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Ann Thorac Surg 2001;71:1777-1778
© 2001 The Society of Thoracic Surgeons
a Section of General Thoracic Surgery, Virginia Mason Medical Center, 1100 Ninth Ave, Seattle, WA 98111-0900, USA
e-mail: gtsdel{at}vmmc.org
The article by Wu and associates is a retrospective report of the results of an immunohistochemical (IHC) assessment of patients with early stage non-small cell lung cancer. However, it is really an acknowledgment of the fact that a significant component of patients with perceived early stage disease will recur following surgical therapy alone, verifying the perception that a large percentage of lung cancer patients are under-staged using current techniques.
The article examines 103 patients who would historically be considered the most favorable prognostic subset of all patients with non-small cell lung cancer. IHC analysis produced a change in stage in 19.8% of cases. In some, these were dramatic, ie, changes from surgical stage 1A to 3A and 3B. Previous assessments of IHC applications in tumor staging have appropriately included concerns regarding which IHC technique is most appropriate and accurate. Dr Wu’s analysis is compelling because they have validated the accuracy of their IHC results with follow-up demonstrating a significant difference in five year survival between patients with micrometastasis (61.9%) compared to those without micrometastasis (86.3%).
Their assessments have included the identification of a subset of patients, specifically those with poorly differentiated tumors and lymphatic invasion, which are more likely to demonstrate micrometastasis with IHC. They have also supported the perception that certain subtypes of bronchoalveolar cell cancers (specifically type A and B) have a significantly decreased risk of early lymphatic spread as manifested by a virtual absence of micrometastasis in this group and the identification of 100% 5-year survivorship.
This article reinforces the importance of anatomic resection and careful lymph node analysis to obtain appropriate staging information even in individuals presenting with early stage disease. The overall accuracy of any staging approach will still be contingent on the completeness of nodal sampling at mediastinoscopy and thoracotomy, and the acuity of the assessment of the standard H&E slides. In our laboratory, IHC assessment costs approximately $50 per slide, although this would superficially appear to increase the expense of managing these patients, the cost would be considered small if it resulted in improved staging and treatment decisions in 20% of patients initially thought to have early stage disease.
This report raises the question as to whether IHC techniques should be applied in all patients undergoing mediastinoscopy. Improving the accuracy of the assessment to differentiate early stage patients from those with 3A and 3B disease prior to thoracotomy would greatly facilitate the decision regarding neoadjuvant therapy in this patient population. Dr Wu’s data suggest that the most cost effective approach should direct IHC analysis at all patients with poorly differentiated tumors and lymphatic invasion. The results would also provide additional support to the evolving concept that patients with early stage type A and B bronchoalveolar cell carcinomas may be managed appropriately with non-anatomic resections.
How much weight to ultimately give IHC assessment will evolve as experience broadens and the accuracy and cost of individual methods of IHC analysis improves. Improving the accuracy of staging non-small cell lung cancer patients will facilitate more appropriate application of prognostic information, decision making especially with respect to neoadjunvant and adjuvant treatment protocols, and potentially improved initial stage allocation within clinical trials. Wu’s data supports previous publications [1, 2] which show that IHC identification of micrometastasis in patients strongly correlates with early relapse and decrease in disease-free survival. There is no general agreement, however, as to what type of IHC analysis is the most accurate or cost effective [3].
Lung cancer currently has a poorer prognosis than breast, prostate, and colon cancer. This in part is explained by the inability of current techniques to identify micrometastatic disease when it exists. This situation may be improved with increased application of PET scanning, however, its accuracy with true micrometastatic disease will likely be limited. As systemic therapy for non-small cell lung cancer continues to improve, long term survival in patients with micrometastatic disease will become increasingly common. Immunohistochemical analysis is likely to play an increasing role in improving overall staging accuracy in non-small cell lung cancer patients thereby decreasing the incidence of under-staged patients and ensuring that patients receive a treatment plan appropriate for their level of disease.
References
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