Annals of Surgical Oncology

, Volume 25, Issue 12, pp 3483–3491 | Cite as

CA19-9 on Postoperative Surveillance in Pancreatic Ductal Adenocarcinoma: Predicting Recurrence and Changing Prognosis over Time

  • Caroline J. Rieser
  • Mazen Zenati
  • Ahmad Hamad
  • Amr I. Al Abbas
  • Nathan Bahary
  • Amer H. Zureikat
  • Herbert J. ZehIII
  • Melissa E. HoggEmail author
Pancreatic Tumors



Serum carbohydrate antigen 19-9 (CA19-9) correlates with response to therapy and overall survival (OS) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to define the chronologic relationship between CA19-9 elevation and radiographic recurrence to develop a model that can predict the risk of recurrence (RFS) and prognosis during interval surveillance for patients with resected PDAC.


A retrospective review examined patients undergoing surgery for pancreatic adenocarcinoma from January 2010 to May 2016. Their CA19-9 levels were classified at diagnosis, after surgery, and at 6-month surveillance intervals. Recurrence was defined by radiographic evidence. The CA19-9 levels were correlated with RFS and OS at every time point using multivariate analysis.


The study examined 525 patients. Five patterns of CA19-9 were identified: normal (“nonsecretors,” 18.5%), always elevated, and high at diagnosis but normal after resection involving three patterns with varied behavior during surveillance. These five patterns had implications for RFS and OS. When elevation of CA19-9, as assessed at 6-month intervals, was analyzed relative to detection of radiographic disease, CA19-9 had poor positive predictive value (average, 35%) but high negative predictive value (average, 92%) for radiographic recurrence. Conditional RFS showed that CA19-9 elevation did not equal radiographic recurrence but predicted subsequent RFS. Additionally, conditional OS showed that CA19-9 elevation alone was predictive at each time point.


This study showed that CA19-9 patterns beyond the post-resection period predict RFS and OS. High CA19-9 frequently is discordant with recurrence on imaging and may precede it by more than 6 months. At each surveillance interval, CA19-9 is predictive of prognosis, which may help in counseling patients and could be used to direct protocols of salvage chemotherapy.



Melissa E. Hogg receives salary support from Veterans Affairs. She also recieves grant funding from SAGES and Intuitive Surgical. Caroline J. Rieser, Mazen Zenati, Ahmad Hamad, Amr I. Al Abbas, Nathan Bahary, Amer H. Zureikat, and Herbert J. Zeh III have nothing to disclose.


  1. 1.
    Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.CrossRefGoogle Scholar
  2. 2.
    Hattangadi JA, Hong TS, Yeap BY, Mamon HJ. Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma. Cancer. 2009;115:3640–50.CrossRefGoogle Scholar
  3. 3.
    Ruf J, Lopez Hanninen E, Oettle H, Plotkin M, Pelzer U, Stroszczynski C, et al. Detection of recurrent pancreatic cancer: comparison of FDG-PET with CT/MRI. Pancreatology. 2005;5:266–72.CrossRefGoogle Scholar
  4. 4.
    Jadvar H, Fischman AJ. Evaluation of pancreatic carcinoma with FDG PET. Abdom Imaging. 2001;26:254–9.CrossRefGoogle Scholar
  5. 5.
    Cameron K, Golan S, Simpson W, Peti S, Roayaie S, Labow D, et al. Recurrent pancreatic carcinoma and cholangiocarcinoma: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Abdom Imaging. 2011;36:463–71.CrossRefGoogle Scholar
  6. 6.
    Wong D, Ko AH, Hwang J, Venook AP, Bergsland EK, Tempero MA. Serum CA19-9 decline compared to radiographic response as a surrogate for clinical outcomes in patients with metastatic pancreatic cancer receiving chemotherapy. Pancreas. 2008;37:269–74.CrossRefGoogle Scholar
  7. 7.
    Reni M, Cereda S, Balzano G, Passoni P, Rognone A, Fugazza C, et al. Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinoma. Cancer. 2009;115:2630–9.CrossRefGoogle Scholar
  8. 8.
    Maisey NR, Norman AR, Hill A, Massey A, Oates J, Cunningham D. CA19-9 as a prognostic factor in inoperable pancreatic cancer: the implication for clinical trials. Br J Cancer. 2005;93:740–3.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Haas M, Heinemann V, Kullmann F, Laubender RP, Klose C, Bruns CJ, et al. Prognostic value of CA 19-9, CEA, CRP, LDH, and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy. J Cancer Res Clin Oncol. 2013;139:681–9.CrossRefGoogle Scholar
  10. 10.
    Sugiura T, Uesaka K, Kanemoto H, Mizuno T, Sasaki K, Furukawa H, et al. Serum CA19-9 is a significant predictor among preoperative parameters for early recurrence after resection of pancreatic adenocarcinoma. J Gastrointest Surg. 2012;16:977–85.CrossRefGoogle Scholar
  11. 11.
    Maithel SK, Maloney S, Winston C, Gonen M, D’Angelica MI, Dematteo RP, et al. Preoperative CA 19-9 and the yield of staging laparoscopy in patients with radiographically resectable pancreatic adenocarcinoma. Ann Surg Oncol. 2008;15:3512–20.CrossRefGoogle Scholar
  12. 12.
    Kang CM, Kim JY, Choi GH, Kim KS, Choi JS, Lee WJ, et al. The use of adjusted preoperative CA 19-9 to predict the recurrence of resectable pancreatic cancer. J Surg Res. 2007;140:31–5.CrossRefGoogle Scholar
  13. 13.
    Ferrone CR, Finkelstein DM, Thayer SP, Muzikansky A, Fernandez-delCastillo C, Warshaw AL. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol. 2006;24:2897–902.CrossRefGoogle Scholar
  14. 14.
    Bergquist JR, Puig CA, Shubert CR, Groeschl RT, Habermann EB, Kendrick ML, et al. Carbohydrate antigen 19-9 elevation in anatomically resectable, early stage pancreatic cancer is independently associated with decreased overall survival and an indication for neoadjuvant therapy: a National Cancer Database study. J Am Coll Surg. 2016;223:52–65.CrossRefGoogle Scholar
  15. 15.
    Barton JG, Bois JP, Sarr MG, Wood CM, Qin R, Thomsen KM, et al. Predictive and prognostic value of CA 19-9 in resected pancreatic adenocarcinoma. J Gastrointest Surg. 2009;13:2050–8.CrossRefGoogle Scholar
  16. 16.
    Williams JL, Kadera BE, Nguyen AH, Muthusamy VR, Wainberg ZA, Hines OJ, et al. CA19-9 normalization during pre-operative treatment predicts longer survival for patients with locally progressed pancreatic cancer. J Gastrointest Surg. 2016;20:1331–42.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Tzeng CW, Balachandran A, Ahmad M, Lee JE, Krishnan S, Wang H, et al. Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer. HPB Oxford. 2014;16:430–8.CrossRefGoogle Scholar
  18. 18.
    Reni M, Zanon S, Balzano G, Nobile S, Pircher CC, Chiaravalli M, et al. Selecting patients for resection after primary chemotherapy for non-metastatic pancreatic adenocarcinoma. Ann Oncol. 2017;28:2786–92.CrossRefGoogle Scholar
  19. 19.
    Katz MH, Varadhachary GR, Fleming JB, Wolff RA, Lee JE, Pisters PW, et al. Serum CA 19-9 as a marker of resectability and survival in patients with potentially resectable pancreatic cancer treated with neoadjuvant chemoradiation. Ann Surg Oncol. 2010;17:1794–801.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261:12–7.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Boone BA, Steve J, Zenati MS, Hogg ME, Singhi AD, Bartlett DL, et al. Serum CA 19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol. 2014;21:4351–8.CrossRefGoogle Scholar
  22. 22.
    Piagnerelli R, Marrelli D, Roviello G, Ferrara F, Di Mare G, Voglino C, et al. Clinical value and impact on prognosis of peri-operative CA 19-9 serum levels in stage I and II adenocarcinoma of the pancreas. Tumour Biol. 2016;37:1959–66.CrossRefGoogle Scholar
  23. 23.
    Kondo N, Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, et al. Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol. 2010;17:2321–9.CrossRefGoogle Scholar
  24. 24.
    Imaoka H, Shimizu Y, Senda Y, Natsume S, Mizuno N, Hara K, et al. Post-adjuvant chemotherapy CA19-9 levels predict prognosis in patients with pancreatic ductal adenocarcinoma: a retrospective cohort study. Pancreatology. 2016;16:658–64.CrossRefGoogle Scholar
  25. 25.
    Humphris JL, Chang DK, Johns AL, Scarlett CJ, Pajic M, Jones MD, et al. The prognostic and predictive value of serum CA19.9 in pancreatic cancer. Ann Oncol. 2012;23:1713–22.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Hata S, Sakamoto Y, Yamamoto Y, Nara S, Esaki M, Shimada K, et al. Prognostic impact of postoperative serum CA 19-9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol. 2012;19:636–41.CrossRefGoogle Scholar
  27. 27.
    Hartwig W, Strobel O, Hinz U, Fritz S, Hackert T, Roth C, et al. CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy. Ann Surg Oncol. 2013;20:2188–96.CrossRefGoogle Scholar
  28. 28.
    Abdel-Misih SR, Hatzaras I, Schmidt C, Saab TB, Klemanski D, Muscarella P, et al. Failure of normalization of CA19-9 following resection for pancreatic cancer is tantamount to metastatic disease. Ann Surg Oncol. 2011;18:1116–21.CrossRefGoogle Scholar
  29. 29.
    Hernandez JM, Cowgill SM, Al-Saadi S, Collins A, Ross SB, Cooper J, et al. CA 19-9 velocity predicts disease-free survival and overall survival after pancreatectomy of curative intent. J Gastrointest Surg. 2009;13:349–53.CrossRefGoogle Scholar
  30. 30.
    Kannagi R. Carbohydrate antigen sialyl Lewis a: its pathophysiological significance and induction mechanism in cancer progression. Chang Gung Med J. 2007;30:189–209.PubMedGoogle Scholar
  31. 31.
    Berger AC, Garcia M Jr, Hoffman JP, Regine WF, Abrams RA, Safran H, et al. Post-resection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol. 2008;26:5918–22.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Caroline J. Rieser
    • 1
  • Mazen Zenati
    • 1
  • Ahmad Hamad
    • 1
  • Amr I. Al Abbas
    • 1
  • Nathan Bahary
    • 2
  • Amer H. Zureikat
    • 1
  • Herbert J. ZehIII
    • 1
  • Melissa E. Hogg
    • 1
    Email author
  1. 1.Department of Surgical OncologyUniversity of PittsburghPittsburghUSA
  2. 2.Department of Medical OncologyUniversity of PittsburghPittsburghUSA

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