Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma

Timothy E. Newhook, Timothy J. Vreeland, James F. Griffin, Rebecca S.S. Tidwell, Laura R. Prakash, Eugene J. Koay, Ethan B. Ludmir, Brandon G. Smaglo, Shubham Pant, Michael Overman, Robert A. Wolff, Naruhiko Ikoma, Jessica Maxwell, Michael P. Kim, Jeffrey E. Lee, Matthew H.G. Katz, Ching Wei D. Tzeng

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


OBJECTIVE: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication.

METHODS: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups.

RESULTS: Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01).

CONCLUSIONS: This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.

Original languageEnglish (US)
Pages (from-to)484-490
Number of pages7
JournalAnnals of surgery
Issue number3
StatePublished - Mar 1 2023


  • CA19-9
  • carbohydrate antigen 19-9
  • neoadjuvant therapy
  • pancreatic adenocarcinoma
  • Pancreatic Neoplasms/surgery
  • Prognosis
  • Adenocarcinoma/surgery
  • Humans
  • Carcinoma, Pancreatic Ductal/surgery
  • Neoadjuvant Therapy
  • Retrospective Studies
  • CA-19-9 Antigen

ASJC Scopus subject areas

  • Surgery


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