ArticleProstate cancer and prostatic diseases2025
A real-world experience of pembrolizumab monotherapy in microsatellite instability-high and/or tumor mutation burden-high metastatic castration-resistant prostate cancer: outcome analysis.
Article in Prostate cancer and prostatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 15 citations in OpenAlex.
- Phase 2 trial of pTVG-HP ± pTVG-AR DNA vaccines and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC).Journal for immunotherapy of cancer · 2026Trial
- Best of 2025 in prostate cancer and prostatic diseases.Prostate cancer and prostatic diseases · 2026Article
- Circulating Tumor DNA as Emerging Predictive and Prognostic Biomarker in Prostate Cancer.Cancers · 2026Review
- Synergistic potential of sipuleucel-T in enhancing immunotherapy for metastatic castration-resistant prostate cancer.Journal for immunotherapy of cancer · 2025Review
- Article
- The diversity of CD8Nature reviews. Immunology · 2025Review
- Microsatellite instability (MSI) and the tumor mutation burden (TMB) as biomarkers of response to immune checkpoint inhibitors in prostate cancer.Translational cancer research · 2025Article
- Pembrolizumab for treatment-related neuroendocrine prostate carcinoma with a high tumor mutational burden: a case report.Frontiers in oncology · 2025Article
- Article
- Ultrasound-guided percutaneous radiofrequency ablation combined with anti-PD-1 for the treatment of prostate cancer: an experimental study.Frontiers in oncology · 2025Article
- The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers.Current oncology (Toronto, Ont.) · 2024Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe efficacy of pembrolizumab monotherapy in metastatic castration-resistant prostate cancer patients (mCRPC) when stratified by MSI-H and/or TMB-H is poorly defined. Additionally, outcomes based on sequencing source (i.e., tissue or liquid biopsy) have not been well described. We sought to assess outcomes of pembrolizumab monotherapy in patients with mCRPC and compare efficacy based on MSI-H and/or TMB-H when identified by tissue or liquid biopsy.
methodsA retrospective analysis was performed of mCRPC patients treated at Mayo Clinic with pembrolizumab monotherapy between 2018 and 2023. Objective response rates (ORR), median progression-free survival (mPFS), and overall survival (mOS), were determined by RECIST v1.1 criteria.
resultsTwenty-two patients with mCRPC received pembrolizumab monotherapy for at least 3 cycles for a MSI-H or TMB-H indication. All patients had next generation sequencing (NGS) performed via tissue (n = 11) or liquid (n = 10) biopsy source. The ORR was 50% (27.3% complete response and 22.7% had partial response). The mPFS for TMB 10-14.9 mut/Mb (n = 4), TMB 15-24.9 mut/Mb (n = 6), and TMB ≥ 25 mut/Mb (n = 10) was 2.1, not reached (NR), and NR, respectively (p = 0.0003). The mOS for these same groups was 5.1 months, 20.5 months, and not reached, respectively. Among patients with TMB-H without co-occurring MSI-H or CDK12 (n = 6), none experienced a response and only one patient had stable disease compared to patients with MSI-H (n = 12) for whom the ORR was 75%. Immunotherapy responsive alterations such as ATRX and PTCH1 mutations were frequently noticed among patients who had complete response (CR).
conclusionsOur hypothesis-generating study suggests that MSI-H drives the efficacy of pembrolizumab in mCRPC with better survival outcomes as TMB increases. Clinicians should consider alternative treatment strategies for advanced prostate cancer when TMB-H is present without co-occurring MSI-H or CDK12.
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