Multimodal Spectroscopy to Detect Urothelial Cancer in Urine

"The Feasibility of a Multimodal Spectroscopy Analysis to Detect Urothelial Cancer in Urine"

To facilitate the follow-up of urothelial tumors and also make them more tolerable and less invasive for patients, there is a minimally invasive and easy to perform examination which is urinary cytology on 3 samples. This test is extremely specific, over 90% chance of cancer if it is positive and is performed by expert cytopathologists, but it is burdened by a very low sensitivity, which is especially acute in the case of low grade tumors. This makes it an extremely useful test in case of positivity, but of little use if negative or doubtful, not being able to consider it reliable.

To overcome this problem, our study aims to bring an approach based on a physical principle, that is spectroscopy, which is fast non-invasive and does not require the use of additional substances or contrast media in the diagnosis of urothelial neoplasms in samples of urine.

In our experience, multimodal optical fiber spectroscopy has proved extremely valid in discriminating healthy urothelial tissue from tumor ex vivo, as well as providing important information on the degree of urothelial neoplasia, with accuracy rates higher than 80%, for which developed the idea of a technique based on multimodal spectroscopy.

If our method proves valid, it could improve the follow up and management of patients with urothelial cancer, being able to support normal cytology and provide further support to the cytopathologist, as well as simplify the diagnosis.

Study Overview

• Status: Recruiting
• Conditions: Urinary Bladder Cancer; Urothelial Carcinoma; Urinary Tract Cancer
• Intervention / Treatment: Device: Urinary Multimodal Fiber Optic Spectroscopy; Diagnostic test: Urine Cytology; Procedure: Surgery

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Simone Morselli, MD; Phone Number: +39 3473050852; Email: simone.morselli.89@gmail.com

Study Locations

• Italy
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Recruiting
      • Careggi Hospital
      • Sub-Investigator: Alekseja Manera, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients who meet the inclusion and exclusion criteria will be enrolled at Urology ward admission. Informed consent will be collected. Patients therapeutic routine will be unaffected.

In the morning before surgery, the patient will collect urine sample. The patient will then continue the previously established diagnostic therapeutic process. The sample will be brought to the spectroscopic and cytological analysis. Samples will not be stored.

According to the sample size calculation based on the asymptotic normal distribution theory, a total of 240 cases and 240 controls will be required if the study is to have 90% power. A series of 5000 simulations generating binary test data with a true positive frequency and a true negative frequency of 80% showed that these sample sizes produce 89% power. Increasing the sample size to 250 cases and 250 controls increases the potency to 90%. Therefore, approximately 250 cases and 250 controls will be enrolled in this phase 2 validation study.

Description

CASES Inclusion criteria

Patients over the age of 18 who are known for urological interventions for the following pathologies will be considered for enrollment in the group of cases:

• Bladder cancer
• Urethral tumor
• Renal Pelvis Tumor
• Ureteral tumor

The exclusion criteria will be:

• Age under 18
• Pregnancy
• Lack of informed consent
• Persons with indwelling catheter
• Presence of prostate cancer
• Presence and / or history of renal cancer, except tumors of the renal pelvis

CHECKS Inclusion criteria

Patients over the age of 18 who are known for urological interventions for the following pathologies will be considered for enrollment in the control group:

• Kidney, ureteral or bladder stones
• BPH

The exclusion criteria will be:

• Age under 18
• Pregnancy
• Lack of informed consent
• Indwelling Catheter wearers
• Presence of prostate cancer
• Presence of kidney cancer, including kidney pelvic tumors
• Presence and / or history of ureteral cancer
• Presence and / or history of bladder cancer
• Presence and / or history of urethral cancer

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients Positive for Urinary Tract Cancer; Patients will undergo urinary cytology, multimodal spectroscopy in urine and urologic surgical intervention The group of cases will consist of patients who meet the inclusion and exclusion criteria in the operative note for: Transurethral Resection of Bladder Neoplasia (TURBT); Radical Cystectomy for Bladder Neoplasia; Diagnostic ureterorenoscopy and / or laser treatment of ureteral and / or renal pelvis neoplasia; Segmental ureterectomy with or without ureteral reimplantation; Nephroureterectomy with or without bladder cuff excission	Device: Urinary Multimodal Fiber Optic Spectroscopy; Approach based on a physical principle, mainly spectroscopy, which is rapid non-invasive and does not require the use of additional substances or contrast media in the diagnosis of urothelial neoplasms in urine samples. It will be administered through a appositely designed device; Diagnostic test: Urine Cytology; An expert cytopathologist will analyze urine samples to detect urinary tract cancer cells. It is the current golden standard to detect urothelial cancer in urine; Procedure: Surgery; It will provide a reliable information on the presence/absence of cancer in the urinary tract (from direct visualization to pathological analysis)
Patients Negative for Urinary Tract Cancer; Patients will undergo urinary cytology, multimodal spectroscopy in urine and urologic surgical intervention The control group will consist of patients who meet the inclusion and exclusion criteria in the operative note for: Transurethral Resection of Prostate (TURP); Other endoscopic treatments of Benign Prostatic Hyperplasia (BPH); Open interventions of prostatic adenomectomy; Endoscopic lithotripsy interventions of bladder stones or cystotomy with removal of bladder stones; Rigid and / or flexible ureterorenoscopy for the treatment of kidney and / or ureteral stones; Placement of ureteral catheter for ureteral and / or renal stones; Bladder Neck Incision (TUIP); Endoscopic urethrotomy	Device: Urinary Multimodal Fiber Optic Spectroscopy; Approach based on a physical principle, mainly spectroscopy, which is rapid non-invasive and does not require the use of additional substances or contrast media in the diagnosis of urothelial neoplasms in urine samples. It will be administered through a appositely designed device; Diagnostic test: Urine Cytology; An expert cytopathologist will analyze urine samples to detect urinary tract cancer cells. It is the current golden standard to detect urothelial cancer in urine; Procedure: Surgery; It will provide a reliable information on the presence/absence of cancer in the urinary tract (from direct visualization to pathological analysis)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine Multimodal Spectroscopy Reliability	Evaluate whether multimodal spectroscopy can discriminate between healthy controls and patients with urothelial neoplasia on urine, with an accuracy at least comparable to urinary cytology on 3 samples	Enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine Multimodal Spectroscopy Grading	Evaluate whether multimodal spectroscopy is able to discriminate between high or low grade urothelial lesions on urine	Enrollment
Urine Multimodal Spectroscopy Site Discrimination	Evaluate whether multimodal spectroscopy is able to discriminate between lower or upper urinary tract lesions on urine	Enrollment

Collaborators and Investigators

• Sponsor: University of Florence
• Collaborators: Careggi Hospital; Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy; European Laboratory for Non-Linear Spectroscopy
• Investigators: Principal Investigator: Mauro Gacci, MD, Careggi University Hospital; Principal Investigator: Enrico Baria, PhD, European Laboratory for Non-Linear Spectroscopy; Principal Investigator: Riccardo Cicchi, PhD, Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy; Principal Investigator: Francesco Saverio Pavone, Prof, University of Florence; Principal Investigator: Gabriella Nesi, Prof, University of Florence

Publications and helpful links

General Publications

• Baria E, Morselli S, Anand S, Fantechi R, Nesi G, Gacci M, Carini M, Serni S, Cicchi R, Pavone FS. Label-free grading and staging of urothelial carcinoma through multimodal fibre-probe spectroscopy. J Biophotonics. 2019 Nov;12(11):e201900087. doi: 10.1002/jbio.201900087. Epub 2019 Aug 13.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2021
• Primary Completion (Anticipated): December 20, 2023
• Study Completion (Anticipated): January 25, 2024

Study Registration Dates

• First Submitted: January 18, 2021
• First Submitted That Met QC Criteria: January 18, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Urine; Urinary Tract Cancer; Spectroscopy; Laser; Urine Cytology
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Urologic Neoplasms
• Other Study ID Numbers: 17686_BIO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No