Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Department of Thoracic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Cancer Med. 2022 Oct;11(20):3751-3760. doi: 10.1002/cam4.4751. Epub 2022 Apr 17.
Despite 3-year survival being used as a primary endpoint in some randomized controlled trials (RCTs), limited evidence supports the use of intermediate endpoints to evaluate the effect of new therapies in esophageal squamous cell cancer (ESCC). This study aimed to systematically evaluate progression-free survival at 3 years (3-year PFS) and overall survival (OS) among patients with ESCC.
We identified 528 patients newly diagnosed with locally advanced ESCC who received definitive radiotherapy. OS was compared with an age- and sex-matched general Chinese population using the standardized mortality ratio (SMR). Regression analysis was used to validate the correlation between PFS and OS using published data.
The annual risk of progression decreased to 11.5% after 3 years. Patients who did not achieve 3-year PFS had a median postprogression survival (PPS) of 7.3 months, with a 5-year OS rate of 9.6% and a SMR of 15.0 (95% confidence interval [CI], 12.9-17.5). Conversely, the SMR for patients who achieved 3-year PFS was 0.9 (95% CI, 0.6-1.3). We observed a significant correlation between log hazard ratio (HR) (PFS) and log HR (OS) at the trial level (r = 0.89; 95% CI, 0.88-0.90). The strongest correlation was observed between 3-year PFS and 5-year OS in RCTs and retrospective studies.
Patients exhibiting progression within 3 years experienced poor survival, whereas patients achieving 3-year PFS had excellent outcomes. Our study supports 3-year PFS as a reliable primary endpoint for study design and risk stratification in locally advanced ESCC.
尽管 3 年生存率已被一些随机对照试验（RCT）用作主要终点，但有限的证据支持使用中间终点来评估新疗法在食管鳞状细胞癌（ESCC）中的疗效。本研究旨在系统评估 ESCC 患者的无进展生存 3 年（3 年 PFS）和总生存（OS）。
我们确定了 528 例新诊断为局部晚期 ESCC 并接受根治性放疗的患者。使用标准化死亡率比（SMR）比较 OS 与年龄和性别匹配的一般中国人群。使用已发表的数据，回归分析验证 PFS 和 OS 之间的相关性。
3 年后进展的年风险降至 11.5%。未达到 3 年 PFS 的患者中位后进展生存（PPS）为 7.3 个月，5 年 OS 率为 9.6%，SMR 为 15.0（95%置信区间[CI]，12.9-17.5）。相反，达到 3 年 PFS 的患者的 SMR 为 0.9（95% CI，0.6-1.3）。我们在试验水平观察到对数风险比（HR）（PFS）和对数 HR（OS）之间存在显著相关性（r=0.89；95% CI，0.88-0.90）。在 RCT 和回顾性研究中，观察到 3 年 PFS 与 5 年 OS 之间的相关性最强。
在 3 年内出现进展的患者生存不良，而达到 3 年 PFS 的患者则有良好的结局。我们的研究支持将 3 年 PFS 作为局部晚期 ESCC 研究设计和风险分层的可靠主要终点。
