Clinical trial NCT04432909: A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up
Official title: A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Urothelial Carcinoma
Keywords: diagnosis
follow-up
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
Collaborators: name: RenJi Hospital
name: The First Affiliated Hospital of Soochow University
name: Zhejiang Provincial People's Hospital
name: Tongji Hospital
name: Tianjin Medical University Second Hospital
name: Qilu Hospital of Shandong University
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Xibei Hospital
name: West China Hospital
First posted: 2020-06-16
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with urothelial carcinoma or participants in control group from January 2020 to June 2022 in 10 hospitals including Changhai hospital, Renji hospital, The First Affiliated Hospital of Suchow university, Zhejiang Provincial people's hospital, Tongji hospital, The second hospital of Tianjin medical university, Qilu hospital, Second Affiliated Hospital of Sun Yat-Sen University, Xibei hospital, West China 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Sensitivity and Specificity of urinalysis by UroCAD analysis
timeFrame: through study completion, an average of 30 months
measure: Assess the value of UroCAD for urothelial cancer patient follow-up
timeFrame: through study completion, an average of 30 months
Secondary outcomes:
measure: Identification of the correlation between the level of CNV and the grade of the tumor sample
timeFrame: through study completion, an average of 30 months
measure: Identification of the correlation between the level of CNV and the stage of the tumor sample
timeFrame: through study completion, an average of 30 months
measure: Comparison of the sensitivity and specificity of the UroCAD analysis versus urine cytology
timeFrame: through study completion, an average of 30 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
Study officials:
affiliation: Changhai Hospital, Shanghai
name: Chuanliang Xu, M.D.,Ph.D.
role: STUDY_CHAIR
References:
citation: Wadhwa N, Mathew BB, Jatawa SK, Tiwari A. Genetic instability in urinary bladder cancer: An evolving hallmark. J Postgrad Med. 2013 Oct-Dec;59(4):284-8. doi: 10.4103/0022-3859.123156.
citation: Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018 Jan 25;553(7689):467-472. doi: 10.1038/nature25432. Epub 2018 Jan 17.
citation: Liu H, He W, Wang B, Xu K, Han J, Zheng J, Ren J, Shao L, Bo S, Lu S, Lin T, Huang J. MALBAC-based chromosomal imbalance analysis: a novel technique enabling effective non-invasive diagnosis and monitoring of bladder cancer. BMC Cancer. 2018 Jun 15;18(1):659. doi: 10.1186/s12885-018-4571-7.
citation: Hieronymus H, Murali R, Tin A, Yadav K, Abida W, Moller H, Berney D, Scher H, Carver B, Scardino P, Schultz N, Taylor B, Vickers A, Cuzick J, Sawyers CL. Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death. Elife. 2018 Sep 4;7:e37294. doi: 10.7554/eLife.37294.