Salvage metastasis-directed therapy versus elective nodal radiotherapy for oligorecurrent nodal prostate cancer metastases (PEACE V-STORM): a phase 2, open-label, randomised controlled trial.

We aimed to assess whether elective nodal radiotherapy (ENRT) to the pelvis would be superior to metastasis-directed therapy (MDT).

我们旨在评估对盆腔进行选择性淋巴结放疗（ENRT）是否优于转移灶导向治疗（MDT）。

Methods

PEACE V-STORM is a phase 2, open-label, randomised, controlled trial conducted in 21 hospitals in Australia, Belgium, Italy, Norway, Spain, and Switzerland.

PEACE V-STORM 是一项在澳大利亚、比利时、意大利、挪威、西班牙和瑞士的 21 家医院进行的 2 期、开放标签、随机对照试验。

Eligible participants were aged 18 years or older, with WHO performance status 0-1 and a histologically confirmed initial diagnosis of adenocarcinoma of the prostate, with a PET-detected pelvic nodal oligorecurrence (up to five nodes) following radical local treatment.

符合条件的参与者年龄在 18 岁或以上，WHO 表现状态为 0-1，且经组织学证实为前列腺腺癌的初始诊断，且在根治性局部治疗后通过 PET 检测到盆腔淋巴结寡复发（最多五个淋巴结）。

Patients were randomly assigned (1:1) to MDT or ENRT.

患者被随机分配（1:1）到多学科治疗（MDT）组或早期新辅助放射治疗（ENRT）组。

Randomisation was done online by minimisation with randomisation factor 0·80 and was stratified by type of PET tracer (choline vs prostate-specific membrane antigen) and type of MDT used (salvage lymph node dissection vs stereotactic body radiotherapy or simultaneous integrated boost).

随机化是通过在线最小化进行的，随机化因子为0.80，并根据PET示踪剂类型（胆碱与前列腺特异性膜抗原）和使用的MDT类型（挽救性淋巴结切除术与立体定向体放射治疗或同时集成增强）进行分层。

Participants and researchers were not masked to treatment assignment.

参与者和研究人员未对治疗分配进行盲法处理。

Patients in the MDT group had salvage lymph node dissection or stereotactic body radiotherapy (30 Gy in three fractions every other day), with 6 months of androgen deprivation therapy.

多学科治疗(MDT)组的患者接受了挽救性淋巴结清扫术或立体定向体部放疗（每次30 Gy，隔日一次，共三次），并接受了6个月的雄激素剥夺治疗。

Patients in the ENRT group received a 45 Gy dose in 25 fractions to the pelvis with a simultaneous integrated boost of 65 Gy to the PET-positive nodes or salvage lymph node dissection, with 6 months of androgen deprivation therapy.

ENRT组患者接受了25次分割的45 Gy剂量照射到骨盆，并对PET阳性的淋巴结或挽救性淋巴结切除术进行了65 Gy的同时整合性增强照射，同时进行了6个月的雄激素剥夺治疗。

The primary endpoint was metastasis-free survival, defined as the time between randomisation and the appearance of a metastatic recurrence (any M1) on PET imaging or death due to any cause, and was analysed per modified intention to treat.

主要终点是无转移生存期，定义为从随机分组到PET成像上出现任何M1的转移复发或因任何原因导致的死亡之间的时间，并按照修改后的意向治疗分析。

This study is registered with ClinicalTrials.gov, NCT03569241, and the Swiss National Clinical Trials Portal, SNCTP000002947, and is active, not recruiting.

该研究已在ClinicalTrials.gov上注册，编号为NCT03569241，并在瑞士国家临床试验门户网站SNCTP000002947上注册，目前正在进行中，但不再招募新参与者。

Results

Between June 11, 2018, and April 30, 2021, 198 patients were screened for eligibility, 196 of whom were randomly assigned to MDT (n=99) or ENRT (n=97), with 190 evaluable patients (MDT n=97 and ENRT n=93).

在2018年6月11日至2021年4月30日期间，共有198名患者进行了资格筛查，其中196名患者被随机分配到MDT组（n=99）或ENRT组（n=97），最终有190名可评估患者（MDT组n=97，ENRT组n=93）。

All patients were male.

所有患者均为男性。

Data on race and ethnicity were not collected.

未收集关于种族和民族的数据。

Median follow-up was 50 months (IQR 42-58). 4-year metastasis-free survival was 63% (80% CI 56-69) in the MDT group and 76% (69-81) in the ENRT group (HR 0·62 [80% CI 0·44-0·86]; p=0·063).

中位随访时间为50个月（四分位数间距42-58）。MDT组的4年无转移生存率为63%（80%置信区间56-69），而ENRT组为76%（69-81）（风险比0·62 [80%置信区间0·44-0·86]；p=0·063）。

The most common grade 3 adverse events were urinary incontinence (six [6%] of 97 in the MDT group vs nine [10%] in the ENRT group) and diarrhoea (one [1%] in the MDT group vs two [2%] in the ENRT group).

最常见的3级不良事件是尿失禁（MDT组97人中有6人[6%]，ENRT组有9人[10%]）和腹泻（MDT组1人[1%]，ENRT组2人[2%]）。

No treatment-related deaths occurred.

未发生与治疗相关的死亡事件。

interpretation

To our knowledge, this is the first randomised trial for metachronous PET-detected nodal recurrences comparing two local treatment approaches (MDT and ENRT) in combination with 6 months of androgen deprivation therapy.

据我们所知，这是首个针对 PET 检测到的异时性淋巴结复发的随机试验，比较了两种局部治疗方法（MDT 和 ENRT）结合 6 个月雄激素剥夺治疗的效果。

By showing an improved metastasis-free survival with ENRT, this trial establishes ENRT as a potential standard treatment approach, awaiting a phase 3 trial confirming these results.

通过展示ENRT改善了无转移生存期，本试验确立了ENRT作为一种潜在的标准治疗方式，等待第三阶段试验确认这些结果。

funding

Movember Foundation, Kom Op Tegen Kanker, Stichting tegen Kanker.

Movember基金会，Kom Op Tegen Kanker，Stichting tegen Kanker。