Immune-Stromal Landscape in Muscle-Invasive Bladder Cancer

April 7, 2026 updated by: Maryam Adel Ali Ibrahim, Assiut University

The Immune-Stromal Landscape of Muscle-Invasive Urothelial Bladder Carcinoma: A Morphological Histopathological Study

Bladder cancer is a significant global health issue. When the cancer spreads into the muscle layer of the bladder (muscle-invasive bladder cancer), a common treatment is the surgical removal of the bladder (radical cystectomy). However, even after surgery, it can be difficult for doctors to accurately predict how an individual patient's disease will progress using standard staging methods.

This retrospective observational study aims to find better ways to predict patient outcomes by examining the tumor microenvironment, which is the environment immediately surrounding the cancer cells. Specifically, researchers are looking at the relationship between the tumor cells, the surrounding supportive tissue (the stroma), and the patient's natural immune cells.

The study will review existing medical records and archived tumor tissue samples from at least 100 patients who underwent radical cystectomy at the South Egypt Cancer Institute between 2018 and 2024. Under a microscope, researchers will assess three main features:

  • Tumor-Stroma Ratio (TSR): The amount of tumor tissue compared to the surrounding supportive tissue.
  • Tumor-Infiltrating Lymphocytes (TILs): The number of immune cells that have moved into the tumor to try and fight it.
  • Tertiary Lymphoid Structures (TLS): Organized clusters of immune cells that form near the tumor.

By analyzing these features, the researchers hope to determine if specific patterns of immune and supportive cells are linked to better or worse survival rates, such as Overall Survival and Disease-Free Survival. Understanding this immune-stromal landscape could lead to more personalized risk assessments and better treatment plans for future bladder cancer patients.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Urothelial carcinoma is the predominant histological type of bladder cancer, representing about 90% of cases. In Egypt, a substantial shift in histopathological patterns has been observed over recent decades, with urothelial carcinoma emerging as the dominant subtype over squamous cell carcinoma. The clinical outcome of bladder cancer is influenced by established prognostic factors such as tumor stage and histological grade. However, these parameters are frequently unable to fully capture the biological heterogeneity of the disease, limiting their ability to accurately predict individual patient outcomes.

This limitation has prompted interest in identifying additional prognostic markers within the tumor microenvironment. Morphological and immune-related parameters are increasingly recognized as valuable indicators of tumor aggressiveness and epithelial-mesenchymal transition.

To investigate this, histopathological assessment will be performed on the representative slide for each patient featuring the deepest invasion, highest tumor grade, and minimal necrosis. Tumor grade and pathological stage will be determined based on the American Joint Committee on Cancer (AJCC) staging system (8th edition), and histological subtypes will be confirmed according to the 2022 World Health Organization (WHO) classification. Additional parameters to be assessed include coagulative tumor necrosis, surgical margin status, lymph node metastasis, lymphovascular invasion (LVI), and perineural invasion (PNI).

The study will strictly evaluate the following morpho-immune parameters:

  • Tumor-Stroma Ratio (TSR): TSR will be assessed at the invasive tumor front using a standardized scoring system. Tumors will be classified into two categories: stroma-high (> 50% stromal component) and stroma-low (≤ 50% stromal component).
  • Tumor-Infiltrating Lymphocytes (TILs): The density of TILs will be evaluated on H&E-stained sections using the semi-quantitative Klintrup-Mäkinen (KM) scoring system. The immune response will be categorized into four grades (0-3), which will be further stratified into low-grade (0-1) and high-grade (2-3) immune responses.
  • Tertiary Lymphoid Structures (TLS): TLSs will be histologically evaluated focusing on the tumor's invasive edge. The evaluation is based on three quantitative parameters: average density, hotspot density, and maximal diameter.
  • Glasgow Microenvironment Score (GMS): This simplified prognostic tool evaluates the tumor microenvironment by integrating the KM grade and the TSR to stratify patients into three prognostic groups. The GMS Grading Scale will assign patients to GMS 0 (high-grade inflammatory response), GMS 1 (low-grade inflammatory response with low stromal percentage), or GMS 2 (low-grade inflammatory response with a high stromal percentage).

Study Type

Observational

Enrollment (Estimated)

100

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

The study population consists of patients who underwent radical cystectomy for muscle invasive urothelial carcinoma at the South Egypt Cancer Institute (SECI) between 2018 and 2024.

Description

Inclusion Criteria:

  • Patients who underwent radical cystectomy for muscle invasive urothelial carcinoma.
  • Treated at the South Egypt Cancer Institute (SECI) between 2018 and 2024.

Exclusion Criteria:

  • Cases with non-urothelial histological subtypes (e.g., pure squamous cell carcinoma).
  • Patients who received neoadjuvant chemotherapy or radiotherapy.
  • Cases with missing or inaccessible clinical follow-up data.
  • History of prior or concurrent malignancy.

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
Muscle-Invasive Urothelial Carcinoma Cohort
This cohort consists of patients who underwent radical cystectomy for muscle-invasive urothelial carcinoma at the South Egypt Cancer Institute (SECI) between 2018 and 2024. Patients are excluded if they had non-urothelial histological subtypes, received neoadjuvant chemotherapy or radiotherapy, had a history of prior or concurrent malignancy, or lack accessible clinical follow-up data. Archived hematoxylin and eosin (H&E)-stained slides from this cohort will be retrospectively evaluated for morphological and immune-related parameters, specifically Tumor-Stroma Ratio (TSR), Tumor-Infiltrating Lymphocytes (TILs), and Tertiary Lymphoid Structures (TLS).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From the date of radical cystectomy until the date of death from any cause, assessed up to 72 months (6 years).
Overall survival is defined as the length of time from the date of radical cystectomy to the date of death from any cause. This measure will be used to evaluate the prognostic significance of tumor microenvironment parameters, including the tumor-stroma ratio (TSR), tumor-infiltrating lymphocytes (TILs), and tertiary lymphoid structures (TLS).
From the date of radical cystectomy until the date of death from any cause, assessed up to 72 months (6 years).

Collaborators and Investigators

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

Sponsor

Assiut University

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)

May 1, 2026

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

April 7, 2026

First Submitted That Met QC Criteria

April 7, 2026

First Posted (Actual)

April 13, 2026

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MIBC Immune-Stromal Landscape

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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