PSA remains a key biomarker for the diagnosis and monitoring of prostate cancer (PCa). The positive predictive value (PPV) of PSA for PCa detection via biopsy is estimated to be between 30-42% for patients within the PSA gray zone. We conducted a single-center, retrospective, evaluator-blinded, pilot, and pivotal clinical trial to assess the clinical performance of the mirCaP kit (hsv2-miR-H9/has-miR-3659) in aiding physicians’ decision-making for PCa assessments in patients within this gray zone. In the initial clinical trial group, among patients in the PSA gray zone, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 94.29%, 77.50%, 85.33%, 78.57%, and 93.94%, respectively. In the pivotal clinical trial, these values were 94.50%, 82.73%, 87.90%, 81.10%, and 95.04%, respectively. These results suggest that the mirCaP kit may serve as an effective non-invasive diagnostic marker for PCa in patients within the PSA gray zone. The mirCaP kit appears to be a promising tool for guiding decisions regarding prostate biopsy in these patients. Notably, the negative predictive value was over 90%, indicating that in the PSA gray zone, the mirCaP kit could reduce the need for more than 90% of unnecessary prostate biopsies.
Article
Retrospective, Evaluator-Blinded, Pilot and Pivotal Clinical Trials: Assessing the mirCaP Kit (hsv2-miR-H9/has-miR-3659) as a Diagnostic Marker for Prostate Cancer in Patients with PSA Gray Zone Levels
https://doi.org/10.21203/rs.3.rs-4202988/v1
This work is licensed under a CC BY 4.0 License
Version 1
posted
You are reading this latest preprint version
Prostatic Neoplasms
Biomarkers
MicroRNAs
Urine
Diagnosis
Prostate cancer (PCa) is the most commonly diagnosed cancer among men in the United States, with an estimated 288,300 new cases and 34,700 deaths expected in 2023.1 Early detection of PCa is crucial, as it significantly improves survival rates.2 Unfortunately, early stages of PCa may not present any symptoms.
The serum prostate-specific antigen (PSA) is the most widely used biomarker for PCa screening. A study following over 20,000 middle-aged and older men for 10 years found that the sensitivity of the PSA test for PCa detection was 46% at a cutoff of 4.0 ng/mL.3 However, elevated PSA levels are not exclusively indicative of PCa and can be caused by benign prostatic hyperplasia (BPH), urinary tract infections, urinary retention, and ejaculation.3–6 Despite its limitations, PSA remains a key biomarker for PCa diagnosis and monitoring.
The PSA test’s lack of specificity leads to a high rate of negative biopsies, especially in patients with serum PSA levels between 3.0–10.0 ng/mL, a range known as the PSA gray zone. The positive predictive value (PPV) of PSA for prostate cancer detection via biopsy is estimated to be between 30–42% for patients within this PSA gray zone.7 This implies that approximately 60–70% of these patients undergo unnecessary prostate biopsies.
Recent studies suggest that hsv2-miR-H9 and has-miR-3659 could serve as potential diagnostic markers for PCa.8–10 In this study, we conducted a single center, retrospective, evaluator-blinded, pilot and pivotal clinical trial to assess the clinical performance of the mirCaP kit (hsv2-miR-H9/has-miR-3659) to assist physicians in decision-making for PCa inspections in patients with the PSA gray zone.
2.1 Ethics statement
This study adhered to the applicable laws and regulations, good clinical practice, and ethical principles outlined in the Declaration of Helsinki. The study protocol was approved from the Ethics Committee of Chungbuk National University Hospital, with IRB approval numbers for the initial clinical trial (2022-09-038) and pivotal clinical trial (2023-06-034). Prior to enrollment, all patients provided written informed consent. The Institutional Review Board of Chungbuk National University Hospital approved the sample collection and analysis procedures. The clinical trial has been submitted to the Korean Ministry of Food and Drug Safety. The registration number for approval is 20240050719, and it was submitted on March 15, 2024. This study is not subject to prior approval by the Korean Ministry of Food and Drug Safety but underwent a preliminary review, and the results have been submitted as a result report.
2.2 Patients and Samples
In this study, 388 urine samples were collected from the National Biobank of Korea. These included 70 positive and 70 negative samples, with 10 cases each of bladder cancer (BC) or renal cell carcinoma (RCC) in the initial clinical trial, and 109 positive and 139 negative samples in the pivotal clinical trial. Serum PSA concentrations between 3–10 ng/mL were classified as the ‘PSA gray zone’. In this pivotal clinical trial, we exclusively enrolled patients within this gray zone, categorizing them as positive or negative. A positive diagnosis of PCa was confirmed by prostate biopsy, whereas a negative diagnosis was determined when no tumor was reported by transrectal 12-core prostate biopsy.
Voided urine samples were collected prior to surgery. In cases in which patients were underwent biopsy, urine samples were collected immediately before the procedure. Positive urine samples were obtained from patients who underwent radical prostatectomy (RP), palliative transurethral resection of the prostate (TURP), or prostate biopsy and had histologically confirmed adenocarcinoma. Negative urine samples were obtained from patients with BPH who underwent TURP or had no tumors reported by prostate biopsy. Urine samples for BC were obtained from patients who underwent transurethral resection of bladder tumor (TURBT) with histologically confirmed urothelial carcinoma, and for RCC, from patients who underwent radical or partial nephrectomy with histologically confirmed clear RCC.
All the tissue specimens were examined by an experienced senior pathologist. The Gleason grades and TNM 2002 staging were assessed. Patients with urinary tract infections or other diagnosed cancers were also excluded. The study design is shown in Fig. 1.
2.2.1 Basis for determining sample size in the initial clinical trial
The sample size for this clinical performance test was determined based on a literature review. Our literature survey indicated that studies using comparable devices typically collected a certain number of specimens. For example, in the study by Byun et al.11, approximately 40 positive and 40 negative specimens were collected. Likewise, Kang et al.10 gathered approximately 60 specimens of both positive and negative samples. Informed by these precedents, we chose to collect 140 specimens for our initial clinical trial, consisting of 70 positive and 70 negative specimens, thereby exceeding the sample sizes reported in the referenced literature.
2.2.2 Basis for determining sample size in the pivotal clinical trial
The number of positive specimens for the pivotal clinical trial was calculated based on a one-sided significance level of 0.025 and power of 0.95, resulting in a requirement for 98 positive specimens. To account for a potential 10% dropout rate, this number was adjusted to 109 positive specimens. Similarly, the number of negative specimens was determined based on the same statistical parameters, which initially required 125 negative specimens. Considering the same dropout rate of 10%, this number was adjusted to 139 negative specimens. Therefore, to accommodate the anticipated dropout rate, we collected 109 positive and 139 negative specimens. The formula used to calculate the sample numbers is shown in below.
2.3 miRNA purification from urine
Urine samples were processed for miRNA purification using the Genolution Nucleic Acid Extraction Kit (Genolution Pharmaceuticals Inc., Seoul, South Korea). For each urine sample, 500µL of supernatant was transferred to a tube containing the proprietary miRNA separation solution from the Genolution and vortexed for 20 s. Subsequently, 200 µL chloroform was added to the mixture, followed by vortexing for 10 s. The samples were then centrifuged at 13,000 rpm for 10 minutes at 4°C. From the resulting mixture, 650 µL of the upper aqueous phase was carefully removed without disturbing the underlying white precipitate and transferred to a new 15 mL tube. To this, 0.8 mL of isopropanol was added, and the mixture was centrifuged again for 20 min at 15,000 rpm at 4°C. The supernatant was decanted, to ensure that the expected RNA pellet was not dislodged. The pellet was washed with 500 µL of 70% ethanol and centrifuged for an additional 20 min at 15,000 rpm at 4°C. After discarding the residual ethanol, the RNA pellet was resuspended in 40 µL of RNase-free water and stored at -80°C until further analysis.
2.4 cDNA synthesis of urinary cell-free RNA
The concentration and purity of the isolated RNA were assessed using a spectrophotometer. A cell-free RNA concentration ≥ 5 ng/µL was deemed suitable for further processing. An absorbance ratio of 2.0 or less for cell-free RNA was considered indicative of acceptable purity. Following these assessments, cDNA synthesis was performed using the mirCaP Kit™ cDNA Synthesis Kit (Urotech Inc., Cheongju, South Korea), strictly adhering to the manufacturer’s protocol.
2.5 Real-time PCR
To quantify urinary hsv2-miR-H9 and has-miR-3659 expression, RT-PCR was conducted using a Rotor-Gene Q instrument (Qiagen, Valencia, CA) and UROTECH TB premix (Urotech Inc., Cheongju, South Korea). The reactions were carried out in micro-reaction tubes (Corbett Research, Mortlake, NSW, Australia) with a final volume of 10 µL. Chemically synthesized RNA oligonucleotides (Integrated DNA Technologies, Seoul, South Korea), corresponding to the target miRNAs, were employed to construct standard curves, which ranged from 2.25x105 to 2.25x108 copies. The mirCaP A and B primers, specific for hsv2-miR-H9 (A gene) and has-miR-3659 (B gene), respectively, were used for amplification (Urotech Inc., Cheongju, South Korea). All samples were analyzed in triplicate. RT-PCR was performed according to the manufacturer's instructions. Rotor-Gene Q software (Qiagen) was used for acquisition and analysis of the spectral data.
2.6 Statistical analysis
The expression ratio of urinary miRNAs was determined using the upregulated miRNA (hsv2-miR-H9-5p) as the numerator and the downregulated miRNA (has-miR-3659) as the denominator. An independent two-sample t-test was used to compare age between the two groups. The Wilcoxon rank-sum test was used to compare PSA levels, expression of hsv2-miR-H9 and has-miR-3659, and the expression ratio of urinary hsv2-miR-H9 to has-miR-3659 between the groups. To determine the cut-off values in the initial clinical trial, the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve was calculated using the Euclidean Method, based on the expression ratio of hsv2-miR-H9 and has-miR-3659. All statistical analyses was performed using SAS software (SAS, Cary, NC, USA) Results with p-values less than 0.05 were considered statistically significant.
3.1 Baseline characteristics
The clinical characteristics of patients in the initial and pivotal clinical trials are presented in Supplementary Table 1. In the initial clinical trial, the positive group had a mean age of 67.50 ± 6.19 years, with a median baseline PSA was 8.72 (interquartile range [IQR], 5.08-13.57) ng/mL. The negative group, on the other hand, had a mean age of 63.97 ± 9.30 years, with a median baseline PSA was 5.21 (IQR, 3.34-9.13) ng/mL. In the pivotal clinical trial, the positive group had a mean age of 69.19 ± 6.79 years and a median baseline PSA of 5.92 (IQR, 4.63-7.63) ng/mL. The negative group in this trial had a mean age of 64.56 ± 7.92 years, with a median baseline PSA of 5.80 (IQR, 4.50-7.23) ng/mL.
3.2 Diagnostic value of mirCaP kit (hsv2-miR-H9 to has-miR-3659 expression ratio) in the initial clinical trial
The ratio of hsv2-miR-H9 to has-miR-3659 was significantly higher in the positive group than in the negative group (p<0.0001, Supplementary Table 2). The AUC of the expression ratio of urinary hsv2-miR-H9 to has-miR-3659 was 0.8237 (95% CI, 0.7539-0.8934) (Fig. 2A), which was comparable to that of PSA (AUC, 0.6622; 95% CI, 0.5723-0.7522) (Fig. 2B). The optimal cut-off value for the miRCaP kit, determined by the Euclidean Method, was 80.64 (Supplementary Table 3). The sensitivity, specificity, accuracy, and positive and negative predictive values were 77.14%, 72.86%, 75.00%, 73.97%, and 76.12%, respectively (Table 1). Applying this cut-off value could increase the diagnostic value in patients within the PSA gray zone. In these patients, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 94.29%, 77.50%, 85.33%, 78.57%, and 93.94%, respectively (Table 2).
3.3 Diagnostic value of mirCaP kit (hsv2-miR-H9 to has-miR-3659 expression ratio) in patients within the PSA gray zone in the pivotal clinical trial
The ratio of hsv2-miR-H9 to has-miR-3659 was significantly higher in the positive group than in the negative group (p<0.0001, Supplementary Table 4). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 94.50%, 82.73%, 87.90%, 81.10%, and 95.04%, respectively (Table 3).
In a previous study, we determined that the urinary hsv2-miR-H9 to has-miR-3659 expression ratio was a reliable non-invasive diagnostic marker for PCa.10 In this study, we evaluated the diagnostic and cut-off values of the ‘miRCaP’ kit (hsv2-miR-H9/has-miR-3659) in the initial clinical trial, and validated its performance as a non-invasive diagnostic marker in a pivotal clinical trial, particularly for patients within the PSA gray zone.
Given the low specificity of PSA, numerous studies have attempted to overcome these limitations. Adjustments such as aged-adjusted PSA, free PSA (fPSA), PSA density (PSAd), PSA velocity (PSAV), and PSA doubling time (PSADT) have been explored to optimize PSA or PSA derivatives.12–15 Additionally, prostate health index (Phi), 4K score (four-kallikrein panel), and PCA gene 3 (PCA3) have been used, but, they have shown weak clinical performance in real-world clinical practice.16–18 Chen et al.19 reported that the optimal cutoff values of the Prostate Imaging Reporting and Data System (PI-RADS) v2.1 in men within the PSA gray zone were 4 for predicting clinically significant PCa with acceptable sensitivity (81.82%) and specificity (77.14%), and 3 for lesions with a sensitivity (97.10%) and specificity (30.67%). Although MRI provides high-quality imaging, its cost-effectiveness is a concern.
Recently, liquid biopsy (LB), which includes the analysis of circulating tumor material in blood or urine, has emerged as a significant tool for detecting PCa. However, circulating tumor cells (CTCs) and ctDNA are either undetectable or detected at rates similar to biopsy-negative controls in early-stage PCa.20,21 CTCs PSA mRNA, however, has potential as a biomarker to replace serum PSA in metastatic stages of PCa.22 ExoDx™ Prostate IntelliScore, an established LB diagnostic marker for early PCa, has been shown to avoid 26% of unnecessary biopsies with a negative predictive value of 89% in men over 50 with borderline PSA elevation (2–10 ng/mL).23,24 A panel including miR-141, miR-1290, miR-100, and miR-335 could serve as biomarkers for diagnosing BPH and PCa using serum and tissues.25 The present study demonstrates the diagnostic performance of urinary miRNAs as LB. Although RNAs are highly unstable molecules, miRNAs are stable in serum and urine and resistant to RNase activity, extreme pH, temperature, and multiple freeze-thaw cycles.26,27 In a previous study, the expression ratio of urinary miR-H9 to miR-3659 could be a relevant non-invasive biomarker for PCa diagnosis. In this study, we analyzed the accurate cut-off value of the mirCaP kit (miR-H9 to miR-3659) and validated its clinical performance in a validation cohort within the PSA gray zone. The results show that the mirCaP kit has higher sensitivity and specificity than PSA, suggesting its potential use as a urinary miRNA diagnostic marker for PCa. Notably, the negative predictive values (NPVs) in the two cohorts within the PSA gray zone were 93.94% and 95.04%, respectively, indicating that if patients received a negative result from the mirCaP Kit, their likelihood of being tumor-free was 95%. This suggests that the mirCaP kit can reduce the need for more than 90% of unnecessary prostate biopsies in patients with negative mirCaP results.
This present study had both limitations and strength. A limitation is that these two clinical trials were not multicenter studies. However, as a strength, we conducted evaluator-blinded, pilot, and pivotal sequential studies. The sample size was calculated by statistical experts, and the studies were managed by the Expert Contract Research Organization (CRO) for approval by the Korean National Institute of Food and Drug Safety Evaluation.
The expression ratio of urinary hsv-miR-H9 to has-miR-3659 (mirCaP Kit) could serve as a highly effective non-invasive diagnostic markerfor PCa in patients with PSA gray zone. The mirCaP kit shows promise as a tool for determining the need for prostate biopsy in these patients.
PCa: Prostate cancer
PPV: Positive predictive value
NPV: Negative predictive value
PSA: Prostate-specific antigen
BPH: Benign prostatic hyperplasia
BC: Bladder cancer
RCC: Renal cell carcinoma
RP: Radical prostatectomy
TURP: Transurethral resection of the prostate
TURBT: Transurethral resection of bladder tumor
AUC: Area Under the Curve
ROC: Receiver Operating Characteristics
IQR: Interquartile range
fPSA: free PSA
PSAd: PSA density
PSAV: PSA velocity
PSADT: PSA doubling time
LB: Liquid biopsy
CTC: Circulating tumor cell
Acknowledgements
The biospecimens used in this study were provided by Chungbuk National University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health, Welfare and Family Affairs. All samples provided by the National Biobank of Korea for this study were obtained with informed consent under protocols approved by the institutional review board.
Funding Support: None
Ethics Statement
This study was deemed exempt from Institutional Review Board review. (IRB No. 2022-09-038 and 2023-06-034) The clinical trial has been submitted to the Korean Ministry of Food and Drug Safety. The registration number for approval is 20240050719, and it was submitted on March 15, 2024. This study is not subject to prior approval by the Korean Ministry of Food and Drug Safety but underwent a preliminary review, and the results have been submitted as a result report.
Conflict of Interest
The authors have no conflicts of interest to disclose.
Data Availability Statement
The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Author Contributions
Conception and design: WTK; Data analysis and interpretation: WTK; Data acquisition: KK, HWK, YJB, XMP, YJK, SCL, SJY; Critical revision of the manuscript for scientific and factual content: YSH, JK, IYK; Drafting the manuscript: WTK; Statistical analysis: WTK; Supervision: IYK
- Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. Cancer statistics, 2023. Ca-a Cancer Journal for Clinicians 73, 17-48 (2023).
- Obirieze, A. C., Moten, A., Allen, D. & Ahaghotu, C. A. African-American Men with Low-Risk Prostate Cancer: Modern Treatment and Outcome Trends. Journal of Racial and Ethnic Health Disparities 2, 295-302 (2015).
- Gann, P. H., Hennekens, C. H. & Stampfer, M. J. A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer. Jama-Journal of the American Medical Association 273, 289-294 (1995).
- Shahab, A. A. et al. Prostate-specific antigen and prostate-specific antigen density cutoff points among Indonesian population suspected for prostate cancer. Prostate International 1, 23-30 (2013).
- Stamey, T. A. et al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. New England Journal of Medicine 317, 909-916 (1987).
- Kobayashi, M., Kijima, T., Yashi, M. & Kamai, T. Prostate-specific antigen kinetics contributes to decision making for biopsy referral: the predictive implication for PSA retest in patients with elevated PSA levels. Prostate International 11, 27-33 (2023).
- Wilson, S. & Crawford, E. D. Screening for prostate cancer: current recommendations. Urologic Clinics of North America 31, 219-226 (2004).
- Yun, S. J. et al. Urinary MicroRNAs of Prostate Cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p Could Be Valuable Diagnostic Markers. International Neurourology Journal 19, 74-84 (2015).
- Byun, Y. J. et al. Expression of hsv1-miR-H18 and hsv2-miR-H9 as a field defect marker for detecting prostate cancer. Prostate International 10, 1-6 (2022).
- Kang, H. W. et al. Urinary hsv2-miR-H9 to hsa-miR-3659 ratio is an effective marker for discriminating prostate cancer from benign prostate hyperplasia in patients within the prostate-specific antigen grey zone. Investigative and Clinical Urology 63, 238-244 (2022).
- Byun, Y. J. et al. Urinary microRNA-1913 to microRNA-3659 expression ratio as a non-invasive diagnostic biomarker for prostate cancer. Investigative and Clinical Urology 62, 340-348 (2021).
- Oesterling, J. E., Jacobsen, S. J. & Cooner, W. H. The use of age-specific reference ranges for serum prostate specific antigen in men 60 years old or older. Journal of Urology 153, 1160-1163 (1995).
- Lee, R., Localio, A. R., Armstrong, K., Malkowicz, S. B. & Schwartz, J. S. A meta-analysis of the performance characteristics of the free prostate-specific antigen test. Urology 67, 762-768 (2006).
- Tang, P. et al. Transition zone PSA density improves the prostate cancer detection rate both in PSA 4.0-10.0 and 10.1-20.0 ng/ml in Chinese men. Urologic Oncology-Seminars and Original Investigations 31, 744-748 (2013).
- Carter, H. B. et al. Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability. Jnci-Journal of the National Cancer Institute 98, 1521-1527 (2006).
- Lepor, A., Catalona, W. J. & Loeb, S. The Prostate Health Index: Its Utility in Prostate Cancer Detection. Urologic Clinics of North America 43, 1-6 (2016).
- Parekh, D. J. et al. A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. European Urology 68, 464-470 (2015).
- Wei, J. T. et al. Can urinary PCA3 supplement PSA in the early detection of prostate cancer? Journal of Clinical Oncology 32, 4066-4072 (2014).
- Chen, Y. et al. Cutoff Values of Prostate Imaging Reporting and Data System Version 2.1 Score in Men With Prostate-specific Antigen Level 4 to 10 ng/mL: Importance of Lesion Location. Clinical Genitourinary Cancer 19, 288-295 (2021).
- Davis, J. W. et al. Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer. Journal of Urology 179, 2187-2191; discussion 2191 (2008).
- Lau, E. et al. Detection of ctDNA in plasma of patients with clinically localised prostate cancer is associated with rapid disease progression. Genome Medicine 12, 72-72 (2020).
- Cho, H. et al. Association of serum prostate-specific antigen (PSA) level and circulating tumor cell-based PSA mRNA in prostate cancer. Prostate International 10, 14-20 (2022).
- McKiernan, J. et al. A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy. Jama Oncology 2, 882-889 (2016).
- McKiernan, J. et al. A Prospective Adaptive Utility Trial to Validate Performance of a Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer in Patients with Prostate-specific Antigen 2-10ng/ml at Initial Biopsy. European Urology 74, 731-738 (2018).
- Manoj, A. et al. Screening and validation of novel serum panel of microRNA in stratification of prostate cancer. Prostate International 11, 150-158 (2023).
- Yun, S. J. et al. Cell-free microRNAs in urine as diagnostic and prognostic biomarkers of bladder cancer. International Journal of Oncology 41, 1871-1878 (2012).
- Glinge, C. et al. Stability of Circulating Blood-Based MicroRNAs - Pre-Analytic Methodological Considerations. Plos One 12, e0167969-e0167969 (2017).
Table 1. Diagnostic value of miRCaP kit in the initial clinical trial
|
|
Reference Standard (N = 140) |
||
|
Positive (N=70) |
Negative (N=70) |
||
|
Results of miRCaP kit (Cut-off = 80.64) |
Positive (N=73) |
54 |
19 |
|
Negative (N=67) |
16 |
51 |
|
|
Sensitivity (%) 95% Confidence Interval |
77.14 (65.55, 86.33) |
||
|
Specificity (%) 95% Confidence Interval |
72.86 (60.90, 82.80) |
||
|
Accuracy (%) 95% Confidence Interval |
75.00 (66.98, 81.93) |
||
|
Positive predictive value (%) 95% Confidence Interval |
73.97 (62.83, 83.55) |
||
|
Negative predictive value (%) 95% Confidence Interval |
76.12 (64.14, 85.69) |
||
Table 2. Diagnostic value of miRCaP kit in the PSA Gray zone (3-10ng/ml) in the initial clinical trial
|
|
Reference Standard (N = 75) |
||
|
Positive (N=35) |
Negative (N=40) |
||
|
Results of miRCaP kit (Cut-off = 80.64) |
Positive (N=42) |
33 |
9 |
|
Negative (N=33) |
2 |
31 |
|
|
Sensitivity (%) 95% Confidence Interval |
94.29 (80.84, 99.30) |
||
|
Specificity (%) 95% Confidence Interval |
77.50 (61.55, 89.16) |
||
|
Accuracy (%) 95% Confidence Interval |
85.33 (75.27, 92.44) |
||
|
Positive predictive value (%) 95% Confidence Interval |
78.57 (63.19, 89.70) |
||
|
Negative predictive value (%) 95% Confidence Interval |
93.94 (79.77, 99.26) |
||
Table 3. Diagnostic value of miRCaP kit in the PSA Gray zone (3-10ng/ml) in the pivotal clinical trial
|
|
Reference Standard (N = 248) |
||
|
Positive (N=109) |
Negative (N=139) |
||
|
Results of miRCaP kit (Cut-off = 80.64) |
Positive (N=127) |
103 |
24 |
|
Negative (N=121) |
6 |
115 |
|
|
Sensitivity (%) 95% Confidence Interval |
94.50 (88.40, 97.95) |
||
|
Specificity (%) 95% Confidence Interval |
82.73 (75.41, 88.61) |
||
|
Accuracy (%) 95% Confidence Interval |
87.90 (83.18, 91.69) |
||
|
Positive predictive value (%) 95% Confidence Interval |
81.10 (73.20, 87.50) |
||
|
Negative predictive value (%) 95% Confidence Interval |
95.04 (89.52, 98.16) |
||
No competing interests reported.