DISCUSSION
toxicity, toxicities, UC, MIBC, tumors, PD‐L1
RECURRENCE, SECONDARY, TUMORS, TUMORIGENESIS
The neoadjuvant treatment of local advanced MIBC patients with three cycles of camrelizumab plus GC demonstrated preliminary anti‐tumor activity in this single‐arm stage. The results of this pilot study met the primary endpoint, and the subsequent randomized stage is currently ongoing to compare camrelizumab plus GC with GC alone as neoadjuvant treatment for patients with local advanced MIBC. These preliminary findings are consistent with other studies that have investigated the use of ICI‐chemotherapy combination regimens as neoadjuvant treatment for MIBC patients. Two pilot studies involving four cycles of pembrolizumab combined with GC demonstrated pCR rates of 36% and 44%, respectively,The pathologic downstaging rate, as a secondary endpoint, in this study was similar to rates reported in previous studies. Two separate studies that administered four cycles of pembrolizumab combined with GC regimen as neoadjuvant treatment for MIBC patients reported pathological downstaging rates of 56% and 61.1% after resection.The optimal timing and duration of neoadjuvant therapy for MIBC remain topics of ongoing debate. Previous studies have suggested that delaying cystectomy after neoadjuvant therapy may negatively impact patients' outcomes.Patients who achieved pCR in this study had a more favorable 1‐year survival status compared to those who did not achieve pCR. Previous studies have also shown that patients who responded well to neoadjuvant ICI‐chemotherapy had significantly better recurrence‐free survival compared to non‐responders.RC is the standard treatment for MIBC. However, some patients may not be eligible for surgery or may prefer to avoid RC due to concerns about quality of life. Therefore, bladder preservation therapies have emerged as an alternative treatment method.The hematologic toxicity profile of this study was similar to that of other MIBC patients treated with neoadjuvant ICI‐chemotherapy.No significant correlation was found between PD‐L1 expression and pathologic response in this study or in other studies of ICI‐chemotherapy as neoadjuvant treatment for MIBC patients.Recent studies suggest that mutations in the DDR pathway in UC may be associated with improved responses to NAC and prolonged survival.FRG1 has been found to play a role in both tumorigenesis and angiogenesis, and several previous studies have demonstrated an association between FRG1 expression and OS in various types of tumors.There are several limitations to this study that should be considered. First, the results presented are from the single‐arm stage of the study, and therefore, further evidence from the ongoing randomized stage is required to strengthen the findings. Second, the follow‐up period may have been inadequate to capture all instances of recurrence, and longer follow‐up is needed to provide a more comprehensive understanding of the survival benefit of ICI‐chemotherapy as neoadjuvant treatment for MIBC patients. Moreover, some patients opted not to undergo RC, which may result in an overestimation of the efficacy of our analysis, as our analysis primarily focused on patients who underwent RC. Furthermore, patients who declined RC did not have available data for EFS. This issue will be addressed in the ongoing randomized controlled trial. Lastly, toxicities were only assessed for 90 days, and delayed irAEs may not have been detected within this timeframe.