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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm1(cCR=cT0, cTa) | Experimental |
| |
| Arm2 (non-cCR) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tislelizumab | Drug | Tislelizumab 200 mg I.V. Q3W on the day 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| BIDFS at one year | BIDFS, bladder intact disease free survival, was defined as the time from the start of regimen until MIBC recurrence, regional pelvic recurrence, distant metastasis, bladder cancer-related death, or cystectomy. | one year |
| Measure | Description | Time Frame |
|---|---|---|
| MFS at two years | MFS, metastatic free survival, was defined as time from the start of regimen to first diagnosis of distant metastasis | two years |
| BIDFS at two years | BIDFS, bladder intact disease free survival, was defined as the time from the start of regimen until MIBC recurrence, regional pelvic recurrence, distant metastasis, bladder cancer-related death, or cystectomy. |
| Measure | Description | Time Frame |
|---|---|---|
| utDNA | Urine tumor DNA analysis | two years |
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:
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
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)
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yijun Shen, M.D. | Contact | 862164175590 | yijunshen@urocancer.org |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | China |
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| ID | Term |
|---|---|
| D001749 | Urinary Bladder Neoplasms |
| ID | Term |
|---|---|
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000707970 | tislelizumab |
| D000093542 | Gemcitabine |
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| gemcitabine and cisplatin | Drug | Cisplatin 70mg/m2 I.V. Q3W on the day 1, dose fractionation is allowed ;Gemcitabine 1000mg/m2 I.V. Q3W on the day 1 and day 8 |
|
| Modified hypofractionation | Radiation |
|
|
| two years |
| Treatment-related adverse events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | two years |
| cCR after first treatment stage | cCR, clinical complete response, defined as cT0, which is clarified as negative cystoscope, negative urine cytology and no disease evidence on imaging at the end of the first phase of treatment, and cTa, which is assessed as papillary bladder cancer by cystoscope, urine cytology and imaging. | two years |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |