Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis
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 per...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-07-01
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| Series: | BMJ Oncology |
| Online Access: | https://bmjoncology.bmj.com/content/3/1/e000335.full |
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| Summary: | 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. |
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| ISSN: | 2752-7948 |