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A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up

Conditions
Urothelial Carcinoma
Interventions
Diagnostic Test: The level of CNV
Registration Number
NCT04432909
Lead Sponsor
Changhai Hospital
Brief Summary

Urothelial carcinoma (UC) is common malignancy and is considered to be one of the costliest cancers. The traditional diagnostic methods of UC present with some shortcomings. For example, the specificity of CTU remains low while cystoscopy is invasive and expensive. Therefore, a noninvasive diagnostic method with high accuracy is urgently needed. Our previous study has proved that UroCAD, which is able to detect chromosomal aberrations of the urine exfoliated cells, is a reliable method in diagnosing UC with sensitivity and specificity of 82.5% and 96.9%, respectively. But its potential in UC patient follow-up hasn't been assessed yet and the the accuracy of UroCAD in detecting UC still need to be further validated. The investigators here intended to investigate whether UroCAD can be used in UC patient follow-up and further validate the accuracy of UroCAD in diagnosing UC.

Detailed Description

The traditional diagnostic methods of UC include CT urography (CTU) and cystoscopy. To access the upper urinary tract, CTU is commonly used. The sensitivity for detecting upper tract urothelial cancer with CTU has been reported to reach 89%. However, the specificity of CTU is 51% and it cannot get a biopsy sample. Other shortcomings include exposing the patient to high dose of radiation and the contrast material usage may impair the renal function. In the context of diagnosing lower urinary tract cancer, cystoscopy is the "gold standard" diagnostic procedure, which has a sensitivity of 68-83%. But it is invasive, uncomfortable and may miss flat lesions. Furthermore, due to the high recurrence rate of bladder cancer, surveillance of the disease with frequent cystoscopy make it one of the costliest cancers. Therefore, a noninvasive diagnostic method with high accuracy is urgently needed.

Copy number variations (CNVs) refers to the ongoing acquisition of genomic alterations ranging from point mutations to gross chromosomal rearrangements, is a hallmark of cancer which is found in 60-80% of human cancer, and it positively correlates with high tumor stage, poor prognosis, metastasis and therapeutic resistance. Several researches have investigated the value of detecting chromosomal instability with sWGS in either cell-free (cf)DNA or genomic DNA as a noninvasive diagnostic method for cancers and yielded quite fine results. Our previous research has also proved the UroCAD model reached performance of AUC=0.928, with sensitivity, specificity and accuracy of 82.5%, 96.9% and 89.0%, respectively. This test also showed superiority in diagnosing upper tract urothelial cancer compared with urinary cytology test.

Here the investigators intended to conduct a prospective, multicenter, single-blinded research to further validate the value of UroCAD in diagnosing UC and investigate the potential of UroCAD in UC patient follow-up by analyzing the CNV level of patient DNA extracted from urine exfoliated cells and follow UC patient for up to 2 years to determine if there is a correlation between CNV level and patient prognosis. Patient information, which is acquired every 3 months after surgery, including survival status, CNV level in urine exfoliated cells, treatment during this period, medical examination during this period, etc.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
500
Inclusion Criteria
  • Patients diagnosed with urothelial carcinoma and planned to undergo surgery
  • Cancer patient with urine cytology test result
  • Cancer patient willing to provide urine sample before the surgery, 3 months after surgery, 6 months after surgery, 12 month after surgery, 15 months after surgery, 18 months after surgery, 21 months after surgery, 24 months after surgery, and willing to provide patient information.
  • Participants without any tumor disease and willing to attend the study by providing morning urine.
  • Male or female patients aged >= 18 years.
  • Participants signed informed consent form.
Exclusion Criteria
  • Age under 18 years
  • Individuals unwilling to sign the consent form or unwilling to provide morning urine for test or unwilling to provide the medical record.
  • Patient already received suprapubic cystostomy or urethral catheterization.
  • Patient with late-stage uremia and need regular dialysis.
  • Patient with cancer other than urothelial carcinoma.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Urothelial carcinoma groupThe level of CNVPre-surgery patients with urothelial carcinoma will be the experimental group to determine the sensitivity and specificity of UroCAD analysis, the result will be compared with cytology and FISH test.
Non-cancer participantsThe level of CNVPatients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UroCAD analysis.
Primary Outcome Measures
NameTimeMethod
Assess the value of UroCAD for urothelial cancer patient follow-upthrough study completion, an average of 30 months

Compare the CNV level with the patient information gathered by follow-up to determine whether there is a correlation between CNV level and patient prognosis or disease progression

Sensitivity and Specificity of urinalysis by UroCAD analysisthrough study completion, an average of 30 months

number of patients "declared positive" with the UroCAD test among the patients suffered from urothelial carcinoma and number of patients "declared negative" with the UCAD test among the patients without cancer.

Secondary Outcome Measures
NameTimeMethod
Comparison of the sensitivity and specificity of the UroCAD analysis versus urine cytologythrough study completion, an average of 30 months

number of patients "declared positive" with the UroCAD analysis versus patients "declared positive" with the urine cytology and number of patients "declared negative" with the UroCAD analysis versus patients " declared negative " with the urine cytology

Identification of the correlation between the level of CNV and the stage of the tumor samplethrough study completion, an average of 30 months

level of CNV in the urine sample compared with the stage of the tumor confirmed by histopathologic examination

Identification of the correlation between the level of CNV and the grade of the tumor samplethrough study completion, an average of 30 months

level of CNV in the urine sample compared with the grade of the tumor confirmed by histopathologic examination

Trial Locations

Locations (1)

Changhai Hospital

🇨🇳

Shanghai, Shanghai, China

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