Characteristics and prognosis of patients with pancreatic adenocarcinoma not expressing CA19-9: Analysis of the National Cancer Database

Around 5–10 % of pancreatic cancer patients are non-expressors of carbohydrate antigen 19-9 (CA 19-9), which has an unknown impact on the aggressiveness and prognosis of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate the characteristics and the prognosis of PDAC patients who do not express CA 19-9. Patients with PDAC diagnosed between 2010 and 2018 were identified in the National Cancer Database. Clinical characteristics were compared according to CA 19-9 levels stratified in four different groups: non-expressors (≤1.0 U/mL), normal range (1.1–37.0 U/mL), mildly elevated (37.1–97.9 U/mL), and CA 19-9 ≥98.0 U/mL. The characteristics were analyzed in the whole cohort and overall survival (OS) was evaluated in a subgroup of upfront resected patients who had cT1-3 tumors without distant metastases. In total, 88,749 patients were included, of which 4.5 % were CA 19-9 non-expressors. The non-expressors had a higher risk of having distant metastasis at diagnosis, compared to patients with normal-range or mildly elevated CA 19-9 levels. In resected patients (n = 4008), CA 19-9 non-expressors had shorted median OS compared to patients with normal-range CA 19-9 levels (29.3 vs 34.4 months, p = 0.024). This OS association remained in a multivariable Cox regression model (adjusted HR 1.22, 95 % CI 1.04–1.44). CA 19-9 non-expression is associated with distant metastatic disease at diagnosis and with death in resected non-metastatic patients compared to normal-range CA 19-9 levels. This clinically relevant subgroup requires alternative biomarkers, and may need consideration of more extensive preoperative staging and intensive perioperative systemic therapy.