Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2017

01-04-2017 | Colorectal Cancer

Perineural Invasion is a Major Prognostic and Predictive Factor of Response to Adjuvant Chemotherapy in Stage I–II Colon Cancer

Authors: J. A. Cienfuegos, MD, PhD, P. Martínez, MD, J. Baixauli, MD, PhD, C. Beorlegui, MD, S. Rosenstone, MD, BA, J. J. Sola, MD, PhD, J. Rodríguez, MD, PhD, J. L. Hernández-Lizoáin, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2017

Login to get access

Abstract

Background

Perineural invasion (PNI) in colon cancer (CC) has been associated with poorer prognosis even in stage II disease (T3–4 N0 M0). The aim of this study is to analyze prognostic histopathologic factors in stage II colon cancer in patients treated with curative surgery as established in National Comprehensive Cancer Network guidelines.

Methods

From a prospective database of CC cases, 507 patients with stage I–II disease who had undergone curative resection from January 2000 and December 2012 were identified. Of these patients, 17 % received 5-flurouracil-based adjuvant chemotherapy. Together with demographic and anatomic variables, we also studied perineural and lymphovascular invasion, degree of differentiation, and their correlation with disease-free survival.

Results

Perineural invasion was identified in 57 patients (11.2 %) and lymphovascular invasion (LVI) in 82 (16.2 %) of the 507 patients. Perineural invasion was associated with LVI, the depth of invasion of the wall of the colon, and location of the tumor. Overall and disease-free survival of the complete series at 5 and 10 years was 89.5, 85.2, 83.2 and 81.6 %, respectively. In the PNI positive patients, disease-free survival at 5 years was significantly lower than in those without PNI (73.5 vs 88.6 %; p = 0.02). Multivariate analysis showed the presence of PNI to be a significant independent prognostic factor for disease-free survival (p = 0.025). Adjuvant chemotherapy reversed the impact of PNI on 5- to 10-year disease-free survival.

Conclusions

PNI a major prognostic and predictive factor in stage II colon cancer, and our results support the use of adjuvant chemotherapy in patients with PNI.
Literature
1.
2.
3.
American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th ed. New York: Springer New York; 2010.CrossRef
4.
Andre T, de Gramont A, Vernerey D, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33:4176–87.CrossRefPubMed
5.
Quasar Collaborative Group, Gray R, Barnwell J, et al. Adjuvant chemotherapy versus observation in patients with colorectal cancer: A randomised study. Lancet. 2007;370:2020–9.CrossRef
6.
Shah MA, Renfro LA, Allegra CJ, et al. Impact of patient factors on recurrence risk and time dependency of oxaliplatin benefit in patients with colon cancer: Analysis from modern-era adjuvant studies in the adjuvant colon cancer end points (ACCENT) database. J Clin Oncol. 2016;34:843–53.CrossRefPubMedPubMedCentral
7.
O’Connor ES, Greenblatt DY, LoConte NK, Gangnon RE, Liou JI, Heise CP, Smith MA. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011;29:3381–8.CrossRefPubMedPubMedCentral
8.
Tournigand C, Andre T, Bonnetain F, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the multicenter international study of oxaliplatin, fluorouracil, and leucovorin in the adjuvant treatment of colon cancer trial. J Clin Oncol. 2012;30:3353–60.CrossRefPubMed
9.
Benson AB 3rd, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–19.CrossRefPubMed
10.
Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349:247–57.CrossRefPubMedPubMedCentral
11.
Quah HM, Chou JF, Gonen M, et al. Identification of patients with high-risk stage II colon cancer for adjuvant therapy. Dis Colon Rectum. 2008;51:503–7.CrossRefPubMed
12.
13.
14.
Venook AP, Niedzwiecki D, Lopatin M, et al. Biologic determinants of tumor recurrence in stage II colon cancer: validation study of the 12-gene recurrence score in cancer and leukemia group B (CALGB) 9581. J Clin Oncol. 2013;31:1775–81.CrossRefPubMedPubMedCentral
15.
16.
O’Connell MJ, Lavery I, Yothers G, et al. Relationship between tumor gene expression and recurrence in four independent studies of patients with stage II/III colon cancer treated with surgery alone or surgery plus adjuvant fluorouracil plus leucovorin. J Clin Oncol. 2010;28:3937–44.CrossRefPubMedPubMedCentral
17.
Maak M, Simon I, Nitsche U, et al. Independent validation of a prognostic genomic signature (ColoPrint) for patients with stage II colon cancer. Ann Surg. 2013;257:1053–8.CrossRefPubMed
18.
Phipps AI, Limburg PJ, Baron JA, et al. Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology. 2015;148:77–87.e2.CrossRefPubMed
19.
Figueredo A, Charette ML, Maroun J, Brouwers MC, Zuraw L. 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. 2004;22:3395–407.CrossRefPubMed
20.
Tournigand C, de Gramont A. Chemotherapy: is adjuvant chemotherapy an option for stage II colon cancer? Nat Rev Clin Oncol. 2011;8:574–6.CrossRefPubMed
21.
Andre T, Sargent D, Tabernero J, et al. Current issues in adjuvant treatment of stage II colon cancer. Ann Surg Oncol. 2006;13:887–98.CrossRefPubMed
22.
Fang SH, Efron JE, Berho ME, Wexner SD. Dilemma of stage II colon cancer and decision making for adjuvant chemotherapy. J Am Coll Surg. 2014;219:1056–69.CrossRefPubMed
23.
American Society of Anesthesiologists. New classification of physical status. Anesthesiology. 1963;24:111.
24.
West NP, Hohenberger W, Weber K, Perrakis A, Finan PJ, Quirke P. Complete mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon. J Clin Oncol. 2010;28:272–8.CrossRefPubMed
25.
Chang GJ, Kaiser AM, Mills S, Rafferty JF, Buie WD, Standards Practice task force of the American Society of Colon and rectal surgeons. practice parameters for the management of colon cancer. Dis Colon Rectum. 2012;55:831–43.CrossRefPubMed
26.
Washington MK, Berlin J, Branton P, et al. Protocol for the examination of specimens from patients with primary carcinoma of the colon and rectum. Arch Pathol Lab Med. 2009;133:1539–51.PubMedPubMedCentral
27.
Jass JR, O’Brien J, Riddell RH, Snover DC, Association of Directors of Anatomic and Surgical Pathology. Recommendations for the reporting of surgically resected specimens of colorectal carcinoma: association of directors of anatomic and surgical pathology. Am J Clin Pathol. 2008;129:13–23.CrossRefPubMed
28.
American Joint Committee on Cancer. AJCC Cancer Staging Manual. 6th ed. New York: Springer New York; 2006:294.
29.
Hamilton S, Bosman F, Boffetta P, et al. Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban R, Theise ND, eds. WHO Classification of Tumours of the Digestive System. 4th ed. Lyon: International Agency for Research on Cancer; 2010:134–46.
30.
31.
32.
Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: A review of the literature. Cancer. 2009;115:3379–91.CrossRefPubMed
33.
Betge J, Langner C. Vascular invasion, perineural invasion, and tumour budding: Predictors of outcome in colorectal cancer. Acta Gastroenterol Belg. 2011;74:516–29.PubMed
34.
Sato T, Ueno H, Mochizuki H, et al. Objective criteria for the grading of venous invasion in colorectal cancer. Am J Surg Pathol. 2010;34:454–62.CrossRefPubMed
35.
36.
Yothers G, Song N, George TJ, Jr. Cancer hallmark-based gene sets and personalized medicine for patients with stage II colon cancer. JAMA Oncol. 2016;2:23–4.CrossRefPubMed
37.
Gill S, Loprinzi CL, Sargent DJ, et al. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol. 2004;22:1797–806.CrossRefPubMed
38.
Niedzwiecki D, Bertagnolli MM, Warren RS, et al. 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. J Clin Oncol. 2011;29:3146–52.CrossRefPubMedPubMedCentral
39.
McKenzie S, Nelson R, Mailey B, et al. Adjuvant chemotherapy improves survival in patients with American Joint Committee on Cancer stage II colon cancer. Cancer. 2011;117:5493–9.CrossRefPubMed
40.
41.
Yothers G, O’Connell MJ, Lee M, et al. Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin. J Clin Oncol. 2013;31:4512–9.CrossRefPubMedPubMedCentral
42.
Gray RG, Quirke P, Handley K, et al. 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. 2011;29:4611–9.CrossRefPubMed
43.
Kopetz S, Tabernero J, Rosenberg R, et al. Genomic classifier ColoPrint predicts recurrence in stage II colorectal cancer patients more accurately than clinical factors. Oncologist. 2015;20:127–33.CrossRefPubMedPubMedCentral
44.
Gao S, Tibiche C, Zou J, Zaman N, Trifiro M, O’Connor-McCourt M, Wang E. Identification and construction of combinatory cancer hallmark-based gene signature sets to predict recurrence and chemotherapy benefit in stage II colorectal cancer. JAMA Oncol. 2016;2:37–45.CrossRefPubMed
45.
Poeschl EM, Pollheimer MJ, Kornprat P, et al. Perineural invasion: Correlation with aggressive phenotype and independent prognostic variable in both colon and rectum cancer. J Clin Oncol. 2010;28:358–60; author reply e361–2.
46.
Huh JW, Kim HR, Kim YJ. Prognostic value of perineural invasion in patients with stage II colorectal cancer. Ann Surg Oncol. 2010;17:2066–72.CrossRefPubMed
47.
Huh JW, Lee JH, Kim HR, Kim YJ. Prognostic significance of lymphovascular or perineural invasion in patients with locally advanced colorectal cancer. Am J Surg. 2013;206:758–63.CrossRefPubMed
48.
Desolneux G, Burtin P, Lermite E, Bergamaschi R, Hamy A, Arnaud JP. Prognostic factors in node-negative colorectal cancer: A retrospective study from a prospective database. Int J Colorectal Dis. 2010;25:829–34.CrossRefPubMed
49.
Yang Y, Huang X, Sun J, et al. Prognostic value of perineural invasion in colorectal cancer: A meta-analysis. J Gastrointest Surg. 2015;19:1113–22.CrossRefPubMed
50.
Knijn N, Mogk SC, Teerenstra S, Simmer F, Nagtegaal ID. Perineural invasion is a strong prognostic factor in colorectal cancer: a systematic review. Am J Surg Pathol. 2016;40:103–112.CrossRefPubMed
51.
Roth AD, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: Results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol. 2010;28:466–74.CrossRefPubMed
52.
Suzuki T, Suwa K, Ogawa M, et al. Adjuvant chemotherapy for the perineural invasion of colorectal cancer. J Surg Res. 2015;199:84–9.CrossRefPubMed
53.
54.
Zhang JX, Song W, Chen ZH, et al. Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. Lancet Oncol. 2013;14:1295–306.CrossRefPubMed
Metadata
Title
Perineural Invasion is a Major Prognostic and Predictive Factor of Response to Adjuvant Chemotherapy in Stage I–II Colon Cancer
Authors
J. A. Cienfuegos, MD, PhD
P. Martínez, MD
J. Baixauli, MD, PhD
C. Beorlegui, MD
S. Rosenstone, MD, BA
J. J. Sola, MD, PhD
J. Rodríguez, MD, PhD
J. L. Hernández-Lizoáin, MD, PhD
Publication date
01-04-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 4/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5561-0

Other articles of this Issue 4/2017

Annals of Surgical Oncology 4/2017 Go to the issue

Gastrointestinal Oncology

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion in Adolescent and Young Adults with Peritoneal Metastases

Pancreatic Tumors

Survival Analysis and Risk for Progression of Intraductal Papillary Mucinous Neoplasia of the Pancreas (IPMN) Under Surveillance: A Single-Institution Experience

Pancreatic Tumors

Laparoscopic Partial Splenectomy for Unknown Primary Cancer: A Stepwise Approach

Gastrointestinal Oncology

Current Delivery of Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery (CS/HIPEC) and Perioperative Practices: An International Survey of High-Volume Surgeons

Gastrointestinal Oncology

Ushering in a New Era for Regional Therapies

Breast Oncology

Sentinel-Lymph-Node-Based Management or Routine Axillary Clearance? Five-Year Outcomes of the RACS Sentinel Node Biopsy Versus Axillary Clearance (SNAC) 1 Trial: Assessment and Incidence of True Lymphedema