围手术期血清肿瘤标志物轨迹与结直肠癌结局：一项回顾性、多中心纵向队列研究。
Trajectories of Perioperative Serum Tumor Markers and Colorectal Cancer Outcomes: A Retrospective, Multicenter Longitudinal Cohort Study.
机构信息
Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Institute for Medical Dataology, Shandong University, Jinan, 250002, China.
Department of Radiology, the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, China.
出版信息
EBioMedicine. 2021 Dec;74:103706. doi: 10.1016/j.ebiom.2021.103706. Epub 2021 Nov 18.
BACKGROUND
The dynamic monitoring of perioperative carcinoembryonic antigen (CEA) is recommended by current colorectal cancer (CRC) guidelines, while the benefits of additional measurements of carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125) have remained controversial.
METHODS
This retrospective longitudinal cohort included 3539 CRC patients who underwent curative resection. Distinct trajectory groups were identified by the latent class growth mixed model. Patients were grouped into subgroups jointly by CEA, CA19-9, and CA125 according to preoperative levels and longitudinal trajectories, respectively. The end points were overall survival (OS) and recurrence-free survival (RFS).
FINDINGS
Three distinct trajectory groups were characterized for serum CEA, CA19-9, and CA125: low-stable, early-rising, and later-rising. Jointly, patients were grouped into six preoperative (trajectory) joint groups. Compared with the three-low group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) associated with death were 1.87 (1.29-2.70), 3.82 (2.37-6.17), 1.87 (0.97-3.61), 2.81 (1.93-4.11), and 4.99 (2.80-8.86) for the CEA-high, CA19-9-high, CA125-high, two-high, and three-high group, respectively. And compared with the three-stable trajectory group, the corresponding HRs (95% CIs) were 1.59 (1.10-2.30), 1.55 (0.77-3.10), 6.25 (4.02-9.70), 4.05 (2.73-6.02), and 12.40 (5.77-26.70) for the five rising trajectory groups, respectively. Similar associations between joint groups and RFS were observed. Notably, the trajectory joint group still had prognostic significance after adjusting for preoperative levels. The CA19-9-high group (HR: 3.82, 95% CI: 2.37-6.17) was associated with higher risk of death than the two-high group (HR: 2.81, 95% CI: 1.93-4.11). Likewise, for the CA125-rising trajectory group and two-rising trajectory group, the HRs (95% CIs) were 6.13 (3.75-10.00) and 3.99 (2.63-6.05) for death, and 3.08 (2.07-4.58) and 2.10 (1.52-2.90) for recurrence.
INTERPRETATION
In addition to CEA, the dynamic measurements of CA19-9 and CA125 are recommended to monitor the prognosis of CRC patients.
FUNDING
National Natural Science Foundation of China [81973147, 82001986, 81960592, 82073569, 81660545].
背景
目前的结直肠癌（CRC）指南推荐动态监测围手术期癌胚抗原（CEA），而额外测量糖链抗原 19-9（CA19-9）和糖链抗原 125（CA125）的获益仍存在争议。
方法
本回顾性纵向队列纳入了 3539 例接受根治性切除术的 CRC 患者。通过潜在类别增长混合模型确定了不同的轨迹组。根据术前水平和纵向轨迹，分别将患者按 CEA、CA19-9 和 CA125 联合分组。终点为总生存（OS）和无复发生存（RFS）。
结果
CEA、CA19-9 和 CA125 的血清水平可分为三个明显的轨迹组：低稳定、早升和晚升。联合起来，患者根据术前（轨迹）联合组分为六个组。与三低组相比，死亡相关的调整后危险比（HR）和 95%置信区间（CI）分别为 1.87（1.29-2.70）、3.82（2.37-6.17）、1.87（0.97-3.61）、2.81（1.93-4.11）和 4.99（2.80-8.86），分别为 CEA 高、CA19-9 高、CA125 高、双高和三高水平组。与三稳定轨迹组相比，相应的 HR（95%CI）分别为 1.59（1.10-2.30）、1.55（0.77-3.10）、6.25（4.02-9.70）、4.05（2.73-6.02）和 12.40（5.77-26.70），分别为五个上升轨迹组。联合组与 RFS 之间也存在类似的相关性。值得注意的是，即使调整了术前水平，轨迹联合组仍具有预后意义。CA19-9 高组（HR：3.82，95%CI：2.37-6.17）的死亡风险高于双高组（HR：2.81，95%CI：1.93-4.11）。同样，对于 CA125 上升轨迹组和双上升轨迹组，死亡的 HR（95%CI）分别为 6.13（3.75-10.00）和 3.99（2.63-6.05），复发的 HR（95%CI）分别为 3.08（2.07-4.58）和 2.10（1.52-2.90）。
解释
除 CEA 外，还建议动态测量 CA19-9 和 CA125 以监测 CRC 患者的预后。
经费支持
国家自然科学基金[81973147、82001986、81960592、82073569、81660545]。
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