Effect of Single-agent Daily Prednisone on Outcomes and Toxicities in Metastatic Castration-resistant Prostate Cancer: Pooled Analysis of Prospective Studies

Abstract

The clinical effect of prednisone in metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized controlled trials that had or had not administered single-agent prednisone. Randomized controlled trials with a control arm that included single-agent placebo (or no anticancer therapy) or single-agent prednisone (with or without placebo) were eligible for analysis. Patients receiving prednisone combined with other agents in the control arm were excluded. The trial characteristics, baseline demographic data, overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) response, Response Evaluation Criteria In Solid Tumors response, and toxicities were recorded. The effect of prednisone was investigated for significance in bivariate models, adjusting for age, pre- and post-docetaxel status, Eastern Cooperative Oncology Group performance status, and trial publication year. Eighteen trials were included; 9 had control arms that contained prednisone (n = 2831) and 9 did not (n = 2784). No significant differences were identified for OS or toxicities of any grade. A significantly greater PSA response rate (18.8% vs. 2.5%; P = .023) and a trend toward more frequent grade ≥ 3 fluid retention (1.0% vs. 0.4%; P = .097) was seen in the prednisone group. Prednisone was also significantly associated with PFS after adjusting for docetaxel status. Single-agent prednisone for mCRPC did not improve OS but was associated with a greater PSA response rate and PFS. Overall and grade ≥ 3 toxicities were not significantly different with prednisone. With the exception of concurrent use with abiraterone or for palliative purposes, the routine use of prednisone for mCRPC appears unnecessary.

Keywords: Control arms; Prednisolone; Prognosis; Steroids; mCRPC.