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Published on: November 18, 2022
Early postoperative carbohydrate antigen 19-9 normalization drives prognosis after pancreatic ductal adenocarcinoma
Abdulaziz Elemosho1, Odysseas P Chatzipanagiotou1, Meher Angez1
1Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, United States.
Background:
The prognostic utility of carbohydrate antigen 19-9 (CA19-9) may vary based on clinical and gene[A1] tic factors, including FUT2/FUT3 mutations or UGT1A1 alleles. We sought to examine early postoperative changes in CA19-9 relative to prognosis after resection of pancreatic ductal adenocarcinoma (PDAC). [A1]AU: Please ensure that genes (not proteins) are italicized, per journal style.
Methods:
Patients undergoing resection of PDAC were identified from the All of Us Research Program. Patients were categorized into neoadjuvant therapy (NAT) followed by resection (NAT-to-resection) and surgery-first. The primary endpoint was real-world time-to-treatment failure (rwTTF). Genomic and sensitivity analyzes excluded post-treatment draws with total bilirubin levels >2 mg/dL and were restricted to CA19-9 producers.
Results:
Among 283 patients who underwent pancreatic resection, 48 underwent NAT-to-resection and 235 underwent surgery-first. Index years ranged between 1999 and 2023. Baseline CA19-9 distributions differed markedly by pathway. Patients in the NAT-to-resection group had a median pretreatment CA19-9 of 273 U/mL, whereas patients in the surgery-first group had a median pretreatment CA19-9 of 19 U/mL, with 68.7% of patients demonstrating normal values. Carcinoembryonic antigen (CEA) levels were available preoperatively in 88 patients and postoperatively in 41 patients; among phenotypic CA19-9 nonproducers, few individuals had an elevated CEA level. In CA19-9 trajectory analysis, median rwTTF was 1185.5 days with normal-to-normal values, 693 days for elevated-to-normalized, and 138 days for those with elevated-to-persistently-elevated values. After excluding planned adjuvant therapy from the rwTTF endpoint, higher pretreatment CA19-9 and greater postoperative CA19-9 change were independently associated with rwTTF, whereas binary postoperative normalization alone was not.
Conclusion:
Basing a prognosis on a single CA19-9 value or percent drop may be insufficient, particularly because many surgery-first patients had normal baseline CA19-9 values. Perioperative CA19-9 trajectories provided a more clinically informative framework, with persistent postoperative elevation identifying the highest-risk group after PDAC resection.
