Efficacy and biomarker analysis of neoadjuvant disitamab vedotin (RC48-ADC) combined immunotherapy in patients with muscle-invasive bladder cancer: A multi-center real-world study

In this study, 102 cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) who received neoadjuvant RC48-ADC combined with immunotherapy were included. We evaluated the pathological responses and explored multiple clinical characteristics to identify independent predictive indicators of the efficacy. The results showed that neoadjuvant RC48-ADC combined with immunotherapy had promising efficacy. Furthermore, we collected 11 MIBC samples and performed single-cell RNA sequencing. All BLCA epithelial cells were identified as four subclusters. We conducted differential gene expression/functional enrichment analysis, cell proportion analysis, cell cycle analysis, CNV analysis, and pseudotemporal analysis on all tumor cells to evaluate potential efficacy-predictive biomarkers and the evolutionary patterns of tumor cells during neoadjuvant treatment. The results indicated that the combined detection of HER2 and HSPA1A expression in C3 subcluster based on single-cell RNA sequencing is a potential strategy for predicting efficacy. In addition, C3 plays a dominant role in the emergence of drug-resistance during the evolution of BLCA epithelial cells.