Intensity-modulated moderately hypofractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-C): early toxicity results from a randomised, open-label, phase 3, non-inferiority trial.

Stereotactic body radiotherapy (SBRT) is also effective, and has been shown to be non-inferior to MHRT in a lower-risk group of patients who did not require hormone therapy (PACE-B), but randomised data on toxicity for higher-risk patients are lacking.

立体定向体放射治疗（SBRT）同样有效，并且在不需要激素治疗的低风险患者群体中（PACE-B），已被证明与MHRT相当，但对于高风险患者，关于毒性的随机数据尚缺乏。

We aimed to compare the early toxicity of MHRT and SBRT.

我们旨在比较多靶点放射治疗(MHRT)和立体定向放射治疗(SBRT)的早期毒性。

Methods

The randomised, open-label, phase 3, non-inferiority PACE-C trial, conducted at 53 hospitals across the UK, Republic of Ireland, and New Zealand, recruited men aged at least 18 years with intermediate-risk or high-risk histologically confirmed prostate adenocarcinoma (T1-T3a, Gleason 7-8, and prostate specific antigen 10-30 ng/mL) and with WHO performance status of 0-2.

在英国、爱尔兰共和国和新西兰的53家医院进行的随机、开放标签、第三阶段、非劣效性PACE-C试验，招募了至少18岁的男性患者，这些患者具有中危或高危的组织学证实的前列腺腺癌（T1-T3a，Gleason 7-8，前列腺特异性抗原10-30 ng/mL）以及WHO表现状态为0-2。

Participants were centrally randomly assigned (1:1; non-masked; permuted block size of four and six; stratified by centre and risk group) to MHRT (60 Gy; 20 daily fractions over 4 weeks) or SBRT (36·25 Gy; five daily or alternate day fractions; over 1-2 weeks) with an additional mandatory clinical target volume dose target of 40 Gy (no margin) to the prostate, and proximal 1 cm of seminal vesicles. 6 months of androgen deprivation therapy was planned and was started before commencement of radiotherapy.

参与者通过中央随机分配（1:1；非盲法；排列块大小为四和六；按中心和风险组分层）接受多野适形放疗（MHRT）（60 Gy；20次日常分割，持续4周）或立体定向放疗（SBRT）（36.25 Gy；每日或隔日分割，持续1-2周），并附加对前列腺及近端1厘米精囊的强制性临床靶体积剂量目标为40 Gy（无边界）。计划进行6个月的雄激素剥夺治疗，并在放疗开始前开始。

The primary outcome of PACE-C is freedom from biochemical or clinical failure, the data for which are not yet mature.

PACE-C的主要结果是无生化或临床失败的自由，其数据尚未成熟。

The co-primary endpoints for this preplanned safety analysis were the percentages of Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicities at any point during or within 12 weeks of completion of radiotherapy (the early or acute period).

本次预先计划的安全性分析的主要终点是，在放疗期间或放疗完成后的12周内（早期或急性期），出现美国放射肿瘤治疗协作组（RTOG）2级或更严重的胃肠道和泌尿生殖系统毒性反应的百分比。

Analyses are by treatment received, with participants included if they had one or more fractions of MHRT or SBRT, regardless of their allocated treatment.

分析是根据接受的治疗进行的，包括那些接受了一次或多次中等剂量放射治疗（MHRT）或立体定向放射治疗（SBRT）的参与者，无论他们被分配的治疗如何。

Late toxicity and efficacy data are awaited as the trial remains in follow-up.

随着试验仍在随访中，我们期待着晚期毒性和疗效数据。

The study was prospectively registered with ClinicalTrials.gov, NCT01584258.

该研究已前瞻性地在ClinicalTrials.gov上注册，注册号为NCT01584258。

Results

Between Nov 13, 2019, and June 24, 2022, 1208 participants were randomly assigned (601 to MHRT and 607 to SBRT). 608 patients received MHRT and 584 received SBRT, and thus were included in the study analysis. 1136 (95%) of 1192 patients were White, 20 (2%) were Black or Black British, 17 (1%) were Asian or Asian British, and seven (1%) were Chinese or other.

在2019年11月13日至2022年6月24日期间，共有1208名参与者被随机分配（601名接受MHRT，607名接受SBRT）。608名患者接受了MHRT治疗，584名患者接受了SBRT治疗，因此被纳入研究分析。在1192名患者中，有1136名（95%）为白人，20名（2%）为黑人或英国黑人，17名（1%）为亚洲人或英国亚洲人，7名（1%）为中国人或其他人。

During the early period (within 12 weeks of treatment), the co-primary endpoint of RTOG grade 2 or worse genitourinary toxicity was observed in 166 (27%) of 608 patients (95% CI 23·8 to 31·1) receiving MHRT and 162 (28%) of 582 patients (24·3 to 31·7) after SBRT (absolute difference 0·5%, 95% CI -4·7 to 5·7; p=0·89).

在治疗早期（治疗后的12周内），在608名接受MHRT治疗的患者中，有166名（27%）出现了RTOG 2级或更严重的泌尿生殖系统毒性（95%置信区间23.8至31.1），而在582名接受SBRT治疗的患者中，有162名（28%）出现了相同程度的毒性（95%置信区间24.3至31.7）（绝对差异0.5%，95%置信区间-4.7至5.7；p=0.89）。

For grade 2 or worse genitourinary Common Terminology Criteria for Adverse Events (CTCAE), 170 (28%) of 604 patients had events after MHRT and 195 (34%) of 581 patients had events after SBRT (p=0·050).

在2级或更严重的泌尿生殖系统不良事件通用术语标准（CTCAE）中，604名患者中有170名（28%）在接受调强放疗（MHRT）后出现事件，而在581名患者中有195名（34%）在接受立体定向放疗（SBRT）后出现事件（p=0·050）。

Grade 3 CTCAE genitourinary toxicity was observed in three (<1%) patients receiving MHRT and three (1%) patients receiving SBRT.

在接受调强放疗（MHRT）的患者中观察到3例（<1%）3级CTCAE泌尿生殖系统毒性，在接受立体定向放疗（SBRT）的患者中观察到3例（1%）3级CTCAE泌尿生殖系统毒性。

For grade 2 or worse gastrointestinal CTCAE, 60 (10%) of 604 patients had an event after MHRT and 96 (17%) of 581 patients had an event after SBRT (p=0·0011).

对于2级或更严重的胃肠道CTCAE，604名患者中有60名（10%）在接受MHRT后发生事件，而581名患者中有96名（17%）在接受SBRT后发生事件（p=0·0011）。

Grade 3 CTCAE gastrointestinal toxicity was observed in three (<1%) patients receiving MHRT and four (1%) patients receiving SBRT.

在接受MHRT的患者中，有三名（<1%）观察到3级CTCAE胃肠道毒性，在接受SBRT的患者中，有四名（1%）观察到3级CTCAE胃肠道毒性。

During the early period, the co-primary endpoint of RTOG grade 2 or worse gastrointestinal toxicity was observed in 69 (11%) of 608 patients (95% CI 9·0 to 14·2) receiving MHRT and 74 (13%) of 584 patients (10·2 to 15·8) receiving SBRT (absolute difference 1·4%, 95% CI -2·5 to 5·2; p=0·53).

在早期阶段，接受多靶区放疗（MHRT）的608名患者中有69名（11%）观察到RTOG 2级或更严重的胃肠道毒性（95%置信区间9.0至14.2），而接受立体定向放疗（SBRT）的584名患者中有74名（13%）出现此毒性（95%置信区间10.2至15.8）（绝对差异1.4%，95%置信区间-2.5至5.2；p=0.53）。

There were no treatment-related deaths.

没有与治疗相关的死亡事件。

interpretation

Despite an accelerated treatment schedule and a larger treated volume than PACE-B, SBRT and MHRT had similar rates of early RTOG toxicity.

尽管SBRT和MHRT的治疗计划比PACE-B更为加速，且治疗体积更大，但它们的早期RTOG毒性发生率相似。

funding

The Royal Marsden Cancer Charity.

皇家马斯登癌症慈善机构。