Clinical performance of Xpert Bladder Cancer (BC) Monitor, a mRNA-based urine test, in active surveillance (AS) patients with recurrent non-muscle-invasive bladder cancer (NMIBC): results from the Bladder Cancer Italian Active Surveillance (BIAS) project

Hurle, Rodolfo; Casale, Paolo; Saita, Alberto; Colombo, Piergiuseppe; Elefante, Grazia Maria; Lughezzani, Giovanni; Fasulo, Vittorio; Paciotti, Marco; Domanico, L.; Bevilacqua, Giulio; Maffei, Davide; Diana, Pietro; Frego, Nicola; Sandri, Maria Teresa; Maura, Federica; Morenghi, Emanuela; Buffi, Nicolò Maria; Guazzoni, Giorgio; Lazzeri, Massimo

doi:10.1007/s00345-019-03002-3

Cited by 25 publications

(20 citation statements)

References 23 publications

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“…They also proposed that in this setting, the LDA total cut-off would be 0.4. 17 Our data shows that sensitivities of the XBC for predicting positive or suspicious cystoscopic results is considerably higher than for VUC (75.0% vs. 41.2% respectively), and also NPV is improved in comparison to VUC (93.0% vs. 85.4% respectively). The results are comparable to the results of the studies of Van Valenberg et al and Pichler et al (74 % and 84% for sensitivity and 93% and 93% for NPV respectively).…”

Section: Discussionmentioning

confidence: 58%

The performance of the Xpert Bladder Cancer Monitor Test and voided urinary cytology in the follow-up of urinary bladder tumors

Smrkolj

Primozic

Fabjan

et al. 2020

Radiology and Oncology

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BackgroundCystoscopy in complement with urinary cytology represents the gold standard for the follow-up of patients with urinary bladder tumours. Xpert Bladder Cancer Monitor Test (XBC) is a novel mRNA-based urine test for bladder cancer surveillance. The aim of the study was to evaluate the performance of the XBC and voided urinary cytology (VUC) in the follow-up of bladder tumours.Patients and methodsThe XBC was performed on stabilized voided urine and VUC was performed on urine samples. The results were compared to cystoscopic findings and histopathological results after transurethral resection of the bladder lesion.ResultsFor the prediction of malignant histopathological result sensitivity, the specificity and negative predictive value were 76.9%, 9 7.5% and 93.0% for the XBC and 38.4%, 9 7.5% and 83.3%, respectively for VUC. For the prediction of suspicious or positive cystoscopic finding sensitivity, the specificity and negative predictive value were 75.0%, 95.2%, and 93.0% respectively for the XBC and 41.7%, 97.6%, and 85.4% for VUC. The sensitivities for papilary urothelial neoplasms of low malignant potential (PUNLMP), low- and high-grade tumours were 0.0%, 66.7% an d 100.0% for the XBC and 0.0%, 66 .7% and 42.9%, respectively for VUC.ConclusionsThe XBC showed significantly higher overall sensitivity and negative predictive value than VUC and could be used to increase the recommended follow-up cystoscopy time intervals. Complementing the XBC and voided urinary cytology does not improve performance in comparison to the XBC alone.

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Section: Discussionmentioning

confidence: 58%

The performance of the Xpert Bladder Cancer Monitor Test and voided urinary cytology in the follow-up of urinary bladder tumors

Smrkolj

Primozic

Fabjan

et al. 2020

Radiology and Oncology

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“…blood cells) [21,22]. [23][24][25][26][27][28][29][30]. Due to their lack of specificity or sensitivity, these tests are not widely used in routine laboratory.…”

Section: Discussionmentioning

confidence: 99%

A novel ultra-sensitive method for the detection of FGFR3 mutations in urine of bladder cancer patients – Design of the Urodiag® PCR kit for surveillance of patients with non-muscle-invasive bladder cancer (NMIBC)

Roperch¹,

Hennion²

2020

BMC Med Genet

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Background: We have recently developed a highly accurate urine-based test, named Urodiag®, associating FGFR3 mutation and DNA methylation assays for recurrence surveillance in patients with low-, intermediate-, and high-risk NMIBC. Previously, the detection of four FGFR3 mutations (G372C, R248C, S249C and Y375C) required amplification steps and PCR products were analyzed by capillary electrophoresis (Allele Specific-PCR, AS-PCR), which was expensive and time-consuming. Here, we present the development a novel ultra-sensitive multiplex PCR assay as called "Mutated Allele Specific Oligonucleotide-PCR (MASO-PCR)", generating a cost-effective, simple, fast and clinically applicable assay for the detection of FGFR3 mutations in voided urine. Methods: Comparative clinical performances of MASO-PCR and AS-PCR technologies were performed from 263 urine DNA samples (87 FGFR3 mutated and 176 FGFR3 wild-type). In the development of Urodiag® PCR Kit, we studied the stability and reproducibility of each all-in-one PCR master mix (single reaction mixture including all the necessary PCR components) for MASO-PCR and QM-MSPCR (Quantitative Multiplex Methylation-Specific PCR to coamplify SEPTIN9, HS3ST2 and SLIT2 methylated genes) assays. Results: Complete concordance (100%) was observed between the MASO-PCR and AS-PCR results. Each PCR master mix displayed excellent reproducibility and stability after 12 months of storage at − 20°C, with intra-assay standard deviations lower than 0.3 Ct and coefficient of variations (CV) lower than 1%. The limit of detection (LoD) of MASO-PCR was 5% mutant detection in a 95% of wild-type background. The limit of quantification (LoQ) of QM-MSPCR was 10 pg of bisulfite-converted DNA.

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“…A variety of commercially available urinary molecular markers have been introduced for initial diagnosis and detection of tumor recurrence for the follow-up of NMIBC patients. These non-invasive tests include the measurement of markers such as MCM5 protein (ADXBLADDER test, sensitivity/specificity of 76%/69%, $52 per test), 15 DNA methylation patterns (Bladder Epicheck test, overall sensitivity of 67% with 40%/89% in low-/high-risk and specificity 88%, not yet marketed), bladder tumor associated antigen (BTA, sensitivity/specificity of 58%-71%/73%, $40 per test), proteins detected on fixed urothelial cells (ImmunoCyt, sensitivity/specificity of 67%-86%/75%-79%, $200 per test), nuclear matrix protein 22 (NMP22, sensitivity/specificity of 71%-73%/73%-80%, $25 per test), chromosomal aberrations detected by fluorescence in situ hybridization (UroVysion, sensitivity/ specificity of 72%/83%, $800 per test), gene expression levels of five targets (ABL1, CRH, IGF2, UPK1B, ANXA10) by RT-PCR (Xpert BC Monitor, overall sensitivity 46% with 40%/86% in low-/high-risk and specificity 90%, $165 per test) [23][24][25][26][27][28][29][30]. However, due to their limited specificities or sensitivities, the markers proposed to date have not been widely adopted in daily clinical practice.…”

Section: Discussionmentioning

confidence: 99%

A novel ultra-sensitive method for the detection of FGFR3 mutations in urine of bladder cancer patients – Design of the Urodiag® PCR Kit for surveillance of patients with non-muscle-invasive bladder cancer (NMIBC)

ROPERCH¹,

HENNION²

2020

Preprint

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Background We have recently developed a highly accurate urine-based test, named Urodiag®, associating FGFR3 mutation and DNA methylation assays for recurrence surveillance in patients with low-, intermediate-, and high-risk NMIBC. Previously, the detection of four FGFR3 mutations (G372C, R248C, S249C and Y375C) required amplification steps and PCR products were analyzed by capillary electrophoresis (Allele Specific-PCR, AS-PCR), which was expensive and time-consuming. Here, we present the development a novel ultra-sensitive multiplex PCR assay as called “Mutated Allele Specific Oligonucleotide-PCR (MASO-PCR)”, generating a cost-effective, simple, fast and clinically applicable assay for the detection of FGFR3 mutations in voided urine.Methods Comparative clinical performances of MASO-PCR and AS-PCR technologies were performed from 263 urine DNA samples (87 FGFR3 mutated and 176 FGFR3 wild-type). In the development of Urodiag® PCR Kit, we studied the stability and reproducibility of each all-in-one PCR master mix (single reaction mixture including all the necessary PCR components) for MASO-PCR and QM-MSPCR (Quantitative Multiplex Methylation-Specific PCR to co-amplify SEPTIN9, HS3ST2 and SLIT2 methylated genes) assays.Results Complete concordance (100%) was observed between the MASO-PCR and AS-PCR results. Each PCR master mix displayed excellent reproducibility and stability after 12 months of storage at -20°C, with intra-assay standard deviations lower than 0.3 Ct and coefficient of variations (CV) lower than 1%. The limit of detection (LoD) of MASO-PCR was 5% mutant detection in a 95% of wild-type background. The limit of quantification (LoQ) of QM-MSPCR was 10 pg of bisulfite-converted DNA. Conclusions We developed and clinically validated the MASO-PCR assay, generating cost-effective, simple, fast and clinically applicable assay for the detection of FGFR3 mutations in urine. We also designed the Urodiag® PCR Kit, which includes the MASO-PCR and QM-MSPCR assays. Adapted to routine clinical laboratory (simplicity, accuracy), the kit will be a great help to urologists for recurrence surveillance in patients at low-, intermediate- and high-risk NMIBC. Reducing the number of unnecessary cystoscopies, it will have extremely beneficial effects for patients (painless) and for the healthcare systems (low cost).

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Clinical performance of Xpert Bladder Cancer (BC) Monitor, a mRNA-based urine test, in active surveillance (AS) patients with recurrent non-muscle-invasive bladder cancer (NMIBC): results from the Bladder Cancer Italian Active Surveillance (BIAS) project

Cited by 25 publications

References 23 publications

The performance of the Xpert Bladder Cancer Monitor Test and voided urinary cytology in the follow-up of urinary bladder tumors

The performance of the Xpert Bladder Cancer Monitor Test and voided urinary cytology in the follow-up of urinary bladder tumors

A novel ultra-sensitive method for the detection of FGFR3 mutations in urine of bladder cancer patients – Design of the Urodiag® PCR kit for surveillance of patients with non-muscle-invasive bladder cancer (NMIBC)

A novel ultra-sensitive method for the detection of FGFR3 mutations in urine of bladder cancer patients – Design of the Urodiag® PCR Kit for surveillance of patients with non-muscle-invasive bladder cancer (NMIBC)

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