In the development of treatment paradigms for cN0 neck, it is important to be aware that most patients with a cN0 neck presented no cancer cells in the cervical lymph nodes and that over-treating the neck should be avoided.
Systematic review and meta-analysis of the accuracy of diagnostic tests can answer some clinically relevant questions, highlight important gaps in the evidence and aid in the design of further studies. Our results are the first to use meta-analytic data in neck metastasis rate estimation on different pre-test probabilities among different diagnostic imaging techniques. Because most individual studies have a limited number of cases, meta-analysis uses more data and provides more reliable results.
The optimal method for managing cN0 neck in SCC of the head and neck remains controversial. In 1994, Weiss et al. [3
] recommended with decision analysis that when the probability of occult cervical metastases is more than 20% (with a positive predictive rate above 20%), the neck should be electively treated. Based on Bayesian theory, the predictive probability of neck nodal metastasis given that a test is negative or positive depends on the pre-test probability (baseline possibility), and the sensitivity and specificity of the test. According to our results, if the pretest prevalence (baseline possibility) of clinical occult neck metastases was set at 30%, the post-test negative predictive rate with negative CT, MRI, PET, and US results increased to 82%, 84%, 86% and 84%, respectively (with a positive neck lymph node metastasis rate below 20%), meaning a “watchful waiting policy” is possibly justified in these cases. In a recent report [8
], the threshold was estimated even higher (44.4%) for oral tongue cancer. The occult cervical lymph node metastasis rate has been estimated at 25%
35%, except for the glottic larynx, by palpation [9
]. Therefore, a “watchful waiting policy” is feasible for some low pre-test occult metastases in cN0 neck patients, such as clinically T1
2N0M0 lip cancer patients. However, some clinically T4N0 tongue or tongue base cancers may have pre-test probability >60%. Even with a negative imaging result, the post-test probability is still approximately 20% (Figure ), and elected neck dissection is still necessary for these patients. In patients with positive imaging results, even with a very low pretest possibility set at 10%, the positive nodal metastasis probabilities were all above 20% (47%, 27%, 36% and 25% for CT, MRI, PET and US, respectively). Elective neck dissection should be performed for all patients with positive pre-op diagnostic results.
According to our results, the pooled estimates for sensitivity were 52% (95% confidence interval [CI], 39%
65%), 65% (34
87%), 66% (47
80%) and 66% (54
77%) on a per-neck basis for CT, MRI, PET and US, respectively. The pooled estimates for specificity were 93% (87%
97%), 81% (64
91%), 87% (77
93%) and 78% (71
83%) for CT, MRI, PET and US, respectively. Our results are similar to a previous meta-analysis [5
], which compared PET to other traditional imaging modalities (including CT, MRI and US-guided fine-needle aspiration). This previous study concluded that PET was not superior to other imaging modalities in a cN0 neck work-up. However, the study was focused on all nodal statuses and subgroup analysis for N0 patients combined CT, MRI and US-guided fine-needle aspiration (US-FNA) in the same group.
PET exam is the more expensive imaging option for nodal surveillance; however, it did not provide better sensitivity and specificity. Therefore, it should not be routinely used in neck nodal status work-ups. In our opinion, CT or MRI is preferred for cN0 neck pre-op evaluation because CT and MRI had similar diagnostic sensitivities to PET and US. Furthermore, CT and MRI can evaluate the status of primary tumor at the same time. The US is an inexpensive and convenient tool to monitor nodal status and can be used with real-time guided fine-needle aspiration. However, the primary tumor lesion and some deep-seated lymph nodes, such as retropharyngeal nodes, cannot be assessed [10
The alignment of the results between preoperative imaging and histologic specimen after neck dissection should be taken into consideration. According to previous reported literatures [11
], the rate of regional recurrence in pN0 patients varying from 3% to 10%. Applying only the histopathological results as reference standard, one could underestimate the real occult metastasis rate. Therefore, we included studies using either pathological examinations, or clinical follow-up results, or both as references. Besides, the criteria for positive results in pre-operative diagnostic imaging were not uniform in different institutions, and may be operator-dependent. These variations all leaded to heterogeneity in this meta-analysis, and this was the reason to adapt a random effect model for data pooling.
During this review, we found that US-FNA had a very high specificity; if the US-FNA cytology had a positive result, almost all of the histology specimen results also proved positive [1
]. Therefore, in our opinion, US is preferred for neck status follow-up in “watchful waiting” patients, and US-FNA can be performed if nodal metastasis is suspected.
In our review, we did not include US-FNA because US-FNA cytology examination required a cytologist’s assistance and was used after US examination. However, it must be noted that US-FNA had 100% specificity because there were no false-positive cases. Therefore, we did not believe that the comparison of sensitivity, specificity and summary ROC curves were justified between US-FNA and other imaging modalities because the lack of false-positive cases spuriously inflates the value of the area under the ROC curve.
In our review and subsequent meta-analysis, we found modern imaging modalities had fair diagnostic performance in cN0 neck patients. For positive imaging results, elective neck dissection is indicated; for some select low-risk patients with pre-test probability below 30% of nodal metastasis, a “watchful waiting policy” may be an acceptable alternative to neck dissection if strict adherence to a cancer surveillance protocol is followed.