Abstract
Purpose
There is evidence to suggest that a nodal yield <18 is an independent prognostic factor in patients with clinically node negative (cN0) oral squamous cell carcinoma (SCC) treated with elective neck dissection (END). We sought to evaluate this hypothesis with external validation and to investigate for heterogeneity between institutions.
Patients and Methods
We analyzed pooled individual data from 1,567 patients treated at nine comprehensive cancer centers worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional hazard models, stratified by study center, and adjusted for age, sex, pathological T and N stage, margin status, extracapsular nodal spread, time period of primary treatment, and adjuvant therapy. Two-stage random-effects meta-analyses were used to investigate for heterogeneity between institutions.
Results
In multivariable analyses of patients undergoing selective neck dissection, nodal yield <18 was associated with reduced overall survival [hazard ratio (HR) 1.69; 95 % confidence interval (CI) 1.22–2.34; p = 0.002] and disease-specific survival (HR 1.88; 95 % CI 1.21–2.91; p = 0.005), and increased risk of locoregional recurrence (HR 1.53; 95 % CI 1.04–2.26; p = 0.032). Despite significant differences between institutions in terms of patient clinicopathological factors, nodal yield, and outcomes, random-effects meta-analysis demonstrated no evidence of heterogeneity between centers in regards to the impact of nodal yield on disease-specific survival (p = 0.663; I 2 statistic = 0).
Conclusion
Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.
Similar content being viewed by others
References
Ferlay J, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.
Kademani D. Oral cancer. Mayo Clin Proc. 2007;82(7):878–87.
Campana JP, Meyers AD. The surgical management of oral cancer. Otolaryngol Clin N Am. 2006;39(2):331–48.
Clark JR, et al. Established prognostic variables in N0 oral carcinoma. Otolaryngol Head Neck Surg. 2006;135(5):748–53.
Ebrahimi A, Ashford BG, Clark JR. Improved survival with elective neck dissection in thick early-stage oral squamous cell carcinoma. Head Neck. 2012;34(5):709–16.
Huang SH, et al. Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity: a meta-analysis of reported studies. Cancer. 2009;115(7):1489–97.
Brunocilla E, et al. The number of nodes removed as well as the template of the dissection is independently correlated to cancer-specific survival after radical cystectomy for muscle-invasive bladder cancer. Int Urol Nephrol. 2013;45(3):711–9.
Wright JL, Lin DW, Porter MP. The association between extent of lymphadenectomy and survival among patients with lymph node metastases undergoing radical cystectomy. Cancer. 2008;112(11):2401–8.
Weir L, et al. Prognostic significance of the number of axillary lymph nodes removed in patients with node-negative breast cancer. J Clin Oncol. 2002;20(7):1793–9.
Chang GJ, et al. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst. 2007;99(6):433–41.
Le Voyer TE, et al. 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(15):2912–9.
Volpe CM, Driscoll DL, Douglass HO Jr. Outcome of patients with proximal gastric cancer depends on extent of resection and number of resected lymph nodes. Ann Surg Oncol. 2000;7(2):139–44.
Peyre CG, et al. The number of lymph nodes removed predicts survival in esophageal cancer: an international study on the impact of extent of surgical resection. Ann Surg. 2008;248(4):549–56.
Greenstein AJ, et al. Effect of the number of lymph nodes sampled on postoperative survival of lymph node-negative esophageal cancer. Cancer. 2008;112(6):1239–46.
Ebrahimi A, et al. Nodal yield and survival in oral squamous cancer: defining the standard of care. Cancer. 2011;117(13):2917–25.
Stukel TA, et al. Two-stage methods for the analysis of pooled data. Stat Med. 2001;20(14):2115–30.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.
Capote A, et al. Elective neck dissection in early-stage oral squamous cell carcinoma: does it influence recurrence and survival? Head Neck. 2007;29(1):3–11.
Sigurdson ER. Lymph node dissection: is it diagnostic or therapeutic? J Clin Oncol. 2003; 21(6):965–7.
Morris EJ, et al. Identifying stage III colorectal cancer patients: the influence of the patient, surgeon, and pathologist. J Clin Oncol. 2007;25(18):2573–9.
Bilimoria KY, et al. Adequacy and importance of lymph node evaluation for colon cancer in the elderly. J Am Coll Surg. 2008;206(2):247–54.
Author information
Authors and Affiliations
Corresponding author
Additional information
The International Consortium for Outcome Research (ICOR) in Head and Neck Cancer.
Rights and permissions
About this article
Cite this article
Ebrahimi, A., Clark, J.R., Amit, M. et al. Minimum Nodal Yield in Oral Squamous Cell Carcinoma: Defining the Standard of Care in a Multicenter International Pooled Validation Study. Ann Surg Oncol 21, 3049–3055 (2014). https://doi.org/10.1245/s10434-014-3702-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-014-3702-x