ArticleClinical genitourinary cancer2024
A Panel-Based Mutational Signature of Mismatch Repair Deficiency is Associated With Durable Response to Pembrolizumab in Metastatic Castration-Resistant Prostate Cancer.
Article in Clinical genitourinary cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma.American journal of hematology · 2026Article
- NGS-Based Genomic Profiling Identifies Independent Predictors of Time to Castration Resistance in Hormone-Sensitive Prostate Cancer: A Retrospective Real-World Study.Current oncology (Toronto, Ont.) · 2026Article
- Five dominant amino acid substitution signatures shape tumour immunity.Molecular systems biology · 2026Article
- Machine Learning in Biomarker-Driven Precision Oncology: Automated Immunohistochemistry Scoring and Emerging Directions in Genitourinary Cancers.Current oncology (Toronto, Ont.) · 2026Review
- Prostate cancer and solid organ transplantation: patient management and outcomes.BJU international · 2025Article
- The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers.Current oncology (Toronto, Ont.) · 2024Review
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Authors and funding
13 authors at 4 institutions in 1 country.
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Abstract
INTRODUCTION/
backgroundImmune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to demonstrate that a panel-based mutational signature identifies mismatch repair (MMR) deficient (MMRd) PCa and is a biomarker of response to pembrolizumab. PATIENTS AND
methodsClinico-genomic data was obtained for 2664 patients with PCa sequenced at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering (MSK). Clinical outcomes were collected for patients with metastatic castration-resistant PCa (mCRPC) treated with pembrolizumab at DFCI. SigMA was used to characterize tumors as MMRd or MMR proficient (MMRp). The concordance between MMRd with microsatellite instability (MSI-H) was assessed. Radiographic progression-free survival (rPFS) and overall survival (OS) were collected for patients treated with pembrolizumab. Event-time distributions were estimated using Kaplan-Meier methodology.
resultsAcross both cohorts, 100% (DFCI: 12/12; MSK: 43/43) of MSI-H tumors were MMRd. However, 14% (2/14) and 9.1% (6/66) of MMRd tumors in the DFCI and MSK cohorts respectively were microsatellite stable (MSS), and 26% (17/66) were MSI-indeterminate in the MSK cohort. Among patients treated with pembrolizumab, those with MMRd (n = 5) versus MMRp (n = 14) mCRPC experienced markedly improved rPFS (HR = 0.088, 95% CI: 0.011-0.70; P = .0064) and OS (HR = 0.11, 95% CI: 0.014-0.80; P = .010) from start of treatment. Four patients with MMRd experienced remissions of >= 2.5 years.
conclusionSigMA detects additional cases of MMRd as compared to MSI testing in PCa and identifies patients likely to experience durable response to pembrolizumab.
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