – ERG gene fusion status with clinicopathological features of prostate cancer patients. This research consisted of 123 embedded formalin-fixed tissues obtained from the prostate tumor patients. The above gene fusion is detected through the technique of fluorescent in situ hybridization (FISH) by means of a triple color probe. Seven samples have not been scored due to technical difficulties and 46 patients have fusion (39.6%), while the remaining (70) have not been seen with fusion. Of the 46 fusion-positive, 17 (36%) were caused by ERG-translocation, of the other 29 (63%) were caused by the interstitial segment deletion between the two genes due to their sequential position. In order to find a substantial correlation between 116 patients (fusion took place in 46 and non-fusion in 70) with clinicopathological features, the following findings were calculated: Our findings recorded non-significant correlation at age, BMI and tumor size at which (P-value &gt;0.05).While results showed significant association with: pathological T stage (P value = 0.011), Gleason score (P value = 0.002), perineural invasion (P value = 0.047) and PSA (P value = 0.033). The clinicopathological features which had a considerable correlation with fusion status are very important as they aid the doctors in prognosis and treatment of such tumor.

Competing endogenous RNA network features and prostate tumor cell sensitivity to radiotherapy.

e17008 Background: Radiotherapy (RT) is one of the main treatments for prostate cancer (PC). The effectiveness of RT depends on the initial radioresistance of tumor cells provided by their certain molecular features - the transcriptional activity of genes, miRNAs and long non-coding RNAs (lncRNAs). Together, these indicators form a competing endogenous RNAs network (ceRNAs). The aim of this work was to study the ceRNA features in PC patients with different responses to RT. Methods: The study included 400 patients with PC, 90 of them developed biochemical recurrence after RT (Novalis TX, TFD = 75 Gy). Tumor tissue samples were obtained by biopsy. The RNA fraction was isolated and purified using the RNeasy Plus Universal Kits. Bioinformatic search for miRNAs was performed using a modified TarPmiR algorithm. The miRNA-lncRNA interactions were assessed by bioinformatics. Expression of AKT, ATM, BRIP, BRCA1/2, CDK1, CDKN1B, CCND1/3, EXO1, H2AX, KU70, PTEN, RAD50, RAP80, RIF1, RNF168, TOPB1, TP53, XRCC4, BAX, CASP-8, -3, -9, MDM2, BCL2, RBBP8, EP300 genes, miRNA and lncRNA were determined by RT-qPCR. Differences were assessed using the Mann-Whitney test (Bonferroni correction was used). Results: The expression of CDK1, CDKN1B, RBBP8, XRCC4, BRCA2, RAD50 genes in tumor tissues of patients with biochemical recurrence (group 1) was higher (p &lt; 0.005) and the expression of TP53 and BCL2 was lower than the values in tumor tissues in patients without recurrence (group 2). Bioinformatic search for miRNAs targeting the CDK1, CDKN1B, RBBP8, XRCC4, BRCA2, RAD50, TP53 and BCL2 revealed 1725 miRNAs, 78 of which were validated (miRDB) and had a minimum free energy of miRNA-mRNA interaction. Patients in group 1 showed differential expression of miRNAs targeting genes BCL2 (increased miR-139-5p, miR-4446-5p, miR-211-5p); CDK1 (decreased miR-330-3p, miR-5580-3p, miR-429), CDKN1B (decreased miR-6841-3p); RAD50 (decreased miR-433-3p, miR-3691-5p); RBBP8 (decreased miR-130b-3p); TP53 (increased miR-6884-5p, miR-149-3p, miR-6860, miR-4728-5p, let-7b-5p); XRCC4 (decreased miR-4489) and BRCA2 (decreased miR-7151-3p). The interaction of these miRNAs with 160 lncRNAs was mathematically predicted. Patients in group 1 demonstrated increased expression of lncRNAs LINC00641, SCAMP1, MALAT1, MATN1-AS1 (miR-429) , LINC00657 and GAS5 (miR-433-3p), CCAT1 (miR-130b-3p) and reduced expression of S NHG3, DHRS4-AS1 (miR-139-5p) and MAL2 (let-7b-5p). Conclusions: Our study of the ceRNA network features and RT effectiveness for PC established the mechanisms of radioresistance development and its predictors.

Copy number variation of urine exfoliated cells by low-coverage whole genome sequencing for diagnosis of prostate adenocarcinoma: a prospective cohort study.

BackgroundNon-invasive, especially the urine-based diagnosis of prostate cancer (PCa) remains challenging. Although prostate cancer antigen (PSA) is widely used in prostate cancer screening, the false positives may result in unnecessary invasive procedures. PSA elevated patients are triaged to further evaluation of free/total PSA ratio (f/t PSA), to find out potential clinically significant PCa before undergoing invasive procedures. Genomic instability, especially chromosomal copy number variations (CNVs) were proved much more tumor specific. Here we performed a prospective study to evaluate the diagnostic value of CNV via urine-exfoliated cell DNA analysis in PCa.MethodsWe enrolled 28 PSA elevated patients (≥ 4 ng/ml), including 16 PCa, 9 benign prostate hypertrophy (BPH) and 3 prostatic intraepithelial neoplasia (PIN). Fresh initial portion urine was collected after hospital admission. Urine exfoliated cell DNA was analyzed by low coverage Whole Genome Sequencing, followed by CNV genotyping by the prostate cancer chromosomal aneuploidy detector (ProCAD). CNVs were quantified in absolute z-score (|Z|). Serum free/total PSA ratio (f/t PSA) was reported altogether.ResultsIn patients with PCa, the most frequent CNV events were chr3q gain (n = 2), chr8q gain (n = 2), chr2q loss (n = 4), and chr18q loss (n = 3). CNVs were found in 81.2% (95% Confidence Interval (CI) 53.7–95.0%) PCa. No CNV was identified in BPH patients. A diagnosis model was established by incorporating all CNVs. At the optimal cutoff of |Z|≥ 2.50, the model reached an AUC of 0.91 (95% CI 0.83–0.99), a sensitivity of 81.2% and a specificity of 100%. The CNV approach significantly outperformed f/t PSA (AUC = 0.62, P = 0.012). Further analyses showed that the CNV positive rate was significantly correlated with tumor grade. CNVs were found in 90.9% (95% CI 57.1–99.5%) high grade tumors and 60.0% (95% CI 17.0–92.7%) low grade tumors. No statistical significance was found for patient age, BMI, disease history and family history.ConclusionsUrine exfoliated cells harbor enriched CNV features in PCa patients. Urine detection of CNV might be a biomarker for PCa diagnosis, especially in terms of the clinically significant high-grade tumors.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-022-01253-5.

Characteristics of prostate cancer patients captured by facility-based versus geography-based cancer registries.

237 Background: Cancer registries provide valuable information related to cancer epidemiology, treatment, and outcomes. However, the sampling for inclusion can impact generalizability of findings to other settings. We use a population-based cancer registry to evaluate demographics, cancer factors, and treatment patterns based on eligibility for a facility-based cancer registry. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify men diagnosed with prostate cancer (site = C61.9) in 2018. Exposure was whether data were reported from a facility accredited by American College of Surgeons’ Commission on Cancer (CoC), providing eligibility for the National Cancer Database (NCDB) (i.e., NCDB-eligible). Outcomes of interest included demographics, tumor factors (e.g., biopsy grade), and treatment. Bivariate testing and multivariable regression analyses tested for significant associations between exposure and outcomes of interest. Results: We identified 57,713 men diagnosed with prostate cancer in 2018, of which 32,384 (61.9%) were eligible for inclusion in NCDB. NCDB-eligible men were younger (66.6 vs 67.8 years, p &lt; 0.001), less likely to be Hispanic/Latino (8.0% vs 14.4%, p &lt; 0.001), and more likely to reside in a county with median income over $75,000 (39.7% vs 33.3%, p &lt; 0.001). NCDB eligibility varied widely by registry, from 96.1% in Connecticut to 44.7% in Utah. The proportion of localized cancer patients with Grade Group 1 cancer on biopsy was higher among men ineligible for NCDB (41.4% vs 26.9%, p &lt; 0.001). The proportion of patients with more advanced disease at presentation was higher among NCDB-eligible patients (metastatic: 9.4% vs 6.8%; regional: 18.7% vs 8.7%; p &lt; 0.001). For patients with localized or regional cancer, treatment was identified more frequently among NCDB-eligible patients for both low-risk (38.5% vs 22.7%, p &lt; 0.001) and high-risk tumors (84.9% vs 64.2%). Among treated patients, use of radical prostatectomy was more common among NCDB-eligible patients (low risk: 58.9% vs 43.1%; high risk: 53.7% vs 43.4%, p &lt; 0.001). Conclusions: Prostate cancer patients eligible for inclusion in the facility based NCDB have important differences in demographics, severity of cancer risk, and treatment patterns compared to those who are not eligible. Generalizations related to epidemiologic trends, practice patterns, and outcomes for prostate cancer patients in the NCDB should be interpreted with caution.

Prevalence and Demographic Characteristics of Prostate Cancer Patients in Colombia: data from the National Health Registry from 2015 to 2019

Abstract Background and Objective Prostate cancer is a multifactorial disease and is among the top five causes of death in men worldwide. The Colombian Ministry of Health has adopted the Integrated Information System on Social Protection (Sistema Integrado de Información de la Protección Social, SISPRO, by its Spanish acronym) registry to collect comprehensive information from the Colombian health system. The system provides close to universal coverage (around 95%). We aimed to establish the prevalence of prostate cancer in Colombia and to describe its demographics, based on data provided by SISPRO, openly available for scientific analysis. Methods Using the SISPRO data from 2015 through 2019, we analyzed the prevalence and demographic characteristics of patients diagnosed with prostate cancer. Results We identified a total of 43,862 patients with prostate cancer in the 5-year period and estimated a prevalence of 4.54 cases per 1,000 habitants, using as denominator males over 35 years old. We calculated a prevalence of early-onset prostate cancer (i.e., 35–54 years) of 0.14 per 1,000 habitants (791 cases in 5 years). The highest prevalence was observed in patients &gt; 80 years (33.45 per 1,000 habitants). The departments with the highest prevalence were Bogotá, Valle del Cauca, Risaralda, and Boyacá, and the region with the lowest prevalence was Amazonas. Conclusion We describe the prevalence and demographics of prostate cancer in Colombia using the national healthcare system database. We observed that the prevalence has been increasing over time, and the distribution is variable according to regions, which may be related to racial or environmental causes, or access to the urologist. These factors should be addressed in further studies.

ANOVA-Based Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer with Bone Metastasis and Rehabilitation Treatment

This study was to analyze the magnetic resonance imaging (MRI) characteristics of prostate cancer patients with bone metastasis and the difference in the rehabilitation effect of patients with different bone metastases. The MRI, diffusion weighted imaging (DWI), magnetic resonance elastic imaging (MRE), and MRI + DWI + MRE imaging were performed on 200 prostate cancer patients in the First Affiliated Hospital of Kunming Medical University hospital. The prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate volume in patients with bone metastases were analyzed. The sensitivity, specificity, and accuracy of the four detection methods of bone metastases in prostate cancer were detected. In addition, the changes of the bone metabolism index β-special collagen sequence (β-CTX), type I procollagen amino terminal propeptide (PINP), and osteocalcin (BGP) of the patients were analyzed and compared before and after the treatment. The results showed that the levels of PSMA4 (17.35 ± 51.64 ng/mL) and PSA (15.86 ± 6.33 ng/mL) in nonbone metastatic prostate cancer patients were much lower than those of osteogenic bone metastases (668.95 ± 47.13 ng/mL and 202.15 ± 31.53 ng/mL), mixed bone metastases (637.63 ± 41.35 ng/mL and 186.45 ± 24.86 ng/mL) prostate patients. The sensitivity (96.25%), specificity (89.85%), and accuracy (98.53%) of MRI + DWI + MRE in the prostate cancer bone metastasis were obviously higher than those of MRI (86.46%, 78.31%, and 90.31%), DWI (88.11%, 82.53%, and 91.43%), and MRE (83.36%, 76.94%, and 89.76%). The levels of β-CTX (0.41 ± 0.07 ng/mL), PINP (39.04 ± 6.38 ng/mL), and BGP (17.56 ± 4.22 ng/mL) after treatment in patients with nonbone metastasis prostate cancer were greatly lower than those of osteogenic bone metastases (0.66 ± 0.08 ng/mL, 51.45 ± 7.45 ng/mL, and 33.65 ± 6.14 ng/mL) and patients with mixed bone metastases (0.75 ± 0.12 ng/mL, 53.66 ± 9.22 ng/mL, and 31.24 ± 5.73 ng/mL), showing statistically obvious differences ( P &lt; 0.05 ). In short, the sensitivity, specificity, and accuracy of MRI + DWI + MRE in detection of prostate cancer bone metastasis were better than those of a single examination method, showing significant impacts on the rehabilitation of patients with prostate cancer bone metastasis.

A preliminary study procedure for detection of polyamines in plasma samples as a potential diagnostic tool in prostate cancer

BackgroundMany scientific contributions recognize polyamines as important biomarkers for the diagnosis and treatment of cancer. Several authors have suggested the use of LC/MS instruments as an elective method for their measurement, providing good detection limits and specificity; however, many of these procedures suffer from long chromatographic run times, high detection limits and lengthy and expensive sample pre-treatment steps. MethodsUHPLC coupled with high-resolution Orbitrap mass spectrometry (UHPLC/Orbitrap) was set up for the identification and separation ofpolyamines, together with some of their metabolites and catabolites, in the plasma of healthy and prostate cancer human patients. Thirteen metabolites were measured in deproteinized plasma samples through a new analytical approach known as the parallel reaction monitoring (PRM) for targeted quantitative analysis. ResultsThe calibration curves were linear and R2 ranged from 0.9913 to 0.9995 for all analytes. LOQ values are between 0.382 and 25 ng mL−1 and LOD values are between 0.109 and 7.421 ng mL−1. The method shows an accuracy and precision for intra-day and inter-day < 15% RSD and R.E.% for all the QC samples. The matrix effect calculated at different concentration levels did not exceed 15%. ConclusionsThe method developed provides rapid, easy and robust identification and measurement of a wide range of polyamines, and some of their metabolites that can be evaluated as biomarkers to predict the clinical features of prostate cancer patients, avoiding invasive diagnostic procedures.

Histopathological diagnoses and patterns in transrectal ultrasound-guided prostatic biopsy series from a large tertiary care center in Saudi Arabia.

Aim:The aim of the study was to report our transrectal ultrasound (TRUS)-guided prostatic biopsy histopathological diagnoses and clinical findings in our prostate cancer patients in a tertiary care center.Methods:We have reviewed our TRUS biopsy series done in our department from January 2011 to December 2016. We reviewed our patient's prebiopsy prostate-specific antigen (PSA) findings and the histopathological diagnoses and determined the clinical and pathological features of prostate cancer patients in our series.Results:A total of 398 patients underwent 12 core TRUS biopsies. Benign prostatatic hyperplasia was found in 48.5% of the patients and prostate cancer was found in 113 patients (28.4%). Among them, metastatic prostate cancer was found in 51.7% of them. High Gleason score (8–10) was found in 56.6% and a PSA of more than 20 was found in 63.3% of the patients.Conclusion:We recommend a mass public awareness program to encourage our patients to seek early prostate cancer screening and to alert the medical community to encourage more awareness of prostate cancer screening.

External Validation of a Multiparametric Magnetic Resonance Imaging–based Nomogram for the Prediction of Extracapsular Extension and Seminal Vesicle Invasion in Prostate Cancer Patients Undergoing Radical Prostatectomy

The nomogram reported by Gandaglia et al (The key combined value of multiparametric magnetic resonance imaging, and magnetic resonance imaging-targeted and concomitant systematic biopsies for the prediction of adverse pathological features in prostate cancer patients undergoing radical prostatectomy. Eur Urol 2020;77:733–41) predicting extracapsular extension (ECE) or seminal vesicle invasion (SVI) has been developed using multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy. We aimed to validate this nomogram externally by analyzing 566 patients harboring prostate cancer diagnosed on MRI-targeted biopsy followed by radical prostatectomy. At final pathology, 37% and 12% patients had ECE and SVI, respectively. Performance of the nomogram, in comparison with the Memorial Sloan Kettering Cancer Center (MSKCC) model and Partin tables, was evaluated using discrimination, calibration, and decision curve analysis. Regarding ECE prediction, the nomogram showed higher discrimination (71.8% vs 69.8%, p = 0.3 and 71.8% vs 61.3%, p < 0.001), and similar miscalibration and net benefit for probability threshold above 30% when compared with MSKCC model and Partin tables, respectively. Performance of the nomogram with regard to SVI was comparable in terms of discrimination (68.5% vs 70.4% vs 67.8%, p ≥ 0.6), presenting a slight overestimation on calibration plots and a net benefit for probability threshold above 7.5%. This is the first multicentric study that externally validates a nomogram predicting ECE and SVI in patients diagnosed with MRI-targeted biopsy. Its performance was less optimistic than expected, and implementation of MRI in this setting was not associated with a clear improvement in patient selection and clinical usefulness when compared with available models. We proposed an updated version of the nomogram predicting ECE using the recalibration method, which leads to an improvement in its performance and needs to be validated in another external set. Patient summaryWe validate a prediction tool based on multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy predicting extracapsular extension and seminal vesicle invasion at radical prostatectomy. An improvement of patient selection was not clearly demonstrated when compared with available models based on clinical parameters, and implementation of MRI in this setting still needs to be clarified.

Re: The Key Combined Value of Multiparametric Magnetic Resonance Imaging, and Magnetic Resonance Imaging–targeted and Concomitant Systematic Biopsies for the Prediction of Adverse Pathological Features in Prostate Cancer Patients Undergoing Radical Prostatectomy

Re: The Key Combined Value of Multiparametric Magnetic Resonance Imaging, and Magnetic Resonance Imaging–targeted and Concomitant Systematic Biopsies for the Prediction of Adverse Pathological Features in Prostate Cancer Patients Undergoing Radical Prostatectomy

Abstract 4602: Clinicopathological and genetic features of prostate cancer in Algerian patients: First report

Abstract Background: Prostate cancer is the second most frequent malignancy (after lung cancer) in men worldwide. It is the third most common cancer in men in Algeria. We studied for the first time the clinicopathological and genetic features of prostate cancer in Algerian patients. Το date. inherited risk for prostate cancer is associated with aggressive disease and poorer outcomes. Patients with hereditary prostate cancer have been screened for germline mutations in BRCA1, BRCA2, MLH1, MSH2 and PMS2 genes. Patients and Methods: The study population included 769 patients with prostate cancer from 31 provinces of Algeria (among 48) covered by the cancer registry of the anti-cancer center of Blida, Algeria. Patients referred with a biopsy proven diagnosis of carcinoma of the prostate to the anti cancer center of Blida, from January 2013 to April 2019 were studied. Clinical and tumor data: age at diagnosis, PSA value, Gleason score (New grading system groupe 1), TNM stage and family history of prostate cancer have been collected from the medical records of the patients. Five patients and one asymptomatic patient with strong hereditary prostate cancer history have been tested by PCR-direct sequencing for recurrent germline mutations already detected in Algerian patients with family history of breast cancer and prostate cancer or lynch syndrome, respectively. We analysed BRCA1 (exon 3 and 10), BRCA2 (exons 10, 16 and 19), MLH1 (exon 1), MSH2 (exon 5). In addition, for the first time, we screened exons 6 and 10 of PMS2 gene in prostate cancer patients. Results: The median age at diagnosis of prostate cancer was 70.73 years. 41.71 % patients have been diagnosed with prostate cancer under the age of 70 years. Majority of patients (95.39%) presented with a PSA value &amp;gt;4ng/ml. Of the tumors, 36.87% were Gleason score 3+3 (grade 1) and 26.36% were Gleason score 3+4 (grade 2) while Gleason score 4+3 (grade 3), 4+4 (grade 4) and 4+5 (grade 5) disease comprised 16.32%, 11.97 and 8.42% of cases, respectively. Our results showed that 87.5% of prostate cancer were diagnosed at TNM stage I (7.63%), TNM stage II (44.87%), TNM stage III (31.05%), TNM stage IV(3.95%), respectively. 85 patients (11.18%) had a family history of prostate cancer. The BRCA1 recurrent germline mutation c.2125_2126insA has been identified in asymptomatic patient aged of 61 years with a strong family history of prostate cancer and breast cancer. His father and two brothers died of prostate cancer. We detected the intronic variant of uncertain significance (UV) c.989-107_989-106insA in the exon 10 of PMS2 gene in a suspected Lynch syndrome patient diagnosed with colon cancer at age 65 years and a prostate cancer at age 77 years, respectively. Interestingly, one son of this patient has developed colon cancer at age 34 years. BRCA2, MLH1 and MSH2 recurrent germline mutations have not been detected in our prostate cancer patients. Conclusions: The accumulative knowledge about clinicopathological features in prostate cancer patients will have an effect on clinical management in the areas of both prevention and treatment. Genetic testing of hereditary prostate cancer will have an important management implications for Algerian patients and their families. Citation Format: Farid Cherbal, Lydia Ait Braham, Selma Lerari, Kada Boualga. Clinicopathological and genetic features of prostate cancer in Algerian patients: First report [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4602.

Aberrant Expression of Citrate Synthase is Linked to Disease Progression and Clinical Outcome in Prostate Cancer.

PurposeCitrate synthase (CS) is a rate-limiting enzyme in the citrate cycle and is capable of catalyzing oxaloacetate and acetyl-CoA to citrate. CS has been uncovered to be upregulated in a variety of cancers, and its expression and clinical significance in prostate cancer (PCa) remain unknown.MethodsIn this study, we examined the association between CS expression level and clinicopathological features of prostate cancer patients in a TMA cohort and the public cancer database (The Cancer Genome Atlas-Prostate Adenocarcinoma, TCGA-PRAD). The CS knockdown cell lines were constructed to study the effects of CS downregulation on proliferation, colony formation, migration, invasion, and cell cycle of prostate cancer cells in vitro. And the effect of CS downregulation on tumor growth in mice was studied in vivo. In addition, the metabolomics and mitochondrial function were detected in the CS knockdown cell lines.ResultsCS expression level in PCa tissues was higher than that in normal tissues (P < 0.05). CS upregulation was significantly associated with high Gleason score (P < 0.05), advanced pathological stage (P < 0.001), and biochemical recurrence (P < 0.001). Functionally, decreased expression of CS inhibited PCa cell proliferation, colony formation, migration, invasion and cell cycle in vitro, and inhibited tumor growth in vivo. In addition, CS downregulation exerted potential inhibitory effects on the lipid metabolism and mitochondrial function of PCa cells.ConclusionIn conclusion, these findings suggested that CS upregulation may contribute to the aggressive progression and poor prognosis of PCa patients, which might be partially associated with its influences on the cell lipid metabolism and mitochondrial function.

Role of long non-coding RNA NEAT1 in the prognosis of prostate cancer patients.

Prostate cancer is the second leading cause of cancer-related deaths among male population worldwide, its incidence and lethality steadily increase. Nuclear enriched abundant transcript 1 (NEAT1) is a long non-coding RNA (ncRNA), located on chromatin 11. It has been found to function as an oncogene in different kinds of cancer. However, until now, the clinical significance of NEAT1 has not been investigated in prostate cancer.Paired tissue specimens of prostate cancer and matched normal prostate tissues were obtained from 130 patients with prostate cancer between 2014 and 2019 at The Fourth Affiliated Hospital Zhejiang University, School of Medicine. Group means were compared using the Student t test. Chi-Squared test was used for analyzing the correlation of the expression of NEAT1 with clinicopathologic features of prostate cancer patients. Survival data was analyzed using the Kaplan-Meier estimate and log-rank P was calculated. Cox regression model was used for univariate and multivariate analysis for factors related to overall survival.The expression of NEAT1 was increased significantly in prostate cancer tissues, compared with adjacent normal prostate tissues (P < .001). NEAT1 expression was significantly associated with TNM stage (P = .005), lymph nodes metastasis (P = .005), distant metastasis(P = .003), and Gleason score (P = .001). Overall survival rate was significantly lower for prostate cancer patients with a high expression level of NEAT1 than those with a low NEAT1a expression level (P = .048). In multivariate analysis, the results showed that the expression of NEAT1 was an independent prognostic factor for overall patient survival (HR: 2.111, CI: 1.735-10.295, P = .039).In the present study, NEAT1 is identified as an important lncRNA that may predict the prognosis of patients with prostate cancer.

Association of EGLN2 rs10680577 Polymorphism with the Risk and Clinicopathological Features of Patients with Prostate Cancer

Several studies have evaluated the association between EGLN2 4-bp insertion/deletion (ins/del) polymorphism (rs10680577) and many cancers. However, up to date, no study has inspected the impact of rs10680577 polymorphism on prostate cancer (PCa) risk. This case-control study was achieved on 170 pathologically confirmed PCa patients and 196 cancer free men to inspect whether rs10680577 variant is related to the risk and clinicopathological features of patients with PCa. Genotyping was performed by mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The findings did not support an association between the variant with the risk and clinicopathological characteristics of PCa patients. When we pooled our results with six preceding studies, the findings suggested that rs10680577 variant significantly augmented the risk of overall cancer in heterozygous (OR=1.38, 95 % CI=1.26-1.52, p<0.00001, ins/del vs ins/ins), homozygous (OR=1.66, 95 % CI=1.05-2.61, p=0.029, del/del vs ins/ins), codominant (OR=1.44, 95%CI=1.32-1.58, p<0.00001, ins/del+del/del vs ins/ins), and allele (OR=1.32, 95%CI=1.18-1.49, p<0.00001, del vs ins) genetic models. Additional well designed studies with larger sample sizes are necessary to confirm our findings.

YAP1 plays a key role of the conversion of normal fibroblasts into cancer-associated fibroblasts that contribute to prostate cancer progression

BackgroundCancer-associated fibroblasts (CAFs) are an important part of the tumour microenvironment, and their functions are of great concern. This series of experiments aimed to explore how Yes-associated protein 1 (YAP1) regulates the function of stromal cells and how the normal fibroblasts (NFs) convert into CAFs in prostate cancer (PCa).MethodsThe effects of conditioned media from different fibroblasts on the proliferation and invasion of epithelial cells TrampC1 were examined. We then analysed the interaction between the YAP1/TEAD1 protein complex and SRC, as well as the regulatory function of the downstream cytoskeletal proteins and actins. A transplanted tumour model was used to explore the function of YAP1 in regulating tumour growth through stromal cells. The relationship between the expression of YAP1 in tumour stromal cells and the clinical characteristics of PCa patients was analysed.ResultsThe expression level of YAP1 was significantly upregulated in PCa stromal cells. After the expression level of YAP1 was increased, NF was transformed into CAF, enhancing the proliferation and invasion ability of epithelial cells. The YAP1/TEAD1 protein complex had the capability to influence downstream cytoskeletal proteins by regulating SRC transcription; therefore, it converts NF to CAF, and CAF can significantly promote tumour growth and metastasis. The high expression of YAP1 in the tumour stromal cells suggested a poor tumour stage and prognosis in PCa patients.ConclusionYAP1 can convert NFs into CAFs in the tumour microenvironment of PCa, thus promoting the development and metastasis of PCa. Silencing YAP1 in tumour stromal cells can effectively inhibit tumour growth.