Department of Chemotherapy and Radiotherapy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, China.
Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, The Key Laboratory of Nephropathy and the Kidney Disease Immunology Laboratory, The Third Grade Laboratory, 79 Qingchun Road, Hangzhou, Zhejiang, China.
Clin Exp Metastasis. 2019 Jun;36(3):199-209. doi: 10.1007/s10585-019-09963-4. Epub 2019 Apr 8.
Adjuvant therapy with bisphosphonates in prostate cancer is effective in improving bone mineral density and thus reducing fractures and skeletal-related events. We analyzed the effect of bisphosphonates on overall survival (OS) in subgroups of patients with prostate cancer. A systematic literature search was conducted of the PubMed database and the bibliographies of related studies. The long-term OS rates were extracted from every eligible trial. The hazard ratio (HR) was pooled with the fixed effects model, and preplanned subgroup analyses were performed. The search yielded 112 articles, of which 10 articles with 13 patient subgroups met the eligibility criteria. The meta-analysis of all 13 subgroups showed that adjuvant bisphosphonate therapy did not significantly improve OS versus the control group (HR = 0.961, 95% CI 0.899-1.026, p = 0.233) with low heterogeneity (I = 13.47%, degrees of freedom = 12, p = 0.336). There was no significant improvement in OS with the addition of bisphosphonates in the major subgroup analyses (metastatic (M1) versus non-metastatic, clodronate versus zoledronic acid, castration-sensitive prostate cancer (CSPC) versus castration-refractory prostate cancer). When the subgroups were further divided, adjuvant bisphosphonate therapy significantly improved OS in patients with CSPC + M1 (HR = 0.874, 95% CI 0.778-0.982, p = 0.023; I = 0.0%, degrees of freedom = 3, p = 0.579). Our study demonstrated that bisphosphonates do not significantly improve long-term OS in patients with prostate cancer. However, adjuvant bisphosphonate therapy significantly improves OS in the subgroup of patients with CSPC + M1.
辅助用双膦酸盐治疗前列腺癌可有效提高骨密度，从而减少骨折和骨骼相关事件。我们分析了双膦酸盐对前列腺癌患者亚组的总生存（OS）的影响。系统地检索了 PubMed 数据库和相关研究的参考文献。从每个合格试验中提取长期 OS 率。使用固定效应模型汇总风险比（HR），并进行了预先计划的亚组分析。检索结果得到 112 篇文章，其中 10 篇文章的 13 个患者亚组符合入选标准。对所有 13 个亚组的荟萃分析显示，与对照组相比，辅助双膦酸盐治疗并未显著改善 OS（HR=0.961，95%CI 0.899-1.026，p=0.233），异质性低（I=13.47%，自由度=12，p=0.336）。在主要亚组分析中，添加双膦酸盐并未显著改善 OS（M1 期转移性与非转移性，氯膦酸与唑来膦酸，去势敏感前列腺癌[CSPC]与去势抵抗性前列腺癌）。当亚组进一步细分时，辅助用双膦酸盐治疗显著改善了 CSPC+M1 患者的 OS（HR=0.874，95%CI 0.778-0.982，p=0.023；I=0.0%，自由度=3，p=0.579）。我们的研究表明，双膦酸盐不能显著改善前列腺癌患者的长期 OS。然而，辅助用双膦酸盐治疗显著改善了 CSPC+M1 亚组患者的 OS。
