Tumor Budding and T1 Substaging in Urothelial Bladder Cancer

April 8, 2026 updated by: Hasnaa Usama Ahmed, Assiut University

Assessment of Tumor Budding and T1 Substaging as Histopathological Predictors of Outcome in Urothelial Bladder Carcinoma

Bladder cancer is a significant global and local health concern, and predicting how aggressive a patient's tumor will behave is critical for guiding treatment. This observational study aims to evaluate two specific microscopic features of urothelial bladder carcinoma to see if they can reliably predict patient outcomes: the depth of early tumor invasion (T1 substaging) and the presence of small clusters of cancer cells at the tumor's edge (Tumor Budding).

Researchers will retrospectively analyze tissue samples (paraffin blocks) from at least 100 patients who were diagnosed with urothelial bladder carcinoma and underwent transurethral resection (TUR) at the South Egypt Cancer Institute between 2018 and 2024.

The tissue samples will be analyzed in two main ways:

  • Early-stage tumors (pT1 cases): Researchers will carefully measure the exact depth the tumor has invaded the bladder lining using anatomical and micrometric sub-classification systems.
  • More advanced tumors (pT2 cases): Researchers will examine the invasive edge of the tumors under a microscope to count "tumor buds" (single cells or small clusters of cells).

By comparing these detailed microscopic measurements with the patients' historical medical records, the study hopes to determine if T1 substaging and Tumor Budding are strong predictors of disease recurrence, disease progression, and overall patient survival.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Bladder carcinoma remains a major global oncological burden, exerting a substantial impact on patient morbidity and mortality. In Egypt, it constitutes a significant public health concern with distinctive epidemiological characteristics. While squamous cell carcinoma historically predominated, a substantial shift has occurred over recent decades, and urothelial carcinoma has emerged as the dominant subtype, accounting for approximately 75-80% of cases.

Pathological assessment traditionally focuses on histological grade and invasion depth. The precise assessment of invasion depth is critical, particularly in T1 non-muscle-invasive urothelial carcinoma, where the tumor invades the lamina propria. Multiple sub-classification systems exist for T1 tumors, including anatomical approaches relative to the muscularis mucosae and semiquantitative micrometric methods, yet no single method has been adopted universally. Furthermore, in muscle-invasive disease, the morphology of the invasive front provides crucial biological insights. Tumor budding, defined as single isolated cancer cells or small clusters of fewer than five cells at the invasive front, is recognized as a morphological hallmark of epithelial-mesenchymal transition (EMT) and reflects aggressive tumor potential.

This study evaluates archived hematoxylin and eosin (H&E)-stained slides from patients who underwent transurethral resection (TUR) for urothelial carcinoma between 2018 and 2024. Histological subtypes will be confirmed according to the 2022 World Health Organization (WHO) classification, and tumor grade and stage will be determined using the American Joint Committee on Cancer (AJCC) 8th edition. Additional pathological parameters assessed will include tumor size, multifocality, coagulative tumor necrosis, lympho-vascular invasion (LVI), and perineural invasion (PNI).

The histopathological procedures are divided into two primary evaluations:

  • pT1 Substaging: Confirmed pT1 cases will undergo rigorous histopathological substaging. Anatomical substaging (T1a/b/c) will identify the invasion level relative to the muscularis mucosae. Micrometric assessment will utilize a 0.1 mm threshold for semi-quantitative subtyping, alongside the Rete Oncologica Lombarda (ROL) system, which uses a 1.0 mm threshold to define low-risk and high-risk progression groups.
  • Tumor Budding Assessment: Confirmed pT2 cases will be evaluated for tumor budding at the invasive front using the "Hotspot" method to count buds in one high-power field. Cases will be stratified into three grades: Low Budding (BD1: 0-4 buds), Intermediate Budding (BD2: 5-9 buds), and High Budding (BD3: ≥ 10 buds).

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 diagnosed with urothelial bladder carcinoma who underwent transurethral resection (TUR) at the South Egypt Cancer Institute (SECI), Assiut University, between the years 2018 and 2024. The study utilizes retrospectively collected, archived paraffin-embedded tissue blocks along with corresponding clinical, pathological, and survival data retrieved from medical records and electronic pathology reports.

Description

Inclusion Criteria:

  • Patients with a urinary bladder mass, diagnosed by TUR biopsy as urothelial carcinoma.
  • Patients with full clinical data and complete medical reports.

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
pT1 Urothelial Carcinoma Cases
All confirmed pT1 cases will undergo rigorous histopathological substaging. An anatomical substaging (T1a/b/c) will be performed by identifying the level of invasion relative to the muscularis mucosae. Additionally, micrometric assessment will be carried out using a 0.1 mm threshold and the Rete Oncologica Lombarda (ROL) system.
pT2 Urothelial Carcinoma Cases
These cases will be evaluated for Tumor Budding. The "Hotspot" method will be used to count buds in one high power field at the invasive front. Cases will be graded as Low Budding (BD1): 0-4 buds, Intermediate Budding (BD2): 5-9 buds, and High Budding (BD3): ≥ 10 buds.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 72 months (retrospectively assessed spanning the 2018 to 2024 study period).
Overall survival is defined as the length of time from the date of the transurethral resection (TUR) to the date of death from any cause. This outcome will be correlated with the assessed histopathological parameters (T1 substaging and Tumor Budding scores) to evaluate their prognostic significance in urothelial bladder carcinoma.
Up to 72 months (retrospectively assessed spanning the 2018 to 2024 study period).

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 8, 2026

First Submitted That Met QC Criteria

April 8, 2026

First Posted (Actual)

April 14, 2026

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 8, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • T1 & Budding in Bladder Cancer

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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