• Xinzhe Zhu, Zhiwen Xiao, He Liu, Pin Zhang, Shengming Deng, Lei Ding, Jingjing Feng, Jianfeng Luo, Quanxing Ni, Guopei Luo, and Xianjun Yu.
• Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China.
• Ann. Surg. 2023 Dec 5.

ObjectiveTo examine the characteristics of pancreatic cancer patients with long-term survival.BackgroundAlthough pancreatic cancer is a highly lethal malignancy, a minority of patients experience long-term survival. The characteristics of these patients remain largely unidentified.MethodsAn indolent subgroup was established using carbohydrate antigen 19-9 (CA19-9), which is the best-validated biomarker for pancreatic cancer. Of 1558 patients, 13.9% were included in the CA19-9-normal (≤ 37 U/mL) subgroup.ResultsA normal A19-9 level was an independent variable for overall survival (median survival, 18.1 vs. 9.7 months, hazard ratio = 0.53, P < 0.001). The 5-year survival of patients with stage IV CA19-9-normal cancer was higher than that of patients with stage I-IV CA19-9-high cancer (22.4% vs. 6.8%, P = 0.034). The CA19-9-normal subgroup exhibited reduced levels of circulating glucose (P < 0.001) and increased expression of insulin (P < 0.001) compared with the CA19-9-high subgroup. Glucose was a substrate for CA19-9 biosynthesis through the hexosamine biosynthesis pathway. In addition, in pancreatic cancer animal models of diabetes, glucose control decreased CA19-9 levels and improved overall survival. In a clinical trial (NCT05306028) of patients before undergoing major anticancer treatments, glucose control decreased CA19-9 levels in 90.9% of the patients.ConclusionsCA19-9-normal pancreatic cancer is a strikingly indolent subgroup with low glucose and high insulin. Glucose control is a promising therapeutic strategy for pancreatic cancer.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

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