Long-term results of a phase 2 study of neoadjuvant chemotherapy combined with tislelizumab followed by radiotherapy for bladder-preserving treatment in selected high-risk/locally advanced muscle invasive urothelial bladder cancer (HOPE-02).

Abstract

786 Background: The “bladder-sparing” trimodal therapy (TMT) has gained popularity among selected patients with muscle-invasive bladder cancer (MIBC) who are either unfit for or decline radical cystectomy (RC). This Phase 2 study aimed to evaluate the bladder-sparing efficacy of neoadjuvant chemotherapy combined with tislelizumab, followed by radiotherapy for high-risk, locally advanced MIBC, who were considered as non-ideal candidates for bladder-sparing treatment (Trial registration number: ChiCTR2100045213). Methods: Patients diagnosed with cT2-4bN0-3M0-1a MIBC will be included in the study if they demonstrate non-progression of disease (PD) after two cycles of neoadjuvant chemotherapy (gemcitabine and cisplatin or carboplatin) combined with tislelizumab. Radiotherapy will be administered to patients after one or two additional cycles of neoadjuvant therapy, and tislelizumab will continue for up to one year. The primary endpoint is the complete response rate (CR, including T0/Ta/Tis) after radiotherapy, while the secondary endpoints include progression-free survival (PFS), bladder-intact disease-free survival (BI-DFS), overall survival (OS), and toxicity. Results: Preliminary results of safety were presented at the ASCO-GU meeting in 2023, and we are now reporting the long-term outcomes. A total of 45 patients were enrolled. The median follow-up time was 36.10 ± 2.92 months. All participants completed 3 to 4 cycles of neoadjuvant therapy, resulting in a CR rate of 51.11%. Among the patients, 36 completed radiotherapy and underwent efficacy evaluations through imaging and cystoscopic biopsy. However, nine patients withdrew from the study due to personal requests for surgery, traditional Chinese medicine, or changes in systemic therapy. Of the 36 patients, 2 were Tis, and 31 were T0 after radiotherapy, indicating a primary CR rate of 100%. The 2 Tis patients received intravesical BCG vaccine therapy and achieved T0 by the time of the second therapeutic evaluation. No patient underwent radical cystectomy. 3-year PFS rate and 3-year BI-DFS were 76.0%, and 3-year OS was 81.0%. One patient experienced bladder recurrence with T1, while 3 patients developed distant metastases. Four patients died, with 2 deaths attributed to other reasons. Conclusions: Neoadjuvant chemotherapy combined with tislelizumab provides an opportunity for suboptimal candidates to become suitable for bladder-sparing approaches, and radiotherapy-based bladder-preserving treatment demonstrated excellent long-term efficacy and acceptable toxicity, making it a potentially optimal strategy for high-risk, locally advanced MIBC patients who wish to preserve their bladder. Clinical trial information: ChiCTR2100045213.