Synchronous, separate, and similar.

This issue of Journal of Thoracic Oncology includes two separate articles that have a lot of similarities.1,2 Both address the issue of what to do with patients that present with the synchronous finding of a primary lung cancer and an additional separate, yet similar lesion. The article by Finley et al.1 restricts its analysis to patients who were proven to have synchronous primary lung cancers, whereas the article by Kim et al.2 addresses patients who have one or more additional ground glass opacities (GGO), and the task of determining which of these additional lesions is malignant. These articles present a good opportunity to discuss the topic of how we should think of synchronous, separate nodules in patients with lung cancer. The article by Finley et al.1 has several unique features, starting with a new definition of what should be considered a second primary lung cancer. The widely used criteria proposed by Martini and Melamed3 in 1975 were empirically derived and have never been validated. An analysis of data suggests that for metachronous second primary lung cancers, a 4-year interval is better than the traditional 2-year interval.4,5 Finley et al. have added definitions to distinguish synchronous tumors, accepting them as second primary cancers if they are either of a different histologic type or subtype of adenocarcinoma. Because most of adenocarcinomas are of mixed subtypes, distinct tumors are defined by differing proportions of the subtypes. This distinction has been shown to correlate with genetic differences but has the advantage of being apparent by light microscopy.6 I believe that this definition will become the new standard, at least for synchronous tumors. Distinguishing tumors on the basis of genomic signatures remains costly, available only in research laboratories, is sometimes plagued by conflicting results,7–9 and, in fact, genetic features correlate quite well with details apparent by light microscopy.6,10 The study by Finley et al. also used careful staging of the patients to avoid considering patients as having synchronous second primary cancers if in fact they had evidence of metastases to distant sites or mediastinal nodes although full details are not explicit. Not all centers reporting on second primary lung cancers have used such a thorough evaluation, although this is recommended in the American College of Chest Physicians Lung Cancer guidelines.4,5 The survival observed in this study (5-year overall survival 55%) is better than most series of synchronous primary lung cancers (average 5-year survival 30%).11 Is this because of better patient selection (e.g., more careful staging)? Is this due to a changing spectrum of disease, with a greater proportion of more indolent tumors (e.g., due to computed tomography screening, increasing proportion of women or nonsmokers)? Or is this because we are seeing more of a different kind of non-small cell lung cancer that has a propensity for multifocal disease? Unfortunately, there is no information on recurrence patterns. This could shed light on whether we are dealing with “regular” lung cancers that have been carefully selected, in which case we should see primarily distant metastases among those patients that develop recurrent disease. However, if we are dealing with tumors that have a propensity to multifocal disease in the lungs, we would expect a high proportion of “local recur-