Safety and efficacy of bladder preservation therapy for very high-risk non-muscle-invasive bladder cancer: A single-center, single-arm prospective study (CIP-1).

Abstract

805 Background: Radical cystectomy (RC) is the standard treatment for muscle-invasive bladder cancer (MIBC) and very high-risk non–muscle-invasive bladder cancer (NMIBC). However, many patients are unwilling or unable to undergo this surgery. Therefore, maximal tumor resection with concurrent chemoradiotherapy is an option. However, it has not been investigated adequately in NMIBC being received BCG which is prone to unresponsive until now. The study aims to evaluate the safety and efficacy of the comprehensive treatment for very high-risk NMIBC. Methods: The study prospectively selected the patients from January 2019 to July 2023. Inclusion criteria: 1) urothelial carcinoma pathology; 2) age <80 years; 3) tumor is possible to maximal resection; 4) muscle layer invasion-free and mpMRI VI-RADS score of 1-4; 5) no metastasis showed by CT or MRI. Exclusion criteria: 1) anterior urethra invasion; 2) dysfunction in bladder; 3) lymph node and/or distant metastasis; 4) persistent hydronephrosis; 5) absolute contraindications to chemoradiotherapy. After maximal tumor resection, patients with gemcitabine plus cisplatin (GC) neoadjuvant chemotherapy (NAC) as an optional treatment, were concurrent bladder radiotherapy (50-64Gy) and low-dose paclitaxel (50 mg/m2, D1/week) plus cisplatin (20 mg/m2, D1-2/week) chemotherapy. Record the adverse reactions, assess the recurrence and metastasis, and follow-up continued until October 2024 or death. Results: The study included 14 males (93.3%) and 1 female (6.7%); median age 60 (44–78) years, median follow-up 25 (11–75) months. 9 cases (60.0%) were initial presentation and 6 cases (40.0%, including 3 cases of BCG failure) were recurrence. 1 case had pathological subtype or CIS, respectively (6.7%). 7 cases (46.7%) approached GC NAC. The grade ≥III adverse reactions occurred in 10 instances: 6 episodes of leukopenia, 4 cases of radiation proctitis. 1 patient being incomplete the course (1/15) underwent salvage cystectomy (after 5 months). 2 deaths (2/14) occurred: 1 case developed posterior urethral metastasis after 19 months, refused further treatment, and died at 25 months; other case died at 20 months due to unexplained acute liver failure. 4 cases (4/14) experienced bladder recurrence at 10, 15, 20, and 28 months (T1 stage, single, <3cm, treated by TURBT), respectively. Among these 4 recurrence cases, only 1 (14.3%, 1/7) received NAC, while 3 (42.9%, 3/7) not. Patients completed the comprehensive treatment (14/15) had 1-year recurrence-free rate of 92.9% (13/14), tumor-specific mortality of 7.1% (1/14), median duration of response 23 (11–75) months, and post-recurrence bladder preservation survival 15 (5–39) months. Conclusions: The comprehensive treatment strategy for very high-risk NMIBC is safe and feasible, and NAC may improve the recurrence-free rate. Clinical trial information: 2000029504.