Overview

Neoadjuvant chemotherapy plus radical cystectomy is the standard if care for cisplatin-eligible patients with MIBC. Developments in the last two decades suggest that bladder sparing therapy may be a valuable alternative to radical cystectomy. Currently, well-documented TMT regimens, which include complete transurethral resection of bladder tumor (TURBT), chemotherapy, and radiation therapy, demonstrated durable oncologic control and long-term survival in selected patients. Nevertheless, TMT has not been widely used in clinical practice. On the one hand, due to the complexity of TMT, multiple clinical departments are required to cooperate in the assessment, treatment and follow-up of patients. On the other hand, concerns about tumor recurrence, lack of surgical intervention in regional lymph nodes, and organ dysfunction due to the treatment of large doses of pelvic radiation have reduced the clinical acceptance of TMT. In recent years, immunocheckpoint inhibitors such as PD-1/L1, including Nivolumab, Pembrolizumab, and Tislelizumab, have proven to be promising immunotherapy approaches for advanced urothelium cancer, leading to breakthroughs in the treatment of advanced urothelium cancer. Immunocheckpoint inhibitors also showed positive efficacy in patients who did not respond to BCG treatment during perioperative period. Therefore, immunotherapy can be another means of bladder preservation after surgery, chemotherapy and radiotherapy. However, bladder sparing target population is still unclear, among which, the NCCN guidelines recommend patients suitable for bladder preservation: T2-3N0M0, single lesion (longest diameter less than 6 cm), histological type of urothelial carcinoma, no CIS, and no hydronephrosis. Therefore, the focus of bladder preservation treatment is not only on the treatment before and during bladder preservation, but also on maximizing the follow-up treatment of TURBT and exploring its long-term benefits based on response to systematic treatment before maximized TURBT.

Eligibility

Inclusion Criteria:

• Male or female aged 18 and ≤ 85;
• People who want to protect their bladder;
• ECOG PS 0 2 points;
• Subject underwent TURBT surgery and imaging diagnosis of musculothelial invasive bladder urothelial carcinoma (histologic variation accepted, not diffuse CIS lesion);
• Accept maximum TURBT;
• Clinical stages T2-4A, N0-1, M0;
• Normal function of major organs (14 days prior to enrollment), i.e. meeting the following criteria:
  1. Blood routine examination criteria should be met (no blood transfusion and no granulocyte colony were received within 14 days before enrollment Stimulator therapy) :

     HB 90 g/L or higher The ANC acuity 1.5 x 109 / L PLT acuity 100 x 109 / L

  2. No functional organic disease, the following criteria should be met:

        T-bil ≤1.5×ULN upper limit of normal value ALT and AST≤2.5×ULN If liver metastasis, ALT and
        AST≤5×ULN Estimated glomerular filtration rate (EGFR 60mL /min MdRD formula) International
        standardized ratio (INR), activated partial thrombin time aPTT ≤1.5× ULN(this standard is
        only applicable to patients who did not receive anticoagulant therapy; On anticoagulant
        therapy Patients should keep anticoagulants within the therapeutic range)
          -  Men who are fertile or women who are likely to become pregnant must use highly fertile
             men or women who are likely to become pregnant during the trial, Must be used in the
             testing process highly effective contraceptive methods (such as oral contraceptives,
             intrauterine contraceptive device, abstemious sexual desire or barrier contraception
             effective contraceptive methods (such as oral contraceptives, intrauterine
             contraceptive device, abstemious sexual desire or barrier contraceptive method
             combined with spermicide), and at the end of the treatment to birth control in
             combination with spermicide), and birth control for 12 months after the end of the
             treatment;
          -  Subjects voluntarily joined the study and signed informed consent with good compliance
             and follow-up. The subjects voluntarily joined the study and signed informed consent
             with good compliance and follow-up.
        Exclusion Criteria:
          -  Previously received anti-PD-1, anti-PD-L1, and anti-PD-L2 therapy;
          -  Known to be allergic to recombinant humanized anti-PD-1 monoclonal antibody drugs and
             their components;
          -  Received other antineoplastic therapy (including but not limited to corticosteroids)
             within 4 weeks prior to study therapy;
          -  Alcohol therapy, immunotherapy) or other clinical studies, or have not yet recovered
             from the previous toxicity (except 2 degree hair loss and 1 degree neurotoxicity);
          -  Women who are pregnant or breast-feeding, and women who wish to have children (pelvic
             radiation may cause ovarian function Premature aging);
          -  HIV positive;
          -  Patients with active hepatitis B or C; HBsAg or HBcAb positive patients were also
             detected with positive HBV DNA copy number (quantitative). The detection limit is
             500IU/ml, or reaches the positive copy number detected by the research center); For
             such patients study screening must test for HBV DNA; HCV antibody test results are
             positive for patients, only when HCV RNA PCR test results. If it is negative, it can
             be included in this study;
          -  A clear history of active tuberculosis;
          -  Have active autoimmune diseases requiring systemic treatment within the past 2 years
             (e.g., using disease modulations);
          -  Section drugs, corticosteroids, or immunosuppressive drugs), allowing for relevant
             alternative therapies (e.g., thyroid Hormone, insulin, or physiological corticosteroid
             replacement therapy for renal or pituitary insufficiency);
          -  Other serious, uncontrolled comorbidities that may affect protocol compliance or
             interfere with interpretation of results;
          -  Diseases, including active opportunistic infections or advanced (severe) infections,
             uncontrolled diabetes, cardiovascular disease (Defined by the New York Heart
             Association classification as grade ⅲ or ⅳ heart failure, grade ⅱ or higher heart,
             visceral block, myocardial infarction in the past 6 months, unstable arrhythmia or
             instability, angina pectoris, cerebral infarction within 3 months, etc.) or lung
             diseases (interstitial pneumonia, obstructive pulmonary disease; History of pulmonary
             disease and symptomatic bronchial spasm);
          -  Received live vaccine within 4 weeks prior to the start of treatment;
          -  Prior allogeneic hematopoietic stem cell transplantation or solid organ
             transplantation;
          -  Those who have a history of abuse of psychotropic substances and cannot quit or have a
             history of mental disorders; Those who have a history of psychotropic drug abuse and
             cannot quit or have a history of mental disorders;
          -  Large pleural or ascites with clinical symptoms or requiring symptomatic management;
             Large pleural or ascites with clinical symptoms or symptomatic management;
          -  In the past five years have suffered from other malignant tumors, not cured but does
             not include has obvious cured malignant swell years suffered from other malignant
             tumors, not cured but does not include has obvious cure of malignant tumor, or can
             cure cancer, such as basal skin cancer or squamous cell cancer, limitations before
             low-risk tumor, or can be a cure for cancer, Such as basal or squamous cell skin
             cancer, localized low-risk prostate cancer, cervical carcinoma in situ or breast
             carcinoma in situ; Remarks: Localized low-risk prostate cancer (defined as
             adenocarcinoma, carcinoma in situ of the cervix, or carcinoma in situ of the breast;
             Remark: Limits (defined as low-risk prostate cancer stage for stage or less T2a,
             gleason score, gleason scores six points or less, and diagnosis of prostate cancer and
             prostate cancer diagnosis in the PSA 10 ng/mL or less (such as test (e.g.,
             measurement) of the patients received radical amount) of the patients received radical
             surgery operation and without prostate specific antigen (and prostate specific antigen
             (P SA)) biochemical relapses biochemical relapses may participate in this study);
             Participants may participate in this study);
          -  Previous history of pelvic radiation therapy; Previous history of pelvic radiation
             therapy;
          -  Merged UTUC or urethral cancer
          -  May increase risks associated with study participation, or may interfere with study
             participation, according to the researchers. Any other serious, acute or chronic
             medical or mental illness or laboratory abnormality that may increase the risk
             associated with study participation or that may interfere with the interpretation of
             study results or the interpretation of laboratory findings.