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.
- Elias B A Chandran, Genitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland
- Giovanni Maria Iannantuono, Genitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland
- Saad O Atiq, Genitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland
- Dilara Akbulut, Laboratory of Pathology, National Institutes of Health, Bethesda, Maryland
- Ninet Sinaii, Biostatistics and Clinical Epidemiology Service, National Institutes of Health, Bethesda, Maryland
- Nicholas I Simon, Genitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland
- Abdul Rouf Banday, Genitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland
- Salah Boudjadi, Genitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland
- Sandeep Gurram, Urologic Oncology Branch, National Institutes of Health, Bethesda, Maryland
- Amin H Nassar, Department of Hematology/Oncology, Yale New Haven Hospital, New Haven, Connecticut
- Jonathan E Rosenberg, Memorial Sloan Kettering Cancer Center, New York, New York
- Gisela Butera, Division of Library Services, National Institutes of Health, Bethesda, Maryland
- Min Yuen Teo, Memorial Sloan Kettering Cancer Center, New York, New York
- Guru Sonpavde, Medical Oncology, AdventHealth Central Florida, Orlando, Florida
- Jonathan A Coleman, Memorial Sloan Kettering Cancer Center, New York, New York
- Andrea B Apolo, Genitourinary Malignancies Branch, National Institutes of Health, Bethesda, Maryland