Real-world study of chemotherapy plus immunotherapy versus chemotherapy alone as neoadjuvant treatment guided bladder-sparing therapy for localized muscle-invasive bladder cancer.

499 Background: Bladder-preserving combined-modality therapy has been a popular research field as an alternative to radical cystectomy for selected patients with localized muscle-invasive bladder cancer (MIBC). This real-world study aimed to compare the efficacy of neoadjuvant chemotherapy plus immunotherapy versus chemotherapy alone as one of bladder-sparing therapies for localized MIBC. Methods: Patients with cT2-4bN0-3M0-1a pathological and imaging diagnosed MIBC were included in the study. Either chemotherapy (gemcitabine and cisplatin/carboplatin) plus immunotherapy (PD-1 checkpoint inhibitor, including pembrolizumab，tislelizumab and toripalimab) or chemotherapy alone were given as patients’ wish. The primary endpoint was complete response rate (CR, T0/Ta/Tis), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), bladder-intact disease-free survival (BI-DFS) and toxicity. Results: In total, 41 patients were included, 25 in combination group and 16 in chemotherapy group respectively. The baseline characteristics were well balanced in two groups. Median follow-up time was 15.3 ±4.4 months(m). No patient died. The efficacy evaluable population was consisted of 34 pts (22 in combination group; 12 in chemotherapy alone group). The CR rate for combination group was 50.0% and 0 for chemotherapy alone group. One patient suffered from disease progression in combination group and three in chemotherapy group. The DCRs for combination group and chemotherapy group were 95.5% and 66.7%, respectively ( p= 0.003). Twelve patients had radiotherapy and six patients had radical cystectomy followed by neoadjuvant treatments in combination group. And two patients had radiotherapy and three patients had radical cystectomy in chemotherapy group. The one-year PFS rates were 95.5% and 62.5% for combination group and chemotherapy group( p= 0.010), and the one-year BI-DFS were 66.1% versus 27.5% respectively( p= 0.159). The bladder-preserving combined-modality therapies used were well-tolerated with acceptable and manageable toxicities. Grade ¾ hematological system adverse events were 15.9% and 6.4% in combination group and chemotherapy group, respectively ( p= 0.021). Conclusions: Neoadjuvant chemotherapy plus immunotherapy showed better efficacy compared with chemotherapy alone as an important bladder-sparing therapy for locally advanced MIBC with acceptable and manageable toxicities.