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Lymph Node Ratio Improves TNM and Astler-Coller’s Assessment of Colorectal Cancer Prognosis: an Analysis of 761 Node Positive Cases

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Prognosis assessment of node-positive colorectal cancer patients by Astler-Coller (AC) and TNM classifications is suboptimal. Recently, several versions of lymph node ratio (LNR; ratio metastatic/examined nodes) have been proposed but are still mostly unused.

Methods

The prognostic value of several criteria, including LNR (two classes—LNR1 and LNR2—identified by a 15 % cut-off) was studied in 761 consecutive patients, from 2000 through 2010. The relationships between total examined nodes, N, T and LNR were also analysed. LNR1 and LNR2 patients’ survival was analysed within AC and TNM subgroups, and then coupled with them.

Results

Age, tumour location and LNR are independent factors predicting survival. The relationships between LNR, N stage and T stage with examined nodes suggest confusing factors. LNR allows for identification of subgroups with different survival within AC and TNM classifications (p < 0.0001). Patients with LNR class discordant from AC stage (LNR1-C2 and LNR2-C1) have a similar 5-year survival (54 and 57 %, respectively). LNR2 and TNM stage IIIC define a poor 5-year prognosis (33 %).

Conclusions

LNR is a powerful prognosis predictor, easily integrated with TNM and AC classifications to improve prognosis assessment and facilitate clinical use. Possible confusing factors should be considered in future studies.

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References

  1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer 2013; 49:1374–1403

    Article  PubMed  CAS  Google Scholar 

  2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63:11–30

    Article  PubMed  Google Scholar 

  3. Lykke J, Roikjaer O, Jess P; Danish Colorectal Cancer Group. The relation between lymph node status and survival in stage I–III colon cancer: results from a prospective nationwide cohort study. Colorectal Dis. 2013; 15:559–565

    Article  PubMed  CAS  Google Scholar 

  4. Lan YT, Yang SH, Chang SC, Liang WY, Li AF, Wang HS, Jiang JK, Chen WS, Lin TC, Lin JK. Analysis of the seventh edition of American Joint Committee on colon cancer staging. Int J Colorectal Dis 2012; 27:657–6663

    Article  PubMed  Google Scholar 

  5. Sjo OH, Merok MA, Svindland A, Nesbakken A. Prognostic impact of lymph node harvest and lymph node ratio in patients with colon cancer. Dis Colon Rectum 2012; 55:307–315

    Article  PubMed  Google Scholar 

  6. O'Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with the New American Joint Committee on Cancer Sixth Edition Staging. J Natl Cancer Inst. 2004; 96:1420–1425

    Article  PubMed  Google Scholar 

  7. Dukes CE, Bussey HJ. The spread of rectal cancer and its effect on prognosis. Br J Cancer. 1958; 12:309–320

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Fleming ID, Cooper JS, Henson DE et al. American Joint Committee on Cancer. AJCC cancer staging manual, 5th edition. Philadelphia: Lippincott-Raven, 1997

    Google Scholar 

  9. Greene FL, Page DL, Fleming ID et al. American Joint Committee on Cancer. AJCC cancer staging manual, 6th edition. New York: Springer-Verlag, 2002

    Book  Google Scholar 

  10. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. American Joint Committee on Cancer. AJCC cancer staging manual, 7th edition. New York: Springer, 2010

    Google Scholar 

  11. Akagi Y, Adachi Y, Ohchi T, Kinugasa T, Shirouzu K. Prognostic impact of lymphatic invasion of colorectal cancer: a single-center analysis of 1,616 patients over 24 years. Anticancer Res 2013; 33:2965–2970

    PubMed  Google Scholar 

  12. Sato T, Ueno H, Mochizuki H, Shinto E, Hashiguchi Y, Kajiwara Y, Shimazaki H, Hase K. Objective criteria for the grading of venous invasion in colorectal cancer Am J Surg Pathol 2010; 34:454–462

    Article  PubMed  Google Scholar 

  13. De la Chapelle A, Hampel H. Clinical relevance of microsatellite instability in colorectal cancer. J Clin Oncol 2010; 28:3380–3387

    Article  PubMed  PubMed Central  Google Scholar 

  14. Walther A, Houlston R, Tomlinson I. Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis. Gut 2008; 57:941–950

    Article  PubMed  CAS  Google Scholar 

  15. Eklöf V, Wikberg ML, Edin S, Dahlin AM, Jonsson BA, Öberg Å, Rutegård J, Palmqvist R. The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer. Br J Cancer 2013; 108:2153–2163

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cushman-Vokoun AM, Stover DG, Zhao Z, Koehler EA, Berlin JD, Vnencak-Jones CL. Clinical utility of KRAS and BRAF mutations in a cohort of patients with colorectal neoplasms submitted for microsatellite instability testing. Clin Colorectal Cancer 2013; 12:168–178

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Hari DM, Leung AM, Lee JH, Sim MS, Vuong B, Chiu CG, Bilchik AJ. AJCC Cancer Staging Manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg 2013; 217:181–190

    Article  PubMed  Google Scholar 

  18. Prandi M, Lionetto R, Bini A, Francioni G, Accarpio G, Anfossi A, Ballario E, Becchi G, Bonilauri S, Carobbi A, Cavaliere P, Garcea D, Giuliani L, Morziani E, Mosca F, Mussa A, Pasqualini M, Poddie D, Tonetti F, Zardo L, Rosso R. Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy: results of a secondary analysis of a large scale adjuvant trial. Ann Surg 2002; 235:458–463

    Article  PubMed  PubMed Central  Google Scholar 

  19. Caplin S, Cerottini JP, Bosman FT, Constanda MT, Givel JC. Forpatients with Dukes’ B (TNM Stage II) colorectal carcinoma,examination of six or fewer lymph nodes is related to poor prognosis. Cancer 1998; 83:666–672

  20. Fielding LP, Arsenault PA, Chapuis PH, Dent O, Gathright B, Hardcastle JD, Hermanek P, Jass JR, Newland RC. Clinicopathological staging for colorectal cancer: an International Documentation System (IDS) and an International Comprehensive Anatomical Terminology (ICAT). J Gastroenterol Hepatol 1991; 6:325–344

    Article  PubMed  CAS  Google Scholar 

  21. Wong JH, Severino R, Honnebier MB, Tom P, Namiki TS. Number of nodes examined and staging accuracy in colorectal carcinoma. J Clin Oncol 1999; 17:2896–2900

    PubMed  CAS  Google Scholar 

  22. Goldstein NS, Sanford W, Coffey M, Layfield LJ.Lymph node recovery from colorectal resection specimens removed for adenocarcinoma: Trends over time and a recommendation for a minimum number of lymph nodes to be removed. Am J Clin Pathol 1996; 106:209–216

    PubMed  CAS  Google Scholar 

  23. Le Voyer TE, Sigurdson ER, Hanlon AL, Mayer RJ, Macdonald JS, Catalano PJ, Haller DG. Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol 2003; 21:2912–2919

    Article  PubMed  Google Scholar 

  24. Inoue K, Nakane Y, Iiyama H, Sato M, Kanbara T, Nakai K, Okumura S, Yamamichi K, Hioki K. The superiority of ratio-based lymph node staging in gastric carcinoma. Ann Surg Oncol 2002; 9:27–34

    Article  PubMed  Google Scholar 

  25. Riediger H, Keck T, Wellner U, zur Hausen A, Adam U, Hopt UT, Makowiec F. The limph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg 2009; 13:1337–1344

    Article  PubMed  Google Scholar 

  26. Megale Costa LJ, Soares HP, Gaspar HA, Trujillo LG, Santi PX, Pereira RS, de Santana TL, Pinto FN, del Giglio A. Ratio between positive lymph nodes and total dissected axillaries lymph nodes as an independent prognostic factor for disease-free survival in patients with breast cancer. Am J Clin Oncol 2004; 27:304–306

    Article  PubMed  Google Scholar 

  27. Herr HW. Superiority of ratio based lymph node staging for bladder cancer. J Urol 2003; 169:943–945

    Article  PubMed  Google Scholar 

  28. Berger AC, Sigurdson ER, LeVoyer T, Hanlon A, Mayer RJ, Macdonald JS, Catalano PJ, Haller DG. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol 2005; 23:8706–8712

    Article  PubMed  Google Scholar 

  29. Elias E, Mukherji D, Faraj W, Khalife M, Dimassi H, Eloubeidi M, Hattoum H, Abou-Alfa GK, Saleh A, Shamseddine A. Lymph-node ratio is an independent prognostic factor in patients with stage III colorectal cancer: a retrospective study from the Middle East. World J Surg Oncol 2012; 10:63

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rosenberg R, Friederichs J, Schuster T, Gertler R, Maak M, Becker K, Grebner A, Ulm K, Höfler H, Nekarda H, Siewert JR. Prognosis of patients with colorectal cancer is associated with lymph node ratio: a single-center analysis of 3,026 patients over a 25-year time period. Ann Surg 2008; 248:968–978

    Article  PubMed  Google Scholar 

  31. Vather R, Sammour T, Kahokehr A, Connolly AB, Hill AG. Lymph node evaluation and long-term survival in stage II and stage III colon cancer: a national study. Ann Surg Oncol 2009; 16:585–593

    Article  PubMed  Google Scholar 

  32. Kritsanasakul A, Boonpipattanapong T, Wanitsuwan W, Phukaoloun M, Prechawittayakul P, Sangkhathat S. Impact of Lymph Node Retrieval on Surgical Outcomes in Colorectal Cancers. J Surg Oncol 2012; 106:238–242

    Article  PubMed  Google Scholar 

  33. Hong KD, Lee SI, Moon HY. Lymph node ratio as determined by the 7th edition of the American Joint Committee on Cancer staging system predicts survival in stage III colon cancer. J Surg Oncol 2011; 103:406–410

    Article  PubMed  Google Scholar 

  34. Ceelen W, Van Nieuwenhove Y, Pattyn P. Prognostic Value of the Lymph Node Ratio in Stage III Colorectal Cancer: A Systematic Review. Ann Surg Oncol 2010; 17:2847–2855

    Article  PubMed  CAS  Google Scholar 

  35. Faiclough DL Ed. Analysis of quality of life studies in clinical trials, 2nd edition. New York: Chapman & Hall/CRC-Taylor and Francis Group, 2010

    Google Scholar 

  36. Pietra N, Sarli L, Costi R, Ouchemi C, Grattarola M, Peracchia A. Role of follow-up in management of local recurrences of colorectal cancer: a prospective, randomized study. Dis Colon Rectum 1998; 41:1127–1133

    Article  PubMed  CAS  Google Scholar 

  37. Gao P, Song YX, Wang ZN, Xu YY, Tong LL, Zhu JL, Tang QC, Xu HM. Integrated ratio of metastatic to examined lymph nodes and number of metastatic lymph nodes into the AJCC Staging System for Colon Cancer. PLoS One 2012; 7:e35021

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Wang JP, Hassett JM, Dayton MT, Kulaylat MN. Lymph node ratio: role in the staging of node-positive colon cancer. Ann Surg Oncol 2008; 15:1600–1608

    Article  PubMed  Google Scholar 

  39. Derwinger K, Carlsson G, Gustavsson B. A study of lymph node ratio as a prognostic marker in colon cancer. Eur J Surg Oncol 2008; 34:771–775

    Article  PubMed  CAS  Google Scholar 

  40. Lee HY, Choi H, Park K, Shin J, Kwon H, Roh M, Kim C. Prognostic Significance of Metastatic Lymph Node Ratio in Node-Positive Colon Carcinoma. Annals of Surgical Oncology 2007; 14:1712–1717

    Article  PubMed  Google Scholar 

  41. Schumacher P, Dineen S, Barnett C, Fleming J, Anthony T. The metastatic lymph node ratio predicts survival in colon cancer. Am J Surg 2007; 194:827–832

    Article  PubMed  Google Scholar 

  42. Peschaud F, Benoist S, Julie C, et. al. The ratio of metastatic to examined lymph nodes is a powerful independent prognostic factor in rectal cancer. Ann Surg 2008; 248:1067–1073

  43. Thomas M, Biswas S, Mohamed F, Chandrakumaran K, Jha M, Wilson R. Dukes C colorectal cancer: is the metastatic lymph node ratio important? Int J Colorectal Dis 2012; 27:309–317

    Article  PubMed  Google Scholar 

  44. Lee SD, Kim TH, Kim DY, Baek JY, Kim SY, Chang HJ, Park SC, Park JW, Oh JH, Jung KH. Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection. Eur J Surg Oncol 2012; 38:478–483

    Article  PubMed  CAS  Google Scholar 

  45. Park HC. Clinical significance of the metastatic lymph-node ratio in rectal cancer. Ann Coloproctol 2013; 29:89–90

    Article  PubMed  PubMed Central  Google Scholar 

  46. De Ridder M, Vinh-Hung V, Van Nieuwenhove Y, Hoorens A, Sermeus A, Storme G. Prognostic value of the lymph node ratio in node positive colon cancer. Gut 2006; 55:1681

    Article  PubMed  PubMed Central  Google Scholar 

  47. Schiffmann L, Eiken AK, Gock M, Klar E. Is the lymph node ratio superior to the Union for International Cancer Control (UICC) TNM system in prognosis of colon cancer? World J Surg Oncol 2013; 11:79

    Article  PubMed  PubMed Central  Google Scholar 

  48. Tepper JE, O'Connell MJ, Niedzwiecki D, et al. Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 2001; 19:157–163

    PubMed  CAS  Google Scholar 

  49. Feinstein AR, Sosin DM, Wells CK. The Will Rogers phenomenon. Stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med 1985; 312:1604–1608

    Article  PubMed  CAS  Google Scholar 

  50. Shahrier M, Ahnen DJ. Colorectal cancer survival in Europe: the Will Rogers phenomenon revisited. Gut 2000; 47:463–464

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. George S, Primrose J, Talbot R, Smith J, Mullee M, Bailey D, du Boulay C, Jordan H; Wessex Colorectal Cancer Audit Working Group. Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists. Br J Cancer 2006; 95:841–847

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  52. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 1990; 322:352–358

    Article  PubMed  CAS  Google Scholar 

  53. André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A. Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004; 350:2343–2351

    Article  PubMed  Google Scholar 

  54. André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009; 27:3109–3116

    Article  PubMed  Google Scholar 

  55. Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 2011; 29:1465–1471

    Article  PubMed  CAS  Google Scholar 

  56. de Gramont A, Van Cutsem E, Schmoll HJ, Tabernero J, Clarke S, Moore MJ, Cunningham D, Cartwright TH, Hecht JR, Rivera F, Im SA, Bodoky G, Salazar R, Maindrault-Goebel F, Shacham-Shmueli E, Bajetta E, Makrutzki M, Shang A, André T, Hoff PM. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol 2012; 13:1225–1233

    Article  PubMed  Google Scholar 

  57. Peng J, Xu Y, Guan Z, Zhu J, Wang M, Cai G, Sheng W, Cai S. Prognostic significance of the metastatic lymph node ratio in node-positive rectal cancer. Ann Surg Oncol 2008; 15:3118–3123

    Article  PubMed  Google Scholar 

  58. Moug SJ, McColl G, Lloyd SM, Wilson G, Saldanha JD, Diament RH. Comparison of positive lymph node ratio with an inflammation-based prognostic score in colorectal cancer. Br J Surg 2011; 98:282–286

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Dr. Luca Ampollini (Clinica di Chirurgia Toracica, Dipartimento di Scienze Chirurgiche, Università degli Studi di Parma), Dr. Francesco Bozzani (Registro Tumori, Unità Operativa di Oncologia Medica, Azienda Ospedaliero-Universitaria di Parma), Dr. Pier Luigi Losardo (Servizio di Radioterapia, Dipartimento Onco-Ematologico Internistico, Azienda Ospedaliero-Universitaria di Parma) and Dr. Caterina Ghetti (Servizio di Fisica Sanitaria, Azienda Ospedaliera di Parma) for their precious contribution.

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Authors and Affiliations

  1. Sezione di Chirurgia Generale e Terapia Chirurgica, Dipartimento di Scienze Chirurgiche, Università di Parma, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43100, Parma, Italy

    Renato Costi MD, PhD, FACS, Filippo Beggi MD, Valeria Reggiani MD, Francesco Tartamella MD, Vincenzo Violi MD, Luigi Roncoroni MD & Leopoldo Sarli MD

  2. Sezione di Sanità Pubblica, Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali (S.Bi.Bi.T.), Università di Parma, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

    Matteo Riccò MD

  3. Sezione di Anatomia Patologica, Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali (S.Bi.Bi.T.), Università di Parma, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

    Pellegrino Crafa MD

  4. Dipartimento Polispecialistico 1, Unità Operativa di Oncologia Medica, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

    Melissa Bersanelli MD

  5. Dipartimento di Chirurgia Generale e Specialistica, Unità Operativa di Chirurgia Generale, Ospedale di Fidenza, AUSL, Parma, Italy

    Vincenzo Violi MD

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  1. Renato Costi MD, PhD, FACS
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  2. Filippo Beggi MD
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  3. Valeria Reggiani MD
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  4. Matteo Riccò MD
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  7. Francesco Tartamella MD
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  8. Vincenzo Violi MD
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  9. Luigi Roncoroni MD
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  10. Leopoldo Sarli MD
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Correspondence to Renato Costi MD, PhD, FACS.

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Costi, R., Beggi, F., Reggiani, V. et al. Lymph Node Ratio Improves TNM and Astler-Coller’s Assessment of Colorectal Cancer Prognosis: an Analysis of 761 Node Positive Cases. J Gastrointest Surg 18, 1824–1836 (2014). https://doi.org/10.1007/s11605-014-2591-4

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