Background

Although segmentectomy was better than lobectomy in terms of overall survival for patients with non-small-cell lung cancer (NSCLC) with a pure-solid tumour appearance on thin-section CT in the open-label, multicentre, randomised, controlled, phase 3 JCOG0802/WJOG4607L trial, the reasons why segmentectomy was associated with better overall survival were unclear. We aimed to compare the survival, cause of death, and recurrence patterns after segmentectomy versus lobectomy in trial participants with NSCLC with a pure-solid appearance

Methods

We conducted a post-hoc supplemental analysis of the JCO0802/WJOG4607L randomised, controlled, non-inferiority trial for the patients (aged 20–85 years) with small-sized NSCLC with radiologically pure-solid appearance on thin-section CT (≤2 cm, consolidation tumour ratio 1·0). The primary aim was to compare the overall and relapse-free survival, cause of death, and recurrence patterns associated with segmentectomy and lobectomy for patients with radiologically pure-solid NSCLC to determine why the overall survival of segmentectomy was superior to that of lobectomy, even for oncologically invasive lung cancers. JCO0802/WJOG4607L is registered with the UMIN Clinical Trials Registry, UMIN000002317, and is complete.

Findings

Between Aug 10, 2009, and Oct 21, 2014, 1106 patients were randomly assigned to undergo either lobectomy or segmentectomy. Of these participants, 553 (50%) had radiologically pure-solid NSCLC and were eligible for this post-hoc supplemental analysis. Of these 553 participants, 274 (50%) patients underwent lobectomy and 279 (50%) underwent segmentectomy. Median patient age was 67 years (IQR 61–73), 347 (63%) of 553 patients were male and 206 (37%) were female, and data on race and ethnicity were not collected. As of data cutoff (June 13, 2020), after a median follow-up of 7·3 years (IQR 6·0–8·5), the 5-year overall survival rate was significantly higher after segmentectomy than after lobectomy (86·1% [95% CI 81·4–89·7] in the lobectomy group, with 55 deaths vs 92·4% [88·6–95·0] in the segmentectomy group, with 38 deaths; hazard ratio (HR) 0·64 [95% CI 0·41–0·97]; log-rank test p=0·033), whereas the 5-year relapse-free survival was similar between the groups (81·7% [95% CI 76·5–85·8], with 34 events vs 82·0% [76·9–86·0], with 52 events; HR 1·01 [95% CI 0·72–1·42]; p=0·94). Deaths after a median follow-up of 7·3 years due to lung cancer occurred in 20 (7%) of 274 patients after lobectomy and 19 (7%) of 279 after segmentectomy, and deaths due to other causes occurred in 35 (13%) patients after lobectomy compared with 19 (7%) after segmentectomy (lung cancer death vs other cause of death, p=0·19). The locoregional recurrence was higher after segmentectomy (21 [8%] vs 45 [16%]; p=0·0021). In subgroup analyses, better 5-year overall survival after segmentectomy than after lobectomy was observed in the subgroup of patients aged 70 years or older (77·1% [95% CI 68·2–83·8] with lobectomy vs 85·6% [77·5–90·9] with segmentectomy; p=0·013) and in male patients (80·5% [73·7–85·7] vs 92·1% [87·0–95·2]; p=0·0085). By contrast, better 5-year relapse-free survival after lobectomy than after segmentectomy was observed in the subgroup younger than 70 years (87·4% [95% CI 81·2–91·7] with lobectomy vs 84·4% [77·9–89·1] with segmentectomy; p=0·049) and in female patients (94·2% [87·6–97·4] vs 82·2% [73·2–88·4]; p=0·047).

Interpretation

This post-hoc analysis showed improved overall survival after segmentectomy in patients with pure-solid NSCLC compared with lobectomy. However, survival outcomes of segmentectomy depend on the patient's age and sex. Given the results of this exploratory analysis, further research is necessary to determine clinically relevant indications for segmentectomy in radiologically pure-solid NSCLC.

Funding

Japanese National Cancer Center Research and Development Fund and Practical Research for Innovative Cancer Control Fund, and a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan.

中文翻译：

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日本放射学纯实体外观的小型周围型非小细胞肺癌的肺段切除术与肺叶切除术 (JCOG0802/WJOG4607L)：多中心、开放标签、3 期试验的事后补充分析

背景

尽管在开放标签、多中心、随机、对照 3 期研究中，对于薄层 CT 上显示为纯实体瘤的非小细胞肺癌 (NSCLC) 患者，肺段切除术的总体生存率优于肺叶切除术JCOG0802/WJOG4607L 试验中，段切除术与更好的总生存率相关的原因尚不清楚。我们的目的是比较患有纯实体性非小细胞肺癌的试验参与者在肺段切除术与肺叶切除术后的生存率、死亡原因和复发模式

方法

我们对 JCO0802/WJOG4607L 随机、对照、非劣效性试验进行了事后补充分析，受试者为薄层 CT 上放射学纯实体外观（≤2）的小尺寸 NSCLC 患者（年龄 20-85 岁） cm，实变肿瘤比率1·0)。主要目的是比较放射学纯实体 NSCLC 患者与肺段切除术和肺叶切除术相关的总体生存率和无复发生存率、死亡原因以及复发模式，以确定为什么肺段切除术的总体生存率优于肺叶切除术，甚至用于肿瘤侵袭性肺癌。 JCO0802/WJOG4607L 已在 UMIN 临床试验注册处注册，UMIN000002317，并且已完成。

发现

2009年8月10日至2014年10月21日期间，1106名患者被随机分配接受肺叶切除术或肺段切除术。在这些参与者中，553 名 (50%) 患有放射学纯实体非小细胞肺癌，有资格参加本次事后补充分析。在这 553 名参与者中，274 名（50%）名患者接受了肺叶切除术，279 名（50%）名患者接受了肺段切除术。患者中位年龄为 67 岁 (IQR 61-73)，553 名患者中 347 名 (63%) 为男性，206 名 (37%) 为女性，未收集种族和民族数据。截至数据截止（2020年6月13日），中位随访7·3年（IQR 6·0–8·5）后，肺段切除术后的5年总生存率显着高于肺叶切除术后（86肺叶切除组中·1% [95% CI 81·4–89·7]，55 例死亡，而肺段切除组中 92·4% [88·6–95·0]，38 例死亡；风险比 (HR ) 0·64 [95% CI 0·41–0·97]；对数秩检验 p=0·033)，而各组之间的 5 年无复发生存率相似 (81·7% [95% CI 76·5–85·8]，有 34 个事件vs 82·0% [76·9–86·0]，有 52 个事件；HR 1·01 [95% CI 0·72–1·42]；p =0·94）。中位随访 7·3 年后，肺叶切除术后 274 例患者中有 20 例 (7%) 发生肺癌死亡，肺段切除术后 279 例患者中有 19 例 (7%) 发生肺癌死亡，35 例 (13 例) 因其他原因死亡。 %) 肺叶切除术后患者与肺段切除术后 19 (7%) 患者相比（肺癌死亡与其他死因比较，p=0·19）。肺段切除术后局部区域复发率较高（21 [8%] vs 45 [16%]；p=0·0021）。在亚组分析中，70 岁或以上患者亚组中观察到，肺段切除术后 5 年总生存率优于肺叶切除术后（肺叶切除术为 77·1% [95% CI 68·2–83·8] vs 85 · 6） % [77·5–90·9] 进行肺段切除术；p=0·013) 和男性患者 (80·5% [73·7–85·7] vs 92·1% [87·0–95·2] ]；p=0·0085)。相比之下，在年龄小于 70 岁的亚组中，肺叶切除术后 5 年无复发生存率优于肺段切除术后（肺叶切除术为 87·4% [95% CI 81·2–91·7] vs 84·4% [95% CI 81·2–91·7]）。 77·9–89·1] 进行肺段切除术；p=0·049）和女性患者（94·2% [87·6–97·4] vs 82·2% [73·2–88·4]； p=0·047)。

解释

这项事后分析显示，与肺叶切除术相比，纯实体 NSCLC 患者在肺段切除术后的总体生存率有所提高。然而，肺段切除术的生存结果取决于患者的年龄和性别。鉴于这一探索性分析的结果，有必要进一步研究以确定放射学纯实体非小细胞肺癌肺段切除术的临床相关适应症。

资金

日本国家癌症中心研究开发基金和创新癌症控制实践研究基金，以及日本厚生劳动省的科学研究补助金。