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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
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Operationalizing intermediate clinical endpoints: A pragmatic framework for prostate cancer management trials
Xingyu Xiong1, Shiyu Zhang1, Jiajia Du2
1Department of Urology, Center of Biomedical Big Data and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Cancer Treatment Reviews
|April 11, 2025
Summary
Validated surrogate endpoints are crucial for accelerating prostate cancer therapy development. Milestone survival shows promise in advanced stages, but more research is needed for robust validation.
Area of Science:
- Oncology
- Clinical Trials
- Biostatistics
Background:
- Prostate cancer remains a significant cause of mortality despite treatment advancements.
- Developing novel therapies is hindered by lengthy overall survival (OS) assessments in phase III trials.
- Validated intermediate clinical endpoints (ICEs) are needed to expedite drug development.
Purpose of the Study:
- To systematically review and validate intermediate clinical endpoints (ICEs) as alternatives to overall survival (OS) in prostate cancer.
- To assess the methodological rigor of current ICE validation standards.
- To identify promising ICEs for advanced-stage prostate cancer clinical trials.
Main Methods:
- Systematic review and meta-analysis of phase III prostate cancer trials published up to January 2025.
- Inclusion criteria: randomized trials, therapeutic intervention, OS as primary endpoint, at least one ICE (e.g., radiographic progression-free survival (rPFS), milestone survival), and ≥70 participants.
- Surrogacy quantification using two-stage meta-analysis with R² ≥ 0.7 for validity.
Main Results:
- Metastasis-free survival (MFS) is validated as a surrogate endpoint for localized prostate cancer.
- Evidence for validated ICEs in metastatic castration-sensitive (mCSPC) and castration-resistant prostate cancer (mCRPC) is currently insufficient.
- Milestone survival demonstrated a strong trial-level correlation with OS in advanced prostate cancer, indicating its potential as a surrogate.
Conclusions:
- Current validation of ICEs in prostate cancer predominantly focuses on localized disease, limiting therapeutic development in advanced stages.
- Milestone survival is a promising candidate ICE for mCSPC and mCRPC, but methodological challenges in validation persist.
- Standardization of ICEs through unified frameworks and collaborative analyses is essential for advancing prostate cancer research.
Keywords:
Intermediate clinical endpointsMetastasis-free survivalMilestone survivalOverall survivalProstate cancerMore Related Videos
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