CA 19-9 remains the most frequently applied serum indicator in the clinical workup of pancreaticobiliary malignancies (PBMs), yet there is minimal published information describing how patients with PBMs behave when their CA 19-9 levels are undetectable or only minimally elevated (referred to here as “low”). This project aimed to determine how individuals with PBMs and low CA 19-9 values compare—both in presentation and in clinical trajectory—to those whose CA 19-9 concentrations at diagnosis were normal or elevated. We performed a retrospective review of biopsy-verified PBM cases and assigned each individual to one of three diagnostic CA 19-9 categories. Survival probabilities for these groups were produced with the Kaplan–Meier approach, and comparisons were analyzed with Cox proportional hazards regression. Among 283 total patients, 23 (8.1%) fell into the low CA 19-9 group, 70 (24.7%) into the normal range, and 190 (67.1%) into the elevated range. When adjusting for age, sex, body mass index, metastatic disease at presentation, and whether curative-intent therapy was provided, the elevated CA 19-9 cohort demonstrated a hazard ratio for death of 1.993 (95% CI 1.089–3.648; p = 0.025) when contrasted with the low-level group. Elevated CA 19-9 (versus low levels) and the existence of metastases both increased mortality risk, while receiving curative-intent treatment lowered that risk.
