ArticleJCO precision oncology2026
Efficacy of Immune Checkpoint Blockade in Advanced Upper Tract Urothelial Cancer With DNA Mismatch Repair Deficiency or Microsatellite Instability.
Article in JCO precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Multi-omics integration and clinical validation identify CKAP2 as a diagnostic biomarker for bladder cancer.World journal of surgical oncology · 2026Article
- Kidney-sparing immunotherapy for lynch syndrome-associated upper tract urothelial carcinoma following colon cancer: a case report.Frontiers in oncology · 2026Article
- Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis.BMJ oncology · 2024Article
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18 authors.
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Abstract
purposeDeficient DNA mismatch repair (dMMR) and microsatellite instability-high (MSI-H) status, which sensitizes tumors to immune checkpoint inhibitors (ICIs), is three times more common with upper tract urothelial carcinoma (UTUC) than with bladder cancer. However, data on ICI efficacy against dMMR/MSI-H advanced UTUC remain limited. MATERIALS AND
methodsWe retrospectively reviewed records of 24 patients with dMMR/MSI-H advanced UTUC treated with single-agent ICIs at a single institution (2015-2024). Descriptive statistics and the Kaplan-Meier method for survival outcomes were used.
resultsImmunohistochemistry confirmed dMMR in 22 (92%) patients, with loss of MSH2 or MSH6 in 15 (68.2%) patients and loss of PMS2 or MLH1 in seven patients (31.8%). Germline mutation testing confirmed Lynch syndrome in 16 (67%) patients. ICI monotherapy was associated with a median progression-free survival (PFS) time of 65.9 months (95% CI, 31.6 months to nonevaluable [NE]). The PFS rates at 12 and 24 months were 95.2% (95% CI, 86.1% to 100.0%) and 78.8% (95% CI, 60.1% to 97.5%), respectively. At a median follow-up duration of 56.9 months (95% CI, 42.2 to 92.2 months), the median overall survival time was not reached (95% CI, 65.9 months to NE). The confirmed overall response rate was 83%, including 16 complete responses. Four (17%) patients were offered surgical consolidation with these pathologic outcomes: ypTaN0, ypT0N0, and ypT1N0 (two patients). Eight patients (33%) experienced grade ≥3 immune-related adverse events, including bullous pemphigoid (n = 3), hepatitis (n = 1), pancytopenia (n = 1), colitis (n = 1), polyendocrinopathy (n = 1), and polyarthritis with sarcoid-like reaction (n = 1).
conclusionOur hypothesis-generating findings suggest that dMMR/MSI-H may serve as a biomarker of sensitivity to single-agent ICIs in advanced UTUC. External validation in larger, ideally prospective, studies is needed to confirm the effectiveness and durability of immune checkpoint blockade in this molecular subgroup.
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