Tsilimigras Diamantis I, Chatzipanagiotou Odysseas P, Ruzzenente Andrea, Aucejo Federico, Marques Hugo P, Bandovas Joao, Hugh Tom, Bhimani Nazim, Maithel Shishir K, Kitago Minoru, Endo Itaru, Pawlik Timothy M
Department of Surgery, Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA.
Department of Surgery, University of Verona, Verona, Italy.
J Surg Oncol. 2025 Sep;132(3):497-502. doi: 10.1002/jso.70024. Epub 2025 Jun 30.
Baseline serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) levels may predict prognosis among patients undergoing resection for gallbladder cancer (GBC), yet the prognostic utility of the combination of the two markers has not been well established. In addition, the prognostic significance of elevated preoperative CA19-9 levels that normalize after GBC resection is currently unknown.
Patients undergoing resection of GBC between 2002 and 2021 were identified using an international, multi-institutional database. The association of preoperative CA19-9 and CEA levels with recurrence-free survival (RFS) following GBC resection was assessed. The negative predictive value (NPV) of normal vs. normalized (high preoperative/low postoperative levels) CA19-9 levels relative to the development of recurrence within 1 year after GBC resection was evaluated.
Among 194 patients who underwent resection of GBC, median preoperative CA19-9 and CEA levels were 18.8 U/mL (IQR 7.0-88.0) and 2.2 ng/mL (IQR 1.3-3.8), respectively. A total of 92 (47.4%) and 67 (34.5%) patients had elevated CA19-9 (> 20 U/mL) and CEA (> 3 ng/mL) levels before GBC resection, respectively. Individuals with low CA19-9/low CEA had the most favorable 3-year RFS (74.5%) after GBC resection followed by individuals with either high CA19-9 (high CA19-9/low CEA: 41.6%) or high CEA (low CA19-9/high CEA: 60.9%) levels, whereas patients with high CA19-9/high CEA had the worst 3-year RFS (21.5%) following GBC resection (p < 0.001). Patients with normal preoperative CA19-9 levels had better 3-year RFS than patients with high preoperative CA19-9 levels that normalized after resection (74.6% vs. 51.4%, p = 0.03). While the NPV of normal preoperative CA19-9 levels relative to the development of recurrence within 1 year after GBC resection was 94.7%, the NPV of normalized CA19-9 decreased to 70% at 1-year post-resection.
Elevation of both preoperative CA19-9 and CEA levels portended poor prognosis following resection of GBC. Normalization of postoperative CA19-9 levels after GBC resection was still associated with elevated risk of recurrence. While preoperative tumor markers can accurately predict prognosis following resection for GBC, evaluation of traditional tumor markers may not be appropriate markers of occult recurrent disease in the postoperative setting. Better markers are needed to monitor for recurrence following resection of GBC.
基线血清糖类抗原（CA）19-9和癌胚抗原（CEA）水平可能预测接受胆囊癌（GBC）切除术患者的预后，但这两种标志物联合使用的预后价值尚未得到充分证实。此外，GBC切除术后术前升高的CA19-9水平恢复正常的预后意义目前尚不清楚。
利用一个国际多机构数据库确定2002年至2021年间接受GBC切除术的患者。评估术前CA19-9和CEA水平与GBC切除术后无复发生存期（RFS）的相关性。评估正常与恢复正常（术前高/术后低水平）的CA19-9水平相对于GBC切除术后1年内复发的阴性预测值（NPV）。
在194例接受GBC切除术的患者中，术前CA19-9和CEA水平的中位数分别为18.8 U/mL（四分位间距7.0-88.0）和2.2 ng/mL（四分位间距1.3-3.8）。GBC切除术前分别有92例（47.4%）和67例（34.5%）患者的CA19-9（>20 U/mL）和CEA（>3 ng/mL）水平升高。CA19-9低/CEA低的个体在GBC切除术后的3年RFS最有利（74.5%），其次是CA19-9高（CA19-9高/CEA低：41.6%）或CEA高（CA19-9低/CEA高：60.9%）的个体，而CA19-9高/CEA高的患者在GBC切除术后的3年RFS最差（21.5%）（p<0.001）。术前CA19-9水平正常的患者比切除术后恢复正常的术前CA19-9水平高的患者有更好的3年RFS（74.6%对51.4%，p=0.03）。虽然术前CA19-9水平正常相对于GBC切除术后1年内复发的NPV为94.7%，但切除术后1年时恢复正常的CA19-9的NPV降至70%。
术前CA19-9和CEA水平均升高预示GBC切除术后预后不良。GBC切除术后CA19-9水平恢复正常仍与复发风险升高相关。虽然术前肿瘤标志物可准确预测GBC切除术后的预后，但在术后环境中评估传统肿瘤标志物可能不是隐匿性复发性疾病的合适标志物。需要更好的标志物来监测GBC切除术后的复发情况。
