Dataset Information

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

ABSTRACT: 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%.

SUBMITTER: Bhakdi SC

PROVIDER: S-EPMC6721410 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Bhakdi Sebastian Chakrit SC Suriyaphol Prapat P Thaicharoen Ponpan P Grote Sebastian Tobias Karl STK Komoltri Chulaluk C Chaiyaprasithi Bansithi B Charnkaew Komgrid K

Cancers 20190727 8

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 ...[more]

PMID: 31357651

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Project description:BackgroundEndothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients.Patients and methodsChemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m2) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy.ResultsA total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6-3.6 months, 95% CI) and 6.2 months (4.9-7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable.ConclusionIn summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS.Trial registeryclinicaltrialsregister.eu EudraCT 2007-003705-27.

Project description:Background As the novel serum biomarkers, it has not been clearly clarified that the diagnostic accuracy of prostate health index (PHI) and prostate health index density (PHID) are superior to that of percentage free prostate-specific antigen (%fPSA) in detection of clinically significant prostate cancer (csPCa), especially in the gray zone. Therefore, this study aimed to compare the diagnostic value of PHI, PHID, and %fPSA for csPCa in the patients with prostate-specific antigen (PSA) >4 ng/mL and those with PSA within 4–10 ng/mL. Methods In this study, the serum samples and clinicopathological features were prospectively obtained from the patients who underwent prostate biopsy between September 2019 and December 2020. According to the inclusion criteria, the patients with total PSA (tPSA) >4 ng/mL, prostate magnetic resonance imaging or ultrasound clearly suggesting an occupying lesion were enrolled in this study. The patients with Gleason score ≥7 indicated csPCa. The receiver operating characteristic curves and the area under the curve (AUC) values were used to assess the diagnostic performance. Results Among the 296 patients (mean age 67.5 years, median tPSA 7.94 ng/mL) included in this study, there were 54 in the csPCa group (mean age 70.4 years, median tPSA 11.0 ng/mL) and 242 in the non-csPCa group (mean age 66.8 years, median tPSA 7.67 ng/mL). Based on the PSA level, there were 198 patients with PSA within the gray zone, which included 40 patients in the csPCa group and 158 in the non-csPCa group. In all patients, the sensitivity of PHID for detecting csPCa was 96.30%, and the specificity was 33.06% with the cut-off value of 0.51. Moreover, both PHID and PHI did better in the diagnosis of csPCa (AUC: 0.880 and 0.867, respectively) compared with other PSA derivative markers. Similarly, in the patients with PSA level in the gray zone, the diagnostic accuracy of PHID and PHI in predicting csPCa (AUC: 0.788 and 0.777, respectively) were better than other PSA derivative markers. Conclusions PHID presented the better diagnostic accuracy in predicting csPCa in patients with PSA in the gray zone than other PSA derivative markers, which could be a promising biomarker for making the biopsy strategy.

Project description:Circulating tumour cells (CTCs) have potential utility in various clinical applications for cancer management. The present study focused on evaluating the diagnostic role of CTCs in colorectal cancer (CRC). A total of 89 blood samples from 59 patients diagnosed with CRC and 30 healthy individuals were collected for CTC detection. The Cyttel method is an improved CTC detection strategy, which combines negative enrichment with immunofluorescence and fluorescence in situ hybridization. This method effectively detected a significant increase in total CTCs in patients with CRC (49/59) compared with those in healthy controls (3/30). A cut-off value of 2 CTCs/3.2 ml blood yielded a sensitivity of 83.05% and a specificity of 100%. Additionally, three traditional serum tumour markers, namely carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and CA72-4, were examined by immunoassays. The diagnostic sensitivity of CTCs was much higher than that of CEA, CA19-9 and CA72-4 alone or in combination, particularly in patients with early stage CRC. The combined sensitivity of CTCs and CEA reached 91.53%, which was only slightly lower than the sensitivity of all four markers combined (CTCs + CEA + CA19-9 + CA72-4). CTCs with aneuploidy of chromosome 7 or 8 were carefully distinguished, and the associations among different types of CTCs, clinicopathological characteristics and overall survival were statistically analysed. Total CTCs were revealed to be significantly associated with tumour differentiation and nerve invasion. CTCs were more likely to be detected in poorly differentiated CRC tumours than in well- and moderately-differentiated tumours (P=0.026). Furthermore, to the best of our knowledge, the present study was the first to report that CTCs with multiploidy of chromosome 7 were significantly associated with TNM stage. These CTCs exhibited a high chance of being identified in the peripheral blood of patients with late-stage CRC (stage III-IV; P=0.031). The present study suggests that the combination of CTCs and CEA may serve as an effective potential diagnostic and prognostic indicator in patients with CRC. Detection of CTCs with aneuploidy may have increased specificity in predicting highly malignant and invasive tumours in CRC management.

Dataset Information

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

Publications

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

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