|Year : 2008 | Volume
| Issue : 6 | Page : 82-88
|Surgical management of non-small-cell lung cancer
Ahmed Bamousa1, Khaled AlKattan2
1 Riyadh Military Hospital, Riyadh, Saudi Arabia
2 King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Department of Surgery, Riyadh Military Hospital, P.O. Box 7897, Riyadh 11159
| Abstract|| |
Surgery plays a major role in the management of patients with lung cancer. Surgery is not only the main curative treatment modality in patients with early-stage lung cancer but it also has a significant role in the initial workup for the diagnosis and staging of lung cancer. This article describes the surgical management of patients with lung cancer.
Surgical resection for lung cancer is still regarded as the most effective method for controlling the primary tumor, provided it is resectable for cure and the risks of the procedure are low.
The 5-year survival rare following complete resection (R0) of a lung cancer is stage dependent [Table 1]. [1-3] Incomplete resection (R1, R2) rarely, if ever, cures the patient.
Keywords: Lung cancer, surgery, staging
|How to cite this article:|
Bamousa A, AlKattan K. Surgical management of non-small-cell lung cancer. Ann Thorac Med 2008;3, Suppl S2:82-8
| Surgical Principles and Management|| |
- Whenever possible, the tumor and all intrapulmonary lymphatic drainage should be removed completely, most frequently by lobectomy or pneumonectomy.
- Care must be taken not to transgress the tumor during the resection to avoid tumor spillage.
- En bloc resection of closely adjacent or invaded structures.
- Resection margins (bronchial, vascular, and any other margins with close proximity to the tumor) should be assessed by frozen-section analysis. Re-excision is required, whenever possible, if positive resection margins are encountered.
- All accessible mediastinal lymph node stations should be removed or sampled for pathologic evaluation.
Stage I disease (T1-2N0)
Most patients with stage 1 disease have discrete peripheral tumors, presenting as a coin lesion. CT scans are routinely done to assess the mediastinum, the liver, and the adrenal glands. If no mediastinal involvement is suspected and the patient is fit, surgical therapy is the treatment of choice. At the time of thoracotomy, systematic lymph node dissection or sampling is carried out to ensure that no hilar or mediastinal nodal metastasis is present. If optimal surgery cannot be performed, then lesser a resection such as wedge excision or segmentectomy can be used. ,,, Lesser resection is associated with a three-fold higher incidence of local recurrence than lobectomy. Lesser resection therapy should be used only for the patient with limited lung reserve. For tumors protruding from a lobar orifice into the main bronchus, a sleeve lobectomy should be considered whenever possible.
Patient with small tumors (≤ 3 cm in diameter) have a 5-year survival rate of 60-80%, while tumors greater than 3 cm in diameter have a 5-year survival rate of 68%. ,, No adjuvant treatment is recommended for patients with stage I disease following resection. Except for lesions ≥ 4 cm with high-risk features (i.e., poorly differentiated, wedge resection, minimal margins, and vascular invasions) then adjuvant treatment should be considered.  About 20-30% of patients have recurrences, with relapses at distant sites (20% as solitary brain metastasis). Close follow-up is advised for detection of solitary recurrence or second primaries.
Stage II disease (T1-2N1)[Table 1]
This stage accounts for less than 5% of lung cancers and less than 10% of all resected lung cancer. Lobectomy is the procedure of choice in most patients, but pneumonectomy can be used if needed to achieve complete resection (R0). Complete lymph node sampling or dissection should be added for better control. Sleeve resection with ipsilateral mediastinal lymphadenectomy can be used if all involved disease can be removed; it gives results that are identical to that seen after pneumonectomy.
The survival rate following resection depends upon:
1. Size of tumor
Tumors that are 3 cm or less in diameter show a trend for better survival than tumors of 5 cm or more.
2. Number of lymph nodes involved
With a single involved lymph node, the 5-year survival is 45% compared with 31% in patients with multiple involved lymph nodes.
3. Histological type
Local or regional recurrences are more prevalent in patients with squamous carcinoma, while distant metastases occurred more often with adenocarcinoma. Most patient developed distant metastases and, therefore, were more likely to benefit from adjuvant chemotherapy. ,, The incidence of local or regional recurrence can be reduced by postoperative radiation therapy but this has no impact on survival.
Stage II disease (T3N0)
This stage includes tumors invading adjacent structures that can be completely resected by simple en bloc resection techniques.
Tumors invading chest wall
Factors that appear to influence survival in this group of patients include the following:
- Completeness of resection of the tumor
- The extent of invasion of the chest wall
- The presence or absence of regional lymph node metastases
For patients in whom the tumor extends to the parietal pleura, pleural dissection should be performed. If the extension involves muscle and ribs, en block resection should be performed.
For chest wall reconstruction recommendations are as follows:
- No special measures to close the defect caused by removal of one or two small rib segments, especially if located posteriorly beneath large muscle or the scapula
- Taut Marlex mesh or Gore-Tex patch is used to repair bigger defects, to achieve acceptable cosmetic results and chest wall stability if 2-3 rib have been removed or to prevent trapping of the tip of the scapula.
- Marlex Mesh with methylmethacrylate sandwich technique is used for big defects in the sternum or when chest wall instability is anticipated.
Patients with completely excised T3N0 stage tumor will have a survival of up to 40-50%. ,, In patients with macroscopic or microscopic incomplete resection, the 5-year survival rate is zero. Postoperative radiation therapy in this group of patients does not have any impact on their ultimate survival.
Superior sulcus tumors
Superior sulcus tumors (Pancoast tumors) are tumors that invade the pleural apex. Patients are generally symptomatic. Early invasion of the lower brachial plexus, especially the T1 nerve root, is common. Shoulder and arm pain radiating to the inner aspect of the upper arm (T1) and the ulnar distribution in the fourth and fifth fingers of the hand (C8) is a common presenting symptom.
Most patients are diagnosed histologically by fine needle aspiration (FNA) biopsy performed under CT guidance. The majority of the tumors are squamous cell carcinomas or adenocarcinomas, but 3-5% are small-cell carcinomas.
Mediastinoscopy is important, as patients with N2 disease have poor survival: not longer than 1 year if they are treated with a combination of chemotherapy and radiotherapy. The current standard therapy for such patients is preoperative induction chemoradiotherapy, followed-up with surgery and postoperative chemotherapy; this treatment provides 5-year survival up to 44% for all patients, with 54% survival noted after complete resection. ,
Surgery involves en bloc removal of the affected lobe and chest wall, including the entire first rib and the posterior segments of the second, third, and often fourth ribs; the transverse processes of the contiguous thoracic vertebrae; the nerve roots C8 and T1 to T3; the lower trunk of the brachial plexus; and the dorsal sympathetic chain; as well as mediastinal node dissection.
Unresectability may result from the involvement of the subclavian artery or vertebral body with or without cord compression, and widespread involvement of the major division of the brachial plexus.
The adverse prognostic factors include the following:
- N1 or N2 disease
- Incomplete resection
- Wedge (vs. lobectomy) resection of the pulmonary component
The 5-year survival following complete surgical resection was 54%, while it was 9% following R1 or R2 resection only.
Tumors in proximity to the carina
In patient with central tumors that extend within 2 cm of the carina without carinal involvement, nodal involvement severely affect prognosis. This emphasizes the need for preoperative mediastinoscopy. The 5-year survival rate can reach up to 30-40%. Pneumonectomy is the most common resection but sleeve lobectomy can be used as this will provide lower morbidity and mortality and preserve pulmonary function.
Stage III disease
Stage III tumors are those that present with lymphatic metastasis to the mediastinum as N2 or N3 disease, or tumors that invade an unresectable adjacent organ (T4). Distant metastases should be ruled out by CT scan or whole-body PET scan / CT scan. Preoperative mediastinoscopy is an important modality for diagnosis and staging.
- In the presence of nodal disease, the survival rate following complete resection is less than 20% at 5 years ,,
- When diagnosed preoperatively, many of these patients are offered neoadjuvant approach with re-evaluation for response.
There is no evidence that preoperative radiation therapy alone for clinical N1 or N2 disease benefits patients with tumors invading the chest wall. In patients who have evidence of mediastinal lymph node metastases or residual disease, postoperative radiation therapy is usually advised in an attempt to decrease the incidence of local recurrence but this does not impact overall survival.
Preoperative mediastinoscopy identifies those patients unlikely to benefit from primary surgical resection when their tumors have been clinically staged as T3. PET scans may reveal hilar nodal involvement.
N2 disease identified at thoracotomy can benefit from effective management by primary surgery. A report from Memorial Sloan-Kettering Cancer Center suggests that the overall 5-year survival rate is 30% for such patients. There was no statistically significant difference in survival at 5 years between patients with adenocarcinoma (30%) and those with squamous cell carcinoma (32%). Survival rate at 5 years was 46% in patients with small tumors (T1) compared with 27% in those with large tumors (T2) and 14% in those with extension outside the lung or in proximity to the carina (T3); This difference was statistically significant ( P = 0.003).
When nodal involvement was present, the size per se did not affect the survival rate, but the number of nodes affected had a significant effect. Patients with a single involved N2 node did better than those with multiple nodal involvements at one or more levels.
Survival of patients following completely resected N2 disease is dependent on the number of mediastinal nodal stations involved with the tumor. Involvement of a single station offers a better prognosis than multistation nodal involvement. Only patients with clinical N1 disease had survival rates greater than 10% following complete surgical resection.
The role of primary surgery in the management of N2 disease can be summarized as follows  :
- In patients found to have unsuspected N2 disease at thoracotomy, surgery should be continued unless pneumonectomy is needed. Mediastinal lymph node dissection is strongly advisable and postoperative adjuvant chemotherapy is indicated.
- Patients with N2 disease found at the time of mediastinoscopy should be treated with neoadjuvant concurrent chemoradiotherapy or induction chemotherapy followed by assessment of response. , For responders, surgery can be offered with mediastinal lymph node dissection. Nonresponders should be treated with chemotherapy or concurrent chemoradiotherapy if it has not been given before as sole treatment.
Preoperative radiotherapy alone for clinically N2 disease will not improve survival because most of the patients die of distant metastases.
Stage IIIB disease
(T4 or N3)
These patients present with one of the following :
- Supraclavicular or contralateral mediastinal lymph node metastases (N3)
- Invasion of the spine, trachea, carina, esophagus, aorta, or heart (T4), or satellite lesions within the same lobe
- Malignant pleural effusion (T4)
These patients are considered inoperable. Most of these patients are treated by combined chemoradiation.
T4 disease, carinal involvement
Lesions that extend to and invade the carina have a much poorer prognosis than those in the mainstem bronchi. Pneumonectomy with tracheal sleeve resection and direct reanastomosis of the trachea to the contralateral mainstem bronchus has been offered to patients who are good surgical risks, with up to 20-40% 5-year survival, often in the face of 13-30% operative mortality rates. ,,,, This should be reserved for the young healthy patient with N0 disease as determined by mediastinoscopy. All other patients should be treated primarily with chemoradiation without resection. Transbronchoscopic brachytherapy or photodynamic therapy may play a role as a local therapy modality.
Satellite nodules are classified according to location.
- A nodule in the same lobe used to be classified as T3; this was later changed to T4 and now, in the new TNM classification, it has been labeled as T3.
- A nodule in a different lobe on the same side was earlier classified as T4, then changed to M1 and recently, has been considered as T4.
- A nodule in a different lobe on the contralateral side is classified as M1.
Not all of these nodules are malignant (e.g., they can be inflammatory lesions). Biopsy is needed to confirm the diagnosis.
Some T4 lesions can be completely resected in selected instances, offering an occasional cure. This includes direct invasion of the vertebra, superior vena cava, esophagus, and atrium. It is this group of patients in whom the use of induction therapy, either chemotherapy or chemoradiotherapy, is currently being investigated. Induction therapy may downstage the disease allowing lesser resection.
Contralateral mediastinal lymph node metastases are considered by most surgeons as being an absolute contraindication to surgery.
| Solitary Metastases (M1)|| |
Occasionally, patients present with resectable lung cancer and evidence of a solitary metastasis on complete organ scanning. These patients can and should be considered for a combined approach: removal of the primary tumor and the solitary metastasis. ,, PET scanning should prove to be extremely useful for ruling out other sites of disease. Untreated patient with brain metastases have a median survival of less than 3 months. When brain metastases are multiple or advanced or other metastatic disease is present, the treatment is whole-brain irradiation. Solitary brain metastases are treated with surgery. Craniotomy is done first, followed by thoracotomy for removal of the primary tumor. Postoperative brain irradiation should be ordered after removal of the brain metastasis to sterilize the tumor bed.
The overall 5-year survival rate for such patients may reach up to 20%.
Resection of the primary tumor and the solitary metastatic focus should be considered if both are completely resectable. The long-term results of such aggressive therapy are unknown, although some cases of 5-year survival have been reported, whereas no survivors have been reported with nonsurgical therapy. ,
| Palliative Resection|| |
For surgery to be effective in controlling lung cancer, it must be complete and potentially curative. The role of surgery for the palliation of patients with unresectable tumors is debatable. There are specific situations, such as unremitting lung abscess, massive hemoptysis, or painful chest wall involvement, where palliative resection can be done.
| Lung Abscess|| |
An unresolving lung abscess, caused by either a necrotizing tumor (usually a squamous cell carcinoma) or a lung abscess distal to an obstructing tumor, rarely requires surgical resection. Other options are available, such as endobronchial laser therapy to relieve the proximal obstruction followed by external radiotherapy or percutaneous drainage of the abscess. If complete resection is likely, a surgical approach should be considered.
| Massive Hemoptysis|| |
Massive uncontrolled hemoptysis is a rare feature of untreated lung cancer. Most frequently, it is the result of the development of a vascular-bronchial fistula following radiotherapy. Exsanguination or suffocation leads to death. Bronchoscopic treatment by laser coagulation or the placement of an endobronchial blocker, or selective bronchial artery embolization by percutaneous angiography artery may relieve the problem. Rarely, urgent thoracotomy is required even if the tumor is not resectable.
| Postoperative Morbidity and Mortality Rates|| |
Postoperative mortality rates can range from 5 to 20% and morbidity rates may be as high as 40%. Pneumonectomy carries an overall mortality rate of 6-7%, whereas lobectomy and lesser resections should not have postoperative mortality rates in excess of 2%.
| Positive Resection Margins|| |
Bronchial, vascular, and close-proximity margins should be always monitored by frozen-section analysis at the time of surgery. Resection to negative margins is advised whenever a positive margin is identified. Most surgeons advocate postoperative irradiation when close margins are encountered. Residual in situ disease can be treated with endoluminal brachytherapy or photocoagulation using hematoporphyrins.
| Lobectomy vs Pneumonectomy|| |
A decision has to be made whether a lobectomy or a pneumonectomy should be performed, especially in the case of central lesions. ,,, Lobectomy is considered to be complete if all resection margins are confirmed by frozen-section analysis. The 'sump' lymph nodes lying on the pulmonary artery between the upper and lower lobes should be examined. If there is any suspicion that these contain tumor then a larger resection (e.g., pneumonectomy) is indicated. Frozen-section analysis of such lymph nodes should be performed. When an upper lobectomy is performed, involvement of the sump lymph nodes between the upper and lower lobes may necessitate a completion pneumonectomy. Following right lower lobectomy, discovery of the involvement of the sump nodes around the middle lobe requires the addition of a middle lobectomy to the procedure, thus necessitating a bilobectomy for complete resection. In upper lobectomy, any lymph node involvement proximal to the upper lobe takeoff along the mainstem bronchi requires consideration of sleeve resection or pneumonectomy, as does involvement of the lymph nodes around the main pulmonary artery.
| Local Recurrence Following Initial Pulmonary Resection|| |
Two-thirds of recurrence occurs in distant sites, but one-third are initially local. In most patients, local recurrence is a very poor prognostic sign. For symptomatic patients, surgical interventions can afford palliation. In highly selected patients, the local recurrence can be resected with a hope of ultimate cure if there is no evidence of significant regional or widespread metastases.
| Local Recurrence Following Limited Resection|| |
A limited resection (less than lobectomy) is usually reserved for patients who cannot tolerate a larger procedure; although, there is an increased rate of local recurrence. Except for those with severe restrictive disease, most patients can tolerate a lobectomy despite even poor pulmonary function. Serious consideration should be given to reoperation and completion lobectomy. At thoracotomy, if this is not possible, the surgeon has the option of working with the radiotherapy team to apply brachytherapy to the local area.
| Surgical Management of Pleural Effusion|| |
Malignant pleural effusion is a common surgical problem. Patients usually present complaining of shortness of breath. Pleural drainage and bedside pleurodesis using talc or other agents such as tetracycline will result in intense inflammatory reaction in the pleural space. Such reactions will result in obliteration of pleural space and provide some symptomatic relief for patients. For pleurodesis to be successful the lung should expand to fill the pleural space. Lung trap, on the other hand, can be treated with an ambulatory pleural tap or the insertion of a pleural catheter, which can be used to drain the pleural cavity regularly as part of home care support.
Occasionally, patients need thoracoscopic surgery for diagnosis of recurrence in the pleural cavity. During the procedure the surgeon can carry out talc insertion under direct vision and ensure even distribution in the pleural cavity.
Painful recurrence in the chest wall can be also treated with radiotherapy or surgery in rare cases.
| Post-resection Follow-up for NSCLC|| |
Post-resection follow-up of a thoracic malignancy requires a careful balance of clinical examination, diagnostic imaging examination, and consideration of cost-effectiveness. After resection for early-stage lung cancer, second lung cancers develop at a rate of about 2-5% per year. ,
Follow-up of the patient begins in the immediate postoperative period, with the patient's normal convalescence from surgery. The in-hospital recovery phase, including the first 30 days after surgery, is usually considered the early follow-up period from which surgical morbidity and mortality are calculated.  Routine follow-up usually begins about 1 month after discharge, 5-6 weeks after the date of surgery.
Tumors occurring in the lung after resection of a primary lung cancer may be a second primary lung cancer, a local recurrence, or metastatic disease. If it is detected early, these patients may be cured of their recurrent lung cancer with resection.
Second primary lung cancer
After curative (R0) resection with pathologically negative margins and no involved lymph nodes, a new lesion in the lung may well represent a second primary. Generally, when the same history occurs within a 2-year period, this is classified as a metastasis. It is classified as a second primary tumor if there is (1) a different histologic cell type, (2) a tumor-free interval of 24 months, and (3) location in the contralateral lung or, for tumors within the same hemithorax, the new tumor occurs in a separate and distinct ipsilateral lobe.
| Routine Follow-Up: An Evolving Process|| |
Each follow-up visit should include discussion with the patient as to his or her general health and any problems that may exist. The signs and symptoms of local recurrence are shown in [Table 2].
The history should include details regarding the onset or persistence of specific symptoms and the presence or occurrence of late events.
Most commonly, patients would have stopped smoking over the months following the resection of a thoracic neoplasm. If not, aids for smoking cessation, including smoking cessation clinics and counseling, biofeedback, nicotine patches, nicotine gum, pharmaceuticals, and physician counseling, should be offered.
Nonspecific symptoms such as anorexia, malaise, fatigue, and weight loss may occur in up to 70% of patients. Paraneoplastic syndromes are distant manifestations of lung cancer (not of metastases) and are listed in [Table 3].
The patient's physical examination should include a note of weight and changes in performance status. A limited physical examination, with specific attention to the cervical and supraclavicular nodal beds, examination of the surgical wound for healing or local recurrence, should also be performed.
Routine chest radiography
Routinely, a plain chest radiograph is obtained at the first postoperative visit and at every visit thereafter. These radiographs serve as a baseline against which to compare future changes within the chest. The surgeon can evaluate the postoperative appearance and can assess for local, regional, or metastatic disease.
Serial CT of the chest
Patients with previous lung cancer are at the highest risk for developing a second lung cancer. Use of screening CT in patients following pulmonary resection of lung cancer may be effective in identifying recurrences at an earlier (and potentially curable) stage of disease, but this requires further study. Various centers throughout the world are now involved in evaluating large numbers of patients with screening CT scans.
| Metastatic Disease from Primary Lung Cancer|| |
Metastatic disease is common after curative resection of lung cancer and may occur in up to two-thirds of patients. Few patients may have asymptomatic isolated localized recurrence amenable to resection. Criteria for nonresectability are presented in [Table 4].
If neurologic problems, jaundice, or other signs or symptoms that may suggest metastatic disease are present, the patient should be screened for the presence of metastatic disease anywhere in the body. Typically, this screening consists of bone scan, CT of the abdomen and the chest, and a CT evaluation or an MRI of the brain.
Surgical resection of metastasis from lung cancer generally is a curiosity, although many patients with respectable brain metastases do quite well. After excision, patients with a solitary brain metastasis may have up to 15-20% 5-year survival.
| Post-resection Follow-Up Guidelines|| |
Various recommended approaches to follow-up patients with lung cancer are based on the stage and treatment. , Follow-up guidelines suggested by the University of Texas M.D. Anderson Cancer Center are shown in [Table 5].
The frequency of the postoperative follow-up depends on (1) the extent of the resection, and (2) whether the resection was complete or incomplete. An incomplete resection may be defined as R1 (microscopic) or R2 (gross tumor). Incomplete resections leave positive margins, which predisposes to earlier local, or local-regional, recurrence.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]