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NCT Number: NCT06325423

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.

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Key information

Conditions

Muscle-Invasive Bladder Carcinoma

Age range

19 year and older

Sex eligibility

All sexes

Study type

Observational

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

neoadjuvant chemotherapy

Combination Product

platinum-based chemotherapy before radical cystectomy or bladder preservation

Primary outcomes

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
- 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

Secondary outcomes

Local recurrence-free survival (RFS)

Time frame: 2 years

the length of time from radical cystectomy/ bladder preservation to local recurrence.

Study contacts

Contact information is provided by the study sponsor or research team.

Gehad A Abdelrazik, ass.lecturer

CONTACT

[email protected]

01097381211

Hebatullah M Bakri, Lecturer

CONTACT

[email protected]

01007272760

Sponsors and collaborators

Lead sponsor

Assiut University

Other

Registry information

Official study title

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

Important dates

Study start: 2024
Primary completion: 2025
Study completion: 2027
First posted: Mar 22, 2024
Registry last updated: Mar 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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