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University of Milan, Milan, Department of Thoracic Surgery, European Institute of Oncology, Via Ripamonti 435, Milan, 20141 Italy
(Email: lorenzo.spaggiari{at}ieo.it).
The article by Farjah and colleagues [1] is very interesting, and two aspects are relevant; on one hand, only 9% of patients affected by T4 nonsmall cell lung cancer (NSCLC) are eligible for lung resection; on the other, survival of a carefully selected group of patients may be very promising (5 yrs > 40%).
Patients affected by T4 NSCLC present a heterogeneous disease that is often associated with bulky lympho-nodal involvement; concurrent or sequential chemoradiotherapy represents the gold standard treatment, but 5-year survival is less than 10%.
"T4 multiple nodular" disease is a different oncological entity that does not require complex surgical procedures and that has a different oncological impact from "T4 mediastinal" disease. This group of T4 NSCLC (multiple nodules) should be considered separately from the whole T4 group.
Quite rarely, lung neoplasm may infiltrate tracheal carina, superior vena cava, left atrium, thoracic aorta, and the origin of the pulmonary artery without concomitant bulky lympho-nodal involvement (T4N0/N1); this group is the so called "potentially respectable T4 lung cancer." These neoplasms (mainly carinal tumors and tumors invading the superior vena cava) may be radically resected without residual disease, with a 5-yr survival probability greater than 40% in cases with N0 or N1 disease.
The crucial points in T4 NSCLC disease are the lack of N2/N3 disease, and the possibility of a "true" radical resection. For this reason, complete preoperative assessment is mandatory. Radiological imaging evaluation by an expert surgeon is crucial to plan an extended resection. Personally I do not believe that exploratory thoracotomy represents a staging tool to evaluate the feasibility of a surgical resection, and therefore should not be part of the "decision-making" process. The surgeon should be able to evaluate the possibility of a radical resection before thoracotomy, and once resection is decided, the surgical procedure should be done only in highly specialized centers.
Today the use of positron emission tomographic scan, mediastinoscopy, and video thoracoscopy (if minimal pleural effusion is present) is mandatory to exclude mediastinal or pleural involvement (N2/N3) before planning an extended resection.
It is quite surprising how few mediastinoscopies were done in the present series (20%) and that only 28% of patients had radical lymphadenectomy. These data are at the least surprising from an oncological point of view.
The discussion of T4 nowadays relates to the role of induction chemotherapy and how it may helpful to improve long-term survival in this highly selected group of patients. The theoretic benefit of preoperative induction chemotherapy or chemoradiotherapy is yet to be confirmed. However, it is reasonable to believe that induction therapy could offer some advantages as: an early control of systemic micro-metastases; reduction of tumor mass increasing the number of resectable patients; reducing the rate of extended resections; and, finally, to exclude from surgery patients affected by a rapidly progressive disease, causing early failure of surgical treatment. Because chemotherapy has improved long-term survival when associated with surgical treatment in the early stage disease (and in N1/N2 disease), it is reasonable to believe that chemotherapy may also be effective for locally advanced patients, as these cases usually develop systemic and not local recurrence. Even though there is no phase III study comparing induction chemotherapy versus surgery alone in T4 disease, there are some phase II studies reporting a 5-yr survival rate ranging from 42% to 57% in T4 patients who previously had induction chemotherapy.
In conclusion, considering the lack of information from a randomized study, recent experiences of referral centers support the idea that extended resection for T4 (mainly carina and superior vena cava) NSCLC may be considered in highly selected patients without mediastinal involvement (proved by mediastinoscopy) and after induction chemotherapy or chemoradiotherapy.
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  L. Spaggiari Invited commentary. Ann. Thorac. Surg., August 1, 2009; 88(2): 397 - 398. [Full Text] [PDF]
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