Neoadjuvant immunotherapy and chemoimmunotherapy for stage II-III muscle invasive bladder cancer

Abstract

ObjectiveConsidering the striking evidence revealed by immunotherapy in advanced or metastatic bladder cancer, investigators have explored neoadjuvant immunotherapy and chemoimmunotherapy in muscle-invasive bladder cancer (MIBC). Currently, there have been a large number of studies reporting varied efficacy and safety of these approaches. Herein, we pooled the available evidence in terms of oncological outcomes (pathological complete response [pCR] and pathological partial response [pPR]) and safety outcomes (immune-related adverse events [irAEs], treatment-related adverse events [TRAEs]), through a systematic review and meta-analysis.MethodWe searched PubMed, Embase, Cochrane Library, and American Society of Clinical Oncology meeting abstracts to identify relevant studies up to June 2022. Studies were included if they evaluated the neoadjuvant immunotherapy or chemoimmunotherapy in MIBC and reported at least the pCR.ResultsA total of 22 records involving 843 patients were included. For pCR of immunotherapy, the pooled rate of immune checkpoint inhibitor (ICI) monotherapy and dual-ICIs therapy was 24% (95% confidence interval [CI]: 15.3% - 32.8%) and 32.1% (95%CI: 20.6% - 43.7%), respectively. For pCR of chemoimmunotherapy, the overall pooled rate was 42.6% (95% CI: 34.9% - 50.2%). Subgroup of gemcitabine/cisplatin (GC) plus ICI had a pCR rate of 41.7% (95%CI: 35.8% - 47.5%). In terms of safety, the pooled rate of Grade≥3 irAEs was 11.7% (95% CI: 6.5%-16.9%). In subgroup analysis, the Grade≥3 irAEs rate of ICI monotherapy, dual-ICIs therapy, and GC plus ICI therapy was 7.4% (95% CI: 4.3%-10.5%), 30.3% (95% CI: 15.3%-45.3%), and 14.5% (95% CI: 3.5% - 25.4%), respectively. Besides, the pooled Grade≥3 TRAEs rate for chemoimmunotherapy was 32.4% (95% CI: 13.1% - 51.6%).ConclusionNeoadjuvant immunotherapy and chemoimmunotherapy were effective and safe in the treatment of MIBC. Compared to ICI monotherapy, dual-ICIs therapy or chemoimmunotherapy can improve the response rate, while increasing the morbidity of Grade≥ 3 irAEs or Grade≥ 3 TRAEs.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD4202233771.

Machine learning-based identification of tumor-infiltrating immune cell-associated model with appealing implications in improving prognosis and immunotherapy response in bladder cancer patients

“…Compared to ICI alone, the addition of chemotherapy can release large amounts of tumor antigen and boost the effect of effector lymphocytes (31). However, we should bear in mind that the improved response rate and prolonged survival may be at the cost of increased morbidity of adverse effects (32). Urologists and oncologists should balance the benefits and harms of combination therapy for BCa patients of high IRS.…”

An innovative model based on N7-methylguanosine-related lncRNAs for forecasting prognosis and tumor immune landscape in bladder cancer

“…Over the last few decades, the advent of immunotherapy has remodeled the treatment paradigm and accelerated the development of individualized precision therapy for cancers. The immunotherapy, such as PD-1, PD-L1, and CTLA-4 inhibitors, has improved the prognosis of BCa patients but is still in the initial stage, and more clinical trials in multi-center are urgently needed [ 5 , 35 ]. The existing body of studies on m7G suggested that its abnormal expression would heighten the translation of oncogenic mRNAs and boost tumorigenesis, advancement, and metastasis in various cancers, especially in BCa [ 13 – 15 , 36 ].…”

POLR3G promotes EMT via PI3K/AKT signaling pathway in bladder cancer

“…However, despite undergoing standard treatment, 31%–78% of NMIBC patients relapse within five years. Additionally, 10%–30% of NMIBC patients will ultimately progress to MIBC, which requires a more aggressive approach involving radical cystectomy and chemotherapy 3–6 . Unfortunately, some people with MIBC still face poor survival rates even with these treatments 7 .…”

“…Additionally, 10%-30% of NMIBC patients will ultimately progress to MIBC, which requires a more aggressive approach involving radical cystectomy and chemotherapy. [3][4][5][6] Unfortunately, some people with MIBC still face poor survival rates even with these treatments. 7 The increase in publicly available RNA-seq datasets and advanced bioinformatic toolkits have enabled the discovery of numerous new molecular biomarkers.…”