Correlation Between Imaging-Based Intermediate Endpoints and Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer: Analysis of 28 Randomized Trials Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria in 16,511 Patients

We assessed correlation between hazard ratios of imaging-based intermediate endpoints (IBIEs) and overall survival among 28 Prostate Cancer Working Group 2-based phase II-III randomized trials evaluating systemic treatments in 16,511 metastatic castration-resistant prostate cancer patients. The overall correlation was good (R-2 = 0.57). Trials using radiographic progression-free survival showed higher correlation than those using a composite IBIE (including clinical factors in the definition of progression): R-2 = 0.58 vs. 0.00. Introduction/Background: Radiographic progression-free survival (rPFS) based on Prostate Cancer Working Group 2 (PCWG2) has been increasingly used as a meaningful imaging-based intermediate endpoint (IBIE) for overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). In randomized phase Ill trials, rPFS showed good correlation with OS at the individual trial level. We aimed to assess the correlation between the hazard ratios (HR) of IBIE and OS among PCWG2-based randomized trials. Materials and Methods: PubMed and EMBASE databases were systematically searched for randomized trials evaluating systemic treatments on mCRPC using PCWG2 up to April 15, 2020. Hazard ratios for OS and IBIEs were extracted and their correlation was assessed using weighted linear regression. Subgroup analyses were performed according to various clinical settings: prior chemotherapy, drug category, type of IBIE (rPFS vs. composite IBIE, latter defined as progression by imaging and one or a combination of PSA, pain, skeletal-related events, and performance status), and publication year. Results: Twenty-eight phase II-III randomized trials (16,511 patients) were included. Correlation between OS and IBIE was good (R-2 = 0.57, 95% confidence interval [CI], 0.35-0.78). Trials using rPFS showed substantially higher correlation than those using a composite IBIE (R-2 = 0.58, 95% CI, 0.32-0.82 vs. 0.00, 95% CI, -0.01 to 0.01). Correlations between OS and IBIE in other subgroups were at least moderate in nearly all subgroups (R-2 = 0.32-0.91). Conclusion: IBIEs in the era of PCWG2 correlate well with OS in randomized trials for systemic drugs in patients with mCRPC. PCWG2-based rPFS should be used instead of a composite IBIE that includes PSA and other clinical variables. (C) 2021 Elsevier Inc. All rights reserved.