Invasive Staging and Aggressive Surgical Resection: Essential to Management of Central NSCLC

Drs. Backhus and Wood are to be congratulated on their review of the management of centrally located non–small-cell lung cancer (NSCLC), in this issue of ONCOLOGY.[1] The essential premise is that central (T3 or T4) tumors are potentially curable. The authors rightly emphasize key elements required to achieve a satisfactory outcome: a multidisciplinary approach, accurate staging, and surgical exploration.

A multidisciplinary approach requires an experienced, board-certified thoracic surgeon who performs lung cancer surgery, in addition to experienced medical oncologists, thoracic radiologists, and pulmonary physicians. An interdisciplinary evaluation and discussion of the approaches to diagnosis, staging, and management should occur upon initial presentation or prior to final treatment recommendations.

Clinical staging by imaging alone is more likely to be inaccurate with central lung cancers because of the anatomic proximity of adjacent structures. Chest CT scans have a lower specificity for determining invasion of tissue planes. Positron emission tomography (PET) scans, while useful for identifying systemic metastatic disease, have a higher false-negative rate for mediastinal lymph nodes in central tumors. Finally, magnetic resonance imaging (MRI) scans are superior to CT for observing tissue planes but can overestimate disease extent if there is local inflammation at the tumor site. Thus, upon confirmation of the absence of systemic metastases, some form of invasive mediastinal staging is required to accurately stage central lung cancers. The authors favor bronchoscopy and ultrasonographic examination (EBUS, EUS) of adjacent structures with transmural aspiration of suspicious mediastinal nodes. Ideally the thoracic surgeon can do this as an outpatient procedure. With modern imaging and recording technology, however, EBUS and EUS can be performed by a trained interventional pulmonologist with subsequent review of the video and (if obtained) pathology by the surgeon, to assess operative candidacy. This approach has a significant cost advantage over use of these methods at the time of resection.[2] We also favor cervical mediastinoscopy at resection for patients with negative EBUS/EUS staging, to enhance the sensitivity and negative predictive value of the endoscopic staging and to technically facilitate the surgery, particularly in central airway resections.

The cornerstone of surgery for central lung cancers, after staging, is complete surgical resection. All studies of these lung cancer types identify the survival advantage of a complete resection, with this factor even more significant than the actual T stage of the tumor and use of neoadjuvant therapy.[3,4] The majority of studies also confirm the negative prognostic impact of mediastinal nodal (N2) metastases.[5,6] The question of the extent of resection for central lung cancer (with pathologically negative N2 nodes) is realistically constrained only by the limits of the patient’s physiology and the surgeon’s technical expertise. Patients meeting these criteria are a very small minority of those with central lung cancers. Similarly, the degree of surgical expertise required to aggressively resect these lesions, including intraoperative and postoperative management, can be found in only a small percentage of institutions managing lung cancer. However, extending the concept of bronchoplastic resection of central airway lesions to include the tracheal carina, and to electively use cardiopulmonary bypass to facilitate central vascular resections, has been demonstrated to be feasible, and yields long-term survival similar to that achieved with sleeve airway or vascular resection alone.[5,6] Finally, when managed by a multidisciplinary surgical team, extension of superior sulcus tumor resections to include the vertebral bodies has had equivalent outcomes.[7]

As the authors note, neoadjuvant therapy (chemoradiotherapy) improves survival following resection of superior sulcus tumors and has become the standard of care for these lesions. However, pathologic complete response (CR), which correlates significantly with survival, is much higher for superior sulcus tumors (> 50% CR) than for other types of NSCLC.[3,8] The reason for this finding, which has been consistently identified for over a decade, is unclear. Until a similar response rate can be demonstrated for other central lung cancers, there is no indication for neoadjuvant therapy other than for tumors involving the superior sulcus. Metastases to peribronchial lymph nodes (N1) do not appear to adversely impact the outcome of surgical resection of central lung cancers, from a technical or survival standpoint.[3,4] Conversely, N2 metastases do negatively impact survival following resection of these tumors, and remain a contraindication to resection in most cases.[5,7]

In summary, central lung cancers, when appropriately staged, are optimally treated by surgical resection. Initial evaluation is best done by a multidisciplinary team, involving a trained thoracic surgeon. Recognition of the limits of clinical staging with these tumors allows selection of patients with localized disease to be more accurately staged by invasive methods. Patients without N2 disease, who have adequate physiologic reserve, should undergo a planned and coordinated surgical approach to achieve a complete resection. Given the favorable outcomes in terms of morbidity, mortality, and survival, referral to an appropriate thoracic surgical center should be contemplated for such patients in the absence of available surgical expertise.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Backhus LM, Wood DE. Management of centrally located non–small-cell lung cancer. Oncology (Williston Park). 2014;28:215-21.

2. Sharples LD, Jackson C, Wheaton E, et al. Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomized controlled trial. Health Technol Assess. 2012;16:1-75.

3. Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation and surgical resection for superior sulcus non-small cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Clin Oncol. 2007;25:313-8.

4. Merritt RE, Mathisen DJ, Wain JC, et al. Long-term results of sleeve lobectomy in the management of non-small cell lung carcinoma and low grade neoplasms. Ann Thorac Surg. 2009;88:1574-82.

5. dePerrot M, Fadel E, Mercier O, et al. Long-term results after carinal resection for carcinoma: does the benefit warrant the risk? J Thorac Cardiovasc Surg. 2006;131:81-9.

6. Muralidaran A, Detterbeck FC, Boffa DJ, et al. Long-term survival after lung resection for non-small cell lung cancer with circulatory bypass: a systematic review. J Thorac Cardiovasc Surg. 2011;142:1137-42.

7. Fadel E, Missenard G, Court C, et al. Long-term outcomes of en bloc resection of non-small cell lung cancer invading the thoracic inlet and spine. Ann Thorac Surg. 2011;92:1024-30.

8. Koshy M, Fedewa SA, Malik R, et al. Improved survival associated with neoadjuvant chemoradiation in patients with clinical stage IIIA (N2) non-small-cell lung cancer. J Thorac Oncol. 2013;8:915-22.