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

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3373
Author(s):  
Milena Matuszczak ◽  
Jack A. Schalken ◽  
Maciej Salagierski

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.

Author(s):  
Adriano Basso Dias ◽  
Ciara O’Brien ◽  
Jean-Michel Correas ◽  
Sangeet Ghai

Prostate cancer (PCa) is the most common non-cutaneous cancer diagnosed in males. Traditional tools for screening and diagnosis, such as prostate-specific antigen, digital rectal examination and conventional transrectal ultrasound (TRUS), present low accuracy for PCa detection. Multiparametric MRI has become a game changer in the PCa diagnosis pathway and MRI-targeted biopsies are currently recommended for males at risk of clinically significant PCa, even in biopsy-naïve patients. Recent advances in ultrasound have also emerged with the goal to provide a readily accessible and cost-effective tool for detection of PCa. These newer techniques include elastography and contrast-enhanced ultrasound, as well as improved B-mode and Doppler techniques. These modalities can be combined to define a novel ultrasound approach, multiparametric ultrasound. High frequency Micro-ultrasound has emerged as a promising imaging technology for PCa diagnosis. Initial results have shown high sensitivity of Micro-ultrasound in detecting PCa in addition to its potential in improving the accuracy of targeted biopsies, based on targeting under real-time visualization, rather than relying on cognitive/fusion software MRI-transrectal ultrasound-guided biopsy.


Author(s):  
Xavier Filella ◽  
Laura Foj

AbstractmicroRNAs (miRNAs) are small non-coding RNAs that control gene expression posttranscriptionally and are part of the giant non codifying genoma. Cumulating data suggest that miRNAs are promising potential biomarkers for many diseases, including cancer. Prostate cancer (PCa) detection is currently based in the serum prostate-specific antigen biomarker and digital rectal examination. However, these methods are limited by a low predictive value and the adverse consequences associated with overdiagnosis and overtreatment. New biomarkers that could be used for PCa detection and prognosis are still needed. Recent studies have demonstrated that aberrant expressions of microRNAs are associated with the underlying mechanisms of PCa. This review attempts to extensively summarize the current knowledge of miRNA expression patterns, as well as their targets and involvement in PCa pathogenesis. We focused our review in the value of circulating and urine miRNAs as biomarkers in PCa patients, highlighting the existing discrepancies between different studies, probably associated with the important methodological issues related to their quantitation and normalization. The majority of studies have been performed in serum or plasma, but urine obtained after prostate massage appears as a new way to explore the usefulness of miRNAs. Large screening studies to select a miRNA profile have been completed, but bioinformatics tools appear as a new approach to select miRNAs that are relevant in PCa development. Promising preliminary results were published concerning miR-141, miR-375 and miR-21, but larger and prospective studies using standardized methodology are necessary to define the value of miRNAs in the detection and prognosis of PCa.


2008 ◽  
Vol 54 (12) ◽  
pp. 1951-1960 ◽  
Author(s):  
Girish Sardana ◽  
Barry Dowell ◽  
Eleftherios P Diamandis

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.


1994 ◽  
Vol 61 (4) ◽  
pp. 270-276
Author(s):  
M. Calò ◽  
I. Malavolti ◽  
G. Cuscianna ◽  
F. Baldari ◽  
C.A. Pollastri ◽  
...  

To evaluate the usefulness of transrectal ultrasound associated with needle biopsy of the prostate, 365 patients, with age ranging between 50 and 80 years, were studied for a total of 412 biopsies; the ultrasound exam was performed when the clinical or the prostate specific antigen findings were pathological. Our experience confirms the high sensitivity and specificity of transrectal ultrasonography in detecting prostate cancer. It is our opinion that all the patients with positive or negative digital rectal examination but altered prostatic specific antigen or clinical exam should undergo transrectal ultrasonography associated with needle biopsy. The elevated operability of the studied patients shows the capability of ultrasound to detect the pathology in the early stages and its value in screening diagnosis should therefore be considered.


1997 ◽  
Vol 4 (2) ◽  
pp. 102-106 ◽  
Author(s):  
H G T Nijs ◽  
D M R Tordoir ◽  
J H Schuurman ◽  
W J Kirkels ◽  
F H Schroder

Abstract Objectives— To assess motives for attending a randomised population based prostate cancer screening trial, and to assess acceptance of screening and invitation procedures. Methods— First pilot of the European Randomised Study of Screening for Prostate Cancer (ERSPC; 1992/1993). Men aged 55–75 years, randomly selected from the population register of four city districts of Rotterdam, were invited by a single invitation for screening. Screening consisted of prostate specific antigen prescreening followed by either (1) digital rectal examination, transrectal ultrasound, and, on indication, biopsy, or (2) no additional screening. After screening, or in the case of non-attendance, a questionnaire was sent to a random sample of 600 attenders and 400 non-attenders, with a reminder after three weeks. Outcome measures— In both attenders and non-attenders: Knowledge of prostate cancer, attitudes towards screening, motives for attending, procedural aspects and sociodemographic characteristics. In attenders, acceptance of screening procedures. Results— The response rate for the questionnaire was 76%: 94% in attenders and 42% in non-attenders. The main reasons for attending were expected personal benefit (76%) and scientific value (39%), and those for not attending were the absence of urological complaints (41%) and anticipated pain or discomfort (24%). Uptake of screening was 32%, which increased to a sustained 42% in following years. Attenders, compared with non-attenders, were significantly younger, more often married, better educated, and had higher perceived health status, more knowledge about prostate cancer, and a more positive attitude towards screening. Information materials and invitation procedure were adequate. Screening procedures were well accepted (high report marks and satisfaction, and 95% would attend for rescreening). A single prostate specific antigen determination was liked less than a combination of all three screening modalities. Conclusions— (1) The main reasons for attending are personal benefit and science, and those for not attending were absence of urological complaints and anticipated pain or discomfort; (2) knowledge, attitudes, and motives for attending are comparable with other screening programmes; hence, for population based prostate cancer screening, known health promotional aspects should be carefully considered; (3) prostate specific antigen, digital rectal examination and transrectal ultrasound are acceptable to attenders.


Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 188 ◽  
Author(s):  
Jacob Fredsøe ◽  
Anne K. I. Rasmussen ◽  
Peter Mouritzen ◽  
Marianne T. Bjerre ◽  
Peter Østergren ◽  
...  

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


Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 81 ◽  
Author(s):  
Alexey S. Rzhevskiy ◽  
Sajad Razavi Bazaz ◽  
Lin Ding ◽  
Alina Kapitannikova ◽  
Nima Sayyadi ◽  
...  

During the last decade, isolation of circulating tumour cells via blood liquid biopsy of prostate cancer (PCa) has attracted significant attention as an alternative, or substitute, to conventional diagnostic tests. However, it was previously determined that localised forms of PCa shed a small number of cancer cells into the bloodstream, and a large volume of blood is required just for a single test, which is impractical. To address this issue, urine has been used as an alternative to blood for liquid biopsy as a truly non-invasive, patient-friendly test. To this end, we developed a spiral microfluidic chip capable of isolating PCa cells from the urine of PCa patients. Potential clinical utility of the chip was demonstrated using anti-Glypican-1 (GPC-1) antibody as a model of the primary antibody in immunofluorescent assay for identification and detection of the collected tumour cells. The microchannel device was first evaluated using DU-145 cells in a diluted Dulbecco’s phosphate-buffered saline sample, where it demonstrated >85 (±6) % efficiency. The microchannel proved to be functional in at least 79% of cases for capturing GPC1+ putative tumour cells from the urine of patients with localised PCa. More importantly, a correlation was found between the amount of the captured GPC1+ cells and crucial diagnostic and prognostic parameter of localised PCa—Gleason score. Thus, the technique demonstrated promise for further assessment of its diagnostic value in PCa detection, diagnosis, and prognosis.


1992 ◽  
Vol 59 (4) ◽  
pp. 52-55
Author(s):  
M. Moretti ◽  
A. Cichero ◽  
P. Pittaluga ◽  
M. Varaldo ◽  
Aldo V. Bono ◽  
...  

PSA is commonly used in diagnosing prostate cancer but it lacks both specificity and sensitivity; PSA values rise in benign prostatic affections and up to 30% prostate cancers show normal PSA values. Preliminary reports indicate that PSA DENSITY (PSAD), i.e. PSA/prostate-volume ratio, can improve specificity of PSA in diagnosing prostate cancer. We considered PSAD in 55 patients of 160 observed for prostatism: all of them underwent digital rectal examination, transrectal ultrasound and multiple biopsies of the gland. We found cancer in 19 patients (PSAD ranging from 0.17 to 1.77, with a mean value of 0.45), 26 prostatic hyperplasia (PSAD from 0.003 to 0.75, with a mean of 0.13), 6 dysplasia (PSAD from 0.07 to 0.30, with a mean of 0.19). In our experience PSAD > 0.17 or mean value > 0.45 indicate cancer in the absence of significant digital rectal examination and ultrasound findings or normal and borderline PSA values.


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