Patients with normal-range CA19-9 levels represent a distinct subgroup of pancreatic cancer patients.

Pancreatic cancer remains a lethal disease that responds poorly to multiple types of treatment. Therefore, the identification of distinct subgroups that exhibit unique therapeutic responses is an urgent requirement. In the present multicenter study (1,912 cases), the differences between the therapeutic responses and clinical characteristics of two subgroups of pancreatic cancer, carbohydrate antigen 19-9 (CA19-9)-normal (baseline serum level, ≤37 U/ml) and CA19-9-elevated (baseline serum level, >37 U/ml), were analyzed. CA19-9-normal expression was identified to be an independent prognostic factor for patients with stage I-II [hazard ratio (HR)=0.77; P=0.037] and stage III-IV (HR=0.68; P<0.001) pancreatic cancer. The 5-year survival rate of the stage III-IV CA19-9-normal subgroup was increased compared with the stage I-II CA19-9-elevated subgroup (15.4 vs. 13.8%). In the stage I-II CA19-9-normal and CA19-9-elevated subgroups, gemcitabine-based chemotherapy was a significant positive prognostic factor for survival (CA19-9-normal, HR=0.54, P=0.013; CA19-9-elevated, HR=0.55, P<0.001). However, among stage III-IV patients, the CA19-9-normal subgroup exhibited a poor response to gemcitabine-based chemotherapy (HR=0.77; P=0.165), while the CA19-9-elevated subgroup exhibited a favorable response, resulting in a lower rate of mortality (HR=0.70; P<0.001) compared with no chemotherapy. It was concluded that CA19-9-normal pancreatic cancer is a less aggressive subgroup; however, advanced CA19-9-normal pancreatic cancer exhibits a poorer response to gemcitabine-based chemotherapy.