BCR as Surrogate for OS in Prostate Cancer Trials

Core Concepts

BCR is an unreliable surrogate for overall survival in localized prostate cancer trials.

Abstract

TOPLINE BCR is not a reliable surrogate for overall survival in localized prostate cancer trials. METHODOLOGY Meta-analysis of 10,741 patients from 11 randomized clinical trials. Interventions included radiotherapy dose escalation, short-term ADT, and ADT prolongation. Prentice criteria and two-stage meta-analytic approach used to assess BCR as a surrogate endpoint. TAKEAWAY Treatments significantly reduced BCR risk, but only short- and long-term ADT improved overall survival. BCR at 48 months associated with increased mortality risk. No significant treatment effect on overall survival after adjusting for BCR at 48 months. IN PRACTICE BCR-based endpoints should not be primary in localized prostate cancer trials. Metastasis-free survival is a more appropriate measure. SOURCE Led by senior author Amar Kishan, MD, published in the Journal of Clinical Oncology. LIMITATIONS Trials used different definitions of BCR. Some trials were conducted over 20 years ago. Quality of life was not captured.

Stats

The meta-analysis included 10,741 patients from 11 randomized clinical trials; the median follow-up was 9.2 years. BCR was associated with significantly increased mortality risk at 48 months: 2.46-fold for dose escalation, 1.51-fold for short-term ADT, and 2.31-fold for ADT prolongation. After adjusting for BCR at 48 months, there was no significant treatment effect on overall survival.

Quotes

"These results strongly suggest that BCR-based endpoints should not be the primary endpoint in randomized trials conducted for localized prostate cancer." - Authors

Key Insights Distilled From

BCR Is Unreliable Surrogate for OS in Prostate Cancer

by Nancy A. Mel... at www.medscape.com 09-06-2023

https://www.medscape.com/viewarticle/996150

Deeper Inquiries

What are the implications of using metastasis-free survival as a primary endpoint in prostate cancer trials?

Metastasis-free survival as a primary endpoint in prostate cancer trials has significant implications. Unlike biochemical recurrence (BCR), which has shown to be an unreliable surrogate for overall survival, metastasis-free survival provides a more direct measure of disease progression and treatment efficacy. By focusing on the prevention of metastasis, which is a critical factor in determining patient outcomes and quality of life, researchers can better assess the impact of interventions on the long-term health of patients. Additionally, using metastasis-free survival as a primary endpoint allows for a more accurate evaluation of the effectiveness of treatments in delaying disease progression and improving patient prognosis.

How might the evolving definitions of BCR impact the reliability of its use as a surrogate endpoint?

The evolving definitions of BCR, such as the transition from the older American Society of Therapeutic Radiation and Oncology definition to the more current Phoenix criteria, can significantly impact the reliability of its use as a surrogate endpoint. These changes in definitions may lead to inconsistencies in how BCR is identified and measured across different studies, making it challenging to compare results and draw meaningful conclusions. This variability in defining BCR can introduce bias and confound the interpretation of study outcomes, potentially affecting the reliability of BCR as a surrogate endpoint for overall survival. Standardizing the definition of BCR across trials is crucial to ensure the consistency and accuracy of its use as a surrogate endpoint.

How can the lack of capturing quality of life data affect the interpretation of the study results?

The lack of capturing quality of life data in a study can have significant implications for the interpretation of results. Quality of life is a crucial aspect of patient care and treatment outcomes, especially in cancer trials where the goal is not only to prolong survival but also to maintain or improve the patient's well-being. Without assessing quality of life outcomes, researchers may overlook important factors that influence patient satisfaction, treatment adherence, and overall health status. This omission can limit the comprehensive understanding of the impact of interventions on patients and may lead to incomplete conclusions about the effectiveness of treatments. Including quality of life data in studies is essential for providing a holistic view of patient outcomes and ensuring that interventions are not only prolonging survival but also enhancing the overall quality of life for individuals with prostate cancer.