Tumour location predicts occult N1 nodal metastases in clinical stage I non-small-cell lung cancer: is location alone sufficient to justify limiting the extent of resection?

Identification of clinically occult node metastases at the time of surgical resection is commonly referred to as nodal upstaging. In the setting of surgical resection for non-small-cell lung cancer, it is defined as the presence of unsuspected node metastases either in the hilar (N1) or mediastinal (N2) nodes in patients with clinical N0 disease. It has long been recognized to occur in a significant number of patients operated on for lung cancer, dating back the results of CALGB 9761, which showed that nodal upstaging occurred in 28% of patients in the trial—14% upstaged to N1 and 14% to N2 disease [1]. As clinical staging has improved over time, the rate of nodal upstaging has decreased significantly for the N2 node stations to where it is now estimated to occur in ∼5% of patients with stage I disease [2, 3]. However, nodal upstaging remains common in the N1 node stations with recent studies indicating that upstaging still occurs in about 13% of patients who undergo lobectomy by the open thoracotomy technique [4, 5].

As alternatives to open lobectomy are becoming more commonplace, considerable interest has focused on the topic of nodal upstaging as a means of assessing the oncologic ‘soundness’ of different procedures. The known expected rate of occult nodal disease defined by the traditional gold standard open surgical technique can be compared to alternatives including Video-assisted thoracic surgery (VATS) lobectomies and more recently anatomic segmentectomy procedures. Several large nationwide database studies would indicate that the rate of nodal upstaging is lower for VATS lobectomy than for open surgical resections [4, 5]. While less well studied, the rate of nodal upstaging for segmentectomy procedures appears to be even lower in the range of 4–5% [6, 7]. These data emphasize the importance of a complete node dissection as part of a standard lung resection for lung cancer. Unless we can identify reliable clinical predictors of the absence of occult nodal disease, care must be exercised in applying surgical techniques known to result in lower-than-expected rates of nodal upstaging. Otherwise, involved lymph nodes will be left behind leading to the possibility of local recurrence and it risks under staging patients, denying patients with node involvement the beneficial effects of adjuvant chemotherapy.

Previous studies have identified several clinical factors associated with the presence of occult hilar node disease. These include tumour size, maximum Standardized uptake value (SUV) on Positron emission tomography (PET) imaging, Carcinoembryonic antigen (CEA) values and tumour location. Of these, the most reliable predictor is tumour location with significantly lower rates of occult nodal disease for peripherally located tumours. The problem with this variable is that definitions vary with some studies using the outer 1/3, others the outer 1/2 and still others the outer 2/3s of the lung field, and in all cases, the definitions are subjective. Furthermore, neither tumour location or any of the other variables has proven reliable enough on their own to limit or omit a complete hilar node dissection in the setting of a solid tumour of the lung.

In this issue of the European Journal of Cardiothoracic Surgery, Kawamoto et al. [8] have described a novel, objective method of assessing tumour location which they have evaluated as a possible predictor of occult hilar node disease or N1 nodal upstaging. In this study, limited to clinical stage I lung cancer with solid tumour nodules, they observed a frequency of occult hilar nodal metastases of 14.6%, which is very similar to the rate of nodal upstaging referenced above. They defined tumour location based on the distance ratio (DR) defined as the distance from the hilum to the central limit of the tumour divided by the distance to the pleural surface along the same line. Using a threshold of 0.67, they showed that more peripherally located tumours were less likely to have occult nodal disease than were more centrally located tumours (7.4% vs 21.5%). They performed a multivariable analysis including the variables associated with occult hilar node disease mentioned previously and only the DR was an independent predictor of occult nodal disease.

These findings, if confirmed in subsequent studies, may be a step forward in identifying patients in whom an aggressive node dissection can safely be omitted. Clearly, a central tumour with a DR of <0.67 requires a careful and systematic node dissection given their expected rate of nodal upstaging of over 20%. Caution should be exercised in recommending segmental resections in these patients. The question is whether the DR alone is sufficient to identify a group of patients at low enough risk of occult node disease that a systematic hilar node dissection can be omitted. With an expected rate of nodal upstaging of 7.4% for tumours with a DR of >0.67, location alone may not be sufficient.

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