Molecular classification for predicting the efficacy of neoadjuvant tislelizumab combining nab-paclitaxel in Chinese bladder cancer.

Abstract

e14563 Background: Bladder cancer is a molecularly diverse disease with heterogeneous clinical outcomes. Transcriptome-based molecular subtypes of muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC) have been shown to be both prognostic and predictive. However, its predictive role in Chinese bladder cancer remains unclear. The aim of this study was to identify the predictive role of molecular subtypes in China bladder cancer with neoadjuvant therapy. Methods: The study was conducted from May 2020 to August 2021. Patients who were age 18 years or older, were diagnosed with NMIBC or MIBC, and neoadjuvant tislelizumab combining nab-paclitaxel followed by surgery were included. Multigenomic sequencing was performed. Molecular subtypes were identified by published consensus. Results: We prospectively recruited 30 patients for neoadjuvant tislelizumab combining nab-paclitaxel, including 14 patients with NMIBC and 16 patients with MIBC. For bladder cancer, 73.3% (22/33) patients responded to neoadjuvant tislelizumab combining nab-paclitaxel. In NMIBC groups, 64.3% (9/14) patients were pCR. The objective remission rate ( ORR) was 71.4%. 4 molecular classes were identified in Chinese NMIBC, including class 1 (7.1%), class 2a (35.7%), class 2b (50%), class 3 (7.1%). Interesting, ORR was significantly higher for patients with class 2b (5/7, 71.4%) as compared to class 2a (3/5,60%) before neoadjuvant. Molecular classes changed in 35.7% (5/14) of patients before and after neoadjuvant. After neoadjuvant, 80% of class 2b patients responded to neoadjuvant, and all class 2a patients did not respond to neoadjuvant. In MIBC groups, a pPR was achieved by 37.5% patients (6/16). The ORR was 75%. We found 4 molecular classes in Chinese MIBC: basal/squamous (43.8%), luminal unstable (25%), luminal papillary (25%), and stroma-rich (6.2%). Patients with basal/squamous (85.7%) and luminal unstable (75%) had significantly higher ORR than luminal papillary (50%) before neoadjuvant. Molecular classes changed in 44.4% (4/9) of patients before and after neoadjuvant. After neoadjuvant, all patients with stroma-rich responded to neoadjuvant. Conclusions: Molecular classification could predict the efficacy of neoadjuvant tislelizumab combining nab-paclitaxel in Chinese bladder cancer, which may be preferable when studying biomarkers of bladder cancer in the future.