基于医院数据库的研究：新型系统疗法对转移性去势抵抗性前列腺癌患者总生存期的影响。
Impact of new systemic therapies on overall survival of patients with metastatic castration-resistant prostate cancer in a hospital-based registry.
机构信息
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Sapienza Università di Roma, Rome, Italy.
出版信息
Prostate Cancer Prostatic Dis. 2019 Sep;22(3):420-427. doi: 10.1038/s41391-018-0121-2. Epub 2019 Jan 14.
BACKGROUND
In 2004, docetaxel was shown to prolong the overall survival (OS) of patients with metastatic castration-resistance prostate cancer (mCRPC). Since 2010, five new systemic therapies have been shown to prolong OS in men with mCRPC. We sought to evaluate the aggregate impact of these newer therapies on the OS of patients with mCRPC.
METHODS
Two cohorts of patients diagnosed with mCRPC between 2004 and 2007, treated with drugs used in the limited treatment era only (A), and between 2010 and 2013, treated also with newer therapies (B), were identified from the Dana-Farber Cancer Institute database. The analysis endpoint was OS within 5 years after mCRPC diagnosis. Kaplan-Meier method assessed time-to-event distributions with median (95% confidence interval (CI)). A piece-wise regression model assessed the association between endpoint and treatment cohorts with estimate of hazard ratio (HR) with 95% CI within two time segments in univariate and multivariable analyses adjusting for relevant covariates.
RESULTS
Compared to cohort A (n = 318), cohort B (n = 272) patients in newer therapy era demonstrated an OS advantage (2.8 vs. 2.2 years) with a 41% decreased risk of death (HR = 0.59; 95% CI, 0.47-0.74; P < 0.0001), and a 3-year OS rate of 46% vs. 33%. This benefit was accentuated (median OS 2.7 vs. 2.1 years; HR = 0.46; 95% CI, 0.32-0.67; P < 0.0001) in patients who initially presented with de-novo metastatic disease (de-novo). On multivariable analysis, longer OS was associated with cohort B vs. A and performance status 0 vs. 1.
CONCLUSIONS
Using a single-institution registry, mCRPC patients treated since 2010 had a significant survival improvement vs. those treated before 2010. Although the median survival was only modestly improved and less than predicted when simply adding each newer drug survival advantage, the cumulative benefit from the new therapies was more pronounced in longer-term survivors and de-novo patients.
背景
2004 年，多西他赛被证明可延长转移性去势抵抗性前列腺癌（mCRPC）患者的总生存期（OS）。自 2010 年以来，已有五种新的系统疗法被证明可延长 mCRPC 男性的 OS。我们试图评估这些新疗法对 mCRPC 患者 OS 的综合影响。
方法
从 Dana-Farber 癌症研究所数据库中确定了 2004 年至 2007 年期间仅接受有限治疗时代药物治疗的 mCRPC 患者（A 队列）和 2010 年至 2013 年期间也接受新疗法治疗的患者（B 队列）。分析终点为 mCRPC 诊断后 5 年内的 OS。Kaplan-Meier 法评估生存时间的分布，用中位数（95%置信区间（CI））表示。分段回归模型在单变量和多变量分析中评估终点与治疗队列之间的关系，并估计危险比（HR）及其 95%CI，调整了相关协变量。
结果
与 A 队列（n=318）相比，B 队列（n=272）新治疗时代的患者 OS 有优势（2.8 年比 2.2 年），死亡风险降低 41%（HR=0.59；95%CI，0.47-0.74；P<0.0001），3 年 OS 率为 46%比 33%。在初诊为新发转移性疾病（新发）的患者中，这种获益更为显著（中位 OS 2.7 年比 2.1 年；HR=0.46；95%CI，0.32-0.67；P<0.0001）。多变量分析显示，与 A 队列相比，B 队列、ECOG 表现状态 0 比 1 与更长的 OS 相关。
结论
使用单机构注册处，自 2010 年以来接受治疗的 mCRPC 患者的生存状况较 2010 年前接受治疗的患者有显著改善。虽然中位生存时间仅略有改善，且低于简单相加每种新药的生存优势时的预期，但新疗法的累积获益在长期生存者和新发患者中更为明显。
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