BACKGROUND There is a discussion about the optimal timing to initiate or switch treatment in metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis of 3 large trials for men with mCRPC examined the influence of the type of progression at initiation of first-line chemotherapy, as well as the type of progression during treatment, on treatment outcomes. METHODS Data from the phase III studies VENICE (n = 1224), TAX327 (n = 1006) and FIRSTANA (n = 1168) were used as independent data sets. Type of progression was defined as follows: prostate-specific antigen (PSA) only (group 1), radiological (±PSA) (group 2) or pain (±PSA, ± radiological) progression (group 3). The impact of baseline type of progression on overall survival (OS) was evaluated in multivariate Cox regression analysis with backward elimination, stratified for the Eastern Cooperative Oncology Group performance score and treatment arm. RESULTS The median OS (arms combined) from treatment initiation in VENICE was 28.6, 26.3 and 16.9 months for G1, G2 and G3, respectively (hazard ratio: 1.14 [95% confidence interval {CI}: 0.92-1.41%] in G2 and 2.13 [95% CI: 1.75-2.59%] in G3 compared with G1). Multivariate analysis (arms combined) showed that pain progression at baseline was an independent predictor of poor OS. Similar findings were observed in the TAX327 and FIRSTANA data sets. During treatment, pain or radiological progression preceded PSA progression in ~55% of the patients. The retrospective characteristic of this study is a limitation. CONCLUSIONS The type of progression at baseline strongly predicts OS in men with mCRPC treated with first-line chemotherapy. During treatment, pain and/or radiological progression preceded PSA progression as the first progression event in ~55% of the patients. This finding has the prospect to be incorporated in clinical guidelines and to be practice changing because it implies the need for regular imaging and not to rely on PSA progression alone.

中文翻译：

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在三项大型前列腺癌试验中，基线进展和治疗进展事件的影响。

背景技术存在关于在转移性去势抵抗性前列腺癌（mCRPC）中开始或转换治疗的最佳时机的讨论。这项针对3项针对mCRPC的男性的大型试验的事后分析分析了一线化疗开始时的进展类型以及治疗过程中进展类型对治疗结果的影响。方法Ⅲ期研究威尼斯（n = 1224），TAX327（n = 1006）和FIRSTANA（n = 1168）的数据被用作独立的数据集。进展的类型定义如下：仅前列腺特异性抗原（PSA）（第1组），放射学（±PSA）（第2组）或疼痛（±PSA，±放射学）进展（第3组）。在多变量Cox回归分析中，采用向后消除方法，评估了基线进展类型对整体生存（OS）的影响，分为东部合作肿瘤小组的绩效评分和治疗组。结果VENICE中，G1，G2和G3的治疗开始后OS的中位数分别为28.6、26.3和16.9个月（G2和G3的危险比：1.14 [95％置信区间{CI}：0.92-1.41％]）与G1相比，G3为2.13 [95％CI：1.75-2.59％]。多变量分析（两臂合用）显示，基线时疼痛的进展是不良OS的独立预测因素。在TAX327和FIRSTANA数据集中也观察到了类似的发现。在治疗期间，约55％的患者疼痛或放射学进展先于PSA进展。这项研究的回顾性特征是一个局限性。结论基线进展类型强烈预测一线化疗治疗的mCRPC男性的OS。治疗期间 在约55％的患者中，疼痛和/或放射学进展先于PSA进展，是第一个进展事件。这一发现有望被纳入临床指南，并有望改变实践，因为这意味着需要定期成像，而不是仅仅依靠PSA进展。