Background Adjuvant chemotherapy (AC) in Stage II Colon Cancer (CC) is still under debate. Choice should be based on patients and disease characteristics. According to guidelines AC should be considered in high-risk T3N0 patients. No data are available for better option in low-risk patients. The aim of the study is to retrospectively evaluate relapse-free survival (RFS) and disease-free survival (DFS) according to treatment received in T3N0 CC. Methods RFS and DFS are evaluated with Kaplan-Meier method. Multivariate Cox proportional hazard model was developed using stepwise regression, enter limit and remove limit were p = 0.10 and p = 0.15, respectively. Results 834 patients with T3N0 CC were recruited. Median age was 69 (29–93), M/F 463/371, 335 low-risk patients (40.2%), 387 high-risk (46.4%), 112 unknown (13.4%); 127 (15.2%) patients showed symptoms at diagnosis. Median sampled lymph nodes were 15 (1–76); 353 (42.3%) patients were treated with AC. Median follow up was 5 years (range 3–24). The 5-years RFS was 78.4% and the 5-years DFS was 76.7%. At multivariate analysis symptoms, lymph nodes, and adjuvant chemotherapy were prognostic factors for RFS. AC is prognostic factor for all endpoints. In low-risk group 5-years RFS was 87.3% in treated patients and 74.7% in non-treated patients (p 0.03); in high-risk group was respectively 82.7% and 71.4% (p 0.005). Conclusions Data confirmed the role of known prognostic factors and suggest the relevance of adjuvant chemotherapy also in low-risk stage II T3N0 CC patients. However, the highest risk in low-risk subgroup should be identified to be submitted to AC.
References
[1]
Jonker DJ, Spithoff K, Maroun J (2011) Adjuvant Systemic Chemotherapy for Stage II and III Colon Cancer after Complete Resection: An Updated Practice Guideline. Clinical Oncology 23 (5) 314–322.
[2]
Sato H, Maeda K, Sugihara K, Mochizuki H, Kotake K, et al. (2011) High-Risk Stage II Colon Cancer After Curative Resection. Journal of Surgical Oncology doi: 10.1002/jso.21914.
[3]
Stocchi L, Fazio VW, Lavery I, Hammel J (2011) Individual surgeon, pathologist and other factors affecting lymph node harvest in stage II colon carcinoma. Is a minimum of 12 examined lymph nodes sufficient? Ann Surg oncol 18: 405–12.
[4]
NIH Consensus Conference (1990) Adjuvant therapy for patients with colon and rectal cancer. JAMA 264: 1444–50.
[5]
Otchy D, Hyman NH, Simmang C, Anthony T, Buie WD, et al. (2004) Practice parameters for colon cancer. Dis Colon rectum 47: 1269–84.
[6]
National Comprehensive Cancer Network guidelines (2012) version 3. Available: http://www.nccn.org. Accessed 2012 Sept.
[7]
Compton CC, Fielding LP, Burgart LJ, Conley B, Cooper HS, et al. (2000) Prognostic factors in colorectal cancer. College of American Pathologist Consensus Statement 1999. Arch Pathol Lab Med 124: 979–994.
[8]
Benson AB III, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, et al. (2004) American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22: 3408–3419.
[9]
QUASAR Collaborative Group (2007) Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomized study. Lancet 370: 2020–2029.
[10]
Kuebler JP, Wieand HS, O'Connell MJ, Smith RE, Colangelo L, et al. (2007) Oxaliplatin combined with weekly bolus fliorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSAB P C-07. J Clin Oncol 25: 2198–2204.
[11]
Andre T, Boni C, Navarro M, Tabernero J, Hickish T, et al. (2009) 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 27: 3109–3116.
[12]
Gertler R, Rosenberg R, Schuster T, Friess H (2009) Defining a high-risk subgroup with colon cancer stages I and II for possible adjuvant therapy. Eur J Cancer 45: 2992–2999.
[13]
Figueredo A, Charette ML, Maroun J, Brouwers MC, Zuraw L (2004) Adjuvant therapy for stage II colon cancer: a systematic review from the Cancer Care Ontario Program in Evidence-based Care's Gastrointestinal Cancer Disease Site Group. J Clin Oncol 22 (16) 3395–3407.
[14]
Figueredo A, Coombes ME, Mukherjee S (2008) Adjuvant therapy for completely resected stage II colon cancer. Cochrane Database Syst Rev Jul 16 (3) CD005390.
[15]
Quah HM, Chou JF, Gonen M, Jinru S, Schrag D, et al. (2008) Identification of patients with high risk stage II colon cancer for adjuvant chemotherapy. Dis Colon Rectum 51: 503–507.
[16]
Sarli L, Bader G, Iusco D, Salvemini C, Di Mauro D, et al. (2005) Number of lymph nodes examined and prognosis of TNM stage II colon cancer. Eur J Cancer 41: 272–279.
[17]
Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, et al. (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349: 247–257.
[18]
Sargent DJ, Marsoni S, Monges J, Thibodeau SN, Labianca R, et al. (2010) Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28: 3219–3226.
[19]
Schrag D, Rifas-Shiman S, Saltz L, Bach PB, Begg CB, et al. (2002) Adjuvant chemotherapy use for medicare beneficiaries with stage II colon cancer. J Clin Oncol 19: 3999–4005.
[20]
O'Connor ES, Greenblatt DY, LoConte NK, Gangnon RE, Liou J, et al. (2011) Adjuvant Chemotherapy for Stage II Colon Cancer With Poor Prognostic Features. J Clin Oncol 29: 3381–3388.
[21]
International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators (1999) Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol 17: 1356–1363.
[22]
Gill S, Loprinzi CL, Sargent DJ, Thomé SD, Alberts SR, et al. (2004) Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much? J Clin Oncol 22: 1797–1806.
[23]
Sargent D, Sobrero A, Grothey A, O'Connell MJ, Buyse M, et al. (2009) Evidence for cure by adjuvant therapy in colon cancer: Observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol 27: 872–877.
[24]
Le Voyer TE, Sigurdson ER, Hanlon AL, Mayer RJ, Macdonald JS, et al. (2003) Colon cancer survival is associated with increasing number of lymph nodes analyzed: A secondary survey of intergroup trial INT-0089. J Clin Oncol 21: 2912–2919.
[25]
Weisenberger DJ, Siegmund KD, Campan M, Young J, Long T, et al. (2006) CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 38: 787–793.
[26]
Sinicrope FA, Sargent DJ (2009) Clinical implications of microsatellite instability in sporadic colon cancers. Curr Opin Oncol 21: 369–373.
[27]
Kim GP, Colangelo LH, Wieand HS, Paik S, Kirsch IR, et al. (2007) Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: A National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol 25: 767–772.
[28]
Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, et al. (2012) ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Annals of Oncology 23: 2479–2516 doi:10.1093/annonc/mds236.
[29]
Sinicrope FA, Sargent DJ (2012) “Molecular Pathways: Microsatellite Instability in Colorectal. Cancer: Prognostic, Predictive, and Therapeutic Implications.”. Clinical Cancer Res 18 (6) doi:10.1158/1078-0432.CCR-11-1469.
[30]
Poynter JN, Siegmund KD, Weisenberger DJ, Long TI, Thibodeau SN, et al. (2008) Colon Cancer Family Registry Investigators. Molecular characterization of MSI-H colorectal cancer by MLHI promoter meth-ylation, immunohistochemistry, and mismatch repair germline muta- tion screening. Cancer Epidemiol Biomarkers Prev 17: 3208–3215.
[31]
Niedzwiecki D, Bertagnolli MM, Warren RS, Compton CC, Kemeny NE, et al. (2011) Documenting the Natural History of Patients with Resected Stage II Adenocarcinoma of the Colon after Random Assignment to Adjuvant Treatment with Edrecolomab or Observation: Results From CALGB 9581. JCO 29: 3146–3152.
[32]
Roth AD, Delorenzi M, Tejpar S, Yan P, Klingbiel D, et al. (2012) Integrated Analysis of Molecular and Clinical Prognostic Factors in Stage II/III Colon Cancer. J Natl Cancer Inst 104 (21) 1635–1646 doi: 10.1093/jnci/djs427.
[33]
Hutchins G, Southward K, Handley K, Magill L, Beaumont C, et al. (2011) Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer. JCO 29: 1261–1270.
[34]
Salazar R, Roepman P, Capella G, Moreno V, Simon I, et al. (2011) Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. J Clin Oncol 29: 17–24.
[35]
Gray RG, Quirke P, Handley K, Lopatin M, Magill L, et al. (2011) Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol 29: 4611–4619.
[36]
Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA (2007) Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst 99 (6) 433–441.
[37]
Laubert T, Habermann JK, Hemmelmann C, Kleemann M, Oevermann E, et al. (2012) Metachronous metastasis- and survival-analysis show prognostic importance of lymphadenectomy for colon carcinomas. BMC Gastroenterology 12: 24 Available: http://www.biomedcentral.com/1471-230X/1？2/24. accessed 2013 Nov 14.
[38]
Santos C, López-Doriga A, Navarro M, Mateo J, Biondo S, et al. (2012) Clinico-pathological risk factors of stage II colon cancer: results of a prospective study. Colorectal Dis doi: 10.1111/codi.12028.
