No abstract

Purpose Biomarkers for the early detection of pancreatic cancer are urgently needed. The primary objective of this study was to evaluate whether increased levels of serum CA19-9, CA125, CEACAM1 and REG3A are present prior to clinical presentation of pancreatic cancer and to assess the performance of combined markers for early detection and prognosis. Experimental Design This nested case control study within UKCTOCS included 118 single- and 143 serial-serum samples from 154 post-menopausal women who were subsequently diagnosed with pancreatic cancer and 304 matched non-cancer controls. Samples were split randomly into independent training and test sets. CA19-9, CA125, CEACAM1 and REG3A were measured using ELISA and/or CLIA. Performance of markers to detect cancers at different times prior to diagnosis and for prognosis was evaluated. Results At 95% specificity, CA19-9 (>37 U/mL) had a sensitivity of 68% up to 1 year, and 53% up to 2 yrs before diagnosis. Combining CA19-9 and CA125 improved sensitivity as CA125 was elevated (>30 U/mL) in ~20% of CA19-9-negative cases. CEACAM1 and REG3A were late markers adding little in combined models. Average lead times of 20-23 months were estimated for test-positive cases. Pre-diagnostic levels of CA19-9 and CA125 were associated with poor overall survival (HR 2.69 and 3.15, respectively). Conclusions CA19-9 and CA125 have encouraging sensitivity for detecting pre-clinical pancreatic cancer and both markers can be used as prognostic tools. This work challenges the prevailing view that CA19-9 is up-regulated late in the course of pancreatic cancer development.