Intermediate Endpoints After Postprostatectomy Radiotherapy: 5-Year Distant Metastasis to Predict Overall Survival

Area of Science:

• Oncology
• Clinical Trials
• Prostate Cancer Research

Background:

• Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are crucial for optimizing clinical trial design in men undergoing postprostatectomy radiation therapy (PORT).
• Current endpoints may not adequately predict long-term outcomes, necessitating the identification of more robust prognostic markers.

Purpose of the Study:

• To identify a potential intermediate clinical endpoint (ICE) that is prognostic for overall survival (OS) in men receiving postprostatectomy radiation therapy (PORT).
• To evaluate the predictive capabilities of biochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) as ICEs.

Main Methods:

• A multi-institutional retrospective study involving 566 men treated with PORT between 1986 and 2013.
• Evaluation of BF, DM, and CRPC for correlation with OS using time-dependent variables in multivariable Cox proportional hazards models and landmark analyses.
• Assessment of model discrimination using cross-validated concordance (c) indices.

Main Results:

• Overall survival (OS) rates at 1, 3, 5, and 7 years post-PORT were 98%, 95%, 90%, and 82%, respectively.
• Biochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) were all significantly associated with OS.
• Development of distant metastases within 5 years (5-yr DM) demonstrated the highest prognostic capability (c-index=0.78) and greatest increase in discriminatory power compared to other endpoints.

Conclusions:

• The development of distant metastases within 5 years after PORT is a strong predictor of overall survival (OS) in prostate cancer patients.
• Five-year distant metastases (5-yr DM) outperformed biochemical failure (BF) and castrate-resistant prostate cancer (CRPC) as an intermediate clinical endpoint.
• Prospective validation in randomized trials is necessary to confirm 5-yr DM as a surrogate for OS and integrate it into future clinical trial designs.