UTUC, UC (Urothelial Cancer)
Conditions
Keywords
NAC
Brief summary
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)
Interventions
DRUGNAC
Participants in NAC+RNU 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.
Sponsors
Changhai Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 1. * 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Downstaging Rate (≤ ypT1N0) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | Assessed at the time of surgery, approximately 10-14 weeks after initiation of treatment. | The proportion of patients achieving a pathological complete response (ypT0N0) in the surgical specimen in the NAC+Surgery cohort. |
| Incidence of Treatment-Related Adverse Events | From start of NAC through surgery (approximately 10-14 weeks). | Safety and tolerability of neoadjuvant chemotherapy as measured by the incidence, type, and severity of treatment-related adverse events graded according to CTCAE v5.0. |
| Overall Survival (OS) | From enrollment until death from any cause, assessed up to 60 months. | The time from the date of enrollment to the date of death due to any cause. |
| Recurrence-Free Survival (RFS) | From surgery until first documented recurrence or death, assessed up to 60 months. | The time from surgery to the first documented occurrence of local/regional recurrence, distant metastasis, or death from any cause, whichever occurs first. |
| Cancer-Specific Survival (CSS) | From enrollment until death due to cancer, assessed up to 60 months. | The time from enrollment to death directly attributable to upper tract urothelial carcinoma. |
Countries
China
Outcome results
None listed