Prediction of survival in patients with metastatic prostate cancer by single nucleotide polymorphisms of cancer-associated genes.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 177-177
Author(s):  
Takamitsu Inoue ◽  
Norihiko Tsuchiya ◽  
Shigeyuki Matsui ◽  
Tomomi Kamba ◽  
Koji Mitsuzuka ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Metastatic Prostate Cancer ◽  
Target Genes ◽  
Predictive Accuracy ◽  
Risk Groups ◽  
Low Risk ◽  
Rank Test ◽  
Single Nucleotide ◽  
Snp Panel

177 Background: Individual genetic variations may have a significant influence on the survival of metastatic prostate cancer (PCa) patients. We aimed to identify target genes and their variations involved in the survival of PCa patients using a single nucleotide polymorphism (SNP) panel. Methods: A total of 185 PCa patients with bone metastasis at initial diagnosis were analyzed. Each patient was genotyped using a Cancer SNP panel that contained 1421 SNPs in 408 cancer-related genes. SNPs associated with the survival were screened by log rank test. A prognostic scoring index using selected SNPs was developed by incorporating the difference in their effect sizes to classify high-risk and low-risk groups and its predictive accuracy was assessed. Results: Fourteen SNPs in six genes, XRCC4, PSM1, GATA3, IL13, CASP8, and IGF1, were identified to have statistically significant association with the cancer-specific survival. The cancer-specific survivals of patients grouped according to the number of risk genotypes of 6 SNPs selected from the 14 SNPs differed significantly (0-1 vs 2-3 vs 4-6 risk genotypes, P = 7.20×10−8). The predictive model using the 14 SNPs showed a statistically significant cross-validated accuracy in predicting the groups at high and low risk groups for poor survival (P = 0.0050). The high-risk group was independently associated with the survival in a multivariate analysis that included conventional clinicopathological variables (P = 0.0060). Conclusions: Using a panel of the SNPs, the prediction of the survival and optimization of the individualized treatment for patients with advanced PCa may be possible.

The national impact of the COVID-19 pandemic on U.S. prostate cancer community care.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5061-5061
Author(s):  
Matthew R. Cooperberg ◽  
Paul Brendel ◽  
Daniel J. Lee ◽  
Rahul Doraiswami ◽  
Hariesh Rajasekar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Language Processing ◽  
Care Delivery ◽  
Specific Antigen ◽  
Risk Groups ◽  
Low Risk ◽  
T Stage ◽  
Risk Stratum ◽  
The Impact

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]

Analysis of time to castration-resistant prostate cancer (CRPC) after initiating primary androgen depletion therapy (PADT) of prostate cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15106-e15106
Author(s):  
Hideyuki Akaza ◽  
Shiro Hinotsu ◽  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
High Risk ◽  
Risk Groups ◽  
Rank Test ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression ◽  
Lh Rh ◽  
Androgen Depletion

e15106 Background: Recent clinical trials for developing new drugs for castration resistant prostate cancer (CRPC) have been done for the patients who are surgically or medically castrated, with castration level of testosterone. Although patients who received combined androgen blockade (CAB) with anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to study enrollment, such patients are analyzed together with patients with castration monotherapy. Methods: We analyzed the time to CRPC among the patients with primary androgen depletion therapy (PADT); LH-RH agonist or CAB (LH-RH agonist + anti-androgen) who have registered to the J-CaP study and were followed up for >10 years. Time to CRPC was defined as PSA progression or other disease progression. Patients were stratified into three risk groups using JCAPRA score (JCO 2009; 26: 4309). In addition to the time to CRPC, overall survival length (OS) after initiating PADT was analyzed. Results: Time to CRPC was significantly longer in the CAB group than monotherapy group in intermediate and high risk groups (Table). In addition, in the intermediate and high risk groups, OS was significantly longer for the patients with CAB (Log-rank test). Conclusions: The significant differences of the time to CRPC and OS will influence to the outcome of clinical trials of CRPC. It is important to take the type of ADT in to consideration when we analyze the results of clinical study of CRPC. [Table: see text]

scholarly journals Identification of a five-miRNA signature as a novel potential prognostic biomarker in patients with nasopharyngeal carcinoma

Hereditas ◽  
2022 ◽  
Vol 159 (1) ◽  
Author(s):  
Bo Tu ◽  
Ling Ye ◽  
Qingsong Cao ◽  
Sisi Gong ◽  
Miaohua Jiang ◽  
...  
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Prognostic Model ◽  
Target Genes ◽  
Cox Regression ◽  
External Validation ◽  
Risk Groups ◽  
Low Risk ◽  
Mirna Signature ◽  
Cox Regression Analysis

Abstract Background MicroRNAs (miRNAs) are involved in the prognosis of nasopharyngeal carcinoma (NPC). This study used clinical data and expression data of miRNAs to develop a prognostic survival signature for NPC patients to detect high-risk subject. Results We identified 160 differentially expressed miRNAs using RNA-Seq data from the GEO database. Cox regression model consisting of hsa-miR-26a, hsa-let-7e, hsa-miR-647, hsa-miR-30e, and hsa-miR-93 was constructed by the least absolute contraction and selection operator (LASSO) in the training set. All the patients were classified into high-risk or low-risk groups by the optimal cutoff value of the 5-miRNA signature risk score, and the two risk groups demonstrated significant different survival. The 5-miRNA signature showed high predictive and prognostic accuracies. The results were further confirmed in validation and external validation set. Results from multivariate Cox regression analysis validated 5-miRNA signature as an independent prognostic factor. A total of 13 target genes were predicted to be the target genes of miRNA target genes. Both PPI analysis and KEGG analysis networks were closely related to tumor signaling pathways. The prognostic model of mRNAs constructed using data from the dataset GSE102349 had higher AUCs of the target genes and higher immune infiltration scores of the low-risk groups. The mRNA prognostic model also performed well on the independent immunotherapy dataset Imvigor210. Conclusions This study constructed a novel 5-miRNA signature for prognostic prediction of the survival of NPC patients and may be useful for individualized treatment of NPC patients.

Evaluation of Integrated CLL Scoring System (ICSS) in 420 Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5563-5563 ◽  
Author(s):  
Andrea Visentin ◽  
Federica Frezzato ◽  
Silvia Imbergamo ◽  
Valentina Trimarco ◽  
Veronica Martini ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Accuracy ◽  
Lymphocytic Leukemia ◽  
Low Risk ◽  
Rank Test ◽  
High Risk Patients ◽  
Log Rank Test ◽  
Risk Patients ◽  
Normal Fish

Abstract BACKGROUND Chronic Lymphocytic Leukemia (CLL) is one of the most common hematological malignancies in Western countries. The disease is characterized by heterogeneous clinical course and outcome. During the last 15 years several clinical, biological and molecular prognostic factors have been identified, validated and some of them are currently used in patients' and treatment management. To improve the predictive accuracy of these markers, they have been combined into prognostic indexes (W. Wierda, JCO 2011, D. Rossi, Blood 2012, J. Bahlo, Haematologica 2015). Werecently proposed the Integrated CLL Scoring System (ICSS) based on cytogenetic abnormalities by FISH, IGHV mutational status and CD38 expression from 212 patients (A. Visentin et al, Clin Lymph Myeloma & Leuk 2015). The aim of this study was to validate the prognostic power of our index into a larger series of 420 CLL patients. METHODS 420 CLL patients referred to the Hematology Unit of Padua University Hospital from 1989 to 2015 were recruited in this study. According to ICSS, patients were classified as: low-risk, those patients with 13q deletion or normal FISH, IGVH mutated and CD38<30%; high-risk, subjects with 17p or 11q deletion and/or IGVH unmutated and CD38>30%; intermediate-risk, all remaining patients. Treatment free survival (TFS) was calculated as time from diagnosis to treatment (event), death or last known follow-up (censored). Overall survival (OS) was calculated from the date of diagnosis to death for any cause (event) or last known follow-up (censored). TFS and OS were compared with log-rank test and plotted using Kaplan-Meier method. The predictive accuracy of ICSS was evaluated by the Harrel's concordance index (c-index); a value >0.5 implies a good predictive ability. RESULTS The median age of our cohort was 62 years; 64% were male and 85% were Binet stage A at diagnosis. Cytogenetic analysis by FISH showed that 41 patients harbored 17p deletion, 50 11q deletion, 236 13q deletion, 44 trisomy 12 and 49 had normal FISH. 236 (56%) patients had IGHV gene homology >98% (i.e. mutated IGHV) and 103 (25%) expressed more then 30% of CD38. According to ICSS 202 (48%) subjects were classified as low-risk, 83 (20%) intermediate-risk and 135 (32%) high-risk. After a median follow-up of 81 months, the median TFS for ICSS classes of risk were 211, 70 and 27 months (log-rank test, p<0.0001, Figure 1A). The estimated 10-year TFS were 61%, 37% and 10% for low, intermediate and high-risk patients. The median OS were 213 and 136 months for intermediate and high-risk, while it was not reached for low-risk patients (Log-rank test, p<0.0001, Figure 1B). After 10 years from diagnosis the estimated OS were 88%, 79% and 57%, respectively. These data were confirmed by a multivariate analyses. In fact, high-risk patients had 5.3 and 4.0 times risk of start treatment and death than low-risk subjects, respectively (p<0.0001). This model was statistically internally validated, showing c-indexed of 0.712 and 0.693 for TFS and OS, respectively. In multivariate analyses, variables confirmed to predict adverse prognosis were male gender (p=0.0183), age>65years (p<0.0001), Rai III-IV (p=0.0025), Binet C (p=0.0002), 17p deletion (p=0.0002), TP53 abnormalities (p=0.0051), unmutated IGVH (p<0.0001), CD38>30% (p=0.0044) and high-risk ICSS (p<0.0001). CONCLUSIONS We herein provide evidence of the prognostic power and feasibility of ICSS into a large population of CLL patients. The use of this prognostic index could help physician into follow-up schedule, since high-risk patients should be monitored more often given the estimated increased risk of progression. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Stereotactic body radiation therapy for low-, intermediate- and high-risk prostate cancer: Disease control and quality of life at 9 years.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 20-20 ◽  
Author(s):  
Alan J. Katz ◽  
Josephine Kang
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Radiation Therapy ◽  
High Risk ◽  
Stereotactic Body Radiation Therapy ◽  
Risk Groups ◽  
Biochemical Failure ◽  
Low Risk ◽  
Biochemical Control

20 Background: Stereotactic body radiation therapy (SBRT) takes advantage of the prostate’s low α/β ratio to deliver a large radiation dose in a few fractions. This prospective study expands upon prior studies to further evaluate SBRT efficacy and QOL for a large patient population that includes low-, intermediate- and high-risk patients with prostate cancer. Methods: 515 patients with organ-confined prostate cancer (471 T1c and 44 T2a, all N0M0) received robotic SBRT. The median age was 69 years and the median PSA was 6.48 ng/ml. By NCCN criteria, 324 patients were low-risk, 139 were intermediate-risk, and 52 were high-risk. Androgen deprivation therapy was administered to 70 patients for up to one year. 158 patients with Gleason scores < 4+3 received 35 Gy delivered in 5 daily fractions. The remaining patients, from all risk groups, received a total dose of 36.25 Gy in 5 daily fractions. The proximal seminal vesicles were treated except in low-risk cases. Biochemical failure was assessed using the Phoenix criterion and QOL was assessed with EPIC scoring. Results: At a median follow-up of 84 months, 74 patients died (72 from unrelated causes). The median PSA at 78 months was 0.11 ng/ml. The actuarial 9 year freedom from biochemical failure was 95%, 89%, and 66% for the low-, intermediate- and high-risk groups (p = 0.01). For patients with Gleason scores < 4+3, there was no difference in terms of median nadir or biochemical control between doses of 35 and 36.25 Gy. Late RTOG toxicity was mild with 4% grade 2 rectal, 9.5% grade 2 urinary, and 1.9% grade 3 urinary. Late grade 2-3 urinary toxicity was 6.9% for 35 Gy vs. 13.2% for 36.25 Gy (p = 0.01). Mean EPIC urinary and bowel QOL declined at 1 month post-treatment and returned to baseline by 2 years where it remains. EPIC sexual QOL declined by 29% at 78 months. Conclusions: SBRT alone produces excellent biochemical control rates at up to 9 years with mild toxicity and minimal impact on quality of life. These long-term results appear superior to standard IMRT with lower cost and are strikingly similar to HDR therapy. These results also strongly suggest that 35 Gy is as effective as 36.25 Gy for patients with Gleason < 4+3, with less urinary toxicity.

scholarly journals Radiomics and MGMT promoter methylation for prognostication of newly diagnosed glioblastoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Takahiro Sasaki ◽  
Manabu Kinoshita ◽  
Koji Fujita ◽  
Junya Fukai ◽  
Nobuhide Hayashi ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Accuracy ◽  
Risk Group ◽  
Prognostic Score ◽  
Methylation Status ◽  
Low Risk ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Log Rank Test ◽  
Newly Diagnosed Glioblastoma

Abstract We attempted to establish a magnetic resonance imaging (MRI)-based radiomic model for stratifying prognostic subgroups of newly diagnosed glioblastoma (GBM) patients and predicting O (6)-methylguanine-DNA methyltransferase promotor methylation (pMGMT-met) status of the tumor. Preoperative MRI scans from 201 newly diagnosed GBM patients were included in this study. A total of 489 texture features including the first-order feature, second-order features from 162 datasets, and location data from 182 datasets were collected. Supervised principal component analysis was used for prognostication and predictive modeling for pMGMT-met status was performed based on least absolute shrinkage and selection operator regression. 22 radiomic features that were correlated with prognosis were used to successfully stratify patients into high-risk and low-risk groups (p = 0.004, Log-rank test). The radiomic high- and low-risk stratification and pMGMT status were independent prognostic factors. As a matter of fact, predictive accuracy of the pMGMT methylation status was 67% when modeled by two significant radiomic features. A significant survival difference was observed among the combined high-risk group, combined intermediate-risk group (this group consists of radiomic low risk and pMGMT-unmet or radiomic high risk and pMGMT-met), and combined low-risk group (p = 0.0003, Log-rank test). Radiomics can be used to build a prognostic score for stratifying high- and low-risk GBM, which was an independent prognostic factor from pMGMT methylation status. On the other hand, predictive accuracy of the pMGMT methylation status by radiomic analysis was insufficient for practical use.

Validation of a genomic classifier to predict adverse pathology in men diagnosed with low risk prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 71-71
Author(s):  
Hyung Lae Kim ◽  
Ping Li ◽  
Huei-Chung Huang ◽  
Samineh Deheshi ◽  
Beatrice Knudsen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Risk Group ◽  
Cleveland Clinic ◽  
Risk Groups ◽  
Low Risk ◽  
Average Risk ◽  
Grade Group ◽  
Cut Point ◽  
Risk Prostate Cancer

71 Background: The Decipher 22-feature genomic classifier (GC) has been validated to predict metastasis and prostate cancer specific mortality in needle biopsy (Bx) tissue of men with intermediate and high-risk prostate cancer. We validate GC in diagnostic Bx specimens for the prediction of high-grade/stage (HGS) disease at radical prostatectomy (RP) in men with low and favorable-intermediate (fav-int) NCCN risk group disease. Methods: We identified 176 men diagnosed with low or fav-int NCCN risk group disease who had available Bx GC scores and pathological information after RP from Cedars-Sinai, University of Calgary, Cleveland Clinic, MD Anderson, and Johns Hopkins. The GC score was calculated based on a locked random forest model. Scores range from 0-1 with cut points for GC low, intermediate and high risk groups as <0.45, 0.45-0.6, and >0.6, respectively. The primary endpoint was HGS (Gleason group 3-5 or pT3b or lymph node invasion (LNI)). Univariable (UVA) and multivariable (MVA) logistic regression models were used to evaluate GC and CAPRA. Results: Median age of the cohort was 62 years, 87% and 13% had Bx grade group (GG) 1 or 2 disease. 76% and 24% were NCCN low and fav-int risk, respectively. CAPRA classified 70% as low (0-2) and 30% as average risk (3-5). GC classified 80% low, 16% intermediate and 4% high genomic risk. After RP, 41% had RP GG 1, 46% GG 2 and 13% had GG 3-5 disease. pT3b or positive lymph nodes were observed in 7 men (4%), overall 27 (15%) of men had HGS at RP. In the UVA and MVA, GC was the only significant predictor of HGS with odds ratio (OR) of 1.38 and 1.34 per 10% unit increase, before and after adjusting for CAPRA (p=0.011, 0.027). A low risk score (GC<0.45) had a negative predictive value (NPV) of 92% to identify men who do not have HGS at RP. In exploratory analysis, a very low risk cut-point (GC<0.2) was found which had a sensitivity of 96% and an NPV of 99%. 26% of men had GC<0.2. Conclusions: We validated GC in a multi-institutional study to predict HGS at RP among men with NCCN low and fav-int risk disease with high sensitivity and NPV. Future studies will aim to validate the very low risk genomic cut-point to guide decision-making and follow-up biopsy protocols for men considering or in active surveillance.

scholarly journals Use of Evidence-Based Prostate Cancer Imaging in a Nongovernmental Integrated Health Care System

2017 ◽  
Vol 13 (5) ◽  
pp. e441-e450 ◽  
Author(s):  
Ramzi G. Salloum ◽  
Maureen O’Keeffe-Rosetti ◽  
Debra P. Ritzwoller ◽  
Mark C. Hornbrook ◽  
Jennifer Elston Lafata ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Health Care ◽  
High Risk ◽  
Financial Incentives ◽  
Risk Groups ◽  
Integrated Health Care ◽  
Low Risk ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer ◽  
To Receive

Purpose: The overuse of imaging, particularly for staging of low-risk prostate cancer, is well documented and widespread. The existing literature, which focuses on the elderly in fee-for-service settings, points to financial incentives as a driver of overuse and may not identify factors relevant to policy solutions within integrated health care systems, where physicians are salaried. Methods: Imaging rates were analyzed among men with incident prostate cancer diagnosed between 2004 and 2011 within the Colorado and Northwest regions of Kaiser Permanente. The sample was stratified according to indication for imaging, ie, high risk for whom imaging was necessary versus low risk for whom imaging was discouraged. Logistic regression was used to model the association between imaging receipt and clinical/demographic patient characteristics by risk strata. Results: Of the men with low-risk prostate cancer, 35% received nonindicated imaging at diagnosis, whereas 42% of men with high-risk prostate cancer did not receive indicated imaging. Compared with men diagnosed in 2004, those diagnosed in subsequent years were less likely to receive imaging across both risk groups. Men with high-risk cancer diagnosed at ≥ 65 years of age and those with clinical stage ≥ T2 were more likely to receive indicated imaging. Men with comorbidities were more likely to receive imaging across both risk groups. Men with low-risk prostate cancer who had higher median household incomes were less likely to receive nonindicated imaging. Conclusion: Nonindicated imaging for diagnostic staging of patients with low-risk prostate cancer was common, but has decreased over the past decade. These findings suggest that factors other than financial incentives may be driving overuse of imaging.

International Validation of a Preoperative Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy

2002 ◽  
Vol 20 (15) ◽  
pp. 3206-3212 ◽  
Author(s):  
Markus Graefen ◽  
Pierre I. Karakiewicz ◽  
Ilias Cagiannos ◽  
David I. Quinn ◽  
Susan M. Henshall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Patient Selection ◽  
Predictive Accuracy ◽  
Risk Group ◽  
Specific Antigen ◽  
High Risk Group ◽  
Low Risk ◽  
Gleason Grade ◽  
Data Set

PURPOSE: We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS: Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification–based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS: The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low–risk group), 39% (intermediate-high–risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION: The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

scholarly journals Chromatin conformation changes in peripheral blood can detect prostate cancer and stratify disease risk groups

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Heba Alshaker ◽  
Robert Mills ◽  
Ewan Hunter ◽  
Matthew Salter ◽  
Aroul Ramadass ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Peripheral Blood ◽  
Risk Groups ◽  
Low Risk ◽  
Risk Category ◽  
Specific Chromosome ◽  
Early Stage Disease ◽  
Conformation Changes ◽  
High Risk Category

Abstract Background Current diagnostic blood tests for prostate cancer (PCa) are unreliable for the early stage disease, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance of negative biopsies in men with PCa. Predicting the risk of PCa is pivotal for making an informed decision on treatment options as the 5-year survival rate in the low-risk group is more than 95% and most men would benefit from surveillance rather than active treatment. Three-dimensional genome architecture and chromosome structures undergo early changes during tumourigenesis both in tumour and in circulating cells and can serve as a disease biomarker. Methods In this prospective study we screened whole blood of newly diagnosed, treatment naïve PCa patients (n = 140) and cancer-free controls (n = 96) for the presence of 14,241 chromosomal loops in the loci of 425 genes. Results We have detected specific chromosome conformation changes in the loci of ETS1, MAP3K14, SLC22A3 and CASP2 genes in peripheral blood from PCa patients yielding PCa detection with 80% sensitivity and 80% specificity. Further analysis between PCa risk groups yielded prognostic validation sets consisting of HSD3B2, VEGFC, APAF1, BMP6, ERG, MSR1, MUC1, ACAT1 and DAPK1 genes that achieved 80% sensitivity and 93% specificity stratifying high-risk category 3 vs low risk category 1 and 84% sensitivity and 89% specificity stratifying high risk category 3 vs intermediate risk category 2 disease. Conclusions Our results demonstrate specific chromosome conformations in the blood of PCa patients that allow PCa diagnosis and risk stratification with high sensitivity and specificity.

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