Surgical Choices
Controversies in the Surgical
Treatment of Lung Cancer

By Harry J. D'Agostino, Jr., MD, FACS


It is generally agreed that surgery is the best treatment for lung cancer in that it offers the only real potential for cure. However, there is substantial debate regarding the various aspects of surgical treatment. Some of the major controversies regarding the surgical treatment of lung cancer are summarized here.

Mediastinoscopy

Mediastinoscopy is a minimal access procedure to biopsy mediastinal lymph nodes to determine the presence of metastases. A 3 cm incision is made at the base of the neck, just above the sternal notch. The trachea is located and the scope advanced along its anterior surface into the mediastinum. Lymph nodes in the superior mediastinum, tracheobronchial angles, and subcarinal region can be sampled. Although it usually performed under general anesthesia, it is an outpatient procedure with little patient discomfort or morbidity and almost no mortality. The presence of cancer in mediastinal nodes usually precludes an immediate surgical resection and other treatment modalities are offered. Therefore, mediastinoscopy is important for proper cancer staging and subsequent treatment of the lung cancer patient.

It should be noted that mediastinoscopy does not access all mediastinal lymph nodes. The nodes around the aortopulmonary window and aortic arch are difficult to reach, and the prevascular, retrotracheal, paraesophageal, and inferior pulmonary ligament areas are inaccessible. In general, the nodal stations that can be assessed are in a plane anterior to the trachea. If other nodes are enlarged or show tracer uptake on PET scanning, they must be accessed via the thoracic cavity.

The controversies involving mediastinoscopy revolve around the safety of the procedure and when it should be performed. In the past a number, many surgeons have been reluctant to do the procedure because of the close proximity to critical structures. There have been anecdotal experiences with biopsy of the pulmonary artery, aorta, superior vena cava and left atrium with obvious major consequences. Because of the limited incision, bleeding is usually uncontrollable, and an open chest procedure is required to repair the injury and salvage the patient. Although experience with mediastinoscopy is now widespread and the procedure taught in all thoracic surgery training programs, doubts about it still linger. Recently, a surgical colleague asked the author why he performs that "cavalier" operation!

The fears regarding mediastinoscopy are not as problematic as imagined. Although occasional problems do occur, the complication rates are minimal in experienced hands. A series by Hammoud et al from Washington University in St. Louis noted one death in 2137 mediastinoscopies, a mortality rate of 0.05 %.1

A number of thoracic surgeons believe that mediastinoscopy should be performed in all cases of suspected lung cancer. They cite the extremely low morbidity, as well as sensitivity and specificity rates of approximately 85 % and 100 %, respectively, that exceed those of chest CT (sensitivity 64 %, specificity 62 %).2,3 Other thoracic surgeons have taken a "middle of the road" approach to mediastinoscopy, reserving the procedure for those patients with enlarged mediastinal nodes (> 1 cm) demonstrated on CT scan.4 It is also commonly used in the marginal surgical candidate: the discovery of nodal metastases can obviate thoracotomy in a compromised patient.

The advent of PET scanning has improved the detection of mediastinal lymph node metastases compared to chest CT. In a recent study, PET scanning had a sensitivity of 81 %, specificity 96 %, and positive and negative predictive values of 92 % and 90 %, respectively, which were similar to those achieved by mediastinoscopy.5 PET scanning also identified positive nodes in areas not accessible to mediastinoscopy and redirected the approach to other diagnostic modalities. Because of these advances, PET scan has been touted as an alternative to mediastinoscopy and carries the additional advantage of cancer detection in inaccessible or distant areas. However, mediastinoscopy is still advised because of the false negative and false positive rates and the potential consequences of both understaging and overstaging are significant.

Video-assisted thoracoscopic surgery (VATS)

Video thoracoscopy represents the thoracic equivalent of laparoscopy. Not only can intrathoracic pathology be visualized by minimally invasive means, but also a wide variety of procedures can be carried out. Initially, these were limited to biopsies of lung and pleura, or drainage of pleural effusions. However, with improved equipment and experience, virtually any thoracic procedure can be performed with VATS.

VATS is very useful in the evaluation of lung cancer. The suspected lesion can be removed via small incisions, sparing the patient the morbidity of a major thoracotomy. Mediastinal lymph nodes not accessible by mediastinoscopy can be sampled. Furthermore, evidence of unresectability (e.g. pleural implants or tumor invasion of mediastinal structures) can avert a major thoracotomy. Finally, several centers have reported the use of VATS for major pulmonary resections, including lobectomy and pneumonectomy.6,7

The controversy regarding VATS for lung cancer revolves around its use in major pulmonary resections for cancer. It is generally believed that palpation plays an important role in the assessment of the tumor mass, and its invasion of other structures. This "hands on" evaluation is lost with VATS. In addition, the palpation of the remaining lung for occult tumor nodules is not possible. There is concern regarding the ability to perform a complete resection and a proper lymph node dissection with VATS. Also, even after the intended lobe or lung is separated from adjacent structures, its removal from the pleural cavity requires a much larger incision, the so-called "utility thoracotomy." Thus, the potential advantage of small incisions may be lost. In addition, there is a temptation to perform less than a standard resection for small peripheral lesions. This has significant implications for local control, recurrence, and survival (see below). Finally, there are a number of reports of tumor implants discovered in access port incisions. This incidence appears to be low, less than 1 %, but still represents a failure of tumor eradication.8

Proponents of VATS lobectomy / pneumonectomy show evidence that the ability to provide a standard lung resection and a proper mediastinal lymph node dissection is preserved. There is some evidence that these patients have decreased pain and analgesic requirements, as well as better lung function early after surgery.9 However, these advantages appear to be lost within a few weeks. Finally, although some series suggest that the overall morbidity, mortality, and length of stay are less with thoracoscopic resection, these studies have been poorly controlled. Currently there is no published randomized trial available that addresses this controversy.

There is also interest in the "mini-thoracotomy" approach.10 A 6 _ 8 cm incision is made in the infrascapular region. The chest wall muscles are not divided, but spread along the fiber length. Access is achieved via the appropriate intercostal space, avoiding trauma to or resection of ribs. This procedure is similar to the "utility thoracotomy" necessary for lobe/lung removal in VATS. Most procedures can be done through a mini-thoracotomy using standard techniques and instruments. The patients appear to have better pain control postoperatively, as well as similar or slightly shorter length of stay.

The author has had experience with both VATS and mini-thoracotomy approaches for lung resection and has been favorably impressed by both. Each offers advantages in various clinical situations. Obviously, any new procedure must achieve morbidity, mortality, and long-term survival rates equivalent to those of standard thoracotomy.

For an in-depth discussion of the role of VATS in lung cancer, the reader is referred to the excellent article by Pajaro in this issue of Jacksonville Medicine.

Limited pulmonary resections

The definitive treatment for carcinoma of the lung is lobectomy (or pneumonectomy). However, for patients with borderline pulmonary function, extensive pulmonary resections can carry increased morbidity and mortality, as well as have significant impact on quality (and length) of life. Also, new primary lung cancers can arise over time, requiring further resection and loss of more lung tissue. . Furthermore, the advent of VATS now provides the ability to perform lesser resections through minimal incisions with potential for decreased morbidity. Therefore, surgeons have questioned whether lesser resections (e.g. segmentectomy or wedge excision) in small, peripheral cancers (T1 N0) might give a similar long-term survival rates while sparing precious pulmonary parenchyma.

To address this issue, a randomized trial was conducted by the Lung Cancer Study Group.11 In a group of 246 patients with T1 N0 lung cancers, 122 underwent limited resections (segmentectomy or wedge), while the remaining patients received standard lobectomy. In the limited resection group, the local recurrence rate was tripled and the death rate was increased by 30 % when compared with the lobectomy group. Potential reasons for this may be due to cancer cells in lobar lymphatics or intrapulmonary lymph nodes that may not be removed by a limited resection. The evidence suggests is that lobectomy continues to be the procedure of choice for cure. Lesser resections carry increased risks of local recurrence and reduced survival and should only be done in poor risk individuals.

Mediastinal Lymph Node Dissection

During surgery for lung cancer (and most other cancers), evaluation of regional spread (i.e., nodal metastasis) is important for accurate staging, subsequent treatment, and ultimately, prognosis. It is customary to take lymph node biopsies in the chest at the time of pulmonary resection for carcinoma. However, many thoracic surgeons do not routinely performed a systematic removal of all accessible mediastinal lymph nodes at the time of surgery. Some of the reasons cited for this include 1) the likelihood of systemic spread at the time of presentation, negating the curative (or staging) value of such a procedure; 2) the lack of evidence that survival is improved; 3) technical difficulty; 4) prolonged operative time; 5) increased complication rate.

Not surprisingly, there is a broad range of opinion regarding the utility of a complete mediastinal lymphadenectomy. According to Naruke12, Japanese surgeons consider this a fundamental part of the operation. Procedures that are not accompanied by en bloc nodal dissections are considered "incomplete" and "palliative." Surgeons in the United States do not necessarily share this view.13

A mediastinal lymph node dissection encompasses a region from the superior mediastinum to the diaphragm. This includes the pretracheal tissue, the subcarinal area, the inferior pulmonary ligament, and the region between the esophagus and the aorta. It also includes the aortopulmonary window in left-sided resections and the region of the azygos vein in right-sided resections.

The most direct benefit of a systematic mediastinal lymph node dissection is the accurate staging of the cancer. The discovery of occult disease in mediastinal lymph nodes results in assigning patients to higher cancer stages. Clearly this impacts prognosis and often changes the treatment strategy. For example, radiation and/or chemotherapy may be recommended, with the hope that additional treatment may translate to improvement in long-term survival. It has also been suggested that the removal of tumor-bearing nodes may improve loco-regional control and have an additional impact on long-term survival.

Most studies have failed to demonstrate a survival benefit for complete mediastinal lymph node dissection. However, a recent study from the Eastern Oncology Group found that patients with Stage II and IIIA disease who underwent complete mediastinal lymph node dissection had an improved median survival over those patients who had only lymph node sampling (57.5 versus 29.2 months).14 This was statistically significant only for patients with right lung tumors. However, it does suggest that a more thorough removal of lymph tissue may improve survival. A prospective, randomized controlled trial sponsored by the American College of Surgeons is currently underway to answer this question.

A number of series have shown that mediastinal lymph node dissection adds about 15 to 30 minutes to the operating time. Although there is potential for injury to adjacent structure such as the recurrent laryngeal nerve or the thoracic duct, the actual incidence of complications is extremely low, less than 5 %.14 Therefore, additional risk to the patient from mediastinal lymph node dissection is less of a concern.

There has been significant debate about the utility of mediastinal lymph node dissection or lymph node sampling) in small, peripheral lung cancers (< 3 cm). One study found a 26 % incidence of metastases to hilar or mediastinal lymph nodes.15 Furthermore, there was a 25 % incidence of "skip" metastasis, i.e. mediastinal nodes were found to be positive for tumor when hilar nodes were not. This suggests that evaluation of mediastinal lymph nodes is important even in Stage I lung cancer.

It is the author's current position is that mediastinal lymph node dissection should be performed in every case of lobectomy or pneumonectomy. He has been surprised numerous times by the discovery of occult nodal disease in patients who otherwise would have been classified as Stage I. In each case, adjuvant treatment (i.e., radiation and/or chemotherapy) was offered. It is not yet known whether these patients will experience a survival benefit from the change in treatment strategy. However, at this time, there is every good reason to perform a complete mediastinal lymph node dissection, and no reason to avoid it.

Neoadjuvant Therapy

Surgery for lung cancer (as with most other solid organ cancers) is most effective for local disease. Unfortunately, a number of patients present with involvement of mediastinal lymph nodes, which usually contraindicates surgery. In addition, patients can also present with tumors that are locally confined, but invade critical structures in the mediastinum. Such patients have also been considered "out of bounds" for surgical intervention, and have usually been offered palliative treatment. With the realization that surgery offers the best potential for cure, more attention has been given to making resection possible for these patients through the use of preoperative radiation and/or chemotherapy. This "cart before the horse" approach has produced some limited but significant improvements in survival in selected patient populations.

One of the earliest demonstrations of preoperative therapy was with the Pancoast tumor. This is a locally advanced tumor in which a carcinoma of the apex of the upper lobe extends into the chest wall and brachial plexus. In 1956 Paulson and colleagues encountered such a patient. Believed to be inoperable, the patient was treated with radiation. The tumor decreased in size so significantly that it became operable. Resection was performed, which included the lobe, chest wall, lower cord of the brachial plexus and a portion of the vertebral bodies. The patient not only survived the operation but was cured. In 1961, these surgeons reported positive results with preoperative radiation therapy and radical resection for Pancoast tumor is a series of eighteen patients.16 Later, in an update, it was noted that the original patient had survived for twenty-seven years! This confirmed the utility of preoperative radiotherapy for tumors invading other structures that would ordinarily make surgery difficult, hazardous, or impossible. Later studies extended this concept to include preoperative chemotherapy.

Currently there are a number of protocols for preoperative ("neoadjuvant") therapy followed by surgery. Patients are staged according to standard methods, then treated. Most protocols involve both radiotherapy and chemotherapy, as it appears that the results are better overall with both modalities combined than for either one alone. Patients are then reevaluated (restaged) and suitable candidates proceed to surgery.

Patients engaged in neoadjuvant protocols represent a surgical challenge. Since the disease is locally advanced, more radical procedures, such as intrapericardial pneumonectomy, are often required to achieve complete resection. Furthermore, the tissue quality in the operative field has been altered substantially by the preoperative therapy. Scarring, bleeding, and tissue healing are important issues. In particular, the healing of the bronchus following lung removal is critical. Breakdown of this closure can have catastrophic consequences.

Various studies have noted that up to one-half of patients who undergo surgery will have no living tumor found in the resected specimen. This is referred to as "pathologic complete response" and suggests that the preoperative therapy has actually destroyed the tumor. A pathologic complete response is a favorable factor and correlates with longer survival. It also raises the question as to whether the resection was necessary.

The study by Stamatis et al illustrates these concepts.17 In a group of 56 patients with advanced lung cancer (Stage IIIB) treated with a neoadjuvant protocol, the overall 5-year survival was 26 %. Historically, survival in these patients has been less than 10 %.18 For those patients who were completely resected, the 5-year survival was 43 % and was 50 % in those patients with a pathologic complete response. Half of the operated patients required a pneumonectomy for complete resection. Although these are impressive results, it is important to note that 39 % of the patients did not complete the protocol because of comorbidities or persistence of advanced disease. The 5-year survival rate for these patients was 0 %.

Not surprisingly, patients treated with a neoadjuvant therapy /surgery protocol have higher morbidity and mortality. In a group of 350 patients with small and non-small cell lung cancer, Stages II and III, Stamatis found that the surgical mortality following chemoradiotherapy was 4.9 %.19 However, the morbidity was 44 %. Risk factors for morbidity included increased age, lower functional status, and cardiac disease. Clearly patient selection is critical to the successful application of a neoadjuvant protocol.

The initial results of neoadjuvant therapy protocols appear promising, improving survival in groups of patients with otherwise poor outcome. This has led to a proliferation of protocols combining chemotherapy and radiation in a number of different ways. Also, there has been extreme interest in applying neoadjuvant protocols to those patients with lower stage lung cancers. For example, the 5-year survival for patients with Stage II lung cancer (positive hilar nodes or chest wall invasion) is only about 40 - 50 %.18 Application of a neoadjuvant protocol may improve these results. As noted the complication rates are higher and the long-term results are not yet definitive. Therefore, it appears wisest at this point to consider enrolling eligible patients in an ongoing protocol.

Summary

  1. Mediastinoscopy is a useful procedure for the evaluation of mediastinal lymph nodes.
  2. Video-assisted thoracoscopic surgery (VATS) is useful in biopsy of lung masses, assessing mediastinal lymph nodes and invasion, assessing the pleura, and can even be used in larger pulmonary resections.
  3. Lobectomy / pneumonectomy is the procedure of choice for lung cancer. Lesser pulmonary resections are associated with higher rates of locoregional recurrence and decreased long-term survival.
  4. Systematic mediastinal lymph node dissection improves the accuracy of staging in lung cancer. This may alter treatment strategy and improve long-term survival.
  5. Neoadjuvant therapy (with both radiation and chemotherapy) followed by surgery can improve survival in selected patients.

References

  1. Hammoud ZT, Anderson RC, Meyers BF, et al. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg 1999 Nov;118(5):894-9.
  2. Luke WP, Peason FG, Todd TR, et al. Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung. J Thorac Cardiovasc Surg 1986;91:53-6.
  3. Mcloud TC, Bourgouin PM, Greenberg RW, et al. Bronchogenic carcinoma: analysis of staging in the mediastinum with CT by correlative lymph node mapping and sampling. Radiology 1992;182:319-23.
  4. Ettinger DS, Cox JD, Ginsberg RJ, et al. NCCN Non-Small-Cell Lung Cancer Practice Guidelines. The National Comprehensive Cancer Network. Oncology 1996;10:81-111.
  5. Vesselle H, Pugsley JM, Vallieres E, Wood DE. The impact of fluorodeoxyglucose F 18 positron-emission tomography on the surgical staging of non-small cell lung cancer. J Thorac Cardiovasc Surg 2002 Sep;124(3):511-9.
  6. Daniels LJ, Balderson SS, Onaitis MW, D'Amico TA. Thoracoscopic lobectomy: a safe and effective strategy for patients with stage I lung cancer. Ann Thorac Surg 2002 Sep;74(3):860-4.
  7. Lewis RJ, Caccavale RJ, Bocage JP, Widmann MD. Video-assisted thoracic surgical non-rib spreading simultaneously stapled lobectomy: a more patient-friendly oncologic resection. Chest 1999 Oct;116(4):1119-24.
  8. Parekh K, Rusch V, Bains M, Downey R, Ginsberg R. VATS port site recurrence: a technique dependent problem. Ann Surg Onc 2001;8(2):175-8.
  9. Nakata M, Saeki H, Yokoyama N, Kurita A, Takiyama W, Takashima S. Pulmonary function after lobectomy: video-assisted thoracic surgery versus thoracotomy. Ann Thorac Surg 2000 Sep;70(3):938-41.
  10. Quigley RL. Anatomic lung resections using minimally invasive thoracic surgery (MITS). Clinical Lung Cancer 2000;1(3):230-3.
  11. Ginsberg RJ, Rubinstein LV, for the Lung Cancer Study Group. Randomized Trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Ann Thorac Surg 1995;60:615-23.
  12. Naruke T. "Mediastinal lymph node dissection" in Shields TW (ed.). General Thoracic Surgery, Malvern, PA: Williams and Wilkins, 1994, pp 469-480.
  13. Shields TW. The "incomplete" resection. Ann Thorac Surg 1989;47(4):487-8.
  14. Keller SM, Adak S, Wagner H, Johnson DH. Mediastinal lymph node dissection improves survival in patients with stages II and IIIA non-small cell lung cancer. Eastern Cooperative Oncology Group. Ann Thorac Surg 2000 Aug;70(2):358-65.
  15. Asamura H, Nakayama H, Kondo H, et al. Lymph node involvement, recurrence, and prognosis in resected small, peripheral, non-small-cell lung carcinomas: are these carcinomas candidates for video-assisted lobectomy? J Thorac Cardiovasc Surg 1996;111:1125-34.
  16. Shaw RR, Paulson DL, Kee JL. Treatment of the superior sulcus tumor by irradiation followed by resection. Ann Surg 1961;154:29-40.
  17. Stamatis G, Eberhardt W, Stuben G, et al. Preoperative chemoradiotherapy and surgery for selected non-small cell lung cancer IIIB subgroups: long-term results. Ann Thorac Surg 1999 Oct;68(4):1144-9.
  18. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710-17.
  19. Stamatis G, Djuric D, Eberhardt W, et al. Postoperative morbidity and mortality after induction chemoradiotherapy for locally advanced lung cancer: an analysis of 350 operated patients. Eur J Cardiothorac Surg 2002 Aug;22(2):292-7.

Jacksonville Medicine 2003

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