Accuracy of Preoperative Imaging in Detecting Nodal Extracapsular Spread in Oral Cavity Squamous Cell Carcinoma

Discussion

It became clear during our multidisciplinary tumor boards that our clinicians were increasingly relying on the imaging diagnosis of ECS to make major treatment decisions in patients with OPSCC. Escalating therapy to a multimodal approach involves significant morbidity and thus must be appropriately justified. Specifically, our clinicians were deciding against transoral robotic surgery in patients with preoperative radiographic evidence of ECS to avoid trimodality therapy for the patients. Because our institution did not have an adequate sample size to test the accuracy of imaging in diagnosing ECS in patients with OPSCC, we chose to evaluate its accuracy in a well-defined cohort of patients with OCSCC. Our primary objective was to determine the accuracy of imaging in diagnosing ECS so that our tumor board could best plan the treatment of patients with OPSCC, assuming that it is reasonable to extrapolate results based on OCSCC and apply them to OPSCC.

If treatment decisions are going to potentially be based on imaging detection of ECS, then the accuracy and limitations of imaging results must be taken into account. When we reviewed the literature, we found wide variation in the accuracy of imaging, mixed cohorts, and conflicting data. Furthermore, at least for oropharyngeal cancer, the biology has changed; most of our oropharyngeal cancers are related to human papillomavirus rather than to smoking or drinking alcohol.¹⁷ The cystic appearance of many human papillomavirus 16 positive oropharyngeal node metastases may complicate the radiologic evaluation of necrosis. Another important consideration is whether to err on the side of being overly sensitive or of being overly specific.¹⁸

Recently, Prabhu et al¹⁹ examined 432 patients undergoing neck dissections for head and neck cancer. The sensitivity and specificity for radiographically determined ECS were reported to be 43% and 97.7%, respectively. The sensitivity was lower and specificity much higher than previously reported. One possibility for the lower sensitivity of radiographically determined ECS in their study may have been the criteria for radiographically positive and negative ECS. When ECS status was not mentioned in the initial radiology report, it was recorded as radiographically negative for ECS. The preoperative images were not blindly reviewed, because the authors' purpose was to assess the predictive value of the original diagnostic interpretation. Because many of the study patients had OCSCC and the radiographic diagnosis of ECS would have been less critical and had little impact on the decision for neck dissection, it may not have always been reported initially by the neuroradiologist, falsely depressing sensitivity. Our study addressed this potential pitfall with a blinded review for all cases, in addition to the initial report, to validate these preliminary results.

In a second recent study, Chai et al²⁰ concluded that “radiologic findings suggestive of ECS should not be relied on for treatment planning in squamous cell carcinoma of the head and neck.” Chai et al²⁰ used a 5-point scale for the evaluation of radiographically determined ECS, included a wider range of primary tumors, and had 2 different observers with specificities of 54% and 84%, respectively. Our study aimed to limit a few of these variables by restricting the cohort to a single primary tumor for which surgical resection of the primary and cervical lymphatics is the standard initial treatment and by reporting “yes or no” for radiographically determined ECS on the basis of specific imaging features.

Our study not only tested the accuracy of the imaging diagnosis of ECS and interobserver agreement between 2 reviewers (A.H.A. and P.A.H.) but also examined the interobserver agreement between the original report and the subsequent blinded review looking specifically for ECS. It was not surprising that the reviewers detected a few more cases of ECS at the expense of more false-positive results. In other words, reviewers became more sensitive (67% compared with 46% in the original report) but slightly less specific (88% compared with 95% in the original report). Overall, both the review and the original report had high specificities for ruling in macroscopic ECS. Interobserver agreement between an original report and a subsequent blinded review has not been evaluated often, but it has important implications for practical use. We have shown that in a closed head and neck radiology group with a focus on staging head and neck cancers, interobserver agreement and specificity for ECS are strong. Our clinicians prefer a high specificity before recommending chemoradiation over transoral robotic surgery.

A very careful search for ill-defined node borders is key for identifying subtle ECS on imaging. We found that imaging specificity is high when fat stranding and ill-defined borders are identified. In these cases, the clinicians can rely on radiographically determined ECS to make treatment decisions (Fig 1A). When these specific imaging signs are absent, however, pECS is still present in nearly 50% of the cases, and therefore imaging cannot be used to exclude ECS (Fig 2).

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Fig 2.

A left 1-cm level IB lymph node (arrow) with abnormal FDG uptake and rounded morphology. Although it was interpreted from contrast-enhanced CT as a metastatic node, it was thought to be negative for ECS. This was a false-negative result, because ECS was found in the final pathologic examination.

Lymph node necrosis was the most important radiologic factor associated with radiographically determined ECS even when there was no irregularity of borders or stranding (Fig 3). One study reported a strong correlation between ECS and necrosis with 95% sensitivity and 85% specificity.¹⁵ A recent study by Joo et al,²¹ which involved PET/CT for the identification of ECS, showed that fluorodeoxyglucose uptake could elevate sensitivity and specificity for the detection of ECS above those of contrast-enhanced CT or MR imaging alone. The study showed that maximum standardized uptake values were significantly correlated with ECS (standardized uptake value detection cutoff, 2.25 on receiver operating characteristic curve demonstration; sensitivity and specificity, 85% and 88%, respectively).

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Fig 3.

A right 1.2-cm level IIA lymph node (arrow) in a patient with OCSCC. Necrosis was reported and ECS was diagnosed from imaging. This was a true-positive result that was confirmed with pathologic examination.

Limitations of this study include its retrospective nature. We used this cohort of patients with OCSCC to examine radiographic accuracy for diagnosing ECS and to extrapolate the diagnostic test characteristics to make treatment decisions for patients with OPSCC. The pathologic pattern of ECS may differ between these subsites, and therefore results of the imaging accuracy evaluation may have been affected. Second, our finding that lymph node necrosis was significantly correlated with ECS may be less reliable in a population of patients with oropharyngeal cancer because of the distinct pattern of cystic nodes in this population. Finally, the importance of both microscopic and macroscopic pECS was first appreciated in the era when oropharyngeal cancers were largely caused by tobacco and alcohol abuse, and as the virally induced oropharyngeal cancers are better understood, the prognostic effects of ECS may not be confirmed.⁴ At this time, however, pretreatment imaging profoundly influences the management of patients with oropharyngeal cancer, and accuracy remains of paramount importance.