Neoadjuvant Chemotherapy in Non Muscle Invasive T1b Bladder Cancer

January 28, 2020 updated by: heba mahmoud mohamed, Assiut University

Role of Neoadjuvant Chemotherapy in the Conservative Management of Non-muscle Invasive Bladder Cancer (NMIBC) T1b

The aim of our study is to evaluate the benefit of NAC in T1b NMIBC .

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Bladder cancer (BC) is the most common malignancy of the urinary tract and the fourth most frequent cancer in the United States, with 79,030 new cases and 16,870 deaths estimated for 2017.

The most common presenting symptom is hematuria, which occurs in about 85% of patients. Hematuria is typically intermittent, gross, and painless. Bladder irritability, usually presenting as urinary frequency, urgency, and dysuria, occurs in about 20% of patients.

Initial diagnostic workup usually involves cystoscopy and urine cytology. Cystoscopy is the gold standard for the initial diagnosis and staging of bladder cancer. If a bladder mass is detected, a transurethral resection of the bladder tumor (TURBT) is performed for full primary tumor staging. The resected bladder tumor specimen should include muscle to fully assess the depth of tumor invasion. If carcinoma in situ (CIS) is detected, multiple random biopsies, including several different areas of the bladder and the prostatic urethra, may be required to assess the extent of involvement.

Abdominal imaging with either CT or MRI is recommended in patients with a high-grade tumor or muscle invasive disease to assess for local lymph node involvement, loco regional extent of disease and the presence of hydronephrosis.

Approximately 75% of patients with urothelial carcinoma of the bladder present with non-muscle-invasive bladder cancer (NMIBC), either confined to the mucosa (Ta and carcinoma in situ [CIS]) or invading the lamina propria (T1) . Clinical T1 high-grade (cT1HG) NMIBC has the highest rate of local recurrence and carries a significant risk of disease progression, clinical understaging, and death from urothelial carcinoma (UC) . The standard of care for adequately resected cT1HG NMIBC is intravesical Bacillus Calmette-Guerin (BCG) with early radical cystectomy (RC) for recurrent or refractory cT1HG disease Pathological upstaging to pathological tumor -2( pT2) is reported in approximately 50% when muscularis propria is absent from the original biopsy, and up to 25% will have lymph node (LN) metastases , which significantly increases the risk for cancer-specific death . These observations imply that a subset of patients with NMIBC that invades into the lamina propria is at a higher risk for clinical understaging and death from UC and may benefit from more aggressive therapy.

Long-term surveillance thus remains the cornerstone of long-term management, and cystoscopy has represented the gold standard modality for over 80 years.

Cisplatin- Gemcitabine (CG) neoadjuvant chemotherapy (NAC) provides pathological downstaging and improved overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC) undergoing RC.

Chemotherapy administered in a neoadjuvant setting comes with some advantages: the ability to deliver effective systemic therapy while the burden of micrometastatic disease is low and is given in a setting in which the patient's performance status is optimal (patient more fit, no loss of renal function, eligibility to optimal cisplatin-based chemotherapy regimens).

High risk features (HRFs) in NMIBC were defined as follows: lymph-vascular invasion (LVI), thickening or induration on Examination under anesthesia( EUA) , tumor-associated hydronephrosis, and variant histology. Tumors with a primary urothelial component and presence of micropapillary, squamous, sarcomatoid, nested variant, glandular, plasmacytoid, adenocarcinoma, or lymphoepithelioma components were classified as tumors of variant histology ( ,also T1b substage has bad prognosis.

The investigators hypothesized that similar high-risk features (HRFs) might identify a high-risk subset of UC patients that could benefit from NAC in the absence of evidence for muscle invasion.

Study Type

Observational

Enrollment (Anticipated)

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

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients older than 18 years confirmed to have T1b Non muscle invasive bladder cancer by biopsy will take neoadjuvant chemotherapy

Description

Inclusion Criteria:

  1. Patient who are older than 18 years old.
  2. Histologically confirmed to have Non-muscle invasive bladder cancer, T1bN0M0 ,clinically and radiologically confirmed to have bladder cancer.
  3. Patient should have Eastern Cooperative Oncology Group performances status (ECOG)0-1 with adequate hematologic, hepatic and renal functions including hemoglobin>10 /dl, absolute neutrophil count ≥1,500/mm3, platelets ≥100,000/mm3, serum bilirubin <2 mg/dl ,both Alanine transaminase( ALT) and aspartate aminotransferase( AST) ≤2× upper limit of normal (ULN), alkaline phosphates ≤5×ULN,and serum creatinine ≤1.5 mg/dl or creatinine clearance ≥60 ml/min.

Exclusion Criteria:

  1. Patients with radiographic evidence of nodal or distant metastases.
  2. A past history of upper tract disease, neuroendocrine features.
  3. Non-cisplatin-based NAC .
  4. Prior radiation therapy to their pelvis.
  5. A palpable three-dimensional mass on EUA.
  6. Known to be stage 0, T1a, II, III, IV.
  7. Active serious infection, or a psychiatric illness that would preclude obtaining informed consent or history of cardiac disease will be excluded.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the benefit of NAC in T1b NMIBC .
Time Frame: baseline
assessment of the response in correlation with high risk features.
baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS) and disease-specific survival (DSS).
Time Frame: 2 years
Overall survival (OS) and disease-specific survival (DSS).
2 years

Collaborators and Investigators

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

Sponsor

Assiut University

Investigators

  • Study Director: hoda essa, 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 (Anticipated)

July 1, 2020

Primary Completion (Anticipated)

July 1, 2021

Study Completion (Anticipated)

September 1, 2021

Study Registration Dates

First Submitted

January 26, 2020

First Submitted That Met QC Criteria

January 26, 2020

First Posted (Actual)

January 29, 2020

Study Record Updates

Last Update Posted (Actual)

January 30, 2020

Last Update Submitted That Met QC Criteria

January 28, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NAC in T1 Bladder cancer

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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