Machine Learning-Based Prediction of BCG Response in High-Risk Non-Muscle Invasive Bladder Cancer Patients

This prospective study aims at using Artificial intelligence to create a helpful unbiased machine learning-based model that predicts BCG unresponsiveness in high risk BCG-naïve NMIBC patients incorporating all potential clinico-pathological, radiological and/or molecular prognostic factors.

Study Overview

• Status: Recruiting
• Conditions: Non-Muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: Bacillus Calmette-Guerin

Detailed Description

Introduction:

In the era of BCG shortage and BCG-associated morbidity, the development of prognostic models remains a never-ending topic of research to predict Non Muscle Invasive Bladder Cancer (NMIBC) patients of high risk of BCG unresponsiveness; hence optimize their treatment, achieve survival benefit with minimal long-term morbidity, and prioritize patients with expected good response.

Aim of the study:

This prospective study aims at using Artificial intelligence to create a helpful unbiased machine learning-based model that predicts BCG unresponsiveness in high risk BCG-naïve NMIBC patients incorporating all potential clinico-pathological, radiological and/or molecular prognostic factors.

Patients and Methods:

Patients with diagnosed bladder tumors seen through the outpatient clinic in the urology department (Urology and Nephrology Center, Mansoura University, Egypt) will be assessed for eligibility to the study and inclusion criteria (Ability to give informed consent, High-risk NMIBC, Good performance status and No prior history of BCG intravesical therapy) then asked to participate in this prospective study via an informed consent form.

All patients will be thoroughly evaluated by medical history and physical examination, routine laboratory investigations (including cytology and N/L ratio), mpMRI lower abdomen and pelvis and molecular markers evaluation (Urinary IL-10 levels by solid phase ELISA Immunoassay, Reverse Transcriptase-quantitative Polymerase Chain Reaction (RT qPCR) technology-based assessment of serum TNF-a and Chromosomal anomalies using FISH technique) . Then, all patients will be managed by cystoscopy and initial complete TURBTfollowed by re-staging TUR biopsy 2-6 weeks later on. All patients will be discharged after the re-staging TUR to receive adjuvant intravesical BCG therapy in the outpatient clinic and to be followed-up according to the predetermined protocol. If any patient has new tumour/positive cytology by outpatient cystoscopy after ICR, he will be readmitted to our center and subjected to cystoscopic-guided biopsy. If high grade or CIS proven pathology, BCG unresponsiveness will be considered. Univariate and multivariate analysis will be performed to identify independent prognostic factors associated with BCG unresponsiveness. After that, each of these factors will have a score according to its regression coefficient. Then, these independent factors with their scores will be summed into Artificial Neural Network-based prediction model for predicting BCG unresponsiveness.

Sample size and statistical analysis:

Sample size is calculated for the final analysis 6 months post initial TURBT with α = 0.05 (adjusted for the primary outcome which is BCG unresponsiveness) and a power of 80% (β = 0.20). A sample size of 45 patients per group should be available for final analysis. Since an overall dropout rate of about 10% is expected, 50 patients per group have to be recruited. All statistical analyses will be performed using ABM SPSS program version 20.

Ethical considerations:

A fully informed consent will be taken from all patients. The study will approved by the local ethical committee IRB (Institutional review board), faculty of medicine, Mansoura University. Patients will be managed according to Declaration of Helsinki.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Osama Ezzat, Ass. lect.; Phone Number: 01023990432; Email: osamaezzat1990@gmail.com

Study Locations

• Egypt
  • Outside U.S./Canada
    • Mansoura, Outside U.S./Canada, Egypt, 35511
      • Recruiting
      • Urology and nephrology center
      • Contact: Osama Ezzat, Ass. lect.; Phone Number: 01023990432; Email: osamaezzat1990@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with diagnosed bladder tumors seen through the outpatient clinic in the urology department, Urology and Nephrology Center (Mansoura University, Egypt) will be assessed for eligibility. Patients who are meeting these criteria will be asked to participate in this prospective study and will be provided with an informed consent form. all patients will be thoroughly evaluated by medical history and physical examination, routine laboratory investigations, mpMRI lower abdomen and pelvis. Then, all patients will be managed by complete TURBT followed by re-staging TUR biopsy after 2-6 weeks. All included patients will be discharged to receive adjuvant intravesical BCG therapy and to be followed-up according to the predetermined protocol.

Description

Inclusion Criteria:

1. Ability to give informed consent.
2. High-risk NMIBC (any patient with high grade Ta or high grade T1 or CIS or recurrent multiple large tumors with low grade Ta/T1)
3. Good performance status (Defined as: performance status 0 or 1 at the time of TURBT according to Eastern Cooperative Oncology Group-ECOG-).
4. No prior history of BCG intravesical therapy.

Exclusion Criteria:

1. History of previous radiotherapy or systemic chemotherapy.

2. Post TURBT histopathology report showing any of the following;

   1. Benign histopathology.
   2. Muscle invasive urothelial carcinoma.
   3. Non urothelial carcinoma of the bladder.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
BCG responders; Non-muscle invasive bladder cancer patients who do not have T1/Ta HG recurrence within 6 months of adequate BCG therapy.	Drug: Bacillus Calmette-Guerin; Bacillus Calmette-Guerin (BCG) is immunotherapy to prevent recurrence and progression of non muscle invasive bladder cancer.; Other Names: BCG
BCG non-responders; Non-muscle invasive bladder cancer patients who have T1/Ta HG recurrence within 6 months of adequate BCG therapy or CIS within 12 months of BCG therapy	Drug: Bacillus Calmette-Guerin; Bacillus Calmette-Guerin (BCG) is immunotherapy to prevent recurrence and progression of non muscle invasive bladder cancer.; Other Names: BCG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BCG unresponsiveness	T1/Ta HG recurrence within 6 months of adequate BCG therapy	6 months

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Principal Investigator: Osama Ezzat, Ass. lect., Urology and Nephrology Center , Mansoura university

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2022
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (ACTUAL): April 18, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Prediction; Machine Learning; Non-Muscle Invasive Bladder Cancer; BCG Response
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; BCG Vaccine
• Other Study ID Numbers: MD.22.03.622

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: protocol of the study as well as data of our patients will be available and shared by the end of the study

Drug and device information, study documents

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