Castration resistant prostate cancer (CRPC) is a challenging subset of prostate cancer associated with an extensive metastatic profile and high mortality. Ketoconazole is a nonselective steroid 17α-hydroxylase/17,20 lyase (CYP17A1) inhibitor and is employed as a second line treatment option for CRPC with an established efficacy profile in patients. The aim of this study is to assess the efficacy of ketoconazole containing regimens for CRPC in terms of prostate specific antigen (PSA) decline rate using a systematic review and meta-analysis. In this review, an electronic search was carried out on PubMed, Cochrane CENTRAL, Scopus, and Google Scholar to find relevant literature. Random effects model was used to assess pooled PSA decline rate and 95% CIs. Publication bias was assessed using the funnel plot symmetry and one-tailed Egger's and Begg's test. In all cases, -value <.05 was indicative of significant results. The review is registered with PROSPERO: CRD42023466536. A total of 483 articles were retrieved after database searching, out of which 23 studies (having a total of 1315 patients) were included in the review based on prespecified criteria. The PSA decline rate was reported in the 14 observational studies (having 964 patients) and 9 experimental studies (having 351 patients). Pooled results revealed that 48.6% (95% CI 43.1-54.2; -value <.001; I = 73.24%) of participants achieved more than 50% decline in PSA (602/1315 participants). Sensitivity analysis using the leave-one-out method revealed no substantial change in pooled effect estimates; (Risk Ratio) RR 47.2% to RR 49.8% demonstrating the robustness of our results. There was no evidence of publication bias as assessed from the funnel plot symmetry. Ketoconazole containing regimens have shown moderate efficacy in high risk CRPC patients as demonstrated by the pooled results. Hence, a ketoconazole based chemotherapy can be added to patients’ regimen if there is a persistent rise in PSA levels after androgen deprivation therapy.

中文翻译：

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含酮康唑疗法治疗去势抵抗性前列腺癌的疗效：系统评价和荟萃分析

去势抵抗性前列腺癌 (CRPC) 是前列腺癌的一个具有挑战性的亚型，具有广泛的转移特征和高死亡率。酮康唑是一种非选择性类固醇 17α-羟化酶/17,20 裂解酶 (CYP17A1) 抑制剂，被用作 CRPC 的二线治疗选择，在患者中具有明确的疗效。本研究的目的是通过系统评价和荟萃分析来评估含酮康唑治疗方案在前列腺特异性抗原 (PSA) 下降率方面对 CRPC 的疗效。在这篇综述中，我们在 PubMed、Cochrane CENTRAL、Scopus 和 Google Scholar 上进行了电子检索以查找相关文献。使用随机效应模型评估合并 PSA 下降率和 95% CI。使用漏斗图对称性和单尾艾格和贝格检验评估发表偏倚。在所有情况下，-值<.05 表示结果显着。该评论已在 PROSPERO 注册：CRD42023466536。数据库检索后共检索到483篇文章，其中23项研究（共1315名患者）根据预先设定的标准纳入综述。 14 项观察性研究（964 名患者）和 9 项实验性研究（351 名患者）报告了 PSA 下降率。汇总结果显示，48.6%（95% CI 43.1-54.2；-值 <.001；I = 73.24%）的参与者的 PSA 下降超过 50%（602/1315 名参与者）。使用留一法进行的敏感性分析显示，合并效应估计值没有实质性变化； （风险比）RR 47.2% 到 RR 49.8% 证明了我们结果的稳健性。从漏斗图对称性评估来看，没有证据表明发表偏倚。汇总结果表明，含酮康唑的治疗方案对高危 CRPC 患者具有中等疗效。因此，如果雄激素剥夺治疗后 PSA 水平持续升高，可以在患者的治疗方案中添加基于酮康唑的化疗。