|
1
|
Liu Y, Hatano K, Nonomura N. Liquid Biomarkers in Prostate Cancer Diagnosis: Current Status and Emerging Prospects. World J Mens Health 2025; 43:8-27. [PMID: 38772530 PMCID: PMC11704174 DOI: 10.5534/wjmh.230386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/12/2024] [Accepted: 01/22/2024] [Indexed: 05/23/2024] Open
Abstract
Prostate cancer (PCa) is a major health concern that necessitates appropriate diagnostic approaches for timely intervention. This review critically evaluates the role of liquid biopsy techniques, focusing on blood- and urine-based biomarkers, in overcoming the limitations of conventional diagnostic methods. The 4Kscore test and Prostate Health Index have demonstrated efficacy in distinguishing PCa from benign conditions. Urinary biomarker tests such as PCa antigen 3, MyProstateScore, SelectMDx, and ExoDx Prostate IntelliScore test have revolutionized risk stratification and minimized unnecessary biopsies. Emerging biomarkers, including non-coding RNAs, circulating tumor DNA, and prostate-specific antigen (PSA) glycosylation, offer valuable insights into PCa biology, enabling personalized treatment strategies. Advancements in non-invasive liquid biomarkers for PCa diagnosis may facilitate the stratification of patients and avoid unnecessary biopsies, particularly when PSA is in the gray area of 4 to 10 ng/mL.
Collapse
Affiliation(s)
- Yutong Liu
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Koji Hatano
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
| | - Norio Nonomura
- Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan
| |
Collapse
|
|
2
|
A review on the role of PCA3 lncRNA in carcinogenesis with an especial focus on prostate cancer. Pathol Res Pract 2022; 231:153800. [DOI: 10.1016/j.prp.2022.153800] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 02/05/2022] [Accepted: 02/09/2022] [Indexed: 12/31/2022]
|
|
3
|
SelectMDx and Multiparametric Magnetic Resonance Imaging of the Prostate for Men Undergoing Primary Prostate Biopsy: A Prospective Assessment in a Multi-Institutional Study. Cancers (Basel) 2021; 13:cancers13092047. [PMID: 33922626 PMCID: PMC8122883 DOI: 10.3390/cancers13092047] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/15/2021] [Accepted: 04/20/2021] [Indexed: 01/04/2023] Open
Abstract
Prostate-specific antigen (PSA) testing as the sole indication for prostate biopsy lacks specificity, resulting in overdiagnosis of indolent prostate cancer (PCa) and missing clinically significant PCa (csPCa). SelectMDx is a biomarker-based risk score to assess urinary HOXC6 and DLX1 mRNA expression combined with traditional clinical risk factors. The aim of this prospective multi-institutional study was to evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) when predicting PCa in prostate biopsies. Overall, 310 consecutive subjects were included. All patients underwent mpMRI and SelectMDx prior to prostate biopsy. SelectMDx and mpMRI showed sensitivity and specificity of 86.5% vs. 51.9%, and 73.8% vs. 88.3%, respectively, in predicting PCa at biopsy, and 87.1% vs. 61.3%, and 63.7% vs. 83.9%, respectively, in predicting csPCa at biopsy. SelectMDx was revealed to be a good predictor of PCa, while with regards to csPCa detection, it was demonstrated to be less effective, showing results similar to mpMRI. With analysis of strategies assessed to define the best diagnostic strategy to avoid unnecessary biopsy, SelectMDx appeared to be a reliable pathway after an initial negative mpMRI. Thus, biopsy could be proposed for all cases of mpMRI PI-RADS 4-5 score, and to those with Prostate Imaging-Reporting and Data System (PI-RADS) 1-3 score followed by a positive SelectMDx.
Collapse
|
|
4
|
Salciccia S, Capriotti AL, Laganà A, Fais S, Logozzi M, De Berardinis E, Busetto GM, Di Pierro GB, Ricciuti GP, Del Giudice F, Sciarra A, Carroll PR, Cooperberg MR, Sciarra B, Maggi M. Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes. Int J Mol Sci 2021; 22:ijms22094367. [PMID: 33922033 PMCID: PMC8122596 DOI: 10.3390/ijms22094367] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 04/18/2021] [Accepted: 04/20/2021] [Indexed: 12/13/2022] Open
Abstract
Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers have been developed in recent years. Although several biomarkers have been explored in various scenarios and patient settings, to date, specific guidelines with a high level of evidence on the use of these markers are lacking. Recent advances in metabolomic, genomics, and proteomics have made new potential biomarkers available. A number of studies focused on the characterization of the specific PC metabolic phenotype using different experimental approaches has been recently reported; yet, to date, research on metabolomic application for PC has focused on a small group of metabolites that have been known to be related to the prostate gland. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers. Thanks to a general improvement of the technical equipment to analyze exosomes, we are able to obtain reliable quantitative and qualitative information useful for clinical application. Although some pilot clinical investigations have proposed potential PC biomarkers, data are still preliminary and non-conclusive.
Collapse
Affiliation(s)
- Stefano Salciccia
- Department of Urology, Sapienza Rome University, Policlinico Umberto I, 00161 Rome, Italy; (S.S.); (E.D.B.); (G.B.D.P.); (G.P.R.); (F.D.G.); (M.M.)
| | - Anna Laura Capriotti
- Department of Chemistry, Sapienza Rome University, 00161 Rome, Italy; (A.L.C.); (A.L.); (B.S.)
| | - Aldo Laganà
- Department of Chemistry, Sapienza Rome University, 00161 Rome, Italy; (A.L.C.); (A.L.); (B.S.)
| | - Stefano Fais
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy; (S.F.); (M.L.)
| | - Mariantonia Logozzi
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy; (S.F.); (M.L.)
| | - Ettore De Berardinis
- Department of Urology, Sapienza Rome University, Policlinico Umberto I, 00161 Rome, Italy; (S.S.); (E.D.B.); (G.B.D.P.); (G.P.R.); (F.D.G.); (M.M.)
| | - Gian Maria Busetto
- Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, 71122 Foggia, Italy;
| | - Giovanni Battista Di Pierro
- Department of Urology, Sapienza Rome University, Policlinico Umberto I, 00161 Rome, Italy; (S.S.); (E.D.B.); (G.B.D.P.); (G.P.R.); (F.D.G.); (M.M.)
| | - Gian Piero Ricciuti
- Department of Urology, Sapienza Rome University, Policlinico Umberto I, 00161 Rome, Italy; (S.S.); (E.D.B.); (G.B.D.P.); (G.P.R.); (F.D.G.); (M.M.)
| | - Francesco Del Giudice
- Department of Urology, Sapienza Rome University, Policlinico Umberto I, 00161 Rome, Italy; (S.S.); (E.D.B.); (G.B.D.P.); (G.P.R.); (F.D.G.); (M.M.)
| | - Alessandro Sciarra
- Department of Urology, Sapienza Rome University, Policlinico Umberto I, 00161 Rome, Italy; (S.S.); (E.D.B.); (G.B.D.P.); (G.P.R.); (F.D.G.); (M.M.)
- Correspondence: ; Tel.: +39-0649974201; Fax: +39-0649970284
| | - Peter R. Carroll
- Department of Urology, UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA; (P.R.C.); (M.R.C.)
| | - Matthew R. Cooperberg
- Department of Urology, UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA; (P.R.C.); (M.R.C.)
| | - Beatrice Sciarra
- Department of Chemistry, Sapienza Rome University, 00161 Rome, Italy; (A.L.C.); (A.L.); (B.S.)
| | - Martina Maggi
- Department of Urology, Sapienza Rome University, Policlinico Umberto I, 00161 Rome, Italy; (S.S.); (E.D.B.); (G.B.D.P.); (G.P.R.); (F.D.G.); (M.M.)
| |
Collapse
|
|
5
|
Electrochemical Detection of Prostate Cancer Biomarker PCA3 Using Specific RNA-Based Aptamer Labelled with Ferrocene. CHEMOSENSORS 2021. [DOI: 10.3390/chemosensors9040059] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This paper reports on a feasibility study of electrochemical in-vitro detection of prostate cancer biomarker PCA3 (prostate cancer antigen 3) in direct assay with specific RNA aptamer labelled with a redox group (ferrocene) and immobilized on a screen-printed gold electrode surface. The cyclic voltammograms and electrochemical impedance spectroscopy methods yield encouraging results on the detection of PCA3 in a range of concentrations from 1 μg/mL down to 0.1 ng/mL in buffer solutions. Both anodic and cathodic current values in cyclic voltammograms measurements and charge transfer resistance values in electrochemical impedance spectroscopy experiments correlate with the PCA3 concentration in the sample. Kinetics studies of the binding of the PCA3 to our aptamer demonstrated high specificity of the reaction with a characteristic affinity constant of approximately 4·10−10 molar. The results of this work provide a background for the future development of novel, highly sensitive and cost-effective diagnostic methodologies for prostate cancer detection.
Collapse
|
|
6
|
Brisotto G, Guerrieri R, Colizzi F, Steffan A, Montico B, Fratta E. Long Noncoding RNAs as Innovative Urinary Diagnostic Biomarkers. Methods Mol Biol 2021; 2292:73-94. [PMID: 33651353 DOI: 10.1007/978-1-0716-1354-2_7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The characterization of circulating tumor cells (CTCs) is now widely studied as a promising source of cancer-derived biomarkers because of their role in tumor formation and progression. However, CTCs analysis presents some limitations and no standardized method for CTCs isolation from urine has been defined so far. In fact, besides blood, urine represents an ideal source of noninvasive biomarkers, especially for the early detection of genitourinary tumors. Besides CTCs, long noncoding RNAs (lncRNAs) have also been proposed as potential noninvasive biomarkers, and the evaluation of the diagnostic accuracy of urinary lncRNAs has dramatically increased over the last years, with many studies being published. Therefore, this review provides an update on the clinical utility of urinary lncRNAs as novel biomarkers for the diagnosis of bladder and prostate cancers.
Collapse
Affiliation(s)
- Giulia Brisotto
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
| | - Roberto Guerrieri
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
| | - Francesca Colizzi
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
| | - Agostino Steffan
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
| | - Barbara Montico
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
| | - Elisabetta Fratta
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
| |
Collapse
|
|
7
|
Qin Z, Yao J, Xu L, Xu Z, Ge Y, Zhou L, Zhao F, Jia R. Diagnosis accuracy of PCA3 level in patients with prostate cancer: a systematic review with meta-analysis. Int Braz J Urol 2020; 46:691-704. [PMID: 31961625 PMCID: PMC7822358 DOI: 10.1590/s1677-5538.ibju.2019.0360] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 10/13/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa. MATERIALS AND METHODS A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR-), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model. RESULTS With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR-, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95% CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria. CONCLUSIONS The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.
Collapse
Affiliation(s)
- Zhiqiang Qin
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jianxiang Yao
- Department of Urology, Huzhou first people's hospital, Huzhou, China
| | - Luwei Xu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zheng Xu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yuzheng Ge
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Liuhua Zhou
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Feng Zhao
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Ruipeng Jia
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
8
|
Lee D, Shim SR, Ahn ST, Oh MM, Moon DG, Park HS, Cheon J, Kim JW. Diagnostic Performance of the Prostate Cancer Antigen 3 Test in Prostate Cancer: Systematic Review and Meta-analysis. Clin Genitourin Cancer 2020; 18:402-408.e5. [DOI: 10.1016/j.clgc.2020.03.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 02/26/2020] [Accepted: 03/03/2020] [Indexed: 01/08/2023]
|
|
9
|
Soares JC, Soares AC, Rodrigues VC, Melendez ME, Santos AC, Faria EF, Reis RM, Carvalho AL, Oliveira ON. Detection of the Prostate Cancer Biomarker PCA3 with Electrochemical and Impedance-Based Biosensors. ACS APPLIED MATERIALS & INTERFACES 2019; 11:46645-46650. [PMID: 31765118 DOI: 10.1021/acsami.9b19180] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
Diagnosis of prostate cancer via PCA3 biomarker detection is promising to be much more efficient than with the prostatic specific antigens currently used. In this study, we present the first electrochemical and impedance-based biosensors that are capable of detecting PCA3 down to 0.128 nmol/L. The biosensors were made with a layer of PCA3-complementary single-stranded DNA (ssDNA) probe, immobilized on a layer-by-layer (LbL) film of chitosan (CHT) and carbon nanotubes (MWCNT). They are highly selective to PCA3, which was confirmed in impedance measurements and with polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Using information visualization methods, we could also distinguish between cell lines expressing the endogenous PCA3 long noncoding RNA (lncRNA) from cells that did not contain detectable levels of this biomarker. Since the methods involved in fabrication the biosensors are potentially low cost, one may hope to deploy PCA3 tests in any laboratory of clinical analyses and even for point-of-care diagnostics.
Collapse
Affiliation(s)
- Juliana Coatrini Soares
- São Carlos Institute of Physics , University of São Paulo , 13566-590 São Carlos , Brazil
- National Laboratory of Nanotechnology for Agribusiness (LNNA) , Embrapa Instrumentation , 13560-970 São Carlos , Brazil
| | - Andrey Coatrini Soares
- São Carlos Institute of Physics , University of São Paulo , 13566-590 São Carlos , Brazil
- National Laboratory of Nanotechnology for Agribusiness (LNNA) , Embrapa Instrumentation , 13560-970 São Carlos , Brazil
| | | | - Matias Eliseo Melendez
- Molecular Oncology Research Center , Barretos Cancer Hospital , 14784-400 Barretos , Brazil
| | - Alexandre Cesar Santos
- Molecular Oncology Research Center , Barretos Cancer Hospital , 14784-400 Barretos , Brazil
| | - Eliney Ferreira Faria
- Molecular Oncology Research Center , Barretos Cancer Hospital , 14784-400 Barretos , Brazil
| | - Rui M Reis
- Molecular Oncology Research Center , Barretos Cancer Hospital , 14784-400 Barretos , Brazil
- Life and Health Sciences Research Institute (ICVS), School of Medicine , University of Minho , Braga , Portugal
- ICVS/3B's - PT Government Associate Laboratory , Braga/Guimarães , Portugal
| | - Andre Lopes Carvalho
- Molecular Oncology Research Center , Barretos Cancer Hospital , 14784-400 Barretos , Brazil
| | - Osvaldo N Oliveira
- São Carlos Institute of Physics , University of São Paulo , 13566-590 São Carlos , Brazil
| |
Collapse
|
|
10
|
Lemos AEG, Matos ADR, Ferreira LB, Gimba ERP. The long non-coding RNA PCA3: an update of its functions and clinical applications as a biomarker in prostate cancer. Oncotarget 2019; 10:6589-6603. [PMID: 31762940 PMCID: PMC6859920 DOI: 10.18632/oncotarget.27284] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 09/24/2019] [Indexed: 02/07/2023] Open
Abstract
Prostate cancer antigen 3 (PCA3) is an overexpressed prostate long non-coding RNA (lncRNA), transcribed from an intronic region at the long arm of human chromosome 9q21–22. It has been described that PCA3 modulates prostate cancer (PCa) cell survival through modulating androgen receptor (AR) signaling, besides controlling the expression of several androgen responsive and cancer-related genes, including epithelial–mesenchymal transition (EMT) markers and those regulating gene expression and cell signaling. Also, PCA3 urine levels have been successfully used as a PCa diagnostic biomarker. In this review, we have highlighted recent findings regarding PCA3, addressing its gene structure, putative applications as a biomarker, a proposed origin of this lncRNA, roles in PCa biology and expression patterns. We also updated data regarding PCA3 interactions with cancer-related miRNAs and expression in other tissues and diseases beyond the prostate. Altogether, literature data indicate aberrant expression and dysregulated activity of PCA3, suggesting PCA3 as a promising relevant target that should be even further evaluated on its applicability for PCa detection and management.
Collapse
Affiliation(s)
- Ana Emília Goulart Lemos
- Departamento de Epidemiologia e Métodos Quantitativos em Saúde, Escola Nacional de Saúde Pública/Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.,Programa de Pós-Graduação em Ciências Biomédicas - Fisiologia e Farmacologia, Universidade Federal Fluminense, Rio de Janeiro, Brazil
| | - Aline da Rocha Matos
- Laboratório de Vírus Respiratórios e do Sarampo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | | | - Etel Rodrigues Pereira Gimba
- Programa de Pós-Graduação em Ciências Biomédicas - Fisiologia e Farmacologia, Universidade Federal Fluminense, Rio de Janeiro, Brazil.,Coordenação de Pesquisa, Instituto Nacional do Câncer, Rio de Janeiro, Brazil.,Departamento de Ciências da Natureza (RCN), Instituto de Humanidades e Saúde, Universidade Federal Fluminense, Rio de Janeiro, Brazil
| |
Collapse
|
|
11
|
Jiang Z, Zhao Y, Tian Y. Comparison of diagnostic efficacy by two urine PCA3 scores in prostate cancer patients undergoing repeat biopsies. MINERVA UROL NEFROL 2018; 71:373-380. [PMID: 30203935 DOI: 10.23736/s0393-2249.18.03093-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
INTRODUCTION Urine prostate cancer gene 3 (PCA3) is significantly elevated in patients with prostate cancer and can be used for the diagnosis of prostate cancer, but its cutoff value is still controversial. EVIDENCE ACQUISITION We searched the database on urine PCA3 in the diagnosis of prostate cancer, such as Medline, Web of Science, the Cochrane Library and Embase. Meta-analysis was performed using the random effect model and the sensitivity, specificity, diagnostic odds ratio, and area under the ROC curve (SROC) were calculated. EVIDENCE SYNTHESIS Our meta-analysis included nine studies on PCA3 scores in a total of 1721 suspected prostate cancer patients. When urine PCA3 score was 20, we obtained sensitivity of 0.83, specificity of 0.40, diagnostic odds ratio of 3.11, and the area under the SROC curve was 0.6842 (Q value 0.6404). When urine PCA3 score was 35, we found a lower sensitivity of 0.66, a higher specificity of 0.63 and a relatively lower diagnostic odds ratio of 2.84. The area under the SROC curve was 0.6715, which was slightly lower than urine PCA3 score 20. CONCLUSIONS Our meta-analysis suggested that when the PCA3 score cutoff value was 20, the unnecessary puncture was reduced and obtained a higher diagnostic efficacy.
Collapse
Affiliation(s)
- Zhikui Jiang
- Department of Clinical Laboratory, Dahua Hospital, Shanghai, China -
| | - Ying Zhao
- Department of Clinical Laboratory, Dahua Hospital, Shanghai, China
| | - Yuxiang Tian
- Department of Clinical Laboratory, Dahua Hospital, Shanghai, China
| |
Collapse
|
|
12
|
Abstract
Prostate cancer is the most common non-cutaneous cancer among men in the United States. In the last decade there has been a rapid expansion in the field of biomarker assays for diagnosis, prognosis, and treatment prediction in prostate cancer. The evidence base for these assays is rapidly evolving. With several commercial assays available at each stage of the disease, deciding which genomic assays are appropriate for which patients can be nuanced for physicians. In an effort to help guide these decisions in clinical practice, we aim to give an update on the current status of the biomarker field of prostate cancer.
Collapse
Affiliation(s)
- Zachary Kornberg
- Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Matthew R Cooperberg
- Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Daniel E Spratt
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
| | - Felix Y Feng
- Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| |
Collapse
|
|
13
|
Leach DA, Trotta AP, Need EF, Risbridger GP, Taylor RA, Buchanan G. The prognostic value of stromal FK506-binding protein 1 and androgen receptor in prostate cancer outcome. Prostate 2017; 77:185-195. [PMID: 27718274 DOI: 10.1002/pros.23259] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2015] [Accepted: 09/07/2016] [Indexed: 11/10/2022]
Abstract
BACKGROUND Improving our ability to predict cancer progression and response to conservative or radical intent therapy is critical if we are to prevent under or over treatment of individual patients. Whereas the majority of solid tumors now have a range of molecular and/or immunological markers to help define prognosis and treatment options, prostate cancer still relies mainly on histological grading and clinical parameters. We have recently reported that androgen receptor (AR) expression in stroma inversely associates with prostate cancer-specific survival, and that stromal AR reduces metastasis. For this paper, we tested the hypothesis that the AR-regulated gene FKBP51 could be used as a marker of AR activity to better predict outcome. METHODS Using immunohistochemistry on a cohort of 64 patient-matched benign and malignant prostate tissues, we assessed patient outcome by FKBP51 and AR levels. Immunoblot and RT-qPCR were used to demonstrate androgen regulation of FKBP51 in primary and primary human prostatic fibroblasts and fibroblast cell-lines. RESULTS As predicted by FKBP51 level, high AR activity in cancer stroma was associated with longer median survival (1,306 days) compared with high AR alone (699 days), whereas those with low AR and/or low FKBP51 did poorly (384 and 338 days, respectively). Survival could not be predicted on the basis cancer epithelial AR levels or activity, and was not associated with immunoreactivity in patient matched benign tissues. CONCLUSION FKBP51 improves the ability of stromal AR to predict prostate cancer-specific mortality. By adding additional immunological assessment, similar to what is already in place in a number of other cancers, we could better serve patients with prostate cancer in prognosis and informed treatment choices. Prostate 77:185-195, 2017. © 2016 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Damien A Leach
- The Basil Hetzel Institute for Translational Health Research, and Divisions of Medicine and Surgery, University of Adelaide, Adelaide, SA, Australia
| | - Andrew P Trotta
- The Basil Hetzel Institute for Translational Health Research, and Divisions of Medicine and Surgery, University of Adelaide, Adelaide, SA, Australia
| | - Eleanor F Need
- The Basil Hetzel Institute for Translational Health Research, and Divisions of Medicine and Surgery, University of Adelaide, Adelaide, SA, Australia
| | - Gail P Risbridger
- Cancer Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia
| | - Renea A Taylor
- Cancer Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Victoria, Australia
| | - Grant Buchanan
- The Basil Hetzel Institute for Translational Health Research, and Divisions of Medicine and Surgery, University of Adelaide, Adelaide, SA, Australia
| |
Collapse
|
|
14
|
Nicholson A, Mahon J, Boland A, Beale S, Dwan K, Fleeman N, Hockenhull J, Dundar Y. The clinical effectiveness and cost-effectiveness of the PROGENSA® prostate cancer antigen 3 assay and the Prostate Health Index in the diagnosis of prostate cancer: a systematic review and economic evaluation. Health Technol Assess 2016; 19:i-xxxi, 1-191. [PMID: 26507078 DOI: 10.3310/hta19870] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND There is no single definitive test to identify prostate cancer in men. Biopsies are commonly used to obtain samples of prostate tissue for histopathological examination. However, this approach frequently misses cases of cancer, meaning that repeat biopsies may be necessary to obtain a diagnosis. The PROGENSA(®) prostate cancer antigen 3 (PCA3) assay (Hologic Gen-Probe, Marlborough, MA, USA) and the Prostate Health Index (phi; Beckman Coulter Inc., Brea, CA, USA) are two new tests (a urine test and a blood test, respectively) that are designed to be used to help clinicians decide whether or not to recommend a repeat biopsy. OBJECTIVE To evaluate the clinical effectiveness and cost-effectiveness of the PCA3 assay and the phi in the diagnosis of prostate cancer. DATA SOURCES Multiple publication databases and trial registers were searched in May 2014 (from 2000 to May 2014), including MEDLINE, EMBASE, The Cochrane Library, ISI Web of Science, Medion, Aggressive Research Intelligence Facility database, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number Register and World Health Organization International Clinical Trials Registry Platform. REVIEW METHODS The assessment of clinical effectiveness involved three separate systematic reviews, namely reviews of the analytical validity, the clinical validity of these tests and the clinical utility of these tests. The assessment of cost-effectiveness comprised a systematic review of full economic evaluations and the development of a de novo economic model. SETTING The perspective of the evaluation was the NHS in England and Wales. PARTICIPANTS Men suspected of having prostate cancer for whom the results of an initial prostate biopsy were negative or equivocal. INTERVENTIONS The use of the PCA3 score or phi in combination with existing tests (including histopathology results, prostate-specific antigen level and digital rectal examination), multiparametric magnetic resonance imaging and clinical judgement. RESULTS In addition to documents published by the manufacturers, six studies were identified for inclusion in the analytical validity review. The review identified issues concerning the precision of the PCA3 assay measurements. It also highlighted issues relating to the storage requirements and stability of samples intended for analysis using the phi assay. Fifteen studies met the inclusion criteria for the clinical validity review. These studies reported results for 10 different clinical comparisons. There was insufficient evidence to enable the identification of appropriate test threshold values for use in a clinical setting. In addition, the implications of adding either the PCA3 assay or the phi to clinical assessment were not clear. Furthermore, the addition of the PCA3 assay or the phi to clinical assessment plus magnetic resonance imaging was not found to improve discrimination. No published papers met the inclusion criteria for either the clinical utility review or the cost-effectiveness review. The results from the cost-effectiveness analyses indicated that using either the PCA3 assay or the phi in the NHS was not cost-effective. LIMITATIONS The main limitations of the systematic review of clinical validity are that the review conclusions are over-reliant on findings from one study, the descriptions of clinical assessment vary widely within reviewed studies and many of the reported results for the clinical validity outcomes do not include either standard errors or confidence intervals. CONCLUSIONS The clinical benefit of using the PCA3 assay or the phi in combination with existing tests, scans and clinical judgement has not yet been confirmed. The results from the cost-effectiveness analyses indicate that the use of these tests in the NHS would not be cost-effective. STUDY REGISTRATION This study is registered as PROSPERO CRD42014009595. FUNDING The National Institute for Health Research Health Technology Assessment programme.
Collapse
Affiliation(s)
- Amanda Nicholson
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - James Mahon
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Angela Boland
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Sophie Beale
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Kerry Dwan
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Nigel Fleeman
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Juliet Hockenhull
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Yenal Dundar
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| |
Collapse
|
|
15
|
Cui Y, Cao W, Li Q, Shen H, Liu C, Deng J, Xu J, Shao Q. Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis. Sci Rep 2016; 6:25776. [PMID: 27161545 PMCID: PMC4861967 DOI: 10.1038/srep25776] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 04/20/2016] [Indexed: 11/18/2022] Open
Abstract
Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (−LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63–0.66), 0.73 (95% CI: 0.72–0.74), 2.23 (95% CI: 1.91–2.62), 0.48 (95% CI: 0.44–0.52), 5.31 (95% CI: 4.19–6.73) and 0.75 (95% CI: 0.74–0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.
Collapse
Affiliation(s)
- Yong Cui
- Department of Urology, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215001, P.R. China
| | - Wenzhou Cao
- Department of Urology, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215001, P.R. China
| | - Quan Li
- Department of Urology, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215001, P.R. China
| | - Hua Shen
- Department of Urology, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215001, P.R. China
| | - Chao Liu
- Department of Urology, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215001, P.R. China
| | - Junpeng Deng
- Department of Urology, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215001, P.R. China
| | - Jiangfeng Xu
- Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
| | - Qiang Shao
- Department of Urology, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, 215001, P.R. China
| |
Collapse
|
|
16
|
|
|
17
|
Lazzeri M, Guazzoni G, Montorsi F. Total and Free PSA, PCA3, PSA Density and Velocity. Prostate Cancer 2016. [DOI: 10.1016/b978-0-12-800077-9.00010-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
|
|
18
|
Nimse SB, Sonawane MD, Song KS, Kim T. Biomarker detection technologies and future directions. Analyst 2015; 141:740-55. [PMID: 26583164 DOI: 10.1039/c5an01790d] [Citation(s) in RCA: 157] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Biomarkers play a vital role in disease detection and treatment follow-up. It is important to note that diseases in the early stage are typically treated with the greatest probability of success. However, due to various technical difficulties in current technologies for the detection of biomarkers, the potential of biomarkers is not explored completely. Therefore, the developments of technologies, which can enable the accurate detection of prostate cancer at an early stage with simple, experimental protocols are highly inevitable. This critical review evaluates the current methods and technologies used in the detection of biomarkers. The aim of this article is to provide a comprehensive review covering the advantages and disadvantages of the biomarker detection methods. Future directions for the development of technologies to achieve highly selective and sensitive detection of biomarkers for point-of-care applications are also commented on.
Collapse
Affiliation(s)
- Satish Balasaheb Nimse
- Institute for Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon, 200-702, Korea.
| | | | | | | |
Collapse
|
|
19
|
Rubio-Briones J, Borque A, Esteban LM, Casanova J, Fernandez-Serra A, Rubio L, Casanova-Salas I, Sanz G, Domínguez-Escrig J, Collado A, Gómez-Ferrer A, Iborra I, Ramírez-Backhaus M, Martínez F, Calatrava A, Lopez-Guerrero JA. Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy. BMC Cancer 2015; 15:633. [PMID: 26362197 PMCID: PMC4567811 DOI: 10.1186/s12885-015-1623-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Accepted: 08/21/2015] [Indexed: 11/30/2022] Open
Abstract
Background PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. Methods Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference’s nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. Results We detect 28 % of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20 % at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95 %:0.68–0.79) and 0.786 for HGPCa (C.I.95 %:0.71–0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40 % could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31 % for the threshold probability of 40 %. Conclusions PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40 % should be counseled to undergo an IBx if opportunistic screening is required.
Collapse
Affiliation(s)
- Jose Rubio-Briones
- Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain.
| | - Angel Borque
- Department of Urology, Hospital Universitario Miguel Servet, Zaragoza, Spain.
| | - Luis M Esteban
- Escuela Universitaria Politécnica de La Almunia, Universidad de Zaragoza, Zaragoza, Spain.
| | - Juan Casanova
- Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain.
| | | | - Luis Rubio
- Laboratory of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain.
| | - Irene Casanova-Salas
- Laboratory of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain.
| | - Gerardo Sanz
- Department of Statistical Methods, Universidad de Zaragoza, Zaragoza, Spain.
| | - Jose Domínguez-Escrig
- Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain.
| | - Argimiro Collado
- Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain.
| | - Alvaro Gómez-Ferrer
- Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain.
| | - Inmaculada Iborra
- Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain.
| | - Miguel Ramírez-Backhaus
- Department of Urology, Instituto Valenciano de Oncología, C/ Prof. Beltrán Báguena 8, 46009, Valencia, Spain.
| | | | - Ana Calatrava
- Department of Pathology, Instituto Valenciano de Oncología, Valencia, Spain.
| | - Jose A Lopez-Guerrero
- Laboratory of Molecular Biology, Instituto Valenciano de Oncología, Valencia, Spain.
| |
Collapse
|
|
20
|
Yutkin V, Al-Zahrani A, Williams A, Hidas G, Martinez C, Izawa J, Pode D, Chin J. Role of PCA3 test in clinical decision making for prostate cancer diagnosis. World J Clin Urol 2015; 4:68-74. [DOI: 10.5410/wjcu.v4.i1.68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2014] [Revised: 07/27/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the role of PCA3 urine test in the management of patients with suspected prostate cancer after repeat negative prostate biopsies.
METHODS: Patients with suspected prostate cancer either due to high or rising prostate specific antigen (PSA) levels and with a history of prostate biopsy who were candidates for repeat procedure were prospectively recruited to undergo PCA3 urine test. The recommendations on further management including the decision whether to proceed or not to the biopsy were made based on the PCA3 score. Patients’ adherence with the recommendations and influence of the PCA3 test on clinical decision making were assessed. The contribution of the multivariate model was measured with a decision curve analysis.
RESULTS: Three hundred and fifty-six patients were recruited to the study and underwent the PCA3 test. Twenty-six percent of 263 patients underwent prostate biopsy despite the low risk designation by PCA3 and 30% of 93 men did not proceed to biopsy despite a high risk result, rendering overall adherence of 73%. The variables that significantly correlated with adherence were positive family history of prostate cancer and PSA more than 10 ng/mL. Pre-test clinical stage, the number and the results of previous biopsies were not associated with the adherence. The decision curve analysis gave identical results for cut-off points of 25 and 35. On multivariate analysis the model that included PCA3 score, serum PSA, family history and result of the previous biopsy best performed with Area Under the Curve of 0.77.
CONCLUSION: PCA3 urine test markedly outperforms PSA in a repeat biopsy setting. Urologists and patients demonstrate substantial confidence in this analysis and tend to follow its recommendations.
Collapse
|
|
21
|
Luo Y, Gou X, Huang P, Mou C. The PCA3 test for guiding repeat biopsy of prostate cancer and its cut-off score: a systematic review and meta-analysis. Asian J Androl 2014; 16:487-92. [PMID: 24713827 PMCID: PMC4023384 DOI: 10.4103/1008-682x.125390] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The specificity of prostate-specific antigen (PSA) for early intervention in repeat biopsy is unsatisfactory. Prostate cancer antigen 3 (PCA3) may be more accurate in outcome prediction than other methods for the early detection of prostate cancer (PCa). However, the results were inconsistent in repeated biopsies. Therefore, we performed a systematic review and meta-analysis to evaluate the role of PCA3 in outcome prediction. A systematic bibliographic search was conducted for articles published before April 2013, using PubMed, Medline, Web of Science, Embase and other databases from health technology assessment agencies. The quality of the studies was assessed on the basis of QUADAS criteria. Eleven studies of diagnostic tests with moderate to high quality were selected. A meta-analysis was carried out to synthesize the results. The results of the meta-analyses were heterogeneous among studies. We performed a subgroup analysis (with or without inclusion of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP)). Using a PCA3 cutoff of 20 or 35, in the two sub-groups, the global sensitivity values were 0.93 or 0.80 and 0.79 or 0.75, specificities were 0.65 or 0.44 and 0.78 or 0.70, positive likelihood ratios were 1.86 or 1.58 and 2.49 or 1.78, negative likelihood ratios were 0.81 or 0.43 and 0.91 or 0.82 and diagnostic odd ratios (ORs) were 5.73 or 3.45 and 7.13 or 4.11, respectively. The areas under the curve (AUCs) of the summary receiver operating characteristic curve were 0.85 or 0.72 and 0.81 or 0.69, respectively. PCA3 can be used for repeat biopsy of the prostate to improve accuracy of PCa detection. Unnecessary biopsies can be avoided by using a PCa cutoff score of 20.
Collapse
Affiliation(s)
| | - Xin Gou
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | | | | |
Collapse
|
|
22
|
Shinohara K, Nguyen H, Masic S. Management of an increasing prostate-specific antigen level after negative prostate biopsy. Urol Clin North Am 2014; 41:327-38. [PMID: 24725493 DOI: 10.1016/j.ucl.2014.01.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Patients who have a previously negative biopsy in the setting of clinical suspicion of prostate cancer still have a high risk of harboring significant undiagnosed disease. Various markers such as prostate-specific antigen (PSA) velocity, PSA density, PCA3, and newer markers may aid in repeat biopsy selection. Repeating the same biopsy procedure in such patients does not yield high cancer detection rates. More anteriorly directed transrectal or transperineal biopsies are indicated. Multiparametric magnetic resonance imaging can detect abnormal areas, and lesion-targeted biopsies can improve the cancer detection rate.
Collapse
Affiliation(s)
- Katsuto Shinohara
- Department of Urology, University of California, San Francisco, 1600 Divisadero Street A-634, San Francisco, CA 94143-1695, USA.
| | - Hao Nguyen
- Department of Urology, University of California, San Francisco, 1600 Divisadero Street A-634, San Francisco, CA 94143-1695, USA
| | - Selma Masic
- Department of Urology, University of California, San Francisco, 1600 Divisadero Street A-634, San Francisco, CA 94143-1695, USA
| |
Collapse
|
|
23
|
Schröder FH, Venderbos LD, van den Bergh RC, Hessels D, van Leenders GJ, van Leeuwen PJ, Wolters T, Barentsz JO, Roobol MJ. Prostate Cancer Antigen 3: Diagnostic Outcomes in Men Presenting With Urinary Prostate Cancer Antigen 3 Scores ≥100. Urology 2014; 83:613-6. [DOI: 10.1016/j.urology.2013.12.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2013] [Revised: 11/19/2013] [Accepted: 12/03/2013] [Indexed: 11/24/2022]
|
|
24
|
Cary KC, Cooperberg MR. Biomarkers in prostate cancer surveillance and screening: past, present, and future. Ther Adv Urol 2013; 5:318-29. [PMID: 24294290 DOI: 10.1177/1756287213495915] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The use of biomarkers for prostate cancer (PCa) screening, detection, and prognostication have revolutionized the diagnosis and management of the disease. Current clinical practice has been driven largely by the utilization of prostate-specific antigen (PSA). The lack of specificity of PSA for PCa has led to both unnecessary biopsies and overdiagnosis of indolent cancers. The recent controversial recommendation by the United States Preventive Services Task Force against PCa screening has highlighted the need for novel clinically useful biomarkers. We review the literature on PCa biomarkers in serum, urine, and tissue. While these markers show promise, none seems poised to replace PSA, but rather may augment it. Further validation and consideration of how these novel markers improve clinical outcome is necessary. The discovery of new genetic markers shows promise in stratifying men with aggressive PCa.
Collapse
Affiliation(s)
- K Clint Cary
- University of California, San Francisco, CA, USA
| | | |
Collapse
|
|
25
|
Heidenreich A, Thissen AK. Editorial Comment. Urology 2013; 82:1360-1. [DOI: 10.1016/j.urology.2013.06.081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
|
|
26
|
PCA3 and PCA3-based nomograms improve diagnostic accuracy in patients undergoing first prostate biopsy. Int J Mol Sci 2013; 14:17767-80. [PMID: 23994838 PMCID: PMC3794752 DOI: 10.3390/ijms140917767] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2013] [Revised: 08/07/2013] [Accepted: 08/23/2013] [Indexed: 11/17/2022] Open
Abstract
While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen's and Chun's nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun's and Hansen's nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision.
Collapse
|
|
27
|
PCA3 Molecular Urine Test as a Predictor of Repeat Prostate Biopsy Outcome in Men with Previous Negative Biopsies: A Prospective Multicenter Clinical Study. J Urol 2013; 190:64-9. [DOI: 10.1016/j.juro.2013.02.018] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/08/2013] [Indexed: 11/23/2022]
|
|
28
|
Bradley LA, Palomaki GE, Gutman S, Samson D, Aronson N. Comparative effectiveness review: prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer. J Urol 2013; 190:389-98. [PMID: 23545099 DOI: 10.1016/j.juro.2013.02.005] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2013] [Accepted: 02/01/2013] [Indexed: 01/22/2023]
Abstract
PURPOSE We compared the effectiveness of PCA3 (prostate cancer antigen 3) and select comparators for improving initial or repeat biopsy decision making in men at risk for prostate cancer, or treatment choices in men with prostate cancer. MATERIALS AND METHODS MEDLINE®, EMBASE®, Cochrane Database and gray literature were searched from January 1990 through May 2012. Included studies were matched, and measured PCA3 and comparator(s) within a cohort. No matched analyses were possible. Differences in independent performance estimates between PCA3 and comparators were computed within studies. Studies were assessed for quality using QUADAS (Quality Assessment of Diagnostic Accuracy Studies) and for strength of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. RESULTS Among 1,556 publications identified, 34 observational studies were analyzed (24 addressed diagnostic accuracy and 13 addressed treatment decisions). Most studies were conducted in opportunistic cohorts of men referred for procedures and were not designed to answer key questions. Two study biases (partial verification and sampling) were addressed by analyses, allowing some conclusions to be drawn. PCA3 was more discriminatory than total prostate specific antigen increases (eg at an observed 50% specificity, summary sensitivities were 77% and 57%, respectively). Analyses indicated that this finding holds for initial and repeat biopsies, and that the markers were independent predictors. For all other biopsy decision making comparisons and associated health outcomes, strength of evidence was insufficient. For treatment decision making, strength of evidence was insufficient for all outcomes and comparators. CONCLUSIONS PCA3 had a higher diagnostic accuracy than total prostate specific antigen increases, but strength of evidence was low (limited confidence in effect estimates). Strength of evidence was insufficient to conclude that PCA3 testing leads to improved health outcomes. For all other outcomes and comparators, strength of evidence was insufficient.
Collapse
Affiliation(s)
- Linda A Bradley
- Department of Pathology and Laboratory Medicine, Women & Infants Hospital/Alpert Medical School of Brown University, Providence, Rhode Island, USA.
| | | | | | | | | |
Collapse
|
|
29
|
Hansen J, Chun FKH. Reply from Authors re: Michael R. Abern, Stephen J. Freedland. Prostate Cancer Antigen 3 to Select Men for Prostate Biopsy: Stop, Go, or Proceed with Caution? Eur Urol 2013;63:210–1. Eur Urol 2013. [DOI: 10.1016/j.eururo.2012.09.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
|
|
30
|
Young A, Palanisamy N, Siddiqui J, Wood DP, Wei JT, Chinnaiyan AM, Kunju LP, Tomlins SA. Correlation of urine TMPRSS2:ERG and PCA3 to ERG+ and total prostate cancer burden. Am J Clin Pathol 2012; 138:685-96. [PMID: 23086769 DOI: 10.1309/ajcpu7ppwupyg8oh] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
ERG rearrangements (most commonly transmembrane protease, serine 2 [TMPRSS2]:ERG [T2:ERG] gene fusions) have been identified in approximately 50% of prostate cancers . Quantification of T2:ERG in postdigital rectal examination urine, in combination with PCA3, improves the performance of serum prostate-specific antigen for prostate cancer prediction on biopsy. Here we compared urine T2:ERG and PCA3 scores with ERG+ (determined with immunohistochemical analysis) and total prostate cancer burden in 41 mapped prostatectomies. Prostatectomies had a median of 3 tumor foci (range, 1-15) and 2.6 cm of summed linear tumor dimension (range, 0.6-7.1 cm). Urine T2:ERG score correlated most with summed linear ERG+ tumor dimension and number of ERG+ foci (r(s) = 0.68 and 0.67, respectively, both P < .001). Urine PCA3 score showed weaker correlation with both number of tumor foci (r(s) = 0.34, P = .03) and summed linear tumor dimension (r(s) = 0.26, P = .10). In summary, we demonstrate a strong correlation between urine T2:ERG score and total ERG+ prostate cancer burden at prostatectomy, consistent with high tumor specificity.
Collapse
|