scholarly journals Evaluation of an RNAseq-Based Immunogenomic Liquid Biopsy Approach in Early-Stage Prostate Cancer

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2567
Author(s):  
Leander Van Neste ◽  
Kirk J. Wojno ◽  
Ricardo Henao ◽  
Shrikant Mane ◽  
Howard Korman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Biology ◽  
Early Stage ◽  
Immune Surveillance ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Primary Objective ◽  
Pathologic Features

The primary objective of this study is to detect biomarkers and develop models that enable the identification of clinically significant prostate cancer and to understand the biologic implications of the genes involved. Peripheral blood samples (1018 patients) were split chronologically into independent training (n = 713) and validation (n = 305) sets. Whole transcriptome RNA sequencing was performed on isolated phagocytic CD14+ and non-phagocytic CD2+ cells and their gene expression levels were used to develop predictive models that correlate to adverse pathologic features. The immune-transcriptomic model with the highest performance for predicting adverse pathology, based on a subtraction of the log-transformed expression signals of the two cell types, displayed an area under the curve (AUC) of the receiver operating characteristic of 0.70. The addition of biomarkers in combination with traditional clinical risk factors (age, serum prostate-specific antigen (PSA), PSA density, race, digital rectal examination (DRE), and family history) enhanced the AUC to 0.91 and 0.83 for the training and validation sets, respectively. The markers identified by this approach uncovered specific pathway associations relevant to (prostate) cancer biology. Increased phagocytic activity in conjunction with cancer-associated (mis-)regulation is also represented by these markers. Differential gene expression of circulating immune cells gives insight into the cellular immune response to early tumor development and immune surveillance.

Prostate Cancer: Biology, Incidence, Detection Methods, Treatment Methods, and Vaccines

2020 ◽  
Vol 20 (10) ◽  
pp. 847-854
Author(s):  
Ronald Bartzatt
Keyword(s):  
Prostate Cancer ◽  
Cancer Treatment ◽  
Prostate Specific Antigen ◽  
Cancer Biology ◽  
Early Stage ◽  
Specific Antigen ◽  
Detection Methods ◽  
Hormone Refractory Prostate Cancer ◽  
High Risk Prostate Cancer ◽  
Hormone Refractory

Cancer of the prostate are cancers in which most incidences are slow-growing, and in the U.S., a record of 1.2 million new cases of prostate cancer occurred in 2018. The rates of this type of cancer have been increasing in developing nations. The risk factors for prostate cancer include age, family history, and obesity. It is believed that the rate of prostate cancer is correlated with the Western diet. Various advances in methods of radiotherapy have contributed to lowering morbidity. Therapy for hormone- refractory prostate cancer is making progress, for almost all men with metastases will proceed to hormone-refractory prostate cancer. Smoking cigarettes along with the presence of prostate cancer has been shown to cause a higher risk of mortality in prostate cancer. The serious outcome of incontinence and erectile dysfunction result from the cancer treatment of surgery and radiation, particularly for prostate- specific antigen detected cancers that will not cause morbidity or mortality. Families of patients, as well as patients, are profoundly affected following the diagnosis of prostate cancer. Poor communication between spouses during prostate cancer increases the risk for poor adjustment to prostate cancer. The use of serum prostate-specific antigen to screen for prostate cancer has led to a greater detection, in its early stage, of this cancer. Prostate cancer is the most common malignancy in American men, accounting for more than 29% of all diagnosed cancers and about 13% of all cancer deaths. A shortened course of hormonal therapy with docetaxel following radical prostatectomy (or radiation therapy) for high-risk prostate cancer has been shown to be both safe and feasible. Patients treated with docetaxel-estramustine had a prostate-specific antigen response decline of at least 50%. Cancer vaccines are an immune-based cancer treatment that may provide the promise of a non-toxic but efficacious therapeutic alternative for cancer patients. Further studies will elucidate improved methods of detection and treatment.

scholarly journals Detection limits of significant prostate cancer using multiparametric MR and digital rectal examination in men with low serum PSA: Up-date of the Italian Society of Integrated Diagnostic in Urology

2021 ◽  
Vol 93 (1) ◽  
pp. 92-100
Author(s):  
Andrea B. Galosi ◽  
Erika Palagonia ◽  
Simone Scarcella ◽  
Alessia Cimadamore ◽  
Vito Lacetera ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Early Stage ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Point Of View ◽  
Italian Society ◽  
Rectal Examination ◽  
Normal Limits ◽  
Low Serum

Reasons why significant prostate cancer is still missed in early stage were investigated at the 22nd National SIEUN (Italian Society of integrated diagnostic in Urology, Andrology, Nephrology) congress took place from 30th November to 1st December 2020, in virtual modality. Even if multiparametric magnetic resonance (MR) has been introduced in the clinical practice several, limitations are emerging in patient with regular digital rectal examination (DRE) and serum prostate specific antigen (PSA) levels approaching the normal limits. The present paper summarizes highlights observed in those cases where significant prostate cancer may be missed by PSA or imaging and DRE. The issue of multidisciplinary interest had been subdivided and deepened under four main topics: biochemical, clinical, pathological and radiological point of view with a focus on PI-RADS 3 lesions.

scholarly journals APTIMA PCA3 Molecular Urine Test: Development of a Method to Aid in the Diagnosis of Prostate Cancer

2006 ◽  
Vol 52 (6) ◽  
pp. 1089-1095 ◽  
Author(s):  
Jack Groskopf ◽  
Sheila MJ Aubin ◽  
Ina Lim Deras ◽  
Amy Blase ◽  
Sharon Bodrug ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Prostate Cancer Risk ◽  
Area Under The Curve ◽  
Roc Curve Analysis ◽  
Cancer Risk Factors ◽  
Specimen Processing ◽  
Whole Urine

Abstract Background: Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA that has shown promise as a prostate cancer diagnostic tool. This report describes the characterization of a prototype quantitative PCA3-based test for whole urine. Methods: Whole-urine specimens were collected after digital rectal examination from 3 groups: men scheduled for prostate biopsy (n = 70), healthy men (<45 years of age with no known prostate cancer risk factors; n = 52), and men who had undergone radical prostatectomy (n = 21). PCA3 and prostate-specific antigen (PSA) mRNAs were isolated, amplified, and quantified by use of Gen-Probe DTS400® Systems. Prostate biopsy results were correlated with the PCA3/PSA mRNA ratio, and PSA mRNA concentrations were used to normalize PCA3 signals and confirm the yield of prostate-specific RNA. Assay precision, specimen stability, and mRNA yield were also evaluated. Results: The specimen informative rate (fraction of specimens yielding sufficient RNA for analysis) was 98.2%. In this clinical research study, ROC curve analysis of prebiopsy specimens yielded an area under the curve of 0.746; sensitivity was 69% and specificity 79%. Serum PSA assay specificity was 28% for this same group. PCA3 and PSA mRNAs were undetectable in postprostatectomy specimens except for one man with recurrent prostate cancer. Assay interrun CVs were ≤12%. Both mRNAs were stable in processed urine up to 5 days at 4 °C and after 5 freeze–thaw cycles. Conclusion: The APTIMA® PCA3 assay combines simple specimen processing with precise assays and existing instruments and could add specificity to the current algorithm for prostate cancer diagnosis.

scholarly journals Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 188 ◽  
Author(s):  
Jacob Fredsøe ◽  
Anne K. I. Rasmussen ◽  
Peter Mouritzen ◽  
Marianne T. Bjerre ◽  
Peter Østergren ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Minimally Invasive ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Diagnostic Tools ◽  
Test Set ◽  
Localized Disease ◽  
Clinically Significant

Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAs in plasma, we confirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375*miR-33a-5p/miR-16-5p*miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

scholarly journals Development of a Multiplexed Urine Assay for Prostate Cancer Diagnosis

2008 ◽  
Vol 54 (5) ◽  
pp. 874-882 ◽  
Author(s):  
Tatiana Vener ◽  
Carlo Derecho ◽  
Jonathan Baden ◽  
Haiying Wang ◽  
Yashoda Rajpurohit ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Diagnosis ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Threshold Value ◽  
Premalignant Lesions ◽  
Prostate Cancer Diagnosis ◽  
Rectal Examination ◽  
The Difference

Abstract Background: Several studies have demonstrated the value of DNA methylation in urine-based assays for prostate cancer diagnosis. However, a multicenter validation with a clinical prototype has not been published. Methods: We developed a multiplexed, quantitative methylation-specific polymerase chain reaction (MSP) assay consisting of 3 methylation markers, GSTP1, RARB, and APC, and an endogenous control, ACTB, in a closed-tube, homogeneous assay format. We tested this format with urine samples collected after digital rectal examination from 234 patients with prostate-specific antigen (PSA) concentrations ≥2.5 μg/L in 2 independent patient cohorts from 9 clinical sites. Results: In the first cohort of 121 patients, we demonstrated 55% sensitivity and 80% specificity, with area under the curve (AUC) 0.69. In the second independent cohort of 113 patients, we found a comparable sensitivity of 53% and specificity of 76% (AUC 0.65). In the first cohort, as well as in a combined cohort, the MSP assay in conjunction with total PSA, digital rectal examination status, and age improved the AUC without MSP, although the difference was not statistically significant. Importantly, the GSTP1 cycle threshold value demonstrated a good correlation (R = 0.84) with the number of cores found to contain prostate cancer or premalignant lesions on biopsy. Moreover, samples that exhibited methylation for either GSTP1 or RARB typically contained higher tumor volumes at prostatectomy than those samples that did not exhibit methylation. Conclusions: These data confirm and extend previously reported studies and demonstrate the performance of a clinical prototype assay that should aid urologists in identifying men who should undergo biopsy.

scholarly journals Reducing Unnecessary Biopsy During Prostate Cancer Screening Using a Four-Kallikrein Panel: An Independent Replication

2010 ◽  
Vol 28 (15) ◽  
pp. 2493-2498 ◽  
Author(s):  
Andrew Vickers ◽  
Angel Cronin ◽  
Monique Roobol ◽  
Caroline Savage ◽  
Mari Peltola ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Cancer Screening ◽  
Randomized Study ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Population Based ◽  
Study Cohort ◽  
Low Grade ◽  
Total Psa

PurposeWe previously reported that a panel of four kallikrein forms in blood—total, free, and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2 (hK2)—can reduce unnecessary biopsy in previously unscreened men with elevated total PSA. We aimed to replicate our findings in a large, independent, representative, population-based cohort.Patients and MethodsThe study cohort included 2,914 previously unscreened men undergoing biopsy as a result of elevated PSA (≥ 3 ng/mL) in the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 807 prostate cancers (28%) detected. The cohort was randomly divided 1:3 into a training and validation set. Levels of kallikrein markers were compared with biopsy outcome.ResultsAddition of free PSA, intact PSA, and hK2 to a model containing total PSA and age improved the area under the curve from 0.64 to 0.76 and 0.70 to 0.78 for models without and with digital rectal examination results, respectively (P < .001 for both). Application of the panel to 1,000 men with elevated PSA would reduce the number of biopsies by 513 and miss 54 of 177 low-grade cancers and 12 of 100 high-grade cancers. Findings were robust to sensitivity analysis.ConclusionWe have replicated our previously published finding that a panel of four kallikreins can predict the result of biopsy for prostate cancer in men with elevated PSA. Use of this panel would dramatically reduce biopsy rates. A small number of men with cancer would be advised against immediate biopsy, but these men would have predominately low-stage, low-grade disease.

scholarly journals MRI Screening and MRI/US Fusion-Guided Transperineal Biopsy in Detecting Prostate Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110194
Author(s):  
Hongqing Yin ◽  
Jun Shao ◽  
Huan Song ◽  
Wei Ding ◽  
Bin Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Detection ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Vital Role ◽  
Targeted Biopsy ◽  
Detection Rates ◽  
Transperineal Biopsy ◽  
Systematic Biopsy

Objective: Systematic biopsy plays a vital role in diagnosing prostate cancer, but it can lead to misdiagnoses or undertreatment. Advances in magnetic resonance imaging (MRI) and its guided targeting technology provide the possibility of improving the use of biopsies. This study aimed to evaluate the performance of MRI screening and MRI/ultrasound (MRI/US) fusion-guided transperineal biopsy in the detection of prostate cancer. Methods: We performed a retrospective study on patients with suspected prostate cancer in the Kunshan Hospital Affiliated with Jiangsu University from January 2017 to December 2019. All of the patients underwent MRI examinations, followed by a systematic biopsy (either alone or in combination with MRI/US fusion-guided targeted biopsy, based on MRI-visible lesions). We evaluated the diagnostic accuracy of MRI screening and compared biopsy methods by considering sensitivity, specificity, and area under the curve (AUC) values. Results: A total of 157 patients were enrolled, including 112 patients with MRI-visible lesions and 45 patients without MRI-visible lesions. The cancer detection rate (CDR) was higher in patients with MRI-visible lesions ( P < 0.001); however, the serum prostate-specific antigen (PSA) indicators were similar ( P > 0.05). The AUC of MRI was 0.63, which was superior to the AUC values of ultrasound (AUC = 0.55, P = 0.031) and digital rectal examination (AUC = 0.52, P = 0.041) for screening prostate cancer. Both overall CDR and clinically significant prostate cancer detection rates were improved if we combined systematic biopsy and MRI/US fusion-guided targeted biopsy procedures. Conclusion: Overall, prior MRI screening may serve as a classifier for avoiding the overuse of biopsies. A combination of systematic and MRI/US fusion-guided targeted biopsy procedures offers an optimal regimen for detecting prostate cancer.

scholarly journals Performance of a Single Assay for Both Type III and Type VI TMPRSS2:ERG Fusions in Noninvasive Prediction of Prostate Biopsy Outcome

2008 ◽  
Vol 54 (12) ◽  
pp. 2007-2017 ◽  
Author(s):  
Jarrod P Clark ◽  
Kristofer W Munson ◽  
Jessie W Gu ◽  
Katarzyna Lamparska-Kupsik ◽  
Kevin G Chan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Gleason Grade ◽  
Type Iii ◽  
Standard Curve ◽  
Institutional Review

Abstract Background: TMPRSS2:ERG fusions are promising prostate cancer biomarkers. Because they can occur in multiple forms in a single cancer specimen, we developed a quantitative PCR test that detects both type III and type VI TMPRSS2:ERG fusions. The assay is quantified from a standard curve determined with a plasmid-cloned type III TMPRSS2:ERG fusion target. Methods: We collected expressed prostatic secretion (EPS) under an institutional review board-approved, blinded, prospective study from 74 patients undergoing transrectal ultrasound-guided biopsy for prostate cancer. We compared the characteristic performance of the test for type III and type VI TMPRSS2:ERG fusions in predicting biopsy outcome and distinguishing between high and low Gleason scores with similar tests for the expression of PCA3 and DNA methylation levels of the APC, RARB, RASSF1, and GSTP1 genes. We used logistic regression to analyze the effects of multiple biomarkers in linear combinations. Results: Each test provided a significant improvement in characteristic performance over baseline digital rectal examination (DRE) plus serum prostate-specific antigen (PSA); however, the test for type III and type VI TMPRSS2:ERG fusions yielded the best performance in predicting biopsy outcome [area under the curve (AUC) 0.823, 95% CI 0.728–0.919, P &lt; 0.001] and Gleason grade &gt;7 (AUC 0.844, 95% CI 0.740–0.948, P &lt; 0.001). Conclusions: Although each test appears to have diagnostic value, PSA plus DRE plus type III and type VI TMPRSS2:ERG provided the best diagnostic performance in EPS specimens.

scholarly journals A comparative effectiveness analysis of the PBCG vs. PCPT risks calculators in a multi-ethnic cohort

BMC Urology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Samuel Carbunaru ◽  
Oluwarotimi S. Nettey ◽  
Pooja Gogana ◽  
Irene B. Helenowski ◽  
Borko Jovanovic ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Minority Groups ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Area Under The Curve ◽  
Collaborative Group ◽  
Racial Groups ◽  
Prostate Cancer Prevention ◽  
Comparative Effectiveness Analysis

Abstract Background Predictive models that take race into account like the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPT RC) and the new Prostate Biopsy Collaborative Group (PBCG) RC have been developed to equitably mitigate the overdiagnosis of prostate specific antigen (PSA) screening. Few studies have compared the performance of both calculators across racial groups. Methods From 1485 prospectively recruited participants, 954 men were identified undergoing initial prostate biopsy for abnormal PSA or digital rectal examination in five Chicago hospitals between 2009 and 2014. Discrimination, calibration, and frequency of avoided biopsies were calculated to assess the performance of both risk calculators. Results Of 954 participants, 463 (48.5%) were Black, 355 (37.2%) were White, and 136 (14.2%) identified as Other. Biopsy results were as follows: 310 (32.5%) exhibited no cancer, 323 (33.9%) indolent prostate cancer, and 321 (33.6%) clinically significant prostate cancer (csPCa). Differences in area under the curve (AUC)s for the detection of csPCa between PCPT and PBCG were not statistically different across all racial groups. PBCG did not improve calibration plots in Blacks and Others, as it showed higher levels of overprediction at most risk thresholds. PCPT led to an increased number of avoidable biopsies in minorities compared to PBCG at the 30% threshold (68% vs. 28% of all patients) with roughly similar rates of missed csPCa (23% vs. 20%). Conclusion Significant improvements were noticed in PBCG’s calibrations and net benefits in Whites compared to PCPT. Since PBCG’s improvements in Blacks are disputable and potentially biases a greater number of low risk Black and Other men towards unnecessary biopsies, PCPT may lead to better biopsy decisions in racial minority groups. Further comparisons of commonly used risk calculators across racial groups is warranted to minimize excessive biopsies and overdiagnosis in ethnic minorities.

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