scholarly journals Accuracy of Tumour-Associated Circulating Endothelial Cells as a Screening Biomarker for Clinically Significant Prostate Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1064 ◽  
Author(s):  
Sebastian Chakrit Bhakdi ◽  
Prapat Suriyaphol ◽  
Ponpan Thaicharoen ◽  
Sebastian Tobias Karl Grote ◽  
Chulaluk Komoltri ◽  
...  

Even though more than 350,000 men die from prostate cancer every year, broad-based screening for the disease remains a controversial topic. Guidelines demand that the only commonly accepted screening tool, prostate-specific antigen (PSA) testing, must be followed by prostate biopsy if results are elevated. Due to the procedure’s low positive predictive value (PPV), however, over 80% of biopsies are performed on healthy men or men with clinically insignificant cancer—prompting calls for new ways of vetting equivocal PSA readings prior to the procedure. Responding to the challenge, the present study investigated the diagnostic potential of tumour-associated circulating endothelial cells (tCECs), which have previously been described as a novel, blood-based biomarker for clinically significant cancers. Specifically, the objective was to determine the diagnostic accuracy of a tCEC-based blood test to detect clinically significant prostate cancer (defined as Gleason score ≥ 3 + 4) in high-risk patients. Performed in a blinded, prospective, single-centre set-up, it compared a novel tCEC index test with transrectal ultrasound-guided biopsy biopsy as a reference on a total of 170 patients and found that a tCEC add-on test will almost double the PPV of a standalone PSA test (32% vs. 17%; p = 0.0012), while retaining a negative predictive value above 90%.

2019 ◽  
Vol 65 (4) ◽  
pp. 540-548 ◽  
Author(s):  
Jacob Fredsøe ◽  
Anne K I Rasmussen ◽  
Emma B Laursen ◽  
Yunpeng Cai ◽  
Kenneth A Howard ◽  
...  

Abstract BACKGROUND Detection of prostate cancer (PC) based on serum prostate-specific antigen (PSA) testing leads to many unnecessary prostate biopsies, overdiagnosis, and overtreatment of clinically insignificant tumors. Thus, novel and more accurate molecular biomarkers are required. METHODS Using reverse transcription quantitative PCR, we measured the concentrations of 45 preselected microRNAs (miRNAs) in extracellular vesicle-enriched cell-free urine samples from 4 independent patient cohorts from Spain and Denmark, including 758 patients with clinically localized PC, 289 noncancer controls with benign prostatic hyperplasia (BPH), and 233 patients undergoing initial transrectal ultrasound (TRUS)-guided prostate biopsy owing to PC suspicion (101 with benign and 132 with malignant outcome). Diagnostic potential was assessed by ROC and decision curve analysis. RESULTS We identified and successfully validated 8 upregulated and 21 downregulated miRNAs in urine from PC patients. Furthermore, we validated a previously identified 3-miRNA diagnostic ratio model, uCaP (miR-222–3p*miR-24–3p/miR-30c-5p). High uCaP scores were distinctive of PC in urine samples from BPH vs PC patients in 3 independent cohorts [area under the curve (AUC) = 0.84, 0.71, 0.72]. Additionally, uCaP predicted TRUS biopsy results with greater accuracy than PSA (AUC uCaP = 0.644; AUC PSA = 0.527) for patients within the diagnostic gray zone (PSA ≤ 10 ng/mL). CONCLUSIONS We successfully validated a urine-based diagnostic 3-miRNA signature for PC (uCaP) in 3 independent patient cohorts from 2 countries. In the future, the simple and noninvasive uCaP test may be used to help more accurately select patients for prostate biopsy. Prospective clinical validation is warranted.


Author(s):  
Manas Sharma ◽  
Rajendra B. Nerli ◽  
Sree Harsha Nutalapati ◽  
Shridhar C. Ghagane

Abstract Context The importance of hypoechoic lesions on transrectal ultrasound (TRUS) merits re-assessment in the present era of widespread prostate-specific antigen (PSA) testing. Aims We aimed to investigate the predictive accuracy of hypoechoic lesions on TRUS of prostate in the diagnosis of prostate cancer and to examine the association of hypoechoic lesions with the aggressiveness of prostate cancer. Settings and Design This prospective study was conducted in a tertiary care center in South India from November 2017 to December 2019. Methods and Material We included 151 patients undergoing TRUS-guided 12-core prostate biopsy in view of raised serum PSA with or without suspicious digital rectal examination (DRE) findings in the study. Age, DRE findings, serum PSA level, TRUS findings, and histopathology reports were documented. These were compared between patients with and without hypoechoic lesions on TRUS. Statistical Analysis Used The statistical analysis for this study was performed using SPSS v20.0 software. Results Among 151 men, prostate cancer was diagnosed in 68 (45.03%) with mean age at presentation 69.81 ± 6.49 years. Fifty-eight cases (38.41%) had hypoechoic lesion on TRUS and the cancer detection rate (68.96%) amongst this group was significantly higher than in those without hypoechoic lesion (p <0.0001). Patients with hypoechoic lesion were more likely to have higher grade cancer. Abnormal DRE findings and hypoechoic lesion on TRUS were independent predictors of a clinically significant cancer (p <0.05). Conclusion Hypoechoic lesion on TRUS can be considered as an indicator of clinically significant prostate cancer.


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.


2021 ◽  
Vol 93 (2) ◽  
pp. 132-138
Author(s):  
Francesco Chessa ◽  
Riccardo Schiavina ◽  
Amelio Ercolino ◽  
Caterina Gaudiano ◽  
Davide Giusti ◽  
...  

Introduction and Objective: ExactVuTM is a real-time micro-ultrasound system which provides, according to the Prostate Risk Identification Using Micro-Ultrasound protocol (PRI-MUS), a 300% higher resolution compared to conventional transrectal ultrasound. To evaluate the performance of ExactVuTM in the detection of Clinically significant Prostate Cancer (CsPCa). Materials and methods: Patients with Prostate Cancer diagnosed at fusion biopsy were imaged with ExactVuTM. CsPCa was defined as any Gleason Score ≥ 3+4. ExactVuTM examination was considered as positive when PRI-MUS score was ≥ 3. PRI-MUS scoring system was considered as correct when the fusion biopsy was positive for CsPCa. A transrectal fusion biopsy- proven CsPCa was considered as a gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operator characteristic (ROC) curve (AUC) were calculated. Results: 57 patients out of 68 (84%) had a csPCa. PRI-MUS score was correctly assessed in 68% of cases. Regarding the detection of CsPCa, ExactVuTM ’s sensitivity, specificity, PPV, and NPV was 68%, 73%, 93%, and 31%, respectively and the AUC was 0.7 (95% CI 0.5-0-8). For detecting CsPCa in the transition/ anterior zone the sensitivity, specificity, PPV, and NPV was 45%, 66%, 83% and 25% respectively ant the AUC was 0.5 (95% CI 0.2-0.9). Accounting only the CsPCa located in the peripheral zone, sensitivity, specificity, PPV, and NPV raised up to 74%, 75%, 94%, 33%, respectively with AUC 0.75 (95% CI 0.5-0-9). Conclusions: ExactVuTM provides high resolution of the prostatic peripheral zone and could represent a step forward in the detection of CsPCa as a triage tool. Further studies are needed to confirm these promising results.


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.


2017 ◽  
Vol 59 (3) ◽  
pp. 371-380 ◽  
Author(s):  
Lars Boesen ◽  
Nis Nørgaard ◽  
Vibeke Løgager ◽  
Ingegerd Balslev ◽  
Henrik S Thomsen

Background Multiparametric magnetic resonance imaging (mpMRI) can improve detection of clinically significant prostate cancer (csPCa). Purpose To compare mpMRI score subgroups to systematic transrectal ultrasound-guided biopsies (TRUSbx) and prostate-specific antigen (PSA)-based findings for detection of csPCa in men undergoing repeat biopsies. Material and Methods MpMRI was performed prior to re-biopsy in 289 prospectively enrolled patients. All underwent repeat TRUSbx followed by targeted biopsies (MRITB) of any mpMRI-identified lesion. MpMRI suspicion grade, PSA level, and density (PSAd) were compared with biopsy results and further matched to the radical prostatectomy (RP) specimen if available. Results PCa was detected in 128/289 (44%) patients with median age, PSA, and prior negative TRUSbx of 64 (interquartile range [IQR] = 59–67), 12.0 ng/mL (IQR = 8.3–19.1), and 2 (IQR = 1–3), respectively. TRUSbx detected PCa in 108/289 (37%) patients, of which 49 (45%) had insignificant cancer. MRITB was performed in 271/289 (94%) patients and detected PCa in 96 (35%) with 78 (81%) having csPCa. MpMRI scores showed a high association between suspicion level and biopsy results on both lesion and patient level ( P < 0.001). MpMRI was better than PSA and PSAd ( P < 0.001) to identify patients with missed csPCa. In total, 64/128 (50%) patients underwent RP; 60/64 had csPCa. MpMRI was significantly better in predicting csPCa on RP compared with TRUSbx ( P = 0.019) as MRITB and TRUSbx correctly identified 47/60 (78%) and 35/60 (58%) patients, respectively. Conclusion MpMRI improves detection of missed csPCa and suspicion scores correlate well with biopsy and RP results on both patient and lesion level.


Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 57
Author(s):  
Alvydas Vėželis ◽  
Gediminas Platkevičius ◽  
Marius Kinčius ◽  
Liutauras Gumbys ◽  
Ieva Naruševičiūtė ◽  
...  

Background and objectives: Overdiagnosis, overtreatment, and the need for repeated procedures caused by transrectal ultrasound guided prostate biopsies and their related complications places a heavy burden on healthcare systems. This was a prospective cohort validating study to access the clinical accuracy of systematic and MRI-cognitive targeted transperineal prostate biopsies in detecting clinically significant prostate cancer after a previous negative biopsy and persistent suspicion of malignancy. The primary goal was to assess the ability of multiparametric magnetic resonance imaging (mpMRI) to detect clinically significant prostate cancer with an additional goal to assess the diagnostic value of systematic and MRI-cognitive transperineal biopsies. Materials and Methods: In total, 200 patients were enrolled who had rising serum prostate specific antigen (PSA) levels for at least 4 months after a previous negative transrectal ultrasound (TRUS) biopsy. All eligible men underwent 1.5T prostate mpMRI, reported using the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), followed by a 20-region transperineal prostate systematic biopsy and additional targeted biopsies. Results: Systematic 20-core transperineal prostate biopsies (TPBs) were performed for 38 (19%) patients. Systemic 20-core TPB with additional cognitive targeted biopsies were performed for 162 (81%) patients. Clinically significant prostate cancer (csPC) was detected for 31 (15.5%) patients, of which 20 (64.5%) cases of csPC were detected by systematic biopsy, eight (25.8%) cases were detected by targeted biopsy, and three (9.7%) both by systematic and targeted biopsies. Conclusions: Cognitive mpMRI guided transperineal target biopsies increase the detection rate of clinically significant prostate cancer after a previously negative biopsy. However, in a repeat prostate biopsy setting, we recommend applying a cognitive targeted biopsy with the addition of a systematic biopsy.


2019 ◽  
Vol 17 (5) ◽  
pp. 506-513 ◽  
Author(s):  
Brandon R. Mason ◽  
James A. Eastham ◽  
Brian J. Davis ◽  
Lance A. Mynderse ◽  
Thomas J. Pugh ◽  
...  

Prostate cancer (PCa) represents a significant source of morbidity and mortality for men in the United States, with approximately 1 in 9 being diagnosed with PCa in their lifetime. The role of imaging in the evaluation of men with PCa has evolved and currently plays a central role in diagnosis, treatment planning, and evaluation of recurrence. Appropriate use of multiparametric MRI (mpMRI) and MRI-guided transrectal ultrasound (MR-TRUS) biopsy increases the detection of clinically significant PCa while decreasing the detection of clinically insignificant PCa. This process may help patients with clinically insignificant PCa avoid the adverse effects of unnecessary therapy. In the setting of a known PCa, patients with low-grade disease can be observed using active surveillance, which often includes a combination of prostate-specific antigen (PSA) testing, serial mpMRI, and, if indicated, follow-up systematic and targeted TRUS-guided tissue sampling. mpMRI can provide important information in the posttreatment setting, but PET/CT is creating a paradigm shift in imaging standards for patients with locally recurrent and metastatic PCa. This article examines the strengths and limitations of mpMRI for initial PCa diagnosis, active surveillance, recurrent disease evaluation, and image-guided biopsies, and the use of PET/CT imaging in men with recurrent PCa. The goal of this review is to provide a rational basis for current NCCN Clinical Practice Guidelines in Oncology for PCa as they pertain to the use of these advanced imaging modalities.


2016 ◽  
Vol 2 (2) ◽  
pp. 74
Author(s):  
Serfa Faja ◽  
Amir Shoshi

The PSA test is used primarily to screen for prostate cancer. A PSA test measures the amount of prostate-specific antigen (PSA) in your blood. PSA is a protein produced in the prostate, a small gland that sits below a man's bladder. PSA is mostly found in semen, which also is produced in the prostate. Small amounts of PSA ordinarily circulate in the blood. The PSA test can detect high levels of PSA that may indicate the presence of prostate cancer. However, many other conditions, such as an enlarged or inflamed prostate, can also increase PSA levels. We use ImmunoAssay for Quantitative Measurement of PSA in Human Blood / Serum / Plasma with i-CHROMA TM Reader System with high sensitivity and specifity. We have analysed 120 patients and only 2 of them had very high value of PSA so we can determine for a prostate cancer. Additional factors increase the accuracy of PSA testing and it is not sufficient only the PSA to determine a prostate cancer so we need a rectal examination and transrectal ultrasound.


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