Metastases-directed therapy in addition to standard systemic therapy in oligometastatic castration-resistant prostate cancer in Canada (GROUQ-PCS 9): a multicentre, open-label, randomised, phase 2 trial.

Prostate Cancer Study 9 (PCS-9) aimed to evaluate the benefits of stereotactic body radiotherapy (SBRT) in addition to standard systemic therapy in patients with oligometastatic CRPC.

前列腺癌研究9号（PCS-9）旨在评估在标准全身治疗基础上，对寡转移性去势抵抗性前列腺癌患者进行立体定向体部放射治疗（SBRT）的益处。

Methods

This open-label, randomised, phase 2 trial was conducted across 13 Canadian academic and community oncology centres.

这项开放标签、随机的2期临床试验在加拿大13个学术和社区肿瘤中心进行。

Male patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-2, and histologically confirmed oligometastatic CRPC (≤5 metastases), who had progressed on androgen deprivation therapy (ADT), were randomly assigned (1:1) to ADT-enzalutamide (ENZA; 160 mg once daily) or ADT-ENZA-SBRT to all oligometastatic sites.

年龄在18岁或以上的男性患者，东部肿瘤协作组表现状态为0-2，且经组织学证实为寡转移性去势抵抗性前列腺癌（≤5个转移灶），在雄激素剥夺治疗（ADT）进展后，被随机分配（1:1）接受ADT-恩杂鲁胺（ENZA；每日一次160毫克）或ADT-ENZA-立体定向放射治疗（SBRT）至所有寡转移灶。

Randomisation was completed by sequentially numbered, sealed opaque envelopes, and stratified by the location of the metastasis.

随机分组是通过顺序编号的密封不透明信封完成的，并根据转移部位进行分层。

The primary endpoint was radiographic progression-free survival. Analysis was performed on an intention-to-treatbasis.

主要终点是影像学无进展生存期。分析是基于意向治疗原则进行的。

This study is registered with ClinicalTrials.gov, NCT02685397, and was halted and completed at the phase 2 stage.

该研究已在ClinicalTrials.gov上注册，编号为NCT02685397，并在第二阶段被暂停并完成。

Results

Between Oct 18, 2016, and July 31, 2023, 102 male patients were randomly assigned to ADT-ENZA (n=49) or ADT-ENZA-SBRT (n=53); after excluding one patient per treatment group due to early withdrawal and insufficient data, 48 patients in the ADT-ENZA group and 52 patients in the ADT-ENZA-SBRT group were included in the final analysis.

在2016年10月18日至2023年7月31日期间，102名男性患者被随机分配到ADT-ENZA组（n=49）或ADT-ENZA-SBRT组（n=53）；由于早期退出和数据不足，每组排除了一名患者后，最终分析包括ADT-ENZA组的48名患者和ADT-ENZA-SBRT组的52名患者。

Most patients were White (80 [80%]) and median age was 73·0 years (IQR 67·0-79·5).

大多数患者为白人（80 [80%]），中位年龄为73.0岁（四分位数间距67.0-79.5岁）。

At a median follow-up of 4·8 years (IQR 3·4-5·0), ADT-ENZA-SBRT significantly improved radiographic progression-free survivalcompared with ADT-ENZA alone (median radiographic progression-free survival, 4·6 years [95% CI 3·7-not reached] vs 2·3 years [1·4-3·7]; hazard ratio0·48 [95% CI 0·27-0·86]; p=0·014).

在中位随访4.8年（四分位数间距3.4-5.0年）时，ADT-ENZA-SBRT与单独ADT-ENZA相比显著改善了影像学无进展生存期（中位影像学无进展生存期，4.6年[95%置信区间3.7-未达到]对比2.3年[1.4-3.7年]；风险比0.48[95%置信区间0.27-0.86]；p=0.014）。

The most common grade 3 treatment related adverse eventwas impotence (eight [57%] of 14 patients in the ADT-ENZA group and nine [75%] of 12 patients in the ADT-ENZA-SBRT group).

最常见的3级治疗相关不良事件是阳痿（ADT-ENZA组14名患者中有8名[57%]，ADT-ENZA-SBRT组12名患者中有9名[75%]）

There were no grade 4 toxicities and no treatment-related deaths.

没有4级毒性反应，也没有治疗相关死亡事件。

interpretation

These results demonstrate that SBRT, when combined with ADT-ENZA, prolongs disease control in oligometastatic CRPC by doubling median radiographic progression-free survival, with similar toxicity profiles between the groups.

这些结果表明，当与ADT-ENZA联合使用时，SBRT通过将中位影像学无进展生存期翻倍，延长了寡转移性去势抵抗性前列腺癌（CRPC）的疾病控制，两组之间的毒性特征相似。

These findings support integrating SBRT into the treatment paradigm for oligometastatic CRPC.

这些发现支持将SBRT纳入寡转移性CRPC的治疗范式中。

funding

Jewish General Hospital (Astellas Canada).

犹太总医院（加拿大阿斯利康）