ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026
Additive Clinical Utility of Microsatellite Instability and Tumor Mutational Burden to Predict Immune Checkpoint Inhibitor Effectiveness in Metastatic Castration-Resistant Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- SPEN inactivation drives resistance to androgen receptor pathway inhibitors in metastatic prostate cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- KDM3B Predicts Expression Signature, Prognosis Value, and Immune Characteristics of Cancers: A Pan-Cancer Analysis.BioMed research international · 2026Article
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14 authors.
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Abstract
purposeImmune checkpoint inhibitors (ICI) have shown limited efficacy in unselected patients with metastatic castration-resistant prostate cancer (mCRPC). However, ICIs are approved for biomarker-defined subsets: microsatellite instability-high (MSI-H) and/or high tumor mutational burden (TMB-H). The efficacy of ICIs in TMB-H but not MSI-H disease remains unclear, and limited data exist evaluating ICI outcomes associated with blood-based MSI (bMSI) in mCRPC. EXPERIMENTAL
designThis study used the United States-based deidentified Flatiron Health-Foundation Medicine prostate cancer Clinico-Genomic Database. Patients with tissue-assessed MSI (tMSI) and TMB (tTMB) status by an algorithm supporting an FDA-approved CDx for pembrolizumab were included if treated with single-agent ICI. Separately, outcomes on ICI associated with bMSI were assessed, including if treated with single-agent ICI or taxane.
resultsAmong 2,965 patients with mCRPC, tMSI-H (3.2%) was nearly always also tTMB ≥10 mut/Mb (4.7%). In 84 ICI-treated patients, time to next treatment (TTNT) and overall survival (OS) were more favorable in tMSI-H with any TMB [TTNT HR, 0.18; 95% confidence interval (CI), 0.09-0.37 and OS HR, 0.32; 95% CI, 0.15-0.66] and tTMB ≥10 without tMSI-H (TTNT HR, 0.18; 95% CI, 0.04-0.48 and OS HR, 0.20; 95% CI, 0.05-0.77) compared with tTMB <10 without tMSI-H group. In intrapatient assessments, patients with tTMB ≥10 had more favorable TTNT with subsequent ICI versus prior taxane. Detection of bMSI-H was associated with more favorable TTNT on ICI (HR, 0.34; 95% CI, 0.14-0.83) and OS (HR, 0.21; 95% CI, 0.06-0.75) when tumor fraction ≥1%.
conclusionsThese findings add support for tTMB and tMSI in predicting ICI monotherapy benefit in mCRPC and provide evidence supporting bMSI testing when tissue is unavailable.
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