To determine the sensitivity of contrast-enhanced computed tomography (CECT) in detecting pancreatic ductal adenocarcinoma (PDAC) and identify factors associated with false negatives (FNs).

Patients diagnosed with PDAC in 2014–2015 were retrospectively identified by a cancer registry. CECTs performed during the diagnostic interval were retrospectively classified as true positive (TP), indeterminate, or FN. Sensitivity TP/(TP+FN) was calculated for all CECTs and the following subgroups: protocol (uniphasic vs. biphasic); tumor size (≤ 2 cm vs. > 2 cm); and resectability (potentially resectable vs. unresectable). Multivariate logistic regression was performed to assess which of the following factors were associated with FN: clinical suspicion of PDAC; size >2 cm; presence of metastases; protocol; isoattenuating tumor; and potentially resectable disease on imaging.

In total, 176 CECTs (127 uniphasic; 49 biphasic) in 154 patients (90 men, mean age 72 ± 11 years) were included. Sensitivity was 125/149 (83.9%) overall and 87/106 (82.1%) and 38/43 (88.4%) for uniphasic and biphasic protocols, respectively. Sensitivity was decreased for tumors ≤ 2 cm (45.4% vs. 90.6%), no liver metastases (78.0% vs. 95.9%), and potentially resectable disease (65.3% vs. 93.0%). Factors significantly associated with FN were clinical suspicion (OR, 0.24, 95% CI: 0.07–0.75), size>2 cm (OR, 0.10, 95% CI: 0.02–0.44), absence of liver metastases (OR, 4.94, 95% CI: 1.29–22.99), and potentially resectable disease (OR, 4.13, 95% CI: 1.07–16.65).

In our population, the overall sensitivity of CECT to detect PDAC is 83.9%; however, this is substantially lower in several scenarios, including patients with potentially resectable disease. This finding has important implications for patient outcomes and efforts to maximize CECT sensitivity should be sought.

The sensitivity of CECT to detect PDAC is significantly decreased in the setting of sub-2 cm tumors and potentially resectable disease. A dedicated biphasic pancreatic CECT protocol has higher sensitivity and should be applied in patients with suspected pancreatic disease.

• The sensitivities of contrast-enhanced CT for the detection of PDAC were 87/106 (82.1%) and 38/43 (88.4%) for uniphasic and biphasic protocols, respectively.

• The sensitivity of contrast-enhanced CT was decreased for small tumors ≤ 2 cm (45.4% vs. 90.6%), if there were no liver metastases (78.0% vs. 95.9%), and with potentially resectable disease (65.3% vs. 93.0%).

• Absence of liver metastases (OR, 4.94, 95% CI: 1.29–22.99) and potentially resectable disease (OR, 4.13, 95% CI: 1.07–16.65) were associated with a false--negative (FN) CT result; suspicion of malignancy on the imaging requisition (OR, 0.24, 95% CI: 0.07–0.75) and size > 2 cm (OR, 0.10, 95% CI: 0.02–0.44) were negatively associated with FN.