A phase 2, open-label study of neoadjuvant chemotherapy plus tislelizumab followed by radiotherapy-based, bladder-preserving treatment for high risk/locally advanced muscle invasive urothelial bladder cancer (HOPE-02).

516 Background: Tri-modality therapy (TMT) is an alternative to radical cystectomy for selected muscle-invasive bladder cancer (MIBC) patients with bladder-preserving will. Neoadjuvant treatment makes chance for imperfect patients to turn into ideal bladder-sparing patients. This phase 2 study aimed to explore the efficacy of neoadjuvant chemotherapy plus tislelizumab followed by radiotherapy as a strategy of bladder-sparing therapy for high risk/locally advanced MIBC (Trial registration number: ChiCTR2100045213). Methods: Pathological and imaging diagnosed cT2-4bN0-3M0-1a MIBC received 3-4 cycles of neoadjuvant chemotherapy (gemcitabine and cisplatin or carboplatin) plus tislelizumab (200mg every three weeks for one year). Radiotherapy (60.4-64.4 Gy /1.8Gy/33-35f to bladder with 50.4 Gy/1.8Gy/28f to pelvic) were given to patients with non- progressed disease (PD) after neoadjuvant therapy. The primary endpoint was complete response rate (CR, including T0/Ta/Tis), and the secondary endpoints were progression-free survival (PFS), bladder-intact disease free survival (BI-DFS), overall survival (OS) and toxicity. Results: The simple size is 43 participants. Until now, 28 patients were included, of which 23 patients received radiotherapy and 16 patients finished efficacy evaluation with imaging and cystoscopic biopsy after radiotherapy. Median follow-up time was 14.2 (1.5-17.4) months (m). Two of the 16 patients were Tis and 14 were T0 after radiotherapy, indicating the primary CR rate were 100%. For the 2 patients with Tis received BCG vaccine intravesical perfusion, and T0 was achieved when the second therapy evaluation. No patient died and only one patient had distant metastasis. The one-year PFS rate, one-year BI-DFS and one-year OS were 100%. Grade 3 and 4 hematological system adverse events were 23.3% and 2.3%. One patient had reduced bladder capacity (100-200 mL) with 2-h intervals of micturition, and 3 patients had frequency with urgency, nocturia and dysuria. Three patients had grade1 immunotherapy related abnormality of thyroidal function and 3 patients suffered from grade 2 myositis. The current bladder-preserving therapies research were well-tolerated with acceptable and manageable toxicities. Conclusions: Neoadjuvant chemotherapy plus tislelizumab followed by radiotherapy showed perfect efficacy and acceptable toxicities, which maybe an optimal strategy for high risk/locally advanced MIBC patients with bladder-preserving willingness. Clinical trial information: ChiCTR2100045213 .