On-treatment serum prostate-specific antigen and overall survival in prostate cancer (STAMPEDE platform protocol): a post-hoc analysis of data from five phase 3 trials.

To support clinical use, we evaluated the association between PSA nadir values and survival outcomes, stratified by pre-treatment metastatic volume or, in patients with non-metastatic cancer, stratified by lymph node status.

为了支持临床使用，我们评估了PSA最低值与生存结果之间的关联，根据治疗前的转移体积进行分层，或者在非转移性癌症患者中，根据淋巴结状态进行分层。

Methods

As part of the STAMPEDE platform trial, patients with metastatic or very high-risk non-metastatic prostate adenocarcinoma were recruited to five randomised, controlled, phase 3 trials conducted at 126 hospitals or oncology centres in Switzerland and the UK.

作为STAMPEDE平台试验的一部分，招募了患有转移性或极高风险的非转移性前列腺腺癌患者参与在瑞士和英国的126家医院或肿瘤中心进行的五项随机对照的III期试验。

Patients were randomly assigned to either standard of care (androgren deprivation therapy [ADT] alone or ADT plus docetaxel) or to one of five experimental treatment groups: ADT plus docetaxel with or without zoledronic acid, ADT plus abiraterone acetate with or without enzalutamide, or ADT plus prostate radiotherapy (only patients with metastatic disease).

患者被随机分配到标准治疗组（仅雄激素剥夺治疗[ADT]或ADT加多西他赛）或五个实验治疗组之一：ADT加多西他赛，有或没有唑来膦酸；ADT加醋酸阿比特龙，有或没有恩杂鲁胺；或ADT加前列腺放疗（仅限于转移性疾病的患者）。

We used trial data from these participants to perform landmark analyses to test associations of PSA at 6, 12, and 24 weeks after randomisation with overall survival. Only patients with a PSA value were included in each landmark analysis.

我们使用了这些参与者的试验数据来执行里程碑分析，以测试随机化后6周、12周和24周的前列腺特异性抗原（PSA）与总生存之间的关联。每个里程碑分析仅包括具有PSA值的患者。

The Kaplan-Meier method was used to estimate 96-month overall survivalrates and the corresponding 95% CIs for patients categorised by either metastatic volume or lymph node status.

使用Kaplan-Meier方法估计了按转移体积或淋巴结状态分类的患者96个月的总生存率及其相应的95%置信区间。

The STAMPEDE protocol platform is registered with ClinicalTrials.gov (NCT00268476), EUDRACT (2004-000193-31), and ISRCTN (ISRCTN78818544).

STAMPEDE协议平台已在ClinicalTrials.gov (NCT00268476)、EUDRACT (2004-000193-31)和ISRCTN (ISRCTN78818544)上注册。

Results

This study included 7129 patients from the STAMPEDE platform, who were recruited between Oct 5, 2005, and Sept 2, 2016; 4438 had metastases and 2691 had very high-risk non-metastatic disease.

该研究纳入了来自STAMPEDE平台的7129名患者，这些患者招募于2005年10月5日至2016年9月2日之间；其中4438名患者有转移，2691名患者有非常高的非转移性疾病的危险。

Among patients with metastasis and volumetric assessment, 2211 (55·9%) of 3956 had high-volume metastases, and among those with non-metastatic disease, 1033 (38·4%) were lymph node positive.

在具有转移和体积评估的患者中，3956名患者中有2211名（55.9%）表现为高体积转移，而在无转移疾病的患者中，1033名（38.4%）淋巴结阳性。

A PSA concentration of 0·2 ng/mL or less was less frequent at 6 weeks or 12 weeks, but was associated with equivalent survival rates, compared with a PSA of 0·2 ng/mL or less at 24 weeks.

在6周或12周时，前列腺特异性抗原（PSA）浓度为0.2 ng/mL或更低的情况较少见，但与24周时PSA浓度为0.2 ng/mL或更低的情况相比，其总生存率相当。

Survival rates of PSA subcategories (≤0·2 ng/mL, >0·2 to 1·0 ng/mL, >1·0 to 3·0 ng/mL, and >3·0 ng/mL) differed by metastatic volume or, in patients with non-metastatic disease, by nodal status.

PSA亚组（≤0·2 ng/mL，>0·2至1·0 ng/mL，>1·0至3·0 ng/mL，和>3·0 ng/mL）的生存率因转移体积不同而异，或者在无转移疾病的患者中，因淋巴结状态不同而异。

Survival was longest for patients allocated to abiraterone with or without enzalutamide.

接受阿比特龙单药或联合恩杂鲁胺治疗的患者的生存期最长。

Among patients with metastatic disease in the abiraterone with or without enzalutamide group who had a PSA of 0·2 ng/mL or less at 24 weeks, 96-month overall survivalin patients with low-volume metastatic disease (64·1% [95% CI 57·8-69·8]) was higher than in patients with high-volume metastatic disease (44·6% [37·1-51·9]), but lower than in patients with non-metastatic, node-positive disease (79·4% [73·8-83·9]). 96-month overall survivalwas highest for patients with non-metastatic, node-negative disease (82·8% [95% CI 78·7-86·1]).

在阿比特龙联合或不联合恩杂鲁胺治疗的转移性疾病患者中，24周时PSA≤0.2 ng/mL的患者，低转移性疾病体积患者的96个月总生存率为64.1%（95% CI 57.8-69.8），高于高转移性疾病体积患者的44.6%（37.1-51.9），但低于非转移性疾病、淋巴结阳性患者的79.4%（73.8-83.9）。非转移性疾病、淋巴结阴性患者的96个月总生存率最高，为82.8%（95% CI 78.7-86.1）。

interpretation

Metastatic volume or nodal status influence survival rates associated with on-treatment serum PSA categories, including for undetectable PSA.

转移性疾病体积或淋巴结状态会影响治疗期间血清PSA类别相关的生存率，包括不可检测的PSA。

Radiological features and serum PSA could be combined to better predict survival. PSA at 24 weeks showed strongest associations with overall survival, although a PSA concentration of 0·2 ng/mL or less at any timepoint predicted favourable outcome.

放射学特征和血清PSA可以结合使用以更好地预测生存。24周时的PSA显示出与总生存最强的关联，尽管在任何时间点PSA浓度为0.2 ng/mL或以下预测了有利的结果。

These findings could inform prognosis and warrant evaluation for treatment selection in clinical trials.

这些发现可以为预后提供信息，并且值得在临床试验中评估以选择治疗方案。

funding

Cancer Research UK, Prostate Cancer UK, UK Medical Research Council, and John Black Charitable Foundation.

英国癌症研究UK、前列腺癌UK、英国医学研究委员会以及约翰·布莱克慈善基金会。