Combination of DV and Tislelizumab for Renal Preservation in High-risk UTUC Patients

Inclusion Criteria:

1. ECOG 0~2;

2. HER-2 IHC 0-3+;

3. Subjects underwent cystoscopic/ureteroscopic biopsy, exfoliation cytology, andCT/MRI diagnosis;

4. Patients were judged to be high-risk urothelial carcinoma of the upper urinary tract (meeting any of the following risk factors: hydronephrosis, tumor diameter ≥2cm,high-grade, multiple tumors in cytology, previous history of radical cystectomy forhigh-grade bladder cancer, biopsy pathology with other tissue components);

5. High-risk UTUC(excluding low-risk UTUC),including renal pelvic tumors (cT1-T3, N0)or ureteral tumors (cT1-T3, N0-N1) M0;

6. Patients with indications of absolute or relative renal protection (only kidney,renal insufficiency: eGFR < 60 ml/min)

7. Have the desire to protect the kidney;

8. There is no indication of absolute or relative kidney preservation, but patientshave a strong desire to preserve kidney.

9. Has and agrees to provide cystoscopic/ureteroscopic biopsy tissue specimens and toreserve pre-treatment blood,

10. Urine and biopsied biological samples;

11. Predicted survival ≥3 months;

12. Major organ function is normal (14 days prior to enrollment)

13. International Normalized ratio (INR), activated partial thromboplastin time (aPTT) : ≤1.5× ULN (This criterion only applies to patients who are not receivinganticoagulant therapy; Patients receiving anticoagulant therapy should keepanticoagulants within therapeutic limits);

14. Did not receive systemic corticosteroid medication within 4 weeks prior totreatment;

15. Fertile men or women who are at risk of becoming pregnant must use a highlyeffective contraceptive method during the trial (such as oral contraceptives,intrauterine devices, controlled sexual desire or barrier contraception combinedwith spermicide) and continue using contraception for 12 months after the end oftreatment;

16. The subjects voluntarily joined the study, signed the informed consent, had goodcompliance, and cooperated with follow-up.

Exclusion Criteria:

1. Previously received anti-PD-1, anti-PD-L1, anti-PD-L2 therapy, including adjuvanttherapy stage;

2. Known allergy to recombinant humanized anti-PD-1 monoclonal antibody drugs and theircomponents;

3. Had received other antitumor therapy (including corticosteroid therapy,immunotherapy) or participated in other clinical studies within 4 weeks prior to thestudy treatment, or had not recovered from the previous toxicity (except for 2degrees of hair loss and 1 degree of neurotoxicity);

4. Pregnant or lactating women;

5. Positive HIV test result;

6. People with active hepatitis B or C

7. HBsAg or HBcAb positive patients also detected HBV DNA copy number positive (quantitative detection limit is 500IU/ml, or reach the positive value of the studycenter); Screening studies of such patients must test for HBV DNA;

8. Patients who tested positive for HCV antibodies were enrolled in this study only ifthe PCR results of HCV RNA were negative.

9. A clear history of active tuberculosis;

10. Have active autoimmune diseases that have required systemic treatment within thepast 2 years (e.g., with disease-regulating drugs, corticosteroids, orimmunosuppressive drugs) that allow for relevant replacement therapy (e.g.,thyroxine, pancreatic hormone, or physiologic corticosteroid replacement therapy forrenal or pituitary insufficiency);

11. Other serious, uncontrolled concomitant diseases that may affect protocol adherenceor interfere with interpretation of results, These include active opportunistic orprogressive (severe) infections, uncontrolled diabetes, cardiovascular disease (heart failure of Grade Ⅲ or Ⅳ as defined by the New York Heart Association scale,heart block above grade Ⅱ, myocardial infarction within the past 6 months, unstablearrhythmia or unstable angina, cerebral infarction within 3 months, etc.) Orpulmonary disease (history of interstitial pneumonia, obstructive pulmonary disease,and symptomatic bronchospasm);

12. Received live vaccine within 4 weeks prior to the start of treatment;

13. Have previously received allogeneic hematopoietic stem cell transplantation or solidorgan transplantation;

14. Major surgical procedures (excluding diagnostic surgery) within 4 weeks prior to thestart of treatment; Those who have a history of psychotropic drug abuse and cannotabstain or have a history of mental disorders;

15. A large amount of pleural effusion or ascites accompanied by clinical symptoms orrequiring symptomatic treatment;

16. Have had other unhealed malignancies in the past 5 years, excluding those that areapparently cured or curable, such as basal or squamous cell skin cancer, localizedlow-risk prostate cancer, carcinoma in situ of the cervix or carcinoma in situ ofthe breast; Remarks: Patients with localized low-risk prostate cancer (defined asstage ≤T2a, Gleason score ≤6, and PSA≤10ng/mL at the time of prostate cancerdiagnosis (as measured) who had received radical therapy and had no biochemicalrecurrence of prostate specific antigen (PSA) were eligible to participate in thisstudy);

17. Bladder cancer (MIBC);

18. Other severe, acute, or chronic medical or psychiatric conditions or laboratoryabnormalities that, according to the investigator, may increase the risks associatedwith study participation or may interfere with the interpretation of the studyresults.