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Retrospective monocentric study evaluating different immunohistochemical phenotypes related to mitochondrial functions with treatment outcomes
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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.
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Immunohistochemestry analysis of biomarkers | perform an immunophenotypical analysis to assess the expression of key proteins involved in mitochondrial functionality in recurrent tumors ("non-responders") and non-recurrent tumors ("responders") after intravesical treatment with chemotherapy or immunotherapy. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of biomarker expression with outcome | • To correlate the resulting phenotype with clinical/pathological response to adjuvant treatments (time to recurrence and presence of recurrence). | 1 year |
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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"):
For recurrent tumors ("non-responders"):
Exclusion Criteria:
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Maria Rescigno, PhD | Contact | +390282245431 | maria.rescigno@hunimed.eu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Humanitas reseach hospital (ICH) | Recruiting | Rozzano | Milan | 20089 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33408185 | Derived | 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. |
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Research outcome
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|
| ID | Term |
|---|---|
| D001749 | Urinary Bladder Neoplasms |
| ID | Term |
|---|---|
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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