Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Urinary Bladder Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Jussi Nikkola, MD PhD

Peter Black

Riikka Järvinen

Tuomas Jalanko

Jussi Nikkola

Thea Veitonmäki

Matti Annala

Peter Boström

Otto Ettala

Urothelial cancers of the bladder and upper urinary tract account for over 200,000 deaths and 600,000 diagnoses annually worldwide. The most common presenting symptom is hematuria (blood in urine), triggering a cascade of tests, including an invasive examination of the bladder using a flexible scope (cystoscopy). Millions of cystoscopies are performed every year worldwide for patients presenting with hematuria, but only 10% result in a cancer diagnosis. The UROSCOUT-1 trial is a prospective multicenter observational study that explores the potential of urine tumor DNA (utDNA) testing to replace a significant portion of cystoscopies in the diagnostic setting for hematuria or other reasons to rule out urothelial cancer. The goal is to enhance patient quality of life, reduce healthcare costs, and address increased workloads in urology centers. Sample collection will be conducted by mail, and the samples will be analyzed in a blinded manner, without knowledge of which patients are diagnosed with cancer. Random subsampling will be applied to cancer-negative patients to achieve an approximate 1:1 ratio between cancer-positive and -negative patients.

Prospective Validation Study of High Volume Urine DNA Testing in Individuals With Suspicion of Urothelial Cancer

Observational Prospective Multicenter Validation Study Investigating the Possibility of Replacing Cystoscopies With High Volume Urine DNA Testing in Individuals With Suspicion of Urothelial Cancer (UROSCOUT-1)

Characteristics of urothelial cancers that were not detected by the utDNA test (TNM pathological stage, World Health Organization (WHO) 2004/2016 grade, and tumor size)

Concordance between utDNA and urine cytology results, with respect to positivity of the test

Sensitivity and specificity of utDNA test for urothelial cancer detection, using histologically confirmed cancer diagnoses within 1 year of the diagnostic workup as ground truth

Sensitivity and specificity of cystoscopy for urothelial cancer detection, using histologically confirmed cancer diagnoses within 1 year of the diagnostic workup as ground truth

Sensitivity and specificity or urine cytology for urothelial cancer detection, using histologically confirmed cancer diagnoses within 1 year of the diagnostic workup as ground truth

Time to diagnosis of urothelial cancer in patients with a positive utDNA test but negative cystoscopy

Adverse event rate for cystoscopy, based on CTCAE 5.0

Fraction of all analyzed urine samples for which the analysis met the quality control criteria for a technically successful analysis

Estimated fraction of diagnostic cystoscopies that could have been avoided by pre-screening patients with a utDNA test (calculated as the fraction of all diagnostic utDNA samples that were negative and for which subsequent cystoscopy did not lead to clinical interventions)

Specificity of a high-stringency utDNA threshold (at least 2 known urothelial cancer driver mutations with allele fraction \> 5%) for clinically detectable urothelial cancer

Tampere University

Tampere University Hospital

Symptoms and General Pathology

Neoplasm, Residual

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Carboplatin

Cisplatin

Immunomodulating Agents

Immunologic Factors

muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant chemotherapy

muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant immunotherapy

cisplatin/carboplatin-gemcitabine 4-6 cycles

Adjuvant chemotherapy

adjuvant immunotherapy

jiwei huang, M.D

In our study, the ultra-deep sequencing of circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) were performed to assess whether ctDNA and utDNA can be used as predictive biomarkers for the detection of minimal residual disease (MRD) and early diagnosis of UTUC recurrence, and explored the role of ctDNA and utDNA detection of MRD in the prediction of adjuvant therapy efficacy and prognostic evaluation.

60% of Upper Urinary Tract Urothelial Carcinoma (UTUC) patients with muscle-invasive disease at diagnosis, which progresses rapidly, aggressively, and has a poor prognosis. Up to 30-40% of the patients may develop bladder recurrance after radical nephroureterectomy for primary upper tract urothelial carcinoma.

Minimal residual disease (MRD) refers to the small number of malignant cells that remain after curative treatments (curative intent surgical resection, radiotherapy, and/or chemotherapy). MRD is common in patients with blood cancer, and is known to be associated with recurrence and poor prognosis. Recent studies also reported that MRD-negative in postoperative solid tumors such as colorectal/colon cancer and muscle-invasive bladder cancer is associated with better survival outcomes. However, the clinical values of MRD monitoring for adjuvant therapy in postoperative UTUC remain inadequate.

A total of 103 patients with stage II-IV UTUC will be recruited in this clinical trial. The following plasma samples, urine samples and tumor tissues will be collected from each patient including 1) preoperative plasma and urine samples; 2) surgical tissue samples; 3) plasma and urine samples 1 month after surgery; 4) plasma and urine samples during adjuvant therapy; and 5) plasma and urine samples after adjuvant therapy; 6) plasma and urine samples in follow-up. In addition, demographic and tumor characteristics of the patients will be collected for subsequent analysis, including age, sex, tumor stage, pathological stage, disease couse time, etc. Tumor tissues and matched peripheral blood were collected before treatment and WES was used ctDNA detection techniques. For each patient, we selected up to 30 clonal somatic mutations for personalized, tumor informed ctDNA assay design.Statistical analyses will be performed to analyze the survival outcomes and to explore the clinical value of MRD monitoring for adjuvant therapy in postoperative UTUC.

Circulating Tumour DNA and Urine Tumor DNA Detection of Minimal Residual Disease in Locally Advanced Upper Tract Urothelial Carcinoma With Radical Nephroureterectomy: A Cohort Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Prospective Validation Study of High Volume Urine DNA Testing in Individuals With Suspicion of Urothelial Cancer	NCT06310759	Urothelial Carc...		18 Years - 100 Years	Tampere University Hospital
Circulating Tumour DNA and Urine Tumor DNA Detection of Minimal Residual Disease in Locally Advanced Upper Tract Urothelial Carcinoma With Radical Nephroureterectomy: A Cohort Study	NCT05595408	Muscle Invasive...	Adjuvant chemot... adjuvant immuno...	18 Years -	RenJi Hospital

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