Division of Medical Oncology, Department of Medicine, DUMC, Duke Comprehensive Cancer Center and the Duke Prostate Center, Durham, NC 27715, USA.
Eur J Cancer. 2010 Feb;46(3):517-25. doi: 10.1016/j.ejca.2009.11.007. Epub 2009 Dec 11.
There are no known predictive factors of response in men receiving chemotherapy for metastatic castration-resistant prostate cancer (mCRPC). We investigated pre-treatment factors that predicted a 30% PSA decline (30% PSAD) within 3 months of starting chemotherapy, and assessed performance of a risk group classification in predicting PSA declines and overall survival (OS) in men with mCRPC.
In TAX327, 1006 men with mCRPC were randomized to receive docetaxel (D) in two schedules, or mitoxantrone (M), each with prednisone: 989 provided data on PSA decline within 3 months. Predictive factors for a 30% PSAD were identified using multivariable regression in D-treated men (n=656) and validated in M-treated men (n=333).
Four independent risk factors predicted 30% PSAD: pain, visceral metastases, anaemia and bone scan progression. Risk groups (good: 0-1 factors, intermediate: 2 factors and poor: 3-4 factors) were developed with median OS of 25.7, 18.7 and 12.8 months (p<0.0001); 30% PSAD in 78%, 66% and 58% of men (p<0.001); and measurable disease response in 19%, 9% and 5% of men (p=0.018), respectively. In the validation cohort, similar predictive ability was noted for 30% PSAD, tumour response and OS. PCWG2 subtypes were also predictive but resulted in unequal grouping. C-indices were 0.59 and 0.62 for 30% PSAD and OS in the validation dataset, respectively.
Risk groups have been identified and validated that predict PSAD and OS in men with mCRPC and may facilitate evaluation of new systemic regimens warranting definitive testing in comparison with docetaxel and prednisone. Prospective validation of this classification system is needed.
接受化疗治疗转移性去势抵抗性前列腺癌（mCRPC）的男性中，目前尚无已知的反应预测因素。我们研究了治疗前的因素，这些因素可以预测在开始化疗后 3 个月内 PSA 下降 30%（30% PSAD），并评估了风险组分类在预测 mCRPC 男性的 PSA 下降和总生存期（OS）方面的表现。
在 TAX327 中，1006 名 mCRPC 男性被随机分配接受多西他赛（D）两种方案或米托蒽醌（M）加泼尼松治疗：989 名男性提供了 3 个月内 PSA 下降的数据。在 D 治疗的男性（n=656）中使用多变量回归确定了 30% PSAD 的预测因素，并在 M 治疗的男性（n=333）中进行了验证。
四个独立的危险因素预测了 30% PSAD：疼痛、内脏转移、贫血和骨扫描进展。根据有无 0-1、2、3-4 个危险因素将患者分为风险组（好：0-1 个因素；中：2 个因素；差：3-4 个因素），中位 OS 分别为 25.7、18.7 和 12.8 个月（p<0.0001）；30% PSAD 的患者比例分别为 78%、66%和 58%（p<0.001）；可测量疾病反应的患者比例分别为 19%、9%和 5%（p=0.018）。在验证队列中，30% PSAD、肿瘤反应和 OS 也有类似的预测能力。PCWG2 亚型也具有预测性，但导致分组不均等。在验证数据集，30% PSAD 和 OS 的 C-指数分别为 0.59 和 0.62。
已经确定并验证了风险组，这些风险组可以预测 mCRPC 男性的 PSA 下降和 OS，可能有助于评估新的系统治疗方案，与多西他赛和泼尼松相比，这些方案需要进行明确的测试。需要对该分类系统进行前瞻性验证。
