What question did this study set out to answer?

This research examines the connection between microsatellite instability/mismatch repair deficiency and survival outcomes in upper tract urothelial carcinoma patients.

March 4, 2026

Predictive value of microsatellite instability/mismatch repair deficiency phenotype in upper tract urothelial carcinoma: A systematic review and meta-analysis.

Key Points

This research examines the connection between microsatellite instability/mismatch repair deficiency and survival outcomes in upper tract urothelial carcinoma patients.
Conducted a systematic literature search across major databases from January 2002 to April 2025.
Evaluated clinicopathological features, including family and personal history of malignancy, tumor stage, grade, and lymph node metastasis.
Analyzed overall survival as the primary outcome using meta-analytical techniques.
Lynch syndrome characterized UTUC by a higher history of prior malignancies (OR 6.05).
Patients with Lynch syndrome had lower tumor stages (OR 0.59).
G2 tumors were more prevalent compared to G1 and G3 tumors (OR 0.31 and OR 1.68, respectively).
Patients exhibited a reduced incidence of lymph node metastasis (OR 0.33).
Overall survival was notably improved in Lynch syndrome patients (HR 0.63).

Abstract

701 Background: Lynch syndrome (LS) has been established as a significant risk factor for developing upper tract urothelial carcinoma (UTUC); however, clinicopathological characteristics and survival outcomes in this population remain contentious. This meta-analysis was designed to systematically evaluate clinicopathological features and survival outcomes in UTUC patients with microsatellite instability (MSI) or mismatch repair deficiency (dMMR), phenotypes associated with LS. Methods: A systematic literature search was conducted in PubMed, Web of Science, Embase, and Cochrane databases from January 2002 to April 2025. Clinicopathological endpoints included family history of malignancy, personal history of prior malignancies, tumor stage, tumor grade, and lymph node metastasis (LNM). The primary survival outcome was overall survival (OS). The protocol has been registered with PROSPERO (Registration ID: CRD42024558925). Results: 27 studies, encompassing 3,545 cases, were ultimately included. Meta-analysis revealed that LS-UTUC was significantly associated with: a) a history of prior malignancies (OR 6.05, 95% CI 2.93; 12.48), b) lower tumor stage (OR 0.59, 95% CI 0.44; 0.79), c) predominance of G2 (G1 vs G2: OR 0.31, 95% CI 0.13; 0.72; G2 vs G3: OR 1.68, 95% CI 1.06; 2.67), and d) reduced incidence of LNM (OR 0.33, 95% CI 0.14; 0.78). Furthermore, LS-UTUC patients demonstrated notably improved OS (HR 0.63, 95% CI 0.43; 0.91). However, significant heterogeneity persists in both LS detection methodologies and diagnostic thresholds, and the limited number of included studies precluded assessment of associations with other survival outcomes. Conclusions: The unique profile of LS-UTUC—encompassing high prior cancer risk, early-stage/G2-predominant pathology, and favorable survival—calls for integrated LS screening in UTUC management. These findings advocate for the integration of universal LS screening into UTUC management to enable risk-adapted strategies. Prospective studies are warranted to standardize diagnostics and evaluate the efficacy of targeted therapies, such as immune checkpoint inhibitors, in this unique population.

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