Bladder-sparing treatment for muscle-invasive bladder carcinoma: A single-center, single-arm clinical study of sequential neoadjuvant chemotherapy followed by tislelizumab neoadjuvant immunotherapy.

Abstract

596 Background: Althoughradical cystectomy (RC) in combination with cisplatin-based neoadjuvant chemotherapy is the gold-standard for muscle-invasive bladder carcinoma (MIBC), bladder-sparing treatment have emerged to be an alternative choice for patients who are concerning about the life quality after surgery. The optimal strategy for bladder-sparing treatment such as trimodal therapy (TMT) showed similar effect with RC. Since the TRUCE-01 has illuminated considerable response of neoadjuvant immunotherapy in MIBC, we aim to study whether neoadjuvant chemotherapy plus immunotherapy can improve the bladder-sparing rate in MIBC patients. Methods: 30 planned patients with MIBC (T2-4a N0-1 M0) received cisplatin 70 mg/m2 or carboplatin AUC 4.5 on days 1 every 3 weeks (Q3W) plus gemcitabine 1000 mg/m2 on the 1st and 8th day of each 21-day cycle x 4 cycles. Tislelizumab 200 mg was administered on the 14th day of each 21-day cycle at the 3rd and 4th cycles. CT and cystoscopy imaging were carried out to evaluate disease progression. After the 4th treatment, radical cystectomy, partial cystectomy or TURBT were perform in accordance with the disease status. For continuous bladder-spare treatment, 2 additional cycles of tislelizumab were performed. Bladder-sparing rate was settled as exploratory endpoints based on 2-years follow-up and predictive biomarker will be analyzed. Results: To date, 21 of 30 pts have been enrolled and 17 pts have completed the regimen. 2 pts were excluded because of complicating with other disease (suffering cerebral infraction or rectal cancer during the trail), and 2 pts voluntarily quitted due to intolerance of chemotherapeutic adverse effect (fatigue and gastrointestinal symptoms). 2 pts partially response to the therapy and received RC after disease progression. 1 pt have no response to the therapy and received palliative care as unsuitable for surgery. The resting 10 of 17 pts successfully preserved their bladder by achieving pT0 (58.8%) after treatment. Among them 3 pts have been followed up over 1 year and no relapse was observed. Conclusions: These data support neoadjuvant chemotherapy plus immunotherapy a feasible bladder-sparing choice for patients with MIBC. Further completed follow-up data and biomarker analysis will accurately identify patients who are suitable for this therapy. Clinical trial information: ChiCTR2100050763 .