Predicting Response to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer

March 22, 2024 updated by: Gehad Ahmed Abd El-Razik, Assiut University

The Impact of Tumor Microenvironment and Clinicopathological Features in Predicting Response to Neoadjuvant Chemotherapy in Muscle Invasive Bladder Cancer

Bladder cancer (BC) is the 10th most commonly diagnosed cancer worldwide and the second most common cancer among Egyptian males.

The mainstay of treatment of muscle-invasive BC( MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) or bladder preservation(BP) using maximal transurethral resection of the bladder tumor followed by chemoradiation. The rationale to use NAC before RC or BP is to eradicate micro-metastasis and to downstage the primary tumor.

The 5-year cancer-specific survival for responders to NAC is 90%, in contrast to 30-40% for those not obtaining an objective response. Drawbacks of NAC are disappointing delay of surgery in non-responders and the potential toxicity. So, predictors of response to NAC are necessary to identify patients who may achieve pathologic complete response and will benefit from BP, and the others who may not respond to NAC and spare them NAC toxicity and RC delay.

Tumor microenvironment (TME), including neutrophil extracellular traps (NETs), and CD8+ T lymphocytes is a promising predictor of response to NAC in MIBC.

NETs are reticulated DNA structures decorated with various protein substances (e.g., histones, myeloperoxidase, neutrophil elastase).NETs are involved in tumor growth, metastasis, and treatment resistance. Moreover, NETs can inhibit T cell responses, thereby promoting tumor growth.

On the other hand, immune cells that are present in the TME play a major role in slowing down tumor progression. CD8+T lymphocytes play a central role in immune-mediated control of cancer . Also, they have been found to be a prognostic tool for advanced BC.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Formalin fixed paraffin embedded tissue specimen of the baseline TUR of MIBC will be obtained from pathology laboratory, Pathology Department, Assiut University.

  • Histological diagnosis of H&E stained sections will be confirmed.
  • Immunohistochemical staining for Citrullinated histone H3 (H3Cit) antibody as a hallmark of NETs, and CD8 antibody to quantity density of NETs and CD8 expression, then calculate NETs/CD8 ratio.
  • Baseline clinicopathological features of MIBC patients who received neoadjuvant chemotherapy will be collected from patients' records.
  • Correlation between NETs expression, CD8 expression, NETs/CD8 ratio, and the baseline clinicopathological features with the response to neoadjuvant chemotherapy.
  • develop a risk score based on the significant predictors of response to identify patients who may achieve pathologic complete response and will benefit from BP, and the others who may not respond to NAC and spare them NAC toxicity and RC delay.

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

patients with localised muscle-invasive bladder cancer who received neoadjuvant chemotherapy

Description

Inclusion Criteria:

  • Pathologically proven pure urothelial carcinoma, or morphologic variant of urothelial carcinoma.
  • Patients with ≥T2, N0-1, M0, according to American Joint Committee on Cancer (AJCC) TNM Staging System for Bladder Cancer 8th ed., 2017.
  • Patients who received platinum-based neoadjuvant chemotherapy before RC or BP.
  • Available paraffin-embedded TUR specimens for Immunohistochemistry (IHC).

Exclusion Criteria:

  • Non urothelial carcinoma.
  • Not muscle invasive < T2.
  • Metastatic bladder cancer.
  • No available paraffin-embedded TUR specimens for IHC.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
MIBC patients who received NAC
Patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy before radical cystectomy or bladder preservation
Combination product: neoadjuvant chemotherapy
platinum-based chemotherapy before radical cystectomy or bladder preservation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
- Response to platinum-based chemotherapy in localized MIBC in relation to: NETs expression, CD8 expression, NET/CD8 ratio and baseline clinicopathological features
Time Frame: 6 months
Correlation between NETs expression, CD8 expression, NETs/CD8 ratio and the baseline clinicopathological features of MIBC and the response to neoadjuvant chemotherapy
6 months
Evaluation of the expression of NETs and CD8 in paraffin-embedded TUR biopsies
Time Frame: 6 months
evaluation of the density of Citrullinated Histone H3 as a hallmark of NETs and the density of CD8 in the baseline FFPE TUR specimens
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local recurrence-free survival (RFS)
Time Frame: 2 years
the length of time from radical cystectomy/ bladder preservation to local recurrence.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Investigators

  • Study Director: Amal R Ibrahim, Ass.Prof, Assiut University
  • Study Director: Hanan G Mostafa, Professor, Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2024

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

March 16, 2024

First Submitted That Met QC Criteria

March 16, 2024

First Posted (Actual)

March 22, 2024

Study Record Updates

Last Update Posted (Actual)

March 26, 2024

Last Update Submitted That Met QC Criteria

March 22, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • response to NAC in MIBC

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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