Emerging Biomarkers for the Diagnosis and Prognosis of Prostate Cancer

Abstract Background: Early detection of prostate cancer (CaP), the most prevalent cancer and the second-leading cause of death in men, has proved difficult, and current detection methods are inadequate. Prostate-specific antigen (PSA) testing is a significant advance for early diagnosis of patients with CaP. Content: PSA is produced almost exclusively in the prostate, and abnormalities of this organ are frequently associated with increased serum concentrations. Because of PSA’s lack of specificity for CaP, however, many patients undergo unnecessary biopsies or treatments for benign or latent tumors, respectively. Thus, a more specific method of CaP detection is required to augment or replace screening with PSA. The focus recently has been on creating cost-effective assays for circulating protein biomarkers in the blood, but because of the heterogeneity of CaP, it has become clear that this effort will be a formidable challenge. Each marker will require proper validation to ensure clinical utility. Although much work has been done on variations of the PSA test (i.e., velocity, density, free vs bound, proisoforms) with limited usefulness, there are many emerging markers at various stages of development that show some promise for CaP diagnosis. These markers include kallikrein-related peptidase 2 (KLK2), early prostate cancer antigen (EPCA), PCA3, hepsin, prostate stem cell antigen, and α-methylacyl-CoA racemase (AMACR). We review biomarkers under investigation for the early diagnosis and management of prostate cancer. Summary: It is hoped that the use of panels of markers can improve CaP diagnosis and prognosis and help predict the therapeutic response in CaP patients.

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Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Cancers ◽

10.3390/cancers13133373 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3373

Author(s):

Milena Matuszczak ◽

Jack A. Schalken ◽

Maciej Salagierski

Keyword(s):

Prostate Cancer ◽

Liquid Biopsy ◽

Current Knowledge ◽

Prostate Gland ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Digital Rectal Examination ◽

Cost Effective ◽

Non Invasive ◽

Diagnosis And Prognosis

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

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PSA screening for prostate cancer

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.63.08.722 ◽

2017 ◽

Vol 63 (8) ◽

pp. 722-725 ◽

Cited By ~ 2

Author(s):

Marcus V. Sadi

Keyword(s):

Quality Of Life ◽

Prostate Cancer ◽

Early Diagnosis ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Low Grade ◽

Psa Screening ◽

Psa Testing ◽

Baseline Values

Summary Screening of prostate cancer with prostate-specific antigen (PSA) is a highly controversial issue. One part of the controversy is due to the confusion between population screening and early diagnosis, another derives from problems related to the quality of existing screening studies, the results of radical curative treatment for low grade tumors and the complications resulting from treatments that affect the patient’s quality of life. Our review aimed to critically analyze the current recommendations for PSA testing, based on new data provided by the re-evaluation of the ongoing studies and the updated USPSTF recommendation statement, and to propose a more rational and selective use of PSA compared with baseline values obtained at an approximate age of 40 to 50 years.

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Prostatic Specific Antigen Less then 10 ng/mL in the Diagnostic and Surveillance of Prostate Cancer

Revista de Chimie ◽

10.37358/rc.17.5.5584 ◽

2017 ◽

Vol 68 (5) ◽

pp. 933-936

Author(s):

Nicolae Grigore ◽

Valentin Pirvut ◽

Ionela Mihai ◽

Adrian Hasegan ◽

Sebastian Ioan Cernusca Mitariu

Keyword(s):

Prostate Cancer ◽

Risk Assessment ◽

Early Diagnosis ◽

Clinical Management ◽

Specific Antigen ◽

Prostatic Specific Antigen ◽

Inclusion Criteria ◽

Diagnosis And Prognosis ◽

Therapeutic Decisions ◽

Risk Scale

Prostate cancer (PCa) is the most commonly diagnosed male malignancy after 60 years old. Today, the problem is to distinguish between low-risk and agrressive cancers, especially in patients with Prostatic Specific Antigen (PSA) less than 10 ng/ml The use of PSA as a biomarkers for diagnosis and prognosis of prostate cancer has the potential to improve the clinical management of the patients. PSA levels. together with clinical examination, prostate ultrasound and histopatological examination are esential for the diagnostic of PCa, risk assessment and therapeutic decisions. The aim of our study is to evaluate the patients with PSA values less then 10 ng/mL and to determine the correct indications for tratment depending on the risk scale of the disease. The inclusion criteria for the patients are described in the paper. For improving the early diagnosis of PCa in patients with PSA below 10 ng/mL we developed an algoritm based on current opportunities.

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Update on PSA Testing

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2007.0065 ◽

2007 ◽

Vol 5 (7) ◽

pp. 737-742 ◽

Cited By ~ 10

Author(s):

Mark L. Gonzalgo ◽

H. Ballentine Carter

Keyword(s):

Prostate Cancer ◽

Cancer Screening ◽

Prostate Cancer Screening ◽

Specific Antigen ◽

Cost Effective ◽

The Past ◽

Psa Testing ◽

Screening Strategies ◽

Total Psa ◽

Over Time

The use of prostate-specific antigen (PSA) testing for prostate cancer screening has increased dramatically over the past decade. Determining the most efficient way to use PSA testing and how to interpret total PSA levels and changes in PSA values over time remain challenging. Guidelines for early detection of prostate cancer have a direct impact on the number of unnecessary tests performed and are critical for developing a successful screening approach for prostate cancer. The age at which PSA screening should begin, PSA testing intervals, and the importance of understanding fluctuations in PSA values over time are discussed in the framework of recent discoveries in the field. Results from ongoing randomized trials will confirm whether prostate cancer screening is an effective method for reducing deaths from prostate cancer and what approaches will provide the most cost-effective screening strategies.

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Systematic Review of cost-effectiveness models in prostate cancer: exploring new developments in testing and diagnosis

10.21203/rs.3.rs-32349/v1 ◽

2020 ◽

Author(s):

Edna Keeney ◽

Howard Thom ◽

Emma Turner ◽

Richard M Martin ◽

Josie Morley ◽

...

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Cost Effectiveness ◽

Prostate Cancer Screening ◽

Specific Antigen ◽

Cost Effective ◽

Economic Evaluations ◽

Psa Testing ◽

Mri Guided ◽

The Cost

Abstract Background There is currently no formal prostate cancer screening programme in the UK. Early detection using age-based prostate-specific antigen (PSA) testing is unlikely to be cost-effective due to limited mortality benefit and harms associated with overdetection. However, the discovery of new prostate cancer specific biomarkers and more accurate diagnostic strategies (e.g. magnetic resonance imaging (MRI)) could improve the outcomes of screening. A systematic review was conducted to assess the evidence base on cost-effectiveness of such innovations and areas for further development. Methods To identify model-based economic evaluations of screening and diagnostic tests for prostate cancer, a systematic review of the literature using the NHS Economic Evaluation Database, Medline, EMBASE, HTA databases, NICE guidelines, and UK National Screening Committee guidance was carried out, between 2009 and 2019. Relevant data were extracted on study type, model inputs, modelling methods and cost-effectiveness conclusions and the results narratively synthesized. Results Sixteen studies were included in the review. Seven studies compared the cost-effectiveness of new urinary or blood biomarkers compared to each other or the PSA test and found the biomarkers e.g. the Prostate Health Index (PHI) and SelectMDx, to be the most cost-effective. Seven studies compared newer prostate biopsy methods, including MRI-guided, to TRUS guided biopsy and found MRI-guided methods to be most cost-effective. The newer detection methods showed a reduction in unnecessary biopsies and overtreatment. However, there was uncertainty around the most cost-effective pathway of follow-up strategies (MRI/biomarkers) in men who have a negative initial biopsy. Many studies did not model stage or grade of cancer, cancer progression or the entire testing, screening and treatment pathway. Very few studies fully accounted for uncertainty in their analysis. Conclusions This review brings together the cost-effectiveness literature for novel screening and testing methods used in the diagnosis of prostate cancer. Several limitations of the published models were identified. The models generally either compared new biomarkers or new imaging techniques which highlights the importance of future work in this area, as biomarkers and imaging are likely to be used in combination.

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197: Prostate Cancer Screening Strategies with Rescreening Interval Determined by Individual Baseline Prostate-Specific Antigen Values are Cost-Effective

The Journal of Urology ◽

10.1016/s0022-5347(18)30462-2 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 66-66

Author(s):

Takashi Kobayashi ◽

Rei Goto ◽

Kazuto Ito ◽

Osamu Ogawa

Keyword(s):

Prostate Cancer ◽

Cancer Screening ◽

Prostate Specific Antigen ◽

Prostate Cancer Screening ◽

Specific Antigen ◽

Cost Effective ◽

Screening Strategies

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

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200224100730 ◽

2020 ◽

Vol 20 (10) ◽

pp. 847-854

Author(s):

Ronald Bartzatt

Keyword(s):

Prostate Cancer ◽

Cancer Treatment ◽

Prostate Specific Antigen ◽

Cancer Biology ◽

Early Stage ◽

Specific Antigen ◽

Detection Methods ◽

Hormone Refractory Prostate Cancer ◽

High Risk Prostate Cancer ◽

Hormone Refractory

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

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DNA aptamer-based detection of prostate cancer

Chemical Papers ◽

10.1515/chempap-2015-0025 ◽

2015 ◽

Vol 69 (1) ◽

Cited By ~ 24

Author(s):

Pawan Jolly ◽

Nello Formisano ◽

Pedro Estrela

Keyword(s):

Prostate Cancer ◽

Point Of Care ◽

Specific Antigen ◽

Analytical Techniques ◽

Cost Effective ◽

Dna Aptamer ◽

Clinical Samples ◽

Gradual Transition ◽

Long Term Stability ◽

Promising Tool

AbstractThe use of aptamers in biosensing has attracted considerable attention as an alternative to antibodies because of their unique properties such as long-term stability, cost-effectiveness and adjustability to various applications. Among cancers, the early diagnosis of prostate cancer (PCa) is one of the greatest concerns for ageing men worldwide. One of the most commonly used biomarkers for PCa is prostate-specific antigen (PSA), which can be found in elevated levels in patients with cancer. This review presents the gradual transition of research from antibody-based to aptamerbased biosensors, specifically for PSA. A brief description on aptamer-based biosensing for other PCa biomarkers is also presented. Special attention is given to electrochemical methods as analytical techniques for the development of simple, sensitive and cost-effective biosensors. The review also focuses on the different surface chemistries exploited for fabrication and their applications in clinical samples. The use of aptamers represents a promising tool for the development of point-ofcare biosensors for the early detection of prostate cancer. In view of the unmatched upper hand of aptamers, future prospects are also discussed, not only in the point-of-care format but also in other novel applications.

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Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies

AJP Cell Physiology ◽

10.1152/ajpcell.00048.2021 ◽

2021 ◽

Author(s):

Dan Li ◽

Wenjia Lai ◽

Di Fan ◽

Qiaojun Fang

Keyword(s):

Breast Cancer ◽

Early Diagnosis ◽

Extracellular Vesicles ◽

Liquid Biopsy ◽

Breast Cancer Diagnosis ◽

Extracellular Vesicle ◽

Detection Methods ◽

Protein Markers ◽

Liquid Biopsies ◽

Diagnosis And Prognosis

Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their non-invasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.

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