Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Prognostic Potential of Lymphocyte–C-Reactive Protein Ratio in Patients with Rectal Cancer Receiving Preoperative Chemoradiotherapy



The systemic inflammatory response is attracting increasing attention as a predictive biomarker for oncological outcome in patients with colorectal cancer. This study is aimed at verifying if the lymphocyte–C-reactive protein (CRP) ratio (LCR) could be used as a predictor of oncological outcome in patients with rectal cancer (RC) receiving preoperative chemoradiotherapy (CRT).


We analyzed data for 86 patients with RC who received preoperative CRT followed by total mesorectal excision at our institution. A ratio of 6000 was used as the cut-off value for LCR for further analysis.


The post-CRT LCR was significantly lower than the pre-CRT LCR in patients with RC. Although post-CRT LCR status was not significantly correlated with overall survival (OS), low pre-CRT LCR was significantly associated with shorter recurrence-free survival (RFS: p = 0.02) and OS (p = 0.017) in this population and was an independent prognostic factor for both RFS and OS (hazard ratio (HR) 3.19, 95% confidence interval (CI) 1.33–7.66, p = 0.009; HR 2.83, 95%CI 1.14–7.01, p = 0.025, respectively). Furthermore, low pre-CRT LCR was a stronger indicator of early recurrence (p = 0.001) and poor prognosis (p = 0.025) in RC patients without pathological lymph node metastasis compared with patients with pathological lymph node metastasis, and prognostic potential of pre-CRT LCR was clearly revealed especially RC patients receiving long-course CRT.


Assessment of pretreatment LCR status might aid decision-making regarding postoperative treatment strategies in patients with RC receiving CRT followed by potentially curative resection.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29. doi:https://doi.org/10.3322/caac.20138.

  2. 2.

    Ludmir EB, Palta M, Willett CG, Czito BG. Total neoadjuvant therapy for rectal cancer: An emerging option. Cancer. 2017;123(9):1497–506. doi:https://doi.org/10.1002/cncr.30600.

  3. 3.

    Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet (London, England). 2009;373(9666):811–20. doi:https://doi.org/10.1016/s0140-6736(09)60484-0.

  4. 4.

    Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23. doi:https://doi.org/10.1056/NEJMoa060829.

  5. 5.

    Cedermark B, Dahlberg M, Glimelius B, Pahlman L, Rutqvist LE, Wilking N. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997;336(14):980–7. doi:https://doi.org/10.1056/nejm199704033361402.

  6. 6.

    Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T et al. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007;246(5):693–701. doi:https://doi.org/10.1097/01.sla.0000257358.56863.ce.

  7. 7.

    Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40. doi:https://doi.org/10.1056/NEJMoa040694.

  8. 8.

    MacFarlane JK, Ryall RD, Heald RJ. Mesorectal excision for rectal cancer. Lancet (London, England). 1993;341(8843):457–60.

  9. 9.

    Gollins S, Sebag-Montefiore D. Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer. Clin Oncol (R Coll Radiol). 2016;28(2):146–51. doi:https://doi.org/10.1016/j.clon.2015.11.003.

  10. 10.

    Okugawa Y, Toiyama Y, Yamamoto A, Shigemori T, Ide S, Kitajima T et al. Lymphocyte-C-reactive Protein Ratio as Promising New Marker for Predicting Surgical and Oncological Outcomes in Colorectal Cancer. Annals of Surgery. 2019. doi:https://doi.org/10.1097/sla.0000000000003239.

  11. 11.

    Toiyama Y, Inoue Y, Kawamura M, Kawamoto A, Okugawa Y, Hiro J et al. Elevated platelet count as predictor of recurrence in rectal cancer patients undergoing preoperative chemoradiotherapy followed by surgery. International surgery. 2015;100(2):199–207. doi:https://doi.org/10.9738/intsurg-d-13-00178.1.

  12. 12.

    Cedermark B, Johansson H, Rutqvist LE, Wilking N. The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group. Cancer. 1995;75(9):2269–75.

  13. 13.

    Yoshikawa R, Kusunoki M, Yanagi H, Noda M, Furuyama JI, Yamamura T et al. Dual antitumor effects of 5-fluorouracil on the cell cycle in colorectal carcinoma cells: a novel target mechanism concept for pharmacokinetic modulating chemotherapy. Cancer research. 2001;61(3):1029–37.

  14. 14.

    Japanese Research Society for Cancer of the Colon and Rectum. Kanehara T. General rules for clinical and pathological studies on cancer of the colon, rectum and anus. 2006.

  15. 15.

    Inoue Y, Saigusa S, Hiro J, Toiyama Y, Araki T, Tanaka K et al. Clinical significance of enlarged lateral pelvic lymph nodes before and after preoperative chemoradiotherapy for rectal cancer. Molecular and Clinical Oncology. 2016;4(6):994–1002. doi:https://doi.org/10.3892/mco.2016.855.

  16. 16.

    Okugawa Y, Toiyama Y, Oki S, Ide S, Yamamoto A, Ichikawa T et al. Feasibility of Assessing Prognostic Nutrition Index in Patients With Rectal Cancer Who Receive Preoperative Chemoradiotherapy. JPEN Journal of Parenteral and Enteral Nutrition. 2018;42(6):998–1007. doi:https://doi.org/10.1002/jpen.1041.

  17. 17.

    Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future oncology (London, England). 2010;6(1):149–63. doi:https://doi.org/10.2217/fon.09.136.

  18. 18.

    Nagasaki T, Akiyoshi T, Fujimoto Y, Konishi T, Nagayama S, Fukunaga Y et al. Prognostic Impact of Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Low Rectal Cancer Treated with Preoperative Chemoradiotherapy. Digestive Surgery. 2015;32(6):496–503. doi:https://doi.org/10.1159/000441396.

  19. 19.

    Toiyama Y, Inoue Y, Saigusa S, Kawamura M, Kawamoto A, Okugawa Y et al. C-reactive protein as predictor of recurrence in patients with rectal cancer undergoing chemoradiotherapy followed by surgery. Anticancer Research. 2013;33(11):5065–74.

  20. 20.

    Gu X, Gao XS, Qin S, Li X, Qi X, Ma M et al. Elevated Platelet to Lymphocyte Ratio Is Associated with Poor Survival Outcomes in Patients with Colorectal Cancer. PloS one. 2016;11(9):e0163523. doi:https://doi.org/10.1371/journal.pone.0163523.

  21. 21.

    Okugawa Y, Grady WM, Goel A. Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers. Gastroenterology. 2015;149(5):1204–25.e12. doi:https://doi.org/10.1053/j.gastro.2015.07.011.

  22. 22.

    Kim WR, Han YD, Min BS. C-Reactive Protein Level Predicts Survival Outcomes in Rectal Cancer Patients Undergoing Total Mesorectal Excision After Preoperative Chemoradiation Therapy. Annals of surgical oncology. 2018;25(13):3898–905. doi:https://doi.org/10.1245/s10434-018-6828-4.

  23. 23.

    Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137–48. doi:https://doi.org/10.1016/j.immuni.2004.07.017.

  24. 24.

    Oh SY, Heo J, Noh OK, Chun M, Cho O, Oh YT. Absolute Lymphocyte Count in Preoperative Chemoradiotherapy for Rectal Cancer: Changes Over Time and Prognostic Significance. Technology in cancer research & treatment. 2018;17:1533033818780065. doi:https://doi.org/10.1177/1533033818780065.

  25. 25.

    Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H. Circulating lymphocyte is an important determinant of the effectiveness of preoperative radiotherapy in advanced rectal cancer. BMC cancer. 2011;11:64. doi:https://doi.org/10.1186/1471-2407-11-64.

  26. 26.

    Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. The New England journal of medicine. 2001;345(9):638–46. doi:https://doi.org/10.1056/NEJMoa010580.

  27. 27.

    Quah HM, Chou JF, Gonen M, Shia J, Schrag D, Saltz LB et al. Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer. 2008;113(1):57–64. doi:https://doi.org/10.1002/cncr.23516.

  28. 28.

    Chung MJ, Lee JH, Lee JH, Kim SH, Song JH, Jeong S et al. Adjuvant Chemotherapy in Rectal Cancer Patients Treated With Preoperative Chemoradiation and Total Mesorectal Excision: A Multicenter and Retrospective Propensity-Score Matching Study. International journal of radiation oncology, biology, physics. 2019;103(2):438–48. doi:https://doi.org/10.1016/j.ijrobp.2018.09.016.

  29. 29.

    Garlipp B, Ptok H, Benedix F, Otto R, Popp F, Ridwelski K et al. Adjuvant treatment for resected rectal cancer: impact of standard and intensified postoperative chemotherapy on disease-free survival in patients undergoing preoperative chemoradiation-a propensity score-matched analysis of an observational database. Langenbeck’s archives of surgery. 2016;401(8):1179–90. doi:https://doi.org/10.1007/s00423-016-1530-0.

  30. 30.

    Govindarajan A, Reidy D, Weiser MR, Paty PB, Temple LK, Guillem JG et al. Recurrence rates and prognostic factors in ypN0 rectal cancer after neoadjuvant chemoradiation and total mesorectal excision. Annals of surgical oncology. 2011;18(13):3666–72. doi:https://doi.org/10.1245/s10434-011-1788-y.

  31. 31.

    Ceelen W, Fierens K, Van Nieuwenhove Y, Pattyn P. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: a systematic review and meta-analysis. Int J Cancer. 2009;124(12):2966–72. doi:https://doi.org/10.1002/ijc.24247.

  32. 32.

    De Caluwe L, Van Nieuwenhove Y, Ceelen WP. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. The Cochrane database of systematic reviews. 2013(2):CD006041. doi:https://doi.org/10.1002/14651858.CD006041.pub3.

  33. 33.

    Latkauskas T, Paskauskas S, Dambrauskas Z, Gudaityte J, Saladzinskas S, Tamelis A et al. Preoperative chemoradiation vs radiation alone for stage II and III resectable rectal cancer: a meta-analysis. Colorectal Dis. 2010;12(11):1075–83. doi:https://doi.org/10.1111/j.1463-1318.2009.02015.x.

  34. 34.

    Yamamoto A, Toiyama Y, Okugawa Y, Saigusa S, Ide S, Fujikawa H et al. Identification of Predictors of Recurrence in Patients with Lower Rectal Cancer Undergoing Neoadjuvant Chemotherapy: A Direct Comparison of Short-Course and Long-Course Chemoradiotherapy. Oncology. 2019;96(2):70–8. doi:https://doi.org/10.1159/000492617.

Download references


We thank Susan Furness, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Author information

Correspondence to Yoshinaga Okugawa.

Ethics declarations

Written informed consent was obtained from each patient, and the study was approved by the institutional review boards of our institution.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Okugawa, Y., Toiyama, Y., Fujikawa, H. et al. Prognostic Potential of Lymphocyte–C-Reactive Protein Ratio in Patients with Rectal Cancer Receiving Preoperative Chemoradiotherapy. J Gastrointest Surg (2020). https://doi.org/10.1007/s11605-019-04495-4

Download citation


  • Lymphocyte–C-reactive protein ratio
  • Rectal cancer
  • Chemoradiotherapy