Department of Medicine, Division of Medical Oncology, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, North Carolina 102002, USA.
Clin Cancer Res. 2010 Jan 1;16(1):203-11. doi: 10.1158/1078-0432.CCR-09-2514. Epub 2009 Dec 15.
We sought to evaluate predictors of overall survival following progression after systemic chemotherapy in men with metastatic castration-resistant prostate cancer.
For our study population, we used the TAX327 multicenter randomized phase III trial comparing administration of docetaxel and prednisone every 3 weeks, weekly administration of docetaxel and prednisone, and administration of mitoxantrone and prednisone every 3 weeks. Progression was defined as the earliest of prostate-specific antigen (PSA), tumor, or pain progression. We analyzed predictors of postprogression survival according to both prechemotherapy and postchemotherapy variables with adjustment for potential confounders.
Among 1,006 men, 640 had evaluable information on protocol-defined progression leading to further therapy. Median postprogression survival was 14.5 months. In the multivariable analysis, several pretreatment factors were associated with postprogression survival: pain, performance status, alkaline phosphatase, number of sites of metastatic disease, liver metastases, hemoglobin, PSA, and time since diagnosis. In addition, we found that the number of progression factors (PSA, pain, and tumor size), the duration of first-line chemotherapy, and whether progression occurred during chemotherapy independently predicted postprogression survival. We found evidence for the benefit of continuation of chemotherapy beyond progression only for men who had isolated worsening of pain. A nomogram was constructed and internally validated with a concordance index of 0.70.
An internally validated model to predict postchemotherapy survival was developed. Evaluation of men in the postdocetaxel setting should consider the type of progression, duration of therapy, and known pretreatment prognostic factors. Definitions of progression in castration-resistant prostate cancer that include pain should also consider composite measures of tumor or PSA progression. External validation is planned.
我们旨在评估转移性去势抵抗性前列腺癌（mCRPC）患者在全身化疗后进展后的总生存预测因素。
在我们的研究人群中，我们使用了 TAX327 多中心随机 III 期试验，该试验比较了每 3 周给予多西他赛和泼尼松、每周给予多西他赛和泼尼松以及每 3 周给予米托蒽醌和泼尼松的疗效。进展定义为 PSA、肿瘤或疼痛进展的最早时间。我们根据化疗前和化疗后变量分析了预后生存的预测因素，并对潜在混杂因素进行了调整。
在 1006 名男性中，640 名有可评估的协议定义进展导致进一步治疗的信息。中位预后生存时间为 14.5 个月。在多变量分析中，一些预处理因素与预后生存相关：疼痛、表现状态、碱性磷酸酶、转移性疾病部位数、肝转移、血红蛋白、PSA 和诊断后时间。此外，我们发现进展因素（PSA、疼痛和肿瘤大小）的数量、一线化疗的持续时间以及进展是否发生在化疗期间独立预测预后生存。我们仅发现对于孤立性疼痛恶化的患者，继续化疗超过进展期有获益的证据。构建了一个列线图，并通过一致性指数 0.70 进行了内部验证。
开发了一种预测化疗后生存的内部验证模型。在评估接受多西他赛后的男性时，应考虑进展类型、治疗持续时间和已知的预处理预后因素。包括疼痛的去势抵抗性前列腺癌的进展定义也应考虑肿瘤或 PSA 进展的综合指标。计划进行外部验证。
