Evaluating the Application Value of Neoadjuvant Chemotherapy Compared to Upfront Surgery in Patients With Upper Tract Urothelial Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Pathological Downstaging Rate (≤ ypT1N0)
研究概览
简要总结
This is a single-center, open-label, non-randomized controlled trial comparing the efficacy and safety of neoadjuvant chemotherapy (NAC) followed by radical surgery versus upfront radical surgery alone in patients with high-risk, non-metastatic upper tract urothelial carcinoma (UTUC).
The study aims to answer the following key questions:
Does NAC improve pathologic response rates (defined as downstaging to <ypT2N0) compared to immediate surgery? What is the rate of pathologic complete response (pCR; ypT0N0) in the NAC group? How do the two treatment strategies compare in terms of overall survival, cancer-specific survival, and recurrence-free survival? What is the safety and tolerability profile of NAC using gemcitabine and cisplatin in this patient population? Eligible participants will be assigned to either the NAC-plus-surgery group or the surgery-only group based on clinical evaluation and patient preference. The study will also explore potential biomarkers (e.g., chromosomal instability in liquid biopsies) for predicting treatment response.
Key Eligibility Criteria:
Adults with histologically confirmed high-risk UTUC Clinical stage ≤N1 M0 Adequate renal function (GFR ≥45 mL/min) and ECOG performance status 0-1
Primary Outcome:
Pathologic response rate (proportion of patients with <ypT2N0)
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 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
- •Histologically confirmed upper tract urothelial carcinoma (UTUC). For mixed histology, urothelial carcinoma must be the predominant component (≥50%).
- •Clinically non-metastatic disease (cN≤1, M0) as determined by cross-sectional imaging (CT or MRI of chest/abdomen/pelvis).
- •Planned treatment with radical nephroureterectomy (RNU).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate renal function, defined as glomerular filtration rate (GFR) ≥ 45 mL/min, making the patient a potential candidate for cisplatin-based neoadjuvant chemotherapy.
- •Adequate organ and bone marrow function as determined by standard screening tests.
- •Recovery from all reversible toxicities of any prior surgery.
- •Age ≥ 18 years at the time of enrollment.
- •Ability to understand the study and provide signed informed consent.
排除标准
- •Radiographic evidence of ≥cN2 lymph node disease or distant metastases (M1).
- •History of invasive, lymph node-positive, or metastatic urothelial carcinoma within 2 years prior to enrollment, or history of invasive contralateral UTUC.
- •Presence of only a solitary kidney or cisplatin ineligibility.
- •Concurrent participation in another interventional clinical trial at the time of enrollment.
- •History of a non-urothelial malignant tumor unless the patient has been disease-free for at least 1 year (exceptions include adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix).
- •Pregnancy or lactation. Women and men of reproductive potential must agree to use effective contraception.
- •Any other medical condition, comorbidity, or psychiatric illness that, in the investigator's judgment, would make the patient an unsuitable candidate for the study.
研究组 & 干预措施
NAC+RNU
Intervention: Participants in this cohort will receive 3-4 cycles of neoadjuvant chemotherapy (NAC) with the gemcitabine and cisplatin (GC) regimen prior to undergoing definitive surgery. Gemcitabine (1000 mg/m²) will be administered on Day 1 and Day 8, and cisplatin (70 mg/m²) will be administered on Day 2 of each 21-day cycle.
Surgical Intervention: Following the completion of NAC, patients will undergo a radical nephroureterectomy (RNU) with bladder cuff excision. The procedure will be performed via robot-assisted (Da Vinci), laparoscopic, or open approach, based on surgical discretion. Surgery must be performed within 6 weeks (±2 weeks) after the last dose of chemotherapy.
Objective: The primary objective for this cohort is to evaluate the efficacy of NAC in inducing pathological downstaging (defined as achieving pathological stage <ypT2N0 at surgery) and to assess the pathological complete response (pCR) rate (ypT0N0).
干预措施: NAC (Drug)
结局指标
主要结局
Pathological Downstaging Rate (≤ ypT1N0)
时间窗: Assessed at the time of surgery, approximately 10-14 weeks after initiation of treatment for the NAC+Surgery cohort and approximately 2-4 weeks after enrollment for the Surgery Only cohort.
The proportion of patients achieving pathological downstaging to stage ≤ ypT1N0 in the surgical specimen following neoadjuvant chemotherapy and radical nephroureterectomy (RNU), as assessed by central pathology review. Patients in the NAC cohort who do not undergo surgery will be classified as non-responders.
次要结局
- Pathological Complete Response (pCR) Rate(Assessed at the time of surgery, approximately 10-14 weeks after initiation of treatment.)
- Incidence of Treatment-Related Adverse Events(From start of NAC through surgery (approximately 10-14 weeks).)
- Overall Survival (OS)(From enrollment until death from any cause, assessed up to 60 months.)
- Recurrence-Free Survival (RFS)(From surgery until first documented recurrence or death, assessed up to 60 months.)
- Cancer-Specific Survival (CSS)(From enrollment until death due to cancer, assessed up to 60 months.)