Elias B A Chandran, Giovanni Maria Iannantuono, Saad O Atiq, Dilara Akbulut, Ninet Sinaii, Nicholas I Simon, Abdul Rouf Banday, Salah Boudjadi, Sandeep Gurram, Amin H Nassar, Jonathan E Rosenberg, Gisela Butera, Min Yuen Teo, Guru Sonpavde, Jonathan A Coleman, Andrea B Apolo
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引用次数: 0
Abstract
Background: Mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) occur in a subset of cancers and have been shown to confer sensitivity to immune checkpoint inhibition (ICI); however, there is a lack of prospective data in urothelial carcinoma (UC).
Methods and analysis: We performed a systematic review to estimate the prevalence of dMMR and MSI-H in UC, including survival and clinical outcomes. We searched for studies published up to 26 October 2022 in major scientific databases. We screened 1745 studies and included 110. Meta-analyses were performed if the extracted data were suitable.
Results: The pooled weighted prevalences of dMMR in bladder cancer (BC) and upper tract UC (UTUC) were 2.30% (95% CI 1.12% to 4.65%) and 8.95% (95% CI 6.81% to 11.67%), respectively. The pooled weighted prevalences of MSI-H in BC and UTUC were 2.11% (95% CI 0.82% to 5.31%) and 8.36% (95% CI 5.50% to 12.53%), respectively. Comparing localised versus metastatic disease, the pooled weighted prevalences for MSI-H in BC were 5.26% (95% CI 0.86% to 26.12%) and 0.86% (95% CI 0.59% to 1.25%), respectively; and in UTUC, they were 18.04% (95% CI 13.36% to 23.91%) and 4.96% (95% CI 2.72% to 8.86%), respectively. Cumulatively, the response rate in dMMR/MSI-H metastatic UC treated with an ICI was 22/34 (64.7%) compared with 1/9 (11.1%) with chemotherapy.
Conclusion: Both dMMR and MSI-H occur more frequently in UTUC than in BC. In UC, MSI-H occurs more frequently in localised disease than in metastatic disease. These biomarkers may predict sensitivity to ICI in metastatic UC and resistance to cisplatin-based chemotherapy.
背景:错配修复缺陷(dMMR)和微卫星不稳定性高(MSI-H)发生在一部分癌症中,并已被证明可赋予对免疫检查点抑制(ICI)的敏感性;然而,目前缺乏尿路上皮癌(UC)的前瞻性数据:我们进行了一项系统性综述,以估算dMMR和MSI-H在UC中的患病率,包括生存率和临床结果。我们在主要科学数据库中搜索了截至 2022 年 10 月 26 日发表的研究。我们筛选了1745项研究,并纳入了110项。如果提取的数据合适,则进行元分析:膀胱癌(BC)和上尿路膀胱癌(UTUC)中dMMR的汇总加权患病率分别为2.30%(95% CI 1.12%至4.65%)和8.95%(95% CI 6.81%至11.67%)。BC和UTUC中MSI-H的汇总加权患病率分别为2.11%(95% CI 0.82%至5.31%)和8.36%(95% CI 5.50%至12.53%)。比较局部疾病与转移性疾病,MSI-H在BC中的汇总加权患病率分别为5.26%(95% CI 0.86%至26.12%)和0.86%(95% CI 0.59%至1.25%);在UTUC中的汇总加权患病率分别为18.04%(95% CI 13.36%至23.91%)和4.96%(95% CI 2.72%至8.86%)。累计而言,接受 ICI 治疗的 dMMR/MSI-H 转移性 UC 的应答率为 22/34 (64.7%),而接受化疗的应答率为 1/9 (11.1%):结论:UTUC中dMMR和MSI-H的发生率均高于BC。结论:dMMR和MSI-H在UTUC中的发生率高于BC,在UC中,MSI-H在局部疾病中的发生率高于转移性疾病。这些生物标志物可预测转移性 UC 对 ICI 的敏感性以及对顺铂化疗的耐药性。