Related Experiment Video
Updated: Sep 20, 2025
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Radiological progression-free survival as a surrogate for overall survival in patients with metastatic
Neal Shore1, Alicia K Morgans2, Martin Boegemann3
1START Carolinas/Carolina Urologic Research Center, Myrtle Beach, SC, USA.
Background:
Overall survival (OS) is the standard efficacy endpoint in various solid tumor trials; however, it requires longer follow-up time for assessment than potential intermediate endpoints. This study evaluated radiological progression-free survival (rPFS) as a surrogate for OS in metastatic hormone-sensitive prostate cancer (mHSPC) using aggregate-level data from randomized controlled trials (RCTs).
Methods:
A systematic literature review identified mHSPC RCTs published through December 2023, reporting hazard ratios for rPFS (HRrPFS) and OS (HROS). Correlation between HRrPFS and HROS was assessed using bivariate random-effects meta-analysis (BRMA). Predictive validity was assessed with leave-one-out cross-validation (LOOCV). The surrogate threshold effect (STE), or minimum rPFS benefit predicting an OS benefit, was estimated using recent mHSPC trial sample sizes. Sensitivity analyses (1) omitted trials that had only one of the endpoints reported, (2) omitted HRs that violated proportional hazards assumptions, (3) omitted trials that allowed cross-over and (4) investigated different assumed values of the within-study correlation.
Results:
The primary analysis included 35 treatment comparisons from 31 trials. The estimated rPFS-OS correlation was 0.95 (95 % CrI: 0.75, 1.00). LOOCV confirmed HROS were within 95 % prediction intervals. The estimated STE ranged from 0.55 to 0.71 depending on the trial size being predicted. Sensitivity analyses produced strong but slightly lower correlations (0.87, 0.89, 0.91) than the primary analysis, with full coverage of the reported HROS in cross validation. Increasing within-study correlation slightly reduced between-study correlation.
Conclusions:
The derived surrogacy equation enables OS estimation based on reported rPFS benefits in mHSPC, meeting NICE's 95 % surrogate validity threshold. These findings support rPFS as a reliable surrogate for OS, facilitating prediction of OS benefits in future mHSPC trials.
More Related Videos
07:25A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
06:46Competing-Risk Nomogram for Predicting Cancer-Specific Survival in Multiple Primary Colorectal Cancer Patients after Surgery
Published on: September 27, 2024
Related Concept Videos
01:21Cancer Survival Analysis
01:20Comparing the Survival Analysis of Two or More Groups
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...