Division of Surgical Oncology, The Ohio State University Medical Center/James Cancer Hospital, Columbus, OH, USA.
Ann Surg Oncol. 2011 Apr;18(4):1116-21. doi: 10.1245/s10434-010-1397-1. Epub 2010 Nov 2.
Multidisciplinary therapy for pancreatic cancer involves radical resection followed by gemcitabine-based chemotherapy. Carbohydrate antigen 19-9 (CA19-9), when elevated preoperatively, is a useful marker to monitor disease status following resection. However, little has been reported on outcomes of patients in whom CA19-9 never normalizes. We hypothesize that failure of CA19-9 normalization within 6 months is prognostically equivalent to metastatic disease.
From our pancreatectomy database, we identified 93 patients with pancreatic adenocarcinoma and elevated CA19-9 prior to resection with levels recorded postoperatively. Patients were grouped based on normalization or persistent elevation of CA19-9 at 6 months after resection. CA19-9 levels normalized (≤35 u/ml) after resection in 38 (41%) and remained elevated in 55 (59%). Clinicopathologic characteristics were compared using Student's t-test and contingency table analyses. Survival curves were constructed using Kaplan-Meier method and compared by log-rank analysis. Cox regression was used to determine predictors of survival.
The two groups had comparable clinicopathologic characteristics except for nodal status and perineural invasion, which were higher in patients with persistently elevated CA19-9. Persistent CA19-9 conferred shorter median overall survival of 10.8 months compared with 23.8 months in patients with normalization (p < 0.001), which persisted when controlling for nodal status. Multivariate analysis demonstrated persistently elevated CA19-9 as the sole statistically significant negative predictor of survival [hazard ratio (HR) 2.20, p = 0.002].
Persistent CA19-9 elevation after pancreatectomy correlates with shorter survival analogous to unresected or metastatic disease and should be regarded as persistent disease regardless of radiographic findings. These patients should be considered for accrual to clinical trials or initiation of alternative therapy.
胰腺癌的多学科治疗包括根治性切除术加吉西他滨为基础的化疗。术前升高的癌抗原 19-9（CA19-9）是监测切除后疾病状态的有用标志物。然而，关于 CA19-9 从未正常化的患者的结果报道甚少。我们假设 6 个月内 CA19-9 不能正常化与转移性疾病的预后相当。
我们从胰腺切除术数据库中确定了 93 例术前 CA19-9 升高的胰腺腺癌患者，并记录了术后的 CA19-9 水平。根据术后 6 个月 CA19-9 是正常化（≤35u/ml）还是持续升高将患者分为两组。38 例（41%）患者的 CA19-9 水平在手术后正常化，55 例（59%）患者的 CA19-9 水平持续升高。采用 Student's t 检验和列联表分析比较临床病理特征。采用 Kaplan-Meier 法构建生存曲线，并采用对数秩检验比较。采用 Cox 回归分析确定生存的预测因素。
两组患者的临床病理特征相似，但淋巴结状态和神经周围侵犯除外，在持续升高 CA19-9 的患者中更高。与 CA19-9 正常化患者的中位总生存期为 23.8 个月相比，持续升高 CA19-9 的患者中位总生存期更短，为 10.8 个月（p<0.001），在控制淋巴结状态后仍如此。多变量分析表明，持续升高的 CA19-9 是唯一具有统计学意义的生存负预测因素[风险比（HR）2.20，p=0.002]。
胰腺切除术后 CA19-9 持续升高与生存时间缩短相关，类似于未切除或转移性疾病，无论影像学表现如何，均应视为持续性疾病。这些患者应考虑入组临床试验或开始替代治疗。
