Expression of Markers Related to Mitochondrial Functionality in Carcinoma of the Urinary Bladder: Comparative Retrospective Analysis Between Recurrent Tumors ("Non-responders") and Non-recurrent Tumors ("Responders") After Intravesical Treatment With Chemotherapy or Immunotherapy

NCT ID: NCT04256122

Last Updated: 2020-02-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-10-22

Study Completion Date

2020-12-31

Brief Summary

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Retrospective monocentric study evaluating different immunohistochemical phenotypes related to mitochondrial functions with treatment outcomes

Detailed Description

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About 80% of newly diagnosed patients have non-muscle-invasive bladder cancer (NMIBC), including papillary lesions confined to the urothelium (stage Ta) or invading the lamina propria (stage T1), and carcinoma in situ (CIS). These tumors show low progression rates, but high recurrence. In particular, patients with multifocal high-grade urothelial carcinoma have a high risk of both recurrence (∼70% after 1 yr) and progression (5% after 1 yr). Initial NMIBC management is a transurethral resection of bladder tumor (TURBT), followed by adjuvant intravesical treatment with the chemotherapeutic agent Mitomycin C (MMC) or the immunotherapy Bacillus Calmette-Guérin (BCG). However, these therapies lead to variable clinical responses and patients recur shortly after surgery. Despite both therapies have been used for decades in the treatment of NMIBC, at the moment it is not possible to predict after initial staging which patients will benefit from them since neither resistance mechanisms nor genetic markers associated to relapse have been identified yet.

In a preliminary analysis, the invesitigators found that low expression of several proteins involved in mitochondrial functions correlate with a worst prognosis in bladder cancer patients. The aim of this study is to detect markers of mitochondrial dysfunction by immunohistochemistry in recurrent tumors ("non-responders") and non-recurrent tumors ("responders") after intravesical treatment with chemotherapy or immunotherapy, and determine the prognostic relevance of these different markers.

Conditions

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Bladder Cancer

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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Responder patients

Patients with NMIBC at first diagnosis, pTa/pT1 (primary tumors) treated with MMC or BCG after TURBT will be selected from the institutional patient registry.

* Patient treated with adjuvant MMC or BCG that did not experience recurrence for at least 42 months after TURBT
* Patients are tumor-free at the moment of the analysis

No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.

Intervention Type OTHER

evaluate an immunophenotypical profile related to mitochondrial functions in tumors responders vs non-responder to intravescical chemotherapy or immunotherapy. Verify the possible prognostic differences in clinical behavior between the two populations.

Non responder patients

Patients with NMIBC at first diagnosis, pTa/pT1 (primary tumors) treated with MMC or BCG after TURBT will be selected from the institutional patient registry.

o Patient treated with adjuvant MMC or BCG that experienced recurrence in the first 24 months after TURBT.

No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.

Intervention Type OTHER

evaluate an immunophenotypical profile related to mitochondrial functions in tumors responders vs non-responder to intravescical chemotherapy or immunotherapy. Verify the possible prognostic differences in clinical behavior between the two populations.

Interventions

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No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.

evaluate an immunophenotypical profile related to mitochondrial functions in tumors responders vs non-responder to intravescical chemotherapy or immunotherapy. Verify the possible prognostic differences in clinical behavior between the two populations.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* \>18 years of age at diagnosis
* Histologically confirmed NMIBC urothelial carcinoma of the urinary bladder (pTa, pT1, CIS)
* Primary NMIBC or not treated secondary NMIBC, after a primary non-invasive malignancy
* Patients underwent TURBT for NMIBC at Humanitas between 2000 and 2019
* Patients that received intravesical instillations with either MMC or BCG after TURBT at Humanitas between 2000 and 2019
* Written informed consent to research purpose
* For non-recurrent tumors ("responders"):

* Patient treated with adjuvant MMC or BCG that did not experience recurrence for at least 42 months after TURBT
* Patients are tumor-free at the moment of the analysis
* For recurrent tumors ("non-responders"):

* Patient treated with adjuvant MMC or BCG that experienced recurrence in the first 24 months after TURBT.

Exclusion Criteria

* Previous malignancies other that bladder cancer
* Patients with a history of treated bladder cancer recurrences
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Istituto Clinico Humanitas

OTHER

Sponsor Role lead

Responsible Party

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Michele Tedeschi

Head of Clinical Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Humanitas reseach hospital (ICH)

Rozzano, Milan, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Maria Rescigno, PhD

Role: CONTACT

+390282245431

Facility Contacts

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Maria Rescigno, PhD

Role: primary

+390282245431

References

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Oresta B, Pozzi C, Braga D, Hurle R, Lazzeri M, Colombo P, Frego N, Erreni M, Faccani C, Elefante G, Barcella M, Guazzoni G, Rescigno M. Mitochondrial metabolic reprogramming controls the induction of immunogenic cell death and efficacy of chemotherapy in bladder cancer. Sci Transl Med. 2021 Jan 6;13(575):eaba6110. doi: 10.1126/scitranslmed.aba6110.

Reference Type DERIVED
PMID: 33408185 (View on PubMed)

Other Identifiers

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1191

Identifier Type: -

Identifier Source: org_study_id

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