Journal of Gastrointestinal Surgery

, Volume 14, Issue 3, pp 462–469 | Cite as

Association of C-Reactive Protein Levels and Long-Term Survival after Neoadjuvant Therapy and Esophagectomy for Esophageal Cancer

  • Urs Zingg
  • Jens Forberger
  • Branimir Rajcic
  • Christopher Langton
  • Glyn G. Jamieson
Original Article



Preoperative C-reactive protein (CRP) levels have been shown to be prognostic markers of survival in patients undergoing esophagectomy for cancer. No study has evaluated the predictive value for survival of CRP levels after neoadjuvant chemoradiotherapy.


Preoperative CRP levels were assessed in patients undergoing neoadjuvant therapy and esophagectomy for cancer. Groups were defined according to normal value cutoffs of the CRP measurements.


Seventy patients had normal CRP, and 20 patients had raised CRP. The groups did not differ in descriptives, comorbidities, white cell counts, pathological data, or morbidity. In-hospital death was higher in the raised CRP group (three versus one patient, p = 0.048). The Kaplan–Meier survival analysis showed a significant survival advantage of patients with normal CRP compared to patients with raised CRP levels (median survival, 65.4 versus 18.7 months; log rank test, p = 0.027). The Cox regression analysis identified three independent prognostic factors for survival: UICC stage (IIB/III versus I/IIA, HR 3.48, p = 0.007), completeness of resection (HR 6.33, p = 0.002), and CRP levels (raised versus normal, HR 5.07, p = 0.001).


Preoperative CRP levels are an independent prognostic marker for survival after neoadjuvant treatment in patients with esophageal cancer and may be of value in the re-staging process after neoadjuvant treatment.


Esophageal cancer Outcomes Neoadjuvant therapy C-reactive protein 


  1. 1.
    Falk J, Carstens H, Lundell L, Albersson M. Incidence of carcinoma of the oesophagus and gastric cardia. Changes over time and geographical differences. Acta Oncol 2007;46:1070–1074.CrossRefPubMedGoogle Scholar
  2. 2.
    Omloo JM, Lagarde SM, Hulscher JB, Reitsma JB, Fockens P, van dekken H, ten Kate FJ, Obertop H, Tilanus HW, van Lanschot JJ. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus. Ann Surg 2007;246:992–1001.CrossRefPubMedGoogle Scholar
  3. 3.
    Kaklamanos IG, Walker GR, Ferry K, Franceschi D, Livingstone AS. Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal junction: a meta-analysis of randomized clinical trials. Ann Surg Oncol 2003;10:754–761.CrossRefPubMedGoogle Scholar
  4. 4.
    Urschel JD, Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg 2003;185:538–543.CrossRefPubMedGoogle Scholar
  5. 5.
    Kim TJ, Kim HY, Lee KW, Kim MS. Multimodality assessment of esophageal cancer: preoperative staging and monitoring of response to therapy. Radiographics 2009;29:403–421.CrossRefPubMedGoogle Scholar
  6. 6.
    Wong WL, Chambers RJ. Role of PET/PET CT in the staging and restaging of thoracic oesophageal cancer and gastro-oesophageal cancer: a literature review. Abdom Imaging 2008;33:183–190.CrossRefPubMedGoogle Scholar
  7. 7.
    Fareed KR, Kaye P, Soomro IN, Ilyas M, Martin S, Parsons SL, Madhusudan S. Biomarkers of response to therapy in oesophago-gastric cancer. Gut 2009;58:127–143.CrossRefPubMedGoogle Scholar
  8. 8.
    Shimada H, Nabeya Y, Okazumi S, Matsubara H, Shiratori T, Aoki T, Sugaya M, Miyazawa Y, Hayashi H, Miyazaki S, Ochiai T. Elevation of preoperative serum C-reactive protein level is related to poor prognosis in esophageal squamous cell carcinoma. J Surg Oncol 2003;83:248–252.CrossRefPubMedGoogle Scholar
  9. 9.
    Gockel I, Dirksen K, Messow CM, Junginger T. Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus. World J Gastroenterol 2006;12:3746–3750.PubMedGoogle Scholar
  10. 10.
    Nozoe T, Saeki H, Sugimachi K. Significance of preoperative elevation of serum C-reactive protein as an indicator of prognosis in esophageal carcinoma. Am J Surg 2001;182:197–201.CrossRefPubMedGoogle Scholar
  11. 11.
    Ikeda M, Natsugoe S, Ueno S, Baba M, Aikou T. Significant host- and tumor-related factors for predicting prognosis in patients with esophageal carcinoma. Ann Surg 2003;238:197–202.PubMedGoogle Scholar
  12. 12.
    Guillem P, Triboulet JP. Raised serum levels of C-reactive protein are indicative of a poor prognosis in patients with esophageal cancer. Dis Esophagus 2005;18:146–150.CrossRefPubMedGoogle Scholar
  13. 13.
    Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot J-F, Roussel A, Jacob J-H, Segol P, Samama G, Ollivier J-M, Bonvalot S, Gignoux M. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Cancer 1994;73:2680–2688.CrossRefPubMedGoogle Scholar
  14. 14.
    Nozoe T, Korenaga D, Futatsugi M, Saeki H, Maehara Y, Sugimachi K. Immunohistochemical expression of C-reactive protein in squamous cell cancer of the esophagus—significance as a tumor marker. Cancer Lett 2003;192:89–95.CrossRefPubMedGoogle Scholar
  15. 15.
    de Pree C Aapro MS, Spiliopoulos A, Popowski Y, Mermillod B, Mirimanoff RO, Alberto P. Combined chemotherapy and radiotherapy, followed or not by surgery, in squamous cell carcinoma of the esophagus. Ann Oncol 1995;6:551–557.Google Scholar
  16. 16.
    Gill PG, Denham JW, Jamieson GG, Devitt PG, Yeoh E, Olweny C. Patterns of treatment failure and prognostic factors associated with the treatment of esophageal carcinoma with chemotherapy and radiotherapy either as sole treatment or followed by surgery. J Clin Oncol 1992;10:1037–1043.PubMedGoogle Scholar
  17. 17.
    McCulloch P, Ward J, Tekkis PP, ASCOT Group of Surgeons. Mortality and morbidity in gastro-oesophageal cancer surgery: initial results of ASCOT multicentre prospective cohort study. BJM 2003;327:1192–1197.CrossRefGoogle Scholar
  18. 18.
    Bates BA, Detterbeck FC, Bernard SA, Qaqish BF, Tepper JE. Concurrent radiation therapy and chemotherapy followed by esophagectomy for localized esophageal carcinoma. J Clin Oncol 1996;14:156–163.PubMedGoogle Scholar
  19. 19.
    Morita M, Masuda T, Okada S, Yoshinaga K, Saeki H, Tokunaga E, Endo K, Emi Y, Kakeji Y, Maehara Y. Preoperative chemoradiotherapy for esophageal cancer: factors associated with clinical response and postoperative complications. Anticancer Res 2009;29:2555–2562.PubMedGoogle Scholar
  20. 20.
    Guillem P, Fabre S, Mariette C, Triboulet JP. Surgery after induction chemoradiotherapy for oesophageal cancer. Eur J Surg Oncol 2003;29:158–165.CrossRefPubMedGoogle Scholar
  21. 21.
    Blazenby JM, Farndon JR, Donovan J, Alderson D. A prospective longitudinal study examining the quality of life of patients with esophageal carcinoma. Cancer 2000;88:1781–1787.CrossRefGoogle Scholar
  22. 22.
    Lordik F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, Lorenzen S, Schuster T, Wieder H, Herrmann K, Bredenkamp R, Hoefler H, Fink U, Peschel C, Scxhweiger M, Siewert JR. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol 2007;8:797–805.CrossRefGoogle Scholar
  23. 23.
    Levine EA, Farmer MR, Clark P, Mishra G, Ho C, Geisinger KR, Melin SA, Lovato J, Oaks T, Blackstock AW. Predictive value of 18-fluoro-desoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to Chemoradiation therapy for the treatment of locally advanced esophageal cancer. Ann Surg 2006;243:472–478.CrossRefPubMedGoogle Scholar
  24. 24.
    Swisher SG, Maish M, Erasmus JJ, Correa AM, Ajani JA, Bresalier R, Komaki R, Macapinlac H, Munden RF, Putnam JB. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg 2004;78:1152–1160.CrossRefPubMedGoogle Scholar
  25. 25.
    Mahmoud FA, Rivera NI. The role of C-reactive protein as a prognostic indicator in advanced cancer. Curr Oncol Rep 2002;4:250–255.CrossRefPubMedGoogle Scholar
  26. 26.
    Deans DA, Wigmore SJ, de Beaux AC, Paterson-Brown S, Garden OJ, Fearon KC. Clinical prognostic scoring system to aid decision-making in gastro-oesophageal cancer. Br J Surg 2007;94:1501–1508.CrossRefPubMedGoogle Scholar
  27. 27.
    Choti MA. Chemotherapy-associated hepatotoxicity: do we need to be concerned. Ann Surg Oncol 2009;16:2391–2394.CrossRefPubMedGoogle Scholar
  28. 28.
    Field KM, Michael M. Part II: Liver function in oncology: towards safer chemotherapy use. Lancet Oncol 2008;1181–1190.Google Scholar
  29. 29.
    Mariette C, Taillier G, van Seuningen I, Triboulet JP. Factors affecting postoperative course and survival after en bloc resection for esophageal carcinoma. Ann Thorac Surg 2004;78:1177–1183.CrossRefPubMedGoogle Scholar
  30. 30.
    Deeter M, Dorer R, Kuppusamy MK, Koehler RP, Low DE. Assessment of criteria and clinical significance of circumferential resection margins in esophageal cancer. Arch Surg 2009;144:618–624.CrossRefPubMedGoogle Scholar
  31. 31.
    Darling G. The role of lymphadenectomy in esophageal cancer. J Surg Oncol 2009;99:189–193.CrossRefPubMedGoogle Scholar
  32. 32.
    Schneider PM, Baldus SE, Metzger R, Kocher M, Bongartz R, Bollschweiler E, Schaefer H, Thiele J, Dienes HP, Mueller RP, Hoelscher AH. Histomorphologic tumor regression and lymph node metastasis determine prognosis following neoadjuvant radiochemotherapy for esophageal cancer. Ann Surg 2005;242:684–692.CrossRefPubMedGoogle Scholar
  33. 33.
    Donahue JM, Nichols FC, Li Z, Schomas DA, Allen MS, Cassivi SD, Jatoi A, Miller RC, Wigle DA, Shen KR, Deschamps C. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg 2009;87:392–398.CrossRefPubMedGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2009

Authors and Affiliations

  • Urs Zingg
    • 1
  • Jens Forberger
    • 2
  • Branimir Rajcic
    • 1
  • Christopher Langton
    • 1
  • Glyn G. Jamieson
    • 1
  1. 1.Discipline of SurgeryUniversity of Adelaide, Royal Adelaide HospitalAdelaideAustralia
  2. 2.Department of SurgeryTriemli HospitalZurichSwitzerland

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