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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| Language: | English |
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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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| author | Ninet Sinaii Guru Sonpavde Amin H Nassar Min Yuen Teo Andrea B Apolo Jonathan E Rosenberg Giovanni Maria Iannantuono Elias B A Chandran Saad O Atiq Dilara Akbulut Nicholas I Simon Abdul Rouf Banday Salah Boudjadi Sandeep Gurram Gisela Butera Jonathan A Coleman |
| author_facet | Ninet Sinaii Guru Sonpavde Amin H Nassar Min Yuen Teo Andrea B Apolo Jonathan E Rosenberg Giovanni Maria Iannantuono Elias B A Chandran Saad O Atiq Dilara Akbulut Nicholas I Simon Abdul Rouf Banday Salah Boudjadi Sandeep Gurram Gisela Butera Jonathan A Coleman |
| author_sort | Ninet Sinaii |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d3920c29bad4423893885de5201f3040 |
| institution | Kabale University |
| issn | 2752-7948 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Oncology |
| spelling | doaj-art-d3920c29bad4423893885de5201f30402025-01-30T10:30:14ZengBMJ Publishing GroupBMJ Oncology2752-79482024-07-013110.1136/bmjonc-2024-000335Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysisNinet Sinaii0Guru Sonpavde1Amin H Nassar2Min Yuen Teo3Andrea B Apolo4Jonathan E Rosenberg5Giovanni Maria Iannantuono6Elias B A Chandran7Saad O Atiq8Dilara Akbulut9Nicholas I Simon10Abdul Rouf Banday11Salah Boudjadi12Sandeep Gurram13Gisela Butera14Jonathan A Coleman15Biostatistics and Clinical Epidemiology Service, National Institutes of Health, Bethesda, Maryland, USAAdventHealth Cancer Institute, Orlando, Florida, USADepartment of Hematology/Oncology, Yale New Haven Hospital, New Haven, Connecticut, USAMemorial Sloan Kettering Cancer Center, New York, New York, USAGenitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland, USAMemorial Sloan Kettering Cancer Center, New York, New York, USAGenitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland, USAGenitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland, USAGenitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland, USALaboratory of Pathology, National Institutes of Health, Bethesda, Maryland, USAGenitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland, USAGenitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland, USAGenitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland, USAUrologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USADivision of Library Services, National Institutes of Health, Bethesda, Maryland, USAMemorial Sloan Kettering Cancer Center, New York, New York, USABackground 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.https://bmjoncology.bmj.com/content/3/1/e000335.full |
| spellingShingle | Ninet Sinaii Guru Sonpavde Amin H Nassar Min Yuen Teo Andrea B Apolo Jonathan E Rosenberg Giovanni Maria Iannantuono Elias B A Chandran Saad O Atiq Dilara Akbulut Nicholas I Simon Abdul Rouf Banday Salah Boudjadi Sandeep Gurram Gisela Butera Jonathan A Coleman Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis BMJ Oncology |
| title | Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis |
| title_full | Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis |
| title_fullStr | Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis |
| title_full_unstemmed | Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis |
| title_short | Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis |
| title_sort | mismatch repair deficiency and microsatellite instability in urothelial carcinoma a systematic review and meta analysis |
| url | https://bmjoncology.bmj.com/content/3/1/e000335.full |
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