Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston.
Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston.
JAMA Netw Open. 2024 Feb 5;7(2):e240260. doi: 10.1001/jamanetworkopen.2024.0260.
Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma.
To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma.
DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least 1 tumor marker measured at MD Anderson between March 2016 and May 2023. Data were analyzed from January to December 2023.
Association of serum tumor markers with survival in patients with appendiceal adenocarcinoma. Cox proportional hazards regression analyses were also performed to assess associations between clinical factors (serum tumor marker levels, demographics, and patient and disease characteristics) and patient outcomes (overall survival).
A total of 1338 patients with appendiceal adenocarcinoma were included, with a median (range) age at diagnosis of 56.5 (22.3-89.6) years. The majority of the patients had metastatic disease (1080 patients [80.7%]). CEA was elevated in 742 of the patients tested (56%), while CA19-9 and CA125 were elevated in 381 patients (34%) and 312 patients (27%), respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; elevated vs normal was 81% vs 95% for CEA (hazard ratio [HR], 4.0; 95% CI, 2.9-5.6), 84% vs 92% for CA19-9 (HR, 2.2; 95% CI, 1.4-3.4), and 69% vs 93% for CA125 (HR, 4.6; 95% CI, 2.7-7.8) (P < .001 for all). Quantitative evaluation of tumor markers was associated with outcomes. Patients with highly elevated (top 10th percentile) CEA, CA19-9, or CA125 had markedly worse survival, with 5-year survival rates of 59% for CEA (HR, 9.8; 95% CI, 5.3-18.0), 64% for CA19-9 (HR, 6.0; 95% CI, 3.0-11.7), and 57% for CA125 (HR, 7.6; 95% CI, 3.5-16.5) (P < .001 for all). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease, elevated CEA, CA19-9, or CA125 were all still associated worse survival (HR for CEA, 3.4; 95% CI, 2.5-4.8; P < .001; HR for CA19-9, 1.8; 95% CI, 1.2-2.7; P = .002; and HR for CA125, 3.9; 95% CI, 2.4-6.4; P < .001). Interestingly, tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high-grade tumors relative to low-grade tumors (mean value, 18.3 vs 15.0; difference, 3.3; 95% CI, 0.9-3.7; P < .001). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with an 11-fold increased risk of death in patients with all 3 tumor markers elevated relative to those with none elevated. Somatic mutations in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9.
In this retrospective study of serum tumor markers in patients with appendiceal adenocarcinoma, CEA, CA19-9, and CA125 were associated with overall survival in appendiceal adenocarcinoma. Given their value, all 3 biomarkers should be included in the initial workup of patients with a diagnosis of appendiceal adenocarcinoma.
癌胚抗原（CEA）、糖类抗原 19-9（CA19-9）和癌抗原 125（CA125）等血清肿瘤标志物在胃肠道和妇科癌症的治疗中已得到广泛应用；然而，关于这些标志物在阑尾腺癌患者中的应用价值，相关信息有限。
评估血清肿瘤标志物（CEA、CA19-9 和 CA125）与阑尾腺癌患者临床结局及病理和分子特征的相关性。
设计、地点和参与者：这是一项在单一的三级综合癌症中心进行的回顾性队列研究。中位（IQR）随访时间为 52（21-101）个月。使用软件查询 MD 安德森内部患者数据库，以确定 2016 年 3 月至 2023 年 5 月期间在 MD 安德森至少有 1 项肿瘤标志物检测结果的诊断为阑尾腺癌的患者。数据分析于 2023 年 1 月至 12 月进行。
评估血清肿瘤标志物与阑尾腺癌患者生存的相关性。还进行了 Cox 比例风险回归分析，以评估临床因素（血清肿瘤标志物水平、人口统计学和患者及疾病特征）与患者结局（总生存）之间的关系。
共纳入 1338 例阑尾腺癌患者，诊断时的中位（范围）年龄为 56.5（22.3-89.6）岁。大多数患者存在转移性疾病（1080 例[80.7%]）。在接受检测的患者中，CEA 升高者占 742 例（56%），CA19-9 和 CA125 升高者分别占 381 例（34%）和 312 例（27%）。单独来看，CEA、CA19-9 或 CA125 升高与 5 年生存率降低相关；升高与正常相比，CEA 为 81%比 95%（HR，4.0；95%CI，2.9-5.6），CA19-9 为 84%比 92%（HR，2.2；95%CI，1.4-3.4），CA125 为 69%比 93%（HR，4.6；95%CI，2.7-7.8）（所有 P 值均<.001）。肿瘤标志物的定量评估与结局相关。CEA、CA19-9 或 CA125 高度升高（前 10%）的患者生存显著更差，5 年生存率分别为 CEA 59%（HR，9.8；95%CI，5.3-18.0）、CA19-9 64%（HR，6.0；95%CI，3.0-11.7）和 CA125 57%（HR，7.6；95%CI，3.5-16.5）（所有 P 值均<.001）。尽管转移性肿瘤的所有肿瘤标志物水平均较高，但在限制生存分析为 1080 例转移性疾病患者时，CEA、CA19-9 或 CA125 升高仍与生存率降低相关（CEA 的 HR 为 3.4；95%CI，2.5-4.8；P<.001；CA19-9 的 HR 为 1.8；95%CI，1.2-2.7；P=.002；CA125 的 HR 为 3.9；95%CI，2.4-6.4；P<.001）。有趣的是，肿瘤分级与 CEA 或 CA19-9 水平无关，而 CA-125 在高级别肿瘤中略高于低级别肿瘤（平均值分别为 18.3 比 15.0；差值为 3.3；95%CI，0.9-3.7；P<.001）。多变量分析确定，随着升高的肿瘤标志物数量的增加，死亡风险呈指数级增加，与所有 3 种肿瘤标志物均升高的患者相比，无一标志物升高的患者死亡风险增加 11 倍。KRAS 和 GNAS 的体细胞突变与 CEA 和 CA19-9 水平显著升高相关。
在这项对阑尾腺癌患者血清肿瘤标志物的回顾性研究中，CEA、CA19-9 和 CA125 与阑尾腺癌的总生存相关。鉴于它们的价值，所有 3 种生物标志物都应纳入阑尾腺癌患者的初始检查。
