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

• Conditions: Bladder Cancer
• Interventions: Other: No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.

• Registration Number: NCT04256122
• Lead Sponsor: Istituto Clinico Humanitas

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2019-10-22
• Status Verified: 2020-02
• Study First Submitted: 2020-02-03
• Study First Submitted QC: 2020-02-03
• Study First Posted: 2020-02-05
• Last Update Submitted: 2020-02-12
• Last Update Posted: 2020-02-17
• Primary Completion: 2020-10-31
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Responder patients	No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.	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
Non responder patients	No intervantion on patients. retrospective study is performed on paraffin embedded tumor tissue specimens routinely collected during TURBT.	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.

Primary Outcome Measures

Name	Time	Method
Immunohistochemestry analysis of biomarkers	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Correlation of biomarker expression with outcome	1 year	• To correlate the resulting phenotype with clinical/pathological response to adjuvant treatments (time to recurrence and presence of recurrence).

Trial Locations

Locations (1)

Humanitas reseach hospital (ICH); 🇮🇹 Rozzano, Milan, Italy