Elective neck dissection for clinically stage N0 (cN0) disease has been called the gold standard in the management of early-stage oral squamous cell cancer (OSCC), despite advances in imaging technologies and the recent application of sentinel lymph node mapping.
1Approximately 30% of patients with cN0 disease have nodal metastasis found by pathology (pNϩ), [1][2][3][4][5] with poor prognosis, particularly if there is extracapsular spread. 6 To avoid the substantial risk of delayed detection and treatment, 7,8 elective neck dissection has been recommended for cN0 patients with a tumor invasion depth of 4 mm or greater.9 Neck dissection provides nearly definitive information about nodal metastasis. If no positive nodes are found, there is little risk of regional recurrence.5-10 Elective neck dissection alone can often represent sufficient treatment for early-stage disease, while guiding the use of adjuvant radiation and chemotherapy when indicated. Nevertheless, with approximately 70% of cN0 cases also pN0, elective neck dissection raises concern over unnecessary surgery and its associated morbidity.11 Thus, some clinicians instead recommend watchful waiting, hoping to detect and treat any nodal metastasis quickly, 2 whereas others argue that the potential therapeutic benefit of neck dissection outweighs the risk of morbidity.1 Consequently, interest in solving this clinical treatment dilemma has prompted continued investigation into novel ways to improve the management of the cN0 neck in early-stage OSCC.In the article that accompanies this editorial, van Hooff et al 12 report major advances toward a primary-tumor RNA expression signature to help in this choice. With a laboratory-made microarray, this group had previously identified genes whose expression levels in primary oral-cavity tumors were related to nodal metastasis. 13,14 They now have moved their analysis platform to a commercial microarray in a Clinical Laboratory Improvement Amendments/International Organization for Standardization-approved laboratory, finding a gene-expression signature-score cutoff in a "platform transition" cohort that provided 92% negative predictive value in cT1-T2N0 cases (ie, 92% of cases with negative expression signatures were actually metastasis free, based on pathologic evaluation of the neck dissection). They then used that signature cutoff to classify a "validation" cohort of 222 specimens from eight institutions, finding 89% negative predictive value and 86% assay sensitivity for detecting pNϩ cases. Major challenges, however, remain in incorporating these promising technical results into clinical practice.A major reason for Van Hooff et al's successful extension of earlier findings to the more clinically relevant setting of their study is the large number of diagnostic genes-696 genes, with a total of 732 microarray probe sequences-whose primary-tumor expression levels were used quantitatively. The risk of nodal metastasis for each patient was gauged by how closely each of its 732 expression values matched the correspo...