Adjuvant Radiotherapy and Combined Adjuvant Treatment Strategy for UTUC

Study Overview
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Brief Summary
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This study is an ambispective cohort observational study to analyze the efficacy of surgery alone versus postoperative adjuvant therapy (postoperative radiotherapy/postoperative chemotherapy(immunotherapy)/ combined strategy) in patients with the upper urinary tract urothelial carcinoma with high-risk factors (postoperative pathology suggestive of pT2 and above, N+, G3/high-grade and multiple tumors, positive cut margins). A subgroup analysis was performed to obtain the population of patients who might benefit from different treatment approaches. Patients with high risk factors for postoperative recurrence or metastasis will be treated with relevant adjuvant therapy, which in turn will benefit patients.

Detailed Description
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This study is an ambispective cohort observational study to analyze the efficacy of surgery alone versus postoperative adjuvant therapy (postoperative radiotherapy/postoperative chemotherapy(immunotherapy)/ combined strategy) in patients with the upper urinary tract urothelial carcinoma with high-risk factors (postoperative pathology suggestive of pT2 and above, N+, G3/high-grade and multiple tumors, positive cut margins). A subgroup analysis was performed to obtain the population of patients who might benefit from different treatment approaches. Patients with high risk factors for postoperative recurrence or metastasis will be treated with relevant adjuvant therapy, which in turn will benefit patients.

Official Title
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Safety and Efficacy of Adjuvant Radiotherapy and Combined Adjuvant Treatment Strategy for Upper Tract Urothelial Carcinoma: An Ambispective Cohort Study

Conditions
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Urothelial Carcinoma

Intervention / Treatment
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* Radiation: Radiotherapy
* Drug: Chemotherapy and immunotherapy
* Combination Product: Combined adjuvant therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Confirmed pathologic diagnosis as upper urinary tract urothelial carcinoma(UTUC), without any serious complication; 2. Meet any of the following conditions: >= pT2,pN+,tumor G3 grade, multifocality or positive surgical margins (according to AJCC 8th edition); 3. Aged >= 18 years old; Exclusion Criteria: 1. Distant metastases already found at the time of surgery; non-R0 resected patients; 2. History of pelvic and abdominal radiotherapy; history of inflammatory bowel disease; history of systemic chemotherapy; 3. Pregnant or lactating women; or women of childbearing potential who are not using reliable contraception; 4. History of malignant tumors (except skin cancer that is not malignant melanoma and in situ cervical cancer, tumors that have been cured for more than 5 years); 5. Weight loss > 10% within 6 months; 6. Existing or coexisting bleeding disorders, active infection; 7. Clinically significant cardiac disease (e.g., hypertension controlled with medications, unstable angina, New York Heart Association (NYHA) >= Class II congestive heart failure, unstable symptomatic arrhythmia, or >=Class II peripheral vascular disease); 8. Those who are unable to sign informed consent due to psychological, family, social and other factors.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Surveillance alone<br>Participants underwent radical total nephroureterectomy alone (with or without lymph node dissection) without postoperative adjuvant therapy | |
| Adjuvant chemotherapy/immunotherapy<br>Participants underwent radical total nephroureterectomy and adjuvant chemotherapy/immunotherapy postoperatively. | Drug: Chemotherapy and immunotherapy<br>* For patients eligible for enrollment, postoperative adjuvant chemotherapy was initiated at about 4-6 weeks after surgery, for a total of 4 cycles, with the chemotherapy regimen of gemcitabine + cisplatin. Administration: Gemcitabine 1,000 mg/m2 on days 1 and 8 (completed within 30-60 minutes), cisplatin 70 mg/m2 on day 1. Immunotherapeutic agents include (PD-1/PD-L1) to be used every 21 days postoperatively for one year.<br>|
| Adjuvant radiotherapy<br>Participants underwent radical total nephroureterectomy and adjuvant radiotherapy postoperatively. | Radiation: Radiotherapy<br>* For participants eligible for enrollment, radiotherapy was started within 4-6 weeks after surgery. Rotational intensity-modulated radiotherapy (VMAT) with daily image-guided radiotherapy (Daily IGRT) technique was used. Range of irradiation (patients were randomized into two groups - expanded field irradiation group and involved field irradiation group)<br>|
| Adjuvant combined therapy<br>Participants underwent radical total nephroureterectomy (with or without lymph node dissection) with a combination of adjuvant chemotherapy/immunotherapy and radiation therapy postoperatively | Combination Product: Combined adjuvant therapy<br>* For patients eligible for enrollment, sequential adjuvant radiotherapy (same as the radiotherapy group) and systemic drug therapy (same as the chemotherapy group; immunotherapy drugs can be PD-1 or PDL-1) can be started at about 4-6 weeks after surgery. The specific dose of drugs can be adjusted according to the actual tolerability of the patient, such as reducing or replacing the regimen, or interrupting the regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free Survival | 1-year, 3-year and 5-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival | 1-year, 3-year and 5-year | 
| CSS | Cancer specific survival | 1-year, 3-year and 5-year | 
| LRFS | Local recurrence free survival | 1-year, 3-year and 5-year | 
| MFS | Metastasis free survival | 1-year, 3-year and 5-year | 
| IRFS and CRFS | intravesical-recurrence free survival and contralateral-recurrence free survival | 1-year, 3-year and 5-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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upper tract urothelial carcinoma, adjuvant therapy, adjuvant radiotherapy, adjuvant chemotherapy, immunotherapy, combined therapy, safety analysis, survival analysis, real-world study