Impact of Bisphosphonates in Hormone-sensitive Metastatic Prostate Cancer A Systematic Review and Meta-Analysis

Abstract

Introduction: Bone modifying agents (BMA) are part of the management of metastatic hormone-refractory prostate cancer, however its use in hormone-sensitive scenario is controversial. The objective of this meta-analysis is to determine whether the addition of BMA on standard of care (SoC) in metastatic hormone sensitive prostate cancer (mHSPC) improves OS or time to first skeletal related event (SRE).

Patients and methods: A literature search of Web of Science, Pubmed and references lists of relevant articles was conducted. Eligible studies were prospective randomized trials comparing SoC to SoC plus BMA in mHSPC. We extracted data on: SoC option; type, dosing and duration of BMA; adverse events; hazard ratio and confidence interval for time to SRE and OS. Hazard radios were pooled using random-effects model. The main outcomes were OS and time to SRE. Secondary outcomes were the relative risk of grade 3-5 adverse events, osteonecrosis and renal dysfunction.

Results: Among 4949 studies identified, we selected 7 for the meta-analysis. Pooled results showed favorable OS (HR 0.87 [95% CI, 0.79-0.96], P = .007) and time to SRE (HR 0.74 [95% CI, 0.57-0.98], P = .003) for patients treated with bisphosphonates (BP). However, only 1 trial used androgen receptor pathway inhibitors (ARPI) and no trial included anti-RANK-L inhibitors. There was a significant increase in the risk of jaw osteonecrosis (RR 9.6 [95% CI, 1.98-46.82]).

Conclusion: BP may be beneficial in mHSPC, although there is scarcity of data on anti-RANKL agents and association with ARPI.

Keywords: Bone health; Bone-modifying agents; Metastatic castration sensitive prostate cancer; Skeletal-related events; Zoledronic acid.