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Akbari Nakhjavani S, Tokyay BK, Soylemez C, Sarabi MR, Yetisen AK, Tasoglu S. Biosensors for prostate cancer detection. Trends Biotechnol 2023; 41:1248-1267. [PMID: 37147246 DOI: 10.1016/j.tibtech.2023.04.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 03/22/2023] [Accepted: 04/04/2023] [Indexed: 05/07/2023]
Abstract
Prostate cancer (PC) is one of the most common tumors and a leading cause of mortality among men, resulting in ~375 000 deaths annually worldwide. Various analytical methods have been designed for quantitative and rapid detection of PC biomarkers. Electrochemical (EC), optical, and magnetic biosensors have been developed to detect tumor biomarkers in clinical and point-of-care (POC) settings. Although POC biosensors have shown potential for detection of PC biomarkers, some limitations, such as the sample preparation, should be considered. To tackle such shortcomings, new technologies have been utilized for development of more practical biosensors. Here, biosensing platforms for the detection of PC biomarkers such as immunosensors, aptasensors, genosensors, paper-based devices, microfluidic systems, and multiplex high-throughput platforms, are discussed.
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Affiliation(s)
- Sattar Akbari Nakhjavani
- Department of Mechanical Engineering, Koç University, Sariyer, Istanbul 34450, Turkey; Koç University Translational Medicine Research Center (KUTTAM), Koç University, Istanbul 34450, Turkey
| | - Begum K Tokyay
- Koç University Translational Medicine Research Center (KUTTAM), Koç University, Istanbul 34450, Turkey; Department of Biomedical Sciences and Engineering, Koç University, 34450 Istanbul, Turkey
| | - Cansu Soylemez
- Department of Biomedical Sciences and Engineering, Koç University, 34450 Istanbul, Turkey
| | - Misagh R Sarabi
- Department of Biomedical Sciences and Engineering, Koç University, 34450 Istanbul, Turkey; Physical Intelligence Department, Max Planck Institute for Intelligent Systems, Stuttgart, Germany 70569
| | - Ali K Yetisen
- Department of Chemical Engineering, Imperial College, London SW7 2AZ, UK
| | - Savas Tasoglu
- Department of Mechanical Engineering, Koç University, Sariyer, Istanbul 34450, Turkey; Koç University Translational Medicine Research Center (KUTTAM), Koç University, Istanbul 34450, Turkey; Physical Intelligence Department, Max Planck Institute for Intelligent Systems, Stuttgart, Germany 70569; Koç University Arçelik Research Center for Creative Industries (KUAR), Koç University, Istanbul 34450, Turkey; Boğaziçi Institute of Biomedical Engineering, Boğaziçi University, Istanbul 34684, Turkey.
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Carlsson SV, Roobol MJ. Improving the evaluation and diagnosis of clinically significant prostate cancer in 2017. Curr Opin Urol 2017; 27:198-204. [PMID: 28221219 PMCID: PMC5381721 DOI: 10.1097/mou.0000000000000382] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW To provide an overview of the current state of the evidence and highlight recent advances in the evaluation and diagnosis of clinically significant prostate cancer, focusing on biomarkers, risk calculators and multiparametric MRI (mpMRI). RECENT FINDINGS In 2017 there are numerous options to improve early detection as compared to a purely prostate-specific antigen (PSA)-based approach. All have strengths and drawbacks. In addition to repeating the PSA and performing clinical work-up (digital rectal examination and estimation of prostate volume), additional tests investigated in the initial biopsy setting are: %free PSA, Prostate Health Index, 4-kallikrein score, SelectMDx, and Michigan Prostate Score and in the repeat setting: %free PSA, Prostate Health Index, 4-kallikrein score, Prostate Cancer Antigen 3, and ConfirmMDx. Risk calculators are available for both biopsy settings and incorporate clinical data with, or without, biomarkers. mpMRI is an important diagnostic adjunct. SUMMARY There are numerous tests available that can help increase the specificity of PSA, in the initial and repeat biopsy setting. All coincide with a small decrease in sensitivity of detecting high-grade cancer. Cost effectiveness is crucial. The way forward is a multivariable risk assessment on the basis of readily available clinical data, potentially with the addition of PSA subforms, preferably at low cost. MRI in the prediagnostic setting is promising, but is not ready for 'prime time'.
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Affiliation(s)
- Sigrid V Carlsson
- aMemorial Sloan Kettering Cancer Center, Departments of Surgery and Epidemiology & Biostatistics, New York, USA bInstitute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden cDepartment of Urology, Erasmus Medical Center, Rotterdam, The Netherlands
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Wang FB, Chen R, Ren SC, Shi XL, Zhu YS, Zhang W, Jing TL, Zhang C, Gao X, Hou JG, Xu CL, Sun YH. Prostate cancer antigen 3 moderately improves diagnostic accuracy in Chinese patients undergoing first prostate biopsy. Asian J Androl 2017; 19:238-243. [PMID: 26780868 PMCID: PMC5312226 DOI: 10.4103/1008-682x.167715] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Prostate cancer antigen 3 (PCA3) is a biomarker for diagnosing prostate cancer (PCa) identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA (0.750 vs 0.622, P = 0.046) in patients with a PSA of 4.0–10.0 ng ml−1, but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%–40% in patients with a PSA of 4.0–10.0 ng ml−1. However, the AUC of the PCA3 score (0.712) is not superior to %fPSA (0.698) or PSAD (0.773) in patients with a PSA >10.0 ng ml−1. Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0–10.0 ng ml−1.
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Affiliation(s)
- Fu-Bo Wang
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Rui Chen
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Shan-Cheng Ren
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Xiao-Lei Shi
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Ya-Sheng Zhu
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Wei Zhang
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Tai-Le Jing
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Chao Zhang
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Xu Gao
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Jian-Guo Hou
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Chuan-Liang Xu
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Ying-Hao Sun
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China
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Zheng K, Dou Y, He L, Li H, Zhang Z, Chen Y, Ye A, Liu W, Kong L. Improved sensitivity and specificity for prostate cancer diagnosis based on the urine PCA3/PSA ratio acquired by sequence‑specific RNA capture. Oncol Rep 2015; 34:2439-44. [PMID: 26351770 DOI: 10.3892/or.2015.4266] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2015] [Accepted: 07/17/2015] [Indexed: 11/05/2022] Open
Abstract
Prostate cancer antigen 3 (PCA3) is a non-coding RNA fragment that is overexpressed in prostate cancer cells. However, the clinical applications of PCA3 are highly limited due to the instability of RNA and the lack of reliable and efficient RNA extraction and purification methods. Thus, in the present study, we compared three different methods of RNA extraction to further confirm the higher yield of commercial magnetic beads with poly-T functionalization and a capturer strand. The current protocols for RNA extraction of i) the phenol-chloroform method, ii) the affinity column method and iii) magnetic beads with poly-T functionalization and a capturer strand were applied separately for RNA extraction in urine samples. Reverse transcription‑quantitative polymerase chain reaction was performed to evaluate the yield of the three methods of RNA extraction. Furthermore, 52 urine samples after prostate massage from patients suspected of a diagnosis of prostate cancer were collected. The Mag-Cap method and RT-PCR were applied to obtain the PCA3 score. The clinical value of the PCA3 score was investigated by comparison with the pathology of the prostate biopsy. The yield of the Mag-Cap method was higher than that of the phenol‑chloroform method and commercial kits. Thirty‑four patients were pathologically diagnosed with prostate cancer and 18 with benign prostatic hyperplasia (BPH). It was confirmed that the median PCA3 score was higher among the prostate cancer patients than those with benign disease (53.5 vs. 17, p=0.000). A sensitivity of 82.4% and a specificity of 77.8% were obtained when the cut-off value for the PCA3 score was 28.5. The Mag-Cap method was found to be more efficient for RNA extraction. The urinary PCA3 score is a promising method for prostate cancer screening, detection and diagnosis, and has the potential to reduce unnecessary prostate biopsies.
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Affiliation(s)
- Kewen Zheng
- Urology Department, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China
| | - Yaling Dou
- Laboratory Medicine Department, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China
| | - Linfu He
- Institute of Bioengineering, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Hanzhong Li
- Urology Department, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China
| | - Zhicai Zhang
- Institute of Bioengineering, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Yu Chen
- Laboratory Medicine Department, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China
| | - Ali Ye
- Laboratory Medicine Department, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China
| | - Wenjing Liu
- Laboratory Medicine Department, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China
| | - Lingjun Kong
- Laboratory Medicine Department, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China
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Roberts MJ, Chow CWK, Schirra HJ, Richards R, Buck M, Selth LA, Doi SAR, Samaratunga H, Perry-Keene J, Payton D, Yaxley J, Lavin MF, Gardiner RA. Diagnostic performance of expression of PCA3, Hepsin and miR biomarkers inejaculate in combination with serum PSA for the detection of prostate cancer. Prostate 2015; 75:539-49. [PMID: 25597828 DOI: 10.1002/pros.22942] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Accepted: 11/11/2014] [Indexed: 11/08/2022]
Abstract
BACKGROUND AND METHODS Here, we report on the evaluation of the diagnostic performance of ejaculate-derived PCA3, Hepsin, and miRNAs to complement serum PSA to detect prostate cancer. cDNA was prepared from 152 candidate specimens following RNA isolation and amplification for PSA, PCA3 and Hepsin qPCR, with 66 having adequate RNA for all three assays. Small RNA sequencing and examination of PCa-associated miRNAs miR-200b, miR-200c, miR-375 and miR-125b was performed on 20 specimens. We compared findings from prostate biopsies using D'Amico and PRIAS classifications and in relation to whole gland histopathology following radical prostatectomy. Multivariate logistic regression modeling and clinical risk (incorporating standard clinicopathological variables) were performed for all ejaculate-based markers. RESULTS While Hepsin alone was not of predictive value, the Hepsin:PCA3 ratio together with serum PSA, expressed as a univariate composite score based on multivariate logistic regression, was shown to be a better predictor than PSA alone of prostate cancer status (AUC 0.724 vs. 0.676) and risk, using D'Amico (AUC 0.701 vs. 0.680) and PRIAS (AUC 0.679 vs. 0.659) risk stratification criteria as classified using prostate biopsies. It was also possible to analyse a subgroup of patients for miRNA expression with miR-200c (AUC 0.788) and miR-375 (AUC 0.758) showing best single marker performance, while a combination of serum PSA, miR-200c, and miR-125b further improved prediction for prostate cancer status when compared to PSA alone determined by biopsy (AUC 0.869 vs. 0.672; P < 0.05), and risk (D'Amico/PRIAS) as well as by radical prostatectomy histology (AUC 0.809 vs. 0.690). For prostate cancer status by biopsy, at a sensitivity of 90%, the specificity of the test increased from 11% for PSA alone to 67% for a combination of PSA, miR-200c, and miR-125b. CONCLUSIONS These results show that use of a combination of different types of genetic markers in ejaculate together with serum PSA are at least as sensitive as those reported in DRE urine. Furthermore, a combination of serum PSA and selected miRNAs improved prediction of prostate cancer status. This approach may be helpful in triaging patients for MRI and biopsy, when confirmed by larger studies.
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Affiliation(s)
- Matthew J Roberts
- The University of Queensland, Centre for Clinical Research, Brisbane, Qld, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, Australia; The University of Queensland, Centre for Advanced Imaging, Brisbane, Qld, Australia
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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.
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Birnbaum JK, Feng Z, Gulati R, Fan J, Lotan Y, Wei JT, Etzioni R. Projecting Benefits and Harms of Novel Cancer Screening Biomarkers: A Study of PCA3 and Prostate Cancer. Cancer Epidemiol Biomarkers Prev 2015; 24:677-82. [PMID: 25613117 DOI: 10.1158/1055-9965.epi-14-1224] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Accepted: 01/06/2015] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND New biomarkers for early detection of cancer must pass through several phases of development. Early phases provide information on diagnostic properties but not on population benefits and harms. Prostate cancer antigen 3 (PCA3) is a promising prostate cancer biomarker still in early development. We use simulation modeling to project the impact of adding PCA3 to prostate-specific antigen (PSA) screening on prostate cancer detection and mortality in the United States. METHODS We used data from a recent study of PCA3 in men referred for prostate biopsy to extend an existing simulation model of PSA growth, disease progression, and survival. We specified several PSA-PCA3 strategies designed to improve specificity and reduce overdiagnosis. Using these strategies to screen a cohort of men biennially between ages 50 and 74, we projected true- and false-positive tests, overdiagnoses, and lives saved relative to a PSA-based strategy with a cutoff of 4.0 ng/mL for biopsy referral. RESULTS We identified several PSA-PCA3 strategies that substantially reduced false-positive tests and overdiagnoses while preserving the majority of lives saved. PCA3>35 for biopsy referral in men with PSA between 4.0 and 10.0 ng/mL retained 85% of lives saved while approximately halving false positives and reducing overdiagnoses by 25%. CONCLUSIONS Adding PCA3 to PSA screening can significantly reduce adverse screening outcomes. Strategies can be identified that preserve most of the lives saved relative to PSA-based screening. IMPACT Simulation modeling provides advance projections of population outcomes of new screening biomarkers and may help guide early detection research.
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Affiliation(s)
- Jeanette K Birnbaum
- Department of Health Services, University of Washington, Seattle, Washington.
| | - Ziding Feng
- MD Anderson Cancer Center, Houston, Texas. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Biostatistics, University of Washington, Seattle, Washington
| | - Roman Gulati
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Jing Fan
- Department of Biostatistics, University of Washington, Seattle, Washington
| | - Yair Lotan
- Department of Urology, UT Southwestern Medical Center at Dallas, Dallas, Texas
| | - John T Wei
- Department of Urology, University of Michigan, Ann Arbor, Michigan
| | - Ruth Etzioni
- Department of Health Services, University of Washington, Seattle, Washington. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Biostatistics, University of Washington, Seattle, Washington
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Foj L, Milà M, Mengual L, Luque P, Alcaraz A, Jiménez W, Filella X. Real-time PCR PCA3 assay is a useful test measured in urine to improve prostate cancer detection. Clin Chim Acta 2014; 435:53-8. [DOI: 10.1016/j.cca.2014.04.025] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Revised: 04/25/2014] [Accepted: 04/25/2014] [Indexed: 11/16/2022]
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Ralla B, Stephan C, Meller S, Dietrich D, Kristiansen G, Jung K. Nucleic acid-based biomarkers in body fluids of patients with urologic malignancies. Crit Rev Clin Lab Sci 2014; 51:200-31. [PMID: 24878357 DOI: 10.3109/10408363.2014.914888] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
This review focuses on the promising potential of nucleic acids in body fluids such as blood and urine as diagnostic, prognostic, predictive and monitoring biomarkers in urologic malignancies. The tremendous progress in the basic knowledge of molecular processes in cancer, as shown in the companion review on nucleic acid-based biomarkers in tissue of urologic tumors, provides a strong rationale for using these molecular changes as non-invasive markers in body fluids. The changes observed in body fluids are an integrative result, reflecting both tissue changes and processes occurring in the body fluids. The availability of sensitive methods has only recently made possible detailed studies of DNA- and RNA-based markers in body fluids. In addition to these biological aspects, methodological aspects of the determination of nucleic acids in body fluids, i.e. pre-analytical, analytical and post-analytical issues, are particularly emphasized. The characteristic changes of RNA (differential mRNA and miRNA expression) and DNA (concentrations, integrity index, mutations, microsatellite and methylation alterations) in serum/plasma and urine samples of patients suffering from the essential urologic cancers of the prostate, bladder, kidney and testis are summarized and critically discussed below. To translate the promising results into clinical practice, laboratory scientists and clinicians have to collaborate to resolve the challenges of harmonized and feasible pre-analytical and analytical conditions for the selected markers and to validate these markers in well-designed and sufficiently powered multi-center studies.
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Affiliation(s)
- Bernhard Ralla
- Department of Urology, Charité - Universitätsmedizin Berlin , Berlin , Germany
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Stephan C, Ralla B, Jung K. Prostate-specific antigen and other serum and urine markers in prostate cancer. Biochim Biophys Acta Rev Cancer 2014; 1846:99-112. [PMID: 24727384 DOI: 10.1016/j.bbcan.2014.04.001] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2013] [Revised: 03/24/2014] [Accepted: 04/01/2014] [Indexed: 11/16/2022]
Abstract
Prostate-specific antigen (PSA) is one of the most widely used tumor markers, and strongly correlates with the risk of harboring from prostate cancer (PCa). This risk is visible already several years in advance but PSA has severe limitations for PCa detection with its low specificity and low negative predictive value. There is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. From all PSA-based markers, the FDA-approved Prostate Health Index (phi) shows improved specificity over percent free and total PSA. Other serum kallikreins or sarcosine in serum or urine show more diverging data. In urine, the FDA-approved prostate cancer gene 3 (PCA3) has also proven its utility in the detection and management of early PCa. However, some aspects on its correlation with aggressiveness and the low sensitivity at very high values have to be re-examined. The detection of a fusion of the androgen regulated TMPRSS2 gene with the ERG oncogene (from the ETS family), which acts as transcription factor gene, in tissue of ~50% of all PCa patients was one milestone in PCa research. When combining the urinary assays for TMPRSS2:ERG and PCA3, an improved accuracy for PCa detection is visible. PCA3 and phi as the best available PCa biomarkers show an equal performance in direct comparisons.
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Affiliation(s)
- Carsten Stephan
- Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute for Urologic Research, Berlin, Germany.
| | - Bernhard Ralla
- Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Klaus Jung
- Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute for Urologic Research, Berlin, Germany
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Capoluongo E, Zambon CF, Basso D, Boccia S, Rocchetti S, Leoncini E, Palumbo S, Padoan A, Albino G, Todaro A, Prayer-Galetti T, Zattoni F, Zuppi C, Plebani M. PCA3 score of 20 could improve prostate cancer detection: Results obtained on 734 Italian individuals. Clin Chim Acta 2014; 429:46-50. [DOI: 10.1016/j.cca.2013.10.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Revised: 09/23/2013] [Accepted: 10/22/2013] [Indexed: 01/29/2023]
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Imaging and Markers as Novel Diagnostic Tools in Detecting Insignificant Prostate Cancer: A Critical Overview. INTERNATIONAL SCHOLARLY RESEARCH NOTICES 2014; 2014:243080. [PMID: 27351008 PMCID: PMC4897503 DOI: 10.1155/2014/243080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 05/19/2014] [Indexed: 11/22/2022]
Abstract
Recent therapeutic advances for managing low-risk prostate cancer include the active surveillance and focal treatment. However, locating a tumor and detecting its volume by adequate sampling is still problematic. Development of predictive biomarkers guiding individual therapeutic choices remains an ongoing challenge. At the same time, prostate cancer magnetic resonance imaging is gaining increasing importance for prostate diagnostics. The high morphological resolution of T2-weighted imaging and functional MRI methods may increase the specificity and sensitivity of diagnostics. Also, recent studies founded an ability of novel biomarkers to identify clinically insignificant prostate cancer, risk of progression, and association with poor differentiation and, therefore, with clinical significance. Probably, the above mentioned methods would improve tumor characterization in terms of its volume, aggressiveness, and focality. In this review, we attempted to evaluate the applications of novel imaging techniques and biomarkers in assessing the significance of the prostate cancer.
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Pepe P, Fraggetta F, Galia A, Skonieczny G, Aragona F. PCA3 score and prostate cancer diagnosis at repeated saturation biopsy. Which cut-off: 20 or 35? Int Braz J Urol 2013; 38:489-95. [PMID: 22951161 DOI: 10.1590/s1677-55382012000400008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2012] [Indexed: 11/21/2022] Open
Abstract
PURPOSE To compare PCA3 score cut-off of 35 vs 20 in PCa diagnosis in patients undergoing repeated saturation prostate biopsy (SPBx). MATERIAL AND METHODS From January 2010 to May 2011, 118 patients (median 62.5 years) with primary negative extended biopsy underwent a transperineal SPBx (median 30 cores) for persistent suspicion of PCa. The indications for repeated biopsy were: persistently high or increasing PSA values; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA ≤ 25% and ≤ 20 %, respectively; moreover, before performing SPBx urinary PCA3 score was evaluated. RESULTS All patients had negative DRE and median PSA was 8.5 ng/mL (range: 3.7-24 ng/mL). A T1c PCa was found in 32 patients (27.1 %): PCA3 score was 59 (median; range: 7-201) in the presence of PCa and 35 (median; range: 3-253) in the absence of cancer (p < 0.05). In the presence of ASAP and HGPIN median PCA3 score was 109 (range: 42-253) and 40 (range: 30-140), respectively. Diagnostic accuracy, sensitivity, specificity, PPV and NPV of PCA3 score cut-off of 20 vs 35 in PCa diagnosis were 44.9 vs 50 %, 90.6 vs 71.9 %, 27.9 vs 41.8 %, 31.9 vs 31.5 % and 88.9 vs 80 %, respectively. ROC analysis demonstrated an AUC for PCA3 ≥ 20 vs ≥ 35 of 0.678 and 0.634, respectively. CONCLUSIONS Our data suggest that PCA3 is more useful as an exclusion tool; moreover, setting a PCA3 cut-off at 20 vs 35, would have avoided 22.9 vs 38.1 % of biopsies while missing 9.4 % and 28 % diagnosis of PCa.
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Affiliation(s)
- Pietro Pepe
- Urology Unit, Cannizzaro Hospital, Pathology Unit, Cannizzaro Hospital and Department of Economy, University of Catania, Catania, Italy.
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PCA3 in the detection and management of early prostate cancer. Tumour Biol 2013; 34:1337-47. [PMID: 23504524 DOI: 10.1007/s13277-013-0739-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Accepted: 03/05/2013] [Indexed: 01/23/2023] Open
Abstract
Although widely used, the value of prostate-specific antigen (PSA) in the detection of prostate cancer is controversial. The percentage of free PSA increases the specificity of PSA, but results are not enough. Prostate cancer gene 3 (PCA3) has been proposed as an option that may complement these markers in the detection and management of early prostate cancer. Our aim has been to review the value of PCA3 as tumor marker. The available results suggest that PCA3 is particularly useful to select in which patients the biopsy should be repeated when the first biopsy was negative. However, some points should be specified with further studies, including the most appropriate PCA3 cutoff level and the significance of a high PCA3 score in patients with negative biopsy. False-negative results are also a conflictive point in the use of PCA3, because prostate cancer, including aggressive tumors, may be present in patients with a low PCA3 score. Probably, a proper interpretation of this test requires its management together with other tests, through multivariate models for the detection of prostate cancer. On the other hand, several studies showed the relation between PCA3 score and Gleason score, and also the utility of PCA3 to select patients for active surveillance. To summarize, the available studies show the utility of PCA3 in the detection and management of early prostate cancer, although some aspects referred to its use need to be retested after further studies to confirm the actual value and the limitations of this test.
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Perdonà S, Bruzzese D, Ferro M, Autorino R, Marino A, Mazzarella C, Perruolo G, Longo M, Spinelli R, Di Lorenzo G, Oliva A, De Sio M, Damiano R, Altieri V, Terracciano D. Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy. Prostate 2013; 73:227-35. [PMID: 22821756 DOI: 10.1002/pros.22561] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2012] [Accepted: 06/18/2012] [Indexed: 10/28/2022]
Abstract
BACKGROUND Prostate health index (phi) and prostate cancer antigen 3 (PCA3) have been recently proposed as novel biomarkers for prostate cancer (PCa). We assessed the diagnostic performance of these biomarkers, alone or in combination, in men undergoing first prostate biopsy for suspicion of PCa. METHODS One hundred sixty male subjects were enrolled in this prospective observational study. PSA molecular forms, phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay), and other established biomarkers (tPSA, fPSA, and %fPSA) were assessed before patients underwent a 18-core first prostate biopsy. The discriminating ability between PCa-negative and PCa-positive biopsies of Beckman coulter phi and PCA3 score and other used biomarkers were determined. RESULTS One hundred sixty patients met inclusion criteria. %p2PSA (p2PSA/fPSA × 100), phi and PCA3 were significantly higher in patients with PCa compared to PCa-negative group (median values: 1.92 vs. 1.55, 49.97 vs. 36.84, and 50 vs. 32, respectively, P ≤ 0.001). ROC curve analysis showed that %p2PSA, phi, and PCA3 are good indicator of malignancy (AUCs = 0.68, 0.71, and 0.66, respectively). A multivariable logistic regression model consisting of both the phi index and PCA3 score allowed to reach an overall diagnostic accuracy of 0.77. Decision curve analysis revealed that this "combined" marker achieved the highest net benefit over the examined range of the threshold probability. CONCLUSIONS phi and PCA3 showed no significant difference in the ability to predict PCa diagnosis in men undergoing first prostate biopsy. However, diagnostic performance is significantly improved by combining phi and PCA3.
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Affiliation(s)
- Sisto Perdonà
- Urology Unit, IRCCS Fondazione G. Pascale, Napoli, Italy
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De Luca S, Passera R, Milillo A, Coda R, Randone DF. Histological chronic prostatitis and high-grade prostate intra-epithelial neoplasia do not influence urinary prostate cancer gene 3 score. BJU Int 2012; 110:E778-82. [DOI: 10.1111/j.1464-410x.2012.11645.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2012] [Indexed: 11/29/2022]
Affiliation(s)
| | - Roberto Passera
- Division of Nuclear Medicine 2; San Giovanni Battista Hospital and University of Torino; Italy
| | - Angela Milillo
- Department of Laboratory Medicine; Gradenigo Hospital; Italy
| | - Renato Coda
- Department of Pathology; Gradenigo Hospital and University of Torino; Torino; Italy
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Lazzeri M, Briganti A, Scattoni V, Lughezzani G, Larcher A, Gadda GM, Lista G, Cestari A, Buffi N, Bini V, Freschi M, Rigatti P, Montorsi F, Guazzoni G. Serum Index Test %[-2]proPSA and Prostate Health Index are More Accurate than Prostate Specific Antigen and %fPSA in Predicting a Positive Repeat Prostate Biopsy. J Urol 2012; 188:1137-43. [DOI: 10.1016/j.juro.2012.06.017] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2012] [Indexed: 11/29/2022]
Affiliation(s)
- Massimo Lazzeri
- Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy
| | - Alberto Briganti
- Department of Urology, Vita-Salute San Raffaele University, Milan, Italy
| | - Vincenzo Scattoni
- Department of Urology, Vita-Salute San Raffaele University, Milan, Italy
| | - Giovanni Lughezzani
- Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy
| | - Alessandro Larcher
- Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy
| | - Giulio Maria Gadda
- Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy
| | - Giuliana Lista
- Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy
| | - Andrea Cestari
- Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy
| | - Nicolòmaria Buffi
- Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy
| | - Vittorio Bini
- Department of Internal Medicine, University of Perugia, Perugia, Italy
| | - Massimo Freschi
- Department of Pathology, Vita-Salute San Raffaele University, Milan, Italy
| | - Patrizio Rigatti
- Department of Urology, Vita-Salute San Raffaele University, Milan, Italy
| | - Francesco Montorsi
- Department of Urology, Vita-Salute San Raffaele University, Milan, Italy
| | - Giorgio Guazzoni
- Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy
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Ramos CG, Valdevenito R, Vergara I, Anabalon P, Sanchez C, Fulla J. PCA3 sensitivity and specificity for prostate cancer detection in patients with abnormal PSA and/or suspicious digital rectal examination. First Latin American experience. Urol Oncol 2012; 31:1522-6. [PMID: 22687565 DOI: 10.1016/j.urolonc.2012.05.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Revised: 05/05/2012] [Accepted: 05/07/2012] [Indexed: 10/28/2022]
Abstract
INTRODUCTION Prostate Cancer Gene 3 (PCA3) is a recently described and highly specific urinary marker for prostate cancer (CaP). Its introduction in clinical practice to supplement low specificity of prostate specific antigen (PSA) can improve CaP diagnosis and follow-up. However, before its introduction, it is necessary to validate the method of PCA3 detection in distinct geographic populations. OBJECTIVES Our aim was to describe for the first time in Latin America, the application of the PROGENSA PCA3 assay for PCA3 detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate biopsy. MATERIALS AND METHODS Sixty-four Chilean patients (mean age, 64 years) with indication of prostate biopsy because of elevated PSA and/or suspicious digital rectal examination (DRE) were prospectively recruited. PCA3 scores were assessed from urine samples obtained after DRE, before biopsy, and compared with PSA levels and biopsy outcome. RESULTS The median PSA value and mean PCA3 score were 5.8 ng/ml and 31.7, respectively. Using a cutoff PCA3 score of 35, the sensitivity and specificity for detecting CaP were 52% and 87%, respectively. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA, for the same group of patients. In patients with previous negative biopsy, PCA3 specificity increased by 2.2%. CONCLUSIONS This is the first report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those reported in other populations in the literature, demonstrating the reproducibility of the test. PCA3 score was highly specific and we specially recommend its use in patients with persistent elevated PSA and prior negative biopsies.
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Zhu X, Albertsen PC, Andriole GL, Roobol MJ, Schröder FH, Vickers AJ. Risk-based prostate cancer screening. Eur Urol 2011; 61:652-61. [PMID: 22134009 DOI: 10.1016/j.eururo.2011.11.029] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2011] [Accepted: 11/15/2011] [Indexed: 11/30/2022]
Abstract
CONTEXT Widespread mass screening of prostate cancer (PCa) is not recommended because the balance between benefits and harms is still not well established. The achieved mortality reduction comes with considerable harm such as unnecessary biopsies, overdiagnoses, and overtreatment. Therefore, patient stratification with regard to PCa risk and aggressiveness is necessary to identify those men who are at risk and may actually benefit from early detection. OBJECTIVE This review critically examines the current evidence regarding risk-based PCa screening. EVIDENCE ACQUISITION A search of the literature was performed using the Medline database. Further studies were selected based on manual searches of reference lists and review articles. EVIDENCE SYNTHESIS Prostate-specific antigen (PSA) has been shown to be the single most significant predictive factor for identifying men at increased risk of developing PCa. Especially in men with no additional risk factors, PSA alone provides an appropriate marker up to 30 yr into the future. After assessment of an early PSA test, the screening frequency may be determined based on individualized risk. A limited list of additional factors such as age, comorbidity, prostate volume, family history, ethnicity, and previous biopsy status have been identified to modify risk and are important for consideration in routine practice. In men with a known PSA, risk calculators may hold the promise of identifying those who are at increased risk of having PCa and are therefore candidates for biopsy. CONCLUSIONS PSA testing may serve as the foundation for a more risk-based assessment. However, the decision to undergo early PSA testing should be a shared one between the patient and his physician based on information balancing its advantages and disadvantages.
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Affiliation(s)
- Xiaoye Zhu
- Department of Urology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
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Roobol MJ. Prostate cancer biomarkers to improve risk stratification: is our knowledge of prostate cancer sufficient to spare prostate biopsies safely? Eur Urol 2011; 60:223-5; discussion 228-30. [PMID: 21514038 DOI: 10.1016/j.eururo.2011.04.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2011] [Accepted: 04/06/2011] [Indexed: 11/16/2022]
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