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CA19-9 in Potentially Resectable Pancreatic Cancer: Perspective to Adjust Surgical and Perioperative Therapy

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

In pancreatic cancer, genetic markers to aid clinical decision making are still lacking. The present study was designed to determine the prognostic role of perioperative serum tumor marker carbohydrate antigen 19-9 (CA19-9) in pancreatic adenocarcinoma, with a focus on implications for pre- and postoperative therapeutic consequences.

Methods

Of a total of 1,626 consecutive patients who underwent surgery for primary pancreatic adenocarcinoma, data from 1,543 patients with preoperative serum levels of CA19-9 were evaluated for tumor stage, resectability, and prognosis. Preoperative to postoperative CA19-9 changes were analyzed for long-term survival. A control cohort of 706 patients with chronic pancreatitis was used to assess the predictability of malignancy by CA19-9 and the effects of hyperbilirubinemia on CA19-9 levels.

Results

The more that preoperative CA19-9 increased, the lower were tumor resectability and survival rates. Resectability and 5-year survival varied from 80 to 38 % and from 27 to 0 % for CA19-9 <37 versus ≥4,000 U/ml, respectively. The R0 resection rate was as low as 15 % in all patients with CA19-9 levels ≥1,000 U/ml. CA19-9 increased with the stage of the disease and was highest in AJCC stage IV. Patients with an early postoperative CA19-9 increase had a dismal prognosis. Hyperbilirubinemia did not markedly affect CA19-9 levels (correlation coefficient ≤0.135).

Conclusions

In patients with pancreatic adenocarcinoma, CA19-9 predicts resectability, stage of disease, as well as survival. Highly elevated preoperative or increasing postoperative CA19-9 levels are associated with low resectability and poor survival rates, and demand the adjustment of surgical and perioperative therapy.

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References

  1. Hartwig W, Hackert T, Hinz U, Gluth A, Bergmann F, Strobel O, Büchler MW, Werner J. Pancreatic cancer surgery in the new millennium: better prediction of outcome. Ann Surg. 2011;254:311–9.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. Barugola G, Partelli S, Marcucci S, Sartori N, Capelli P, Bassi C, Pederzoli P, Falconi M. Resectable pancreatic cancer: who really benefits from resection? Ann Surg Oncol. 2009;16:3316–22.

    Article  PubMed  Google Scholar 

  4. Barton JG, Bois JP, Sarr MG, Wood CM, Qin R, Thomsen KM, Kendrick ML, Farnell MB. Predictive and prognostic value of CA 19-9 in resected pancreatic adenocarcinoma. J Gastrointest Surg. 2009;13:2050–8.

    Article  PubMed  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. Hess V, Glimelius B, Grawe P, Dietrich D, Bodoky G, Ruhstaller T, Bajetta E, Saletti P, Figer A, Scheithauer W, Herrmann R. CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial. Lancet Oncol. 2008;9:132–8.

    Article  PubMed  CAS  Google Scholar 

  7. Bernhard J, Dietrich D, Glimelius B, Hess V, Bodoky G, Scheithauer W, Herrmann R. Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy. Br J Cancer. 2010;103:1318–24.

    Article  PubMed  CAS  Google Scholar 

  8. Karachristos A, Scarmeas N, Hoffman JP. CA 19-9 levels predict results of staging laparoscopy in pancreatic cancer. J Gastrointest Surg. 2005;9:1286–92.

    Article  PubMed  Google Scholar 

  9. Maithel SK, Maloney S, Winston C, Gonen M, D’Angelica MI, Dematteo RP, Jarnagin WR, Brennan MF, Allen PJ. Preoperative CA 19-9 and the yield of staging laparoscopy in patients with radiographically resectable pancreatic adenocarcinoma. Ann Surg Oncol. 2008;15:3512–20.

    Article  PubMed  Google Scholar 

  10. Halloran CM, Ghaneh P, Connor S, Sutton R, Neoptolemos JP, Raraty MG. Carbohydrate antigen 19.9 accurately selects patients for laparoscopic assessment to determine resectability of pancreatic malignancy. Br J Surg. 2008;95:453–9.

    Article  PubMed  CAS  Google Scholar 

  11. Kilic M, Gocmen E, Tez M, Ertan T, Keskek M, Koc M. Value of preoperative serum CA 19-9 levels in predicting resectability for pancreatic cancer. Can J Surg. 2006;49:241–4.

    PubMed  Google Scholar 

  12. Schlieman MG, Ho HS, Bold RJ. Utility of tumor markers in determining resectability of pancreatic cancer. Arch Surg. 2003;138:951–5.

    Article  PubMed  Google Scholar 

  13. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Olah A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler MW. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304:1073–81.

    Article  PubMed  CAS  Google Scholar 

  14. Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011;18:1319–26.

    Article  PubMed  Google Scholar 

  15. da Cunha SG, Dhani N, Tu D, Chin K, Ludkovski O, Kamel-Reid S, Squire J, Parulekar W, Moore MJ, Tsao MS. Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer: National Cancer Institute of Canada Clinical Trials Group Study PA.3. Cancer. 2010;116:5599–607.

    Article  Google Scholar 

  16. Berger AC, Garcia M Jr, Hoffman JP, Regine WF, Abrams RA, Safran H, Konski A, Benson AB III, MacDonald J, Willett CG. Postresection 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.

    Article  PubMed  Google Scholar 

  17. Humphris JL, Chang DK, Johns AL, Scarlett CJ, Pajic M, Jones MD, Colvin EK, Nagrial A, Chin VT, Chantrill LA, Samra JS, Gill AJ, Kench JG, Merrett ND, Das A, Musgrove EA, Sutherland RL, Biankin AV. The prognostic and predictive value of serum CA19.9 in pancreatic cancer. Ann Oncol. 2012;23(7):1713–22.

    Article  PubMed  CAS  Google Scholar 

  18. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. New York: Springer; 2010.

    Google Scholar 

  19. Singh P, Srinivasan R, Wig JD. Major molecular markers in pancreatic ductal adenocarcinoma and their roles in screening, diagnosis, prognosis, and treatment. Pancreas. 2011;40:644–52.

    Article  PubMed  Google Scholar 

  20. Wasan HS, Springett GM, Chodkiewicz C, Wong R, Maurel J, Barone C, Rosbrook B, Ricart AD, Kim S, Spano JP. CA 19-9 as a biomarker in advanced pancreatic cancer patients randomised to gemcitabine plus axitinib or gemcitabine alone. Br J Cancer. 2009;101:1162–7.

    Article  PubMed  CAS  Google Scholar 

  21. Reni M, Cereda S, Balzano G, Passoni P, Rognone A, Fugazza C, Mazza E, Zerbi A, Di CV, Villa E. Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinoma. Cancer. 2009;115:2630–9.

    Article  PubMed  CAS  Google Scholar 

  22. Turrini O, Schmidt CM, Moreno J, Parikh P, Matos JM, House MG, Zyromski NJ, Nakeeb A, Pitt HA, Lillemoe KD. Very high serum CA 19-9 levels: a contraindication to pancreaticoduodenectomy? J Gastrointest Surg 2009;13:1791–7.

    Article  PubMed  CAS  Google Scholar 

  23. Kondo N, Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, Nakashima A, Sakabe R, Shigemoto N, Kato Y, Ohge H, Sueda T. Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol 2010;17(9):2321–9.

    Article  PubMed  Google Scholar 

  24. Hartwig W, Hackert T, Hinz U, Hassenpflug M, Strobel O, Büchler MW, Werner J. Multivisceral resection for pancreatic malignancies: risk-analysis and long-term outcome. Ann Surg. 2009;250:81–7.

    Article  PubMed  Google Scholar 

  25. Mollberg N, Rahbari NN, Koch M, Hartwig W, Hoeger Y, Büchler MW, Weitz J. Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg. 2011;254:882–93.

    Article  PubMed  Google Scholar 

  26. Takahashi H, Ohigashi H, Ishikawa O, Eguchi H, Gotoh K, Yamada T, Nakaizumi A, Uehara H, Tomita Y, Nishiyama K, Yano M. Serum CA19-9 alterations during preoperative gemcitabine-based chemoradiation therapy for resectable invasive ductal carcinoma of the pancreas as an indicator for therapeutic selection and survival. Ann Surg. 2010; 251:461–9.

    Article  PubMed  Google Scholar 

  27. Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla A, Narayanan G, Ribeiro A, Portelance L, Merchan JR, Levi JU, Rocha-Lima CM. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199.

    Article  PubMed  CAS  Google Scholar 

  28. Hata S, Sakamoto Y, Yamamoto Y, Nara S, Esaki M, Shimada K, Kosuge T. Prognostic impact of postoperative serum CA 19-9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol. 2011;19(2):636–41.

    Article  PubMed  Google Scholar 

  29. Abdel-Misih SR, Hatzaras I, Schmidt C, Saab TB, Klemanski D, Muscarella P, Melvin WS, Ellison EC, Bloomston M. Failure of normalization of CA19-9 following resection for pancreatic cancer is tantamount to metastatic disease. Ann Surg Oncol. 2011;18:1116–21.

    Article  PubMed  Google Scholar 

  30. Reni M, Balzano G, Aprile G, Cereda S, Passoni P, Zerbi A, Tronconi MC, Milandri C, Saletti P, Rognone A, Fugazza C, Magli A, Muzio ND, Carlo VD, Villa E. Adjuvant PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) or gemcitabine followed by chemoradiation in pancreatic cancer: a randomized phase II trial. Ann Surg Oncol. 2012;19:2256–63.

    Article  PubMed  Google Scholar 

  31. Bao PQ, Ramanathan RK, Krasinkas A, Bahary N, Lembersky BC, Bartlett DL, Hughes SJ, Lee KK, Moser AJ, Zeh HJ III. Phase II study of gemcitabine and erlotinib as adjuvant therapy for patients with resected pancreatic cancer. Ann Surg Oncol. 2011;18:1122–9.

    Article  PubMed  Google Scholar 

  32. Haglund C, Roberts PJ, Kuusela P, Scheinin TM, Makela O, Jalanko H. Evaluation of CA 19-9 as a serum tumour marker in pancreatic cancer. Br J Cancer. 1986;53:197–202.

    Article  PubMed  CAS  Google Scholar 

  33. Mery CM, Duarte-Rojo A, Paz-Pineda F, Gomez E, Robles-Diaz G. [Does cholestasis change the clinical usefulness of CA 19-9 in pancreatobiliary cancer?]. Rev Invest Clin. 2001;53:511–7.

    PubMed  CAS  Google Scholar 

  34. Mann DV, Edwards R, Ho S, Lau WY, Glazer G. Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol. 2000;26:474–9.

    Article  PubMed  CAS  Google Scholar 

  35. Katz MH, Varadhachary GR, Fleming JB, Wolff RA, Lee JE, Pisters PW, Vauthey JN, Abdalla EK, Sun CC, Wang H, Crane CH, Lee JH, Tamm EP, Abbruzzese JL, Evans DB. 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.

    Article  PubMed  Google Scholar 

  36. Ortiz-Gonzalez J, Alvarez-Aguila NP, Medina-Castro JM. Adjusted carbohydrate antigen 19-9. Correlation with histological grade in pancreatic adenocarcinoma. Anticancer Res. 2005;25:3625–7.

    PubMed  Google Scholar 

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Acknowledgment

The authors acknowledge Anne Caroline Queisser and Thomas Queisser for their help with manuscript preparation.

Conflict of interest

There are no personal conflicts of interest of any of the authors. The original material has not been previously published or submitted elsewhere for publication.

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Authors and Affiliations

  1. Department of General Surgery, University of Heidelberg, Heidelberg, Germany

    Werner Hartwig MD, Oliver Strobel MD, Ulf Hinz MSc, Stefan Fritz MD, Thilo Hackert MD, Constanze Roth, Markus W. Büchler MD & Jens Werner MD

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  1. Werner Hartwig MD
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Correspondence to Markus W. Büchler MD.

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Hartwig, W., Strobel, O., Hinz, U. et al. CA19-9 in Potentially Resectable Pancreatic Cancer: Perspective to Adjust Surgical and Perioperative Therapy. Ann Surg Oncol 20, 2188–2196 (2013). https://doi.org/10.1245/s10434-012-2809-1

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  • DOI: https://doi.org/10.1245/s10434-012-2809-1

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