Ultra-hypofractionated versus conventionally fractionated radiotherapy for localised prostate cancer (HYPO-RT-PC): 10-year outcomes of an open-label, randomised, phase 3, non-inferiority trial.

This 10-year update reports long-term efficacy and toxicity outcomes.

这项 10 年的更新报告了长期疗效和毒性结果。

Methods

In this open-label, randomised, phase 3, non-inferiority trial done in ten centres in Sweden and two in Denmark, we recruited men aged 75 years or younger with intermediate-risk or high-risk prostate cancer and a WHO performance status between 0 and 2.

在这项开放标签、随机、第三阶段、非劣效试验中，我们在瑞典的十个中心和丹麦的两个中心招募了75岁或以下的中危或高危前列腺癌患者，以及WHO表现状态在0到2之间的男性。

Previous or current androgen deprivation therapy was not permitted.

不允许有先前或当前的雄激素剥夺治疗。

Patients were randomly assigned (1:1) to ultra-hypofractionated radiotherapy (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventionally fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks).

患者被随机分配（1:1）接受超低分割放射治疗（42.7 Gy，分7次，每周3天，持续2.5周）或常规分割放射治疗（78.0 Gy，分39次，每周5天，持续8周）。

Randomisation was performed with a minimisation algorithm balancing T stage, Gleason score, prostate-specific antigen, and trial centre.

随机化是通过最小化算法进行的，平衡了T分期、Gleason评分、前列腺特异性抗原和试验中心。

The primary endpoint was failure-free survival, defined as time from randomisation to the first occurrence of biochemical failure, evidence of clinical progression, initiation of androgen deprivation therapy, or death from prostate cancer, analysed in the per-protocol population.

主要终点是无失败生存期，定义为从随机分组到首次出现生化失败、临床进展证据、开始雄激素剥夺治疗或因前列腺癌死亡的时间，在按方案人群进行分析。

The non-inferiority margin was 4% at 5 years and had previously been met, corresponding to a critical hazard ratio(HR) limit of 1·338.

非劣效性边界在5年时为4%，之前已经满足，对应的关键风险比（HR）极限为1.338。

Toxicity was assessed using the Radiation Therapy Oncology Group morbidity scale.

毒性评估采用放射治疗肿瘤学组的发病率量表。

Here, we report long-term efficacy and safety results at 10 years.

在这里，我们报告了10年长期疗效和安全性结果。

The trial is registered with the ISRCTN registry, ISRCTN45905321, and is closed.

该试验已在ISRCTN注册，注册号为ISRCTN45905321，目前试验已结束。

Results

Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionated radiotherapy (n=602) or ultra-hypofractionated radiotherapy (n=598).

从2005年7月1日到2015年11月4日，共有1200名患者被随机分配接受常规分割放疗（n=602）或超低分割放疗（n=598）。

Ten patients withdrew consent, eight were found to be ineligible, and two died of reasons unrelated to prostate cancer. 1180 patients constituted the per-protocol population (591 in the conventional fractionation group and 589 in the ultra-hypofractionation group).

有十名患者撤回了同意，八名患者被发现不符合资格，还有两名患者因与前列腺癌无关的原因死亡。共有1180名患者构成了符合方案的人群（常规分割组591人，超低分割组589人）。

After a median follow-up of 10·6 years (IQR 9·0-13·0) in the conventional fractionation group and 10·7 years (9·1-12·7) in the ultra-hypofractionation group, 205 and 178 primary events were observed, respectively. 10-year failure-free survival was 65% (95% CI 61-69) in the conventionally fractionated group and 72% (68-76) in the ultra-hypofractionated group.

在常规分割组中位随访时间为10.6年（四分位数间距9.0-13.0年），超低分割组为10.7年（四分位数间距9.1-12.7年），分别观察到205例和178例主要事件。常规分割组的10年无失败生存率为65%（95%置信区间61-69%），超低分割组为72%（95%置信区间68-76%）。

The adjusted HR for the primary endpoint was 0·84 (95% CI 0·69-1·03; Cox regression analysis), confirming non-inferiority.

主要终点的调整后风险比为0.84（95%置信区间0.69-1.03；Cox回归分析），确认了非劣效性。

The 10-year cumulative incidenceof late grade 2 or worse genitourinary toxic effects was 30% (95% CI 26-34) in the conventional fractionation group and 28% (24-32) in the ultra-hypofractionated group (HR 1·01, 95% CI 0·81-1·25; p=0·95).

晚期2级或更严重的泌尿生殖系统毒性效应的10年累积发生率为：常规分割组为30%（95%置信区间26-34），超低分割组为28%（95%置信区间24-32）（风险比1.01，95%置信区间0.81-1.25；p=0.95）。

For late grade 2 or worse gastrointestinal toxic effects, the corresponding figures were 14% (95% CI 11-18) and 14% (11-17; HR 0·94, 95% CI 0·70-1·28; p=0·72).

对于晚期2级或更严重的胃肠道毒性效应，相应的数据为14%（95%置信区间11-18）和14%（11-17；风险比0·94，95%置信区间0·70-1·28；p=0·72）。

interpretation

This 10-year follow-up confirms the non-inferiority of the ultra-hypofractionated radiotherapy regimen compared with the conventionally fractionated, with similar toxicity profiles.

这项10年的随访证实了超低分割放射治疗方案与常规分割方案相比的非劣效性，具有相似的毒性特征。

The findings support the seven-fraction schedule as a safe, effective, and practical standard-of-care option for patients with intermediate-risk prostate cancer.

研究结果支持将七次分割方案作为中危前列腺癌患者的治疗标准，认为其安全、有效且实用。

funding

The Nordic Cancer Union, the Swedish Cancer Society, the Swedish Research Council, the Swedish Prostate Cancer Association, and Cancerforskningsfonden i Norrland.

北欧癌症联盟、瑞典癌症协会、瑞典研究理事会、瑞典前列腺癌协会以及诺尔兰癌症研究基金会。