Surveillance of the Genetic Signature in Circulating Tumor DNA for Guiding Adjuvant Chemotherapy in Urothelial Carcinoma

Inclusion Criteria:

1. aged 18-70 years old;
2. a score of ≤1 for the Eastern Cooperative Oncology Group (ECOG) Performance Status;
3. receiving radical cystectomy (with lymph node dissection) or nephroureterectomy;
4. histologically confirmed (surgical specimen) muscle invasive urothelial carcinoma, and the major histological type should be transitional cell carcinoma;
5. Classification of tumour, node and metastasis (TNM): pT2-4a N0-2M0;
6. absence of microscopic (i.e., positive margin) or gross residual of the tumor (R0 resection) and absence of metastasis, confirmed by a negative CT or MRI scan of pelvis, abdomen and chest within 4 weeks prior to enrolment;
7. adequate hematologic and end-organ function, defined by the following laboratory results obtained within 28 days prior to the first study treatment:

   * ANC≥1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
   * WBC counts \> 2500 cells/μL
   * Lymphocyte count ≥ 300 cells/μL
   * Platelet count ≥ 100,000 cells/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
   * Hemoglobin ≥ 9.0 g/dL
   * AST, ALT, and alkaline phosphatase ≤ 2.5 × the upper limit of normal (ULN),
   * PTT ≤ 1.5 × ULN
   * PT ≤ 1.5 × ULN or INR \< 1.7
   * Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)
8. able to understand and provide written informed consent, and agree to receive the treatment arrangement and study procedures stated in the informed consent

Exclusion Criteria:

1. receiving any approved anti-cancer treatment within 3 weeks prior to study enrolment;
2. participation in another clinical trial with therapeutic intent within 28 days prior to enrolment;
3. suffering from malignancies other than urothelial carcinoma within 5 years prior to study enrolment;
4. conditions that contraindicate chemotherapy, such as renal impairment with creatinine clearance rate (CCr) \<50 mL/min, hearing impairment, and inadequate marrow function;
5. anaphylactic or hypersensitivity reactions or other contraindication to cisplatin and gemcitabine;
6. active or uncontrolled infections, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or tuberculosis;
7. pregnancy or breastfeeding.