Tanaka H, Tamura K, Abe T, et al. - Findings demonstrate diagnostic utility of serum carboxypeptidase A (CPA) activity prior to the emergence of pancreatic atrophy as a marker of localized pancreatic ductal adenocarcinoma (PDAC), including Stage I disease.

• This study involved 345 controls receiving pancreatic surveillance and 190 patients with resectable PDAC.

• Among controls, significantly higher serum CPA levels were detected in those having one or more minor alleles of CPA1 variants rs6955723 or rs2284682 relative to those without.

• Elevated CPA was not detected in any of the PDAC cases with pancreatic atrophy.

• In 122 PDAC cases with no atrophy: serum CPA diagnostic cut-offs defined by a person’s CPA1 variants, afforded a diagnostic sensitivity of 18% at 99% specificity (vs 11.1% sensitivity via a uniform diagnostic cut-off); integrating CPA with variant-stratified CA19-9 offered a sensitivity of 68.0% vs 63.1% for CA19-9 alone; among Stage I PDAC cases, diagnostic sensitivity was 51.9%, vs 37.0% for CA19-9 alone.

• A specificity of 98.2% was conferred by the variant-stratified diagnostic cut-off, in the validation control set.