Trajectories of Perioperative Serum Tumor Markers and Colorectal Cancer Outcomes: A Retrospective, Multicenter Longitudinal Cohort Study
Chunxia Li,
Dafu Zhang,
Xiaolin Pang,
Hongjiang Pu,
Ming Lei,
Bingbing Fan,
Jiali Lv,
Dingyun You,
Zhenhui Li,
Tao Zhang
Affiliations
Chunxia Li
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
Dafu Zhang
Department of Radiology, the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, China
Xiaolin Pang
Department of Radiotherapy, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China
Hongjiang Pu
Department of Colorectal Surgery, the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, China
Ming Lei
Department of Clinical Laboratory Medicine, the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, China
Bingbing Fan
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
Jiali Lv
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
Dingyun You
School of Public Health, Kunming Medical University, Kunming, Yunnan, 650500, China; Dingyun You, MD, School of public health, Kunming Medical University, No.1168 Chunrongxi Road, Chenggong District, Kunming, Yunnan, 650500, China
Zhenhui Li
Department of Radiology, the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, China; Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China; Zhenhui Li, MD, PhD, Department of Radiology, the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, No.519 Kunzhou Road, Xishan District, Kunming, Yunnan, 650118, China
Tao Zhang
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; Corresponding authors: Tao Zhang, MD, PhD, Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, PO Box 100, 44 Wenhuaxi Road, Jinan 250012, China
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].
