Cryobiopsy versus conventional bronchoscopic sampling for peripheral pulmonary lesions (Cryo-RCT): an open-label, parallel-group, randomised trial.

Methods

This international, open-label, randomised trial was done across six centres in Japan, Malaysia, South Korea, and Taiwan.

这项国际、开放标签、随机试验在日本、马来西亚、韩国和台湾的六个中心进行。

Patients aged 18 years or older with peripheral pulmonary lesions up to and including 30 mm visualised using radial endobronchial ultrasound were included.

年龄在18岁或以上的患者，使用径向支气管内超声可见的周围性肺病变，最大直径不超过30毫米，被纳入研究。

Patients with within (ie, concentric) findings or adjacent-to or eccentric findings were randomly assigned (1:1) to stand-alone cryobiopsy or conventional sampling.

具有内（即同心）发现或邻近或偏心发现的患者被随机分配（1:1）到独立冷冻活检组或传统采样组。

In the cryobiopsy group, bronchoscopists used a single-use cryoprobe and aimed to obtain 1-3 specimens, with en bloc removal of the bronchoscope and cryoprobe for each biopsy.

在冷冻活检组中，支气管镜医生使用一次性冷冻探针，并试图获取1-3个标本，每次活检都整体移除支气管镜和冷冻探针。

In the conventional sampling group, bronchoscopists aimed to obtain five or more specimens when feasible using standard bronchoscopic sampling instruments, including forceps, aspiration needles, or both.

在传统采样组中，支气管镜医生在可行的情况下，使用标准支气管镜采样工具，包括钳子、抽吸针或两者，试图获取五个或更多的标本。

The primary endpoint was histology-based diagnostic yield (definitive histological diagnosis consistent with the final diagnosis), which was assessed in all randomly assigned patients with confirmed lesion visualisation who were evaluable for the primary endpoint and tested hierarchically in the prespecified adjacent-to or eccentric cohort, followed by the overall cohort.

主要终点是基于组织学的诊断效率（与最终诊断一致的明确组织学诊断），这在所有随机分配的、确认病变可视化且可评估主要终点的患者中进行评估，并在预设的邻近或偏心队列中按层次测试，然后是整体队列。

Safety was assessed in all eligible randomly assigned patients.

在所有合格的随机分配的患者中评估了安全性。

This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, UMIN000049329, and is completed.

该试验已在大学医院医学信息网络临床试验注册处注册，注册号为UMIN000049329，并已完成。

Results

Between Nov 1, 2022, and March 25, 2025, 660 patients were enrolled; 627 were randomly assigned (314 [50%] to cryobiopsy and 313 [50%] to conventional sampling).

在2022年11月1日至2025年3月25日期间，共有660名患者被纳入研究；其中627名患者被随机分配（314名[50%]接受冷冻活检，313名[50%]接受常规取样）。

Two patients in the conventional sampling group were excluded from the primary analysis after randomisation.

在常规取样组中，有两名患者在随机分组后被排除在主要分析之外。

Median age was 70 years (IQR 61-76), 287 (46%) of 625 patients were female and 338 (54%) were male.

中位年龄为70岁（四分位数间距61-76），625名患者中有287名（46%）为女性，338名（54%）为男性。

In the adjacent-to or eccentric cohort, histology-based diagnostic yield was 77% (128 of 167 patients) with cryobiopsy and 65% (108 of 167) with conventional sampling (estimated difference 12·4% [95% CI 2·8-22·0]; p=0·0060).

在邻近或偏心队列中，基于组织学的诊断效率为77%（128名患者中的167名）使用冷冻活检，以及65%（108名患者中的167名）使用常规取样（估计差异12.4% [95% CI 2.8-22.0]；p=0.0060）。

In the overall cohort, diagnostic yield was 83% (262 of 314) and 75% (233 of 311; estimated difference 8·9% [95% CI 2·8-15·0]; p=0·0023).

在整体队列中，诊断效率为83%（314名患者中的262名）和75%（311名患者中的233名；估计差异8.9% [95% CI 2.8-15.0]；p=0.0023）。

Moderate bleeding occurred in 120 (38%) of 314 patients in the cryobiopsy group and 60 (19%) of 312 patients in the conventional sampling group; severe bleeding was uncommon (two [1%] vs three [1%]).

在冷冻活检组中，有120名（38%）患者出现中度出血，而在常规取样组中，有60名（19%）患者出现中度出血；严重出血不常见（两名[1%]对比三名[1%]）。

Pneumothorax occurred in six (2%) patients in the cryobiopsy group and one (<1%) patient in the conventional sampling group (chest-tube drainage was required in five [2%] patients vs none).

在冷冻活检组中，有六名（2%）患者出现气胸，在常规取样组中，有一名（<1%）患者出现气胸（需要胸管引流的患者为五名[2%]对比无）。

Serious adverse events were infrequent (seven [2%] in the cryobiopsy group vs five [2%] in the conventional sampling group).

严重不良事件发生率较低（冷冻活检组有七例[2%]，传统取样组有五例[2%]）。

interpretation

In patients with peripheral pulmonary lesions undergoing radial endobronchial ultrasound-guided bronchoscopy, cryobiopsy achieved a higher histology-based diagnostic yield than conventional sampling, although moderate bleeding and pneumothorax were more frequent.

在接受径向支气管内超声引导的支气管镜检查的周围肺病变患者中，冷冻活检的组织学诊断效率高于传统取样，尽管中度出血和气胸的发生更频繁。

These findings support cryobiopsy as a valuable tissue-acquisition strategy for peripheral pulmonary lesions, particularly when the probe-lesion relationship is adjacent to or eccentric.

这些发现支持冷冻活检作为一种有价值的组织获取策略，特别是对于周围肺病变，当探头与病变的关系是邻近的或偏心的时。

funding

JSPS KAKENHI.

JSPS科学研究补助金。