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Meta-Analysis
. 2022 Sep 22;17(9):e0275176.
doi: 10.1371/journal.pone.0275176. eCollection 2022.

Do disease status and race affect the efficacy of zoledronic acid in patients with prostate cancer? A systematic review and meta-analysis of randomized control trials

Chiwei Chen  1 , Mandi Lin  2 , Daocheng Yu  3 , Weiting Qin  3 , Jianfu Zhou  1 , Lang Guo  1 , Renlun Huang  1 , Xinxiang Fan  4 , Songtao Xiang  1
Affiliations
Meta-Analysis

Do disease status and race affect the efficacy of zoledronic acid in patients with prostate cancer? A systematic review and meta-analysis of randomized control trials

Chiwei Chen et al. PLoS One. .

Abstract

Background: Zoledronic acid (ZA) does not improve the overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC); however, little is known about the efficacy of ZA in to hormone-sensitive prostate cancer (HSPC), metastatic hormone-sensitive prostate cancer (mHSPC), and non- metastatic castration-resistant prostate cancer (nmCRPC). Therefore, we assessed the efficacy of ZA in patients with prostate cancer (PCa) and different disease statuses.

Methods: Fifteen eligible randomized-control trials (RCTs) with ZA intervention, including 8280 participants with HSPC, mHSPC, nmCRPC, and mCRPC, were analyzed. The primary and secondary outcome were overall survival(OS), and skeletal-related events (SREs), and bone mineral density (BMD).

Results: The participants included 8280 men (7856 non-Asian and 424 Asian). Seven trials yielded a pooled hazard ratio (HR) of 0.95 (0.88, 1.03; P = 0.19) for OS. Subgroup analysis revealed no significant improvement in OS in the HSPC, castration-resistant prostate cancer (CRPC), M0 and M1(bone metastasis) groups, with pooled HR (95%CI) of 0.96 (0.88,1.05), 0.78 (0.46,1.33), 0.95 (0.81,1.13), 0.85 (0.69,1.04) respectively. The Asian group exhibited improved in OS with an HR of 0.67 (0.48, 0.95; P = 0.02), whereas the non-Asian group showed no improvement in OS with an HR of 0.97 (0.90, 1.06; P = 0.52). Five trials yielded pooled odds ratio (OR) of 0.65 (0.45, 0.95; P = 0.02) for SREs. In the subgroup, SREs were significantly decreased in the M1 and Asian groups with ORs of 0.65 (0.45, 0.95; P = 0.02) and 0.42 (0.24, 0.71; P = 0.001), respectively. Six trials yielded a pooled mean difference (MD) of 8.08 (5.79, 10.37; P < 0.001) for BMD. In the HSPC we observed a stable improvement in increased BMD percentage with an MD (95%CI) of 6.65 (5.67, 7.62) (P = 0.001).

Conclusions: ZA intervention does not significantly improve OS in patients with prostate cancer (HSPC, CRPC, M0, M1) but probably improves OS in the Asian populations. M1 and Asian groups had exhibit a significant reduction in SREs regardless of the HSPC or CRPC status after ZA administration. Moreover, ZA treatment increases BMD percentage.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart to screen eligible studies.
Fig 2
Fig 2. Forest plot with HR, OR, MD of OS comparing ZA with control group.
Fig 3
Fig 3. Forest plot with hazard ratio (HR) of OS in subgroup of HSPC and CRPC.
Fig 4
Fig 4. Forest plot with hazard ratio (HR) of OS in subgroup of M1 and M0.
Fig 5
Fig 5. Forest plot with hazard ratio (HR) of OS in subgroup of Asian and not Asian.
Fig 6
Fig 6. Forest plot with hazard ratio (HR) of OS in subgroup of age and GS.
Fig 7
Fig 7. Forest plot odds ratio (OR) of Skeletal related events (SREs) in subgroup of M1.
Fig 8
Fig 8. Forest plot odds ratio (OR) of Skeletal related events (SREs) in subgroup of Asian and not Asian.
Fig 9
Fig 9. Forest plot odds ratio (OR) of Skeletal related events (SREs) in subgroup of HSPC and CRPC.
Fig 10
Fig 10. Forest plot odds ratio (OR) of Skeletal related events (SREs) in subgroup of age and GS.
Fig 11
Fig 11. Forest plot with odds ratio (MD) of bone mineral density (BMD) in subgroup of HSPC.
See this image and copyright information in PMC

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