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
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Immunohistochemestry analysis of biomarkers
研究概览
简要总结
Retrospective monocentric study evaluating different immunohistochemical phenotypes related to mitochondrial functions with treatment outcomes
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>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.
排除标准
- •Previous malignancies other that bladder cancer
- •Patients with a history of treated bladder cancer recurrences
结局指标
主要结局
Immunohistochemestry analysis of biomarkers
时间窗: 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.
次要结局
- Correlation of biomarker expression with outcome(1 year)
研究者
Michele Tedeschi
Head of Clinical Research
Istituto Clinico Humanitas
