Pancoast Syndrome

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Practice Essentials

Pancoast syndrome (sometimes termed Pancoast-Tobias syndrome) typically results when a malignant neoplasm of the superior sulcus of the lung leads to destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion).[1, 2, 3] This produces the following clinical manifestations:

Most Pancoast tumors are non–small cell lung cancer (NSCLC])—specifically, squamous cell carcinoma (SCC) or adenocarcinomas; only 3-5% are small cell carcinomas. Squamous cell carcinoma occurs more frequently, although large cell and undifferentiated types are also common. Very rarely, tumors in this location may have metastasized from other sites.[4, 5]

Once universally fatal, Pancoast tumors are currently treatable with outcomes similar to those of other stage-matched NSCLCs.[6] Careful assessment and appropriate staging are performed before surgery, and patients with resectable tumors receive preoperative concurrent chemoradiation therapy. After an interval of 2-4 weeks, surgical resection is performed. Contraindications to surgical management include the following:

Pathophysiology

Pancoast tumors are a subset of lung cancers that invade the apical chest wall. Because of their location in the pleural apex, they invade adjoining tissue. Although other tumors may have a similar clinical presentation because of their location at the thoracic inlet, the most common cause is believed to be a bronchogenic carcinoma arising in or near the superior sulcus and invading adjacent extrathoracic structures by direct extension. Location, rather than pathology or histology of origin, is significant in producing the tumor’s characteristic clinical manifestations.[7]

The bulk of a true Pancoast tumor is extrathoracic, originating in an extreme peripheral location with a plaquelike extension over the lung apex and principally involving the chest wall structures rather than the underlying lung parenchyma. Bronchogenic carcinomas occurring in the narrow confines of the thoracic inlet invade the lymphatic vessels in the endothoracic fascia and include, by direct extension, the following structures:

Carcinomas in the superior pulmonary sulcus produce Pancoast syndrome, with pain in the shoulder and along the ulnar nerve distribution of the arm and hand.[8] These carcinomas can also cause Horner syndrome. These apical lung tumors tend to be locally invasive early. Nevertheless, in the absence of metastases and regional nodal involvement, many Pancoast tumors can be successfully treated.

The tumor may invade the bony structures of the chest, including the first or second thoracic vertebra or the first, second, or third rib. In a review of 60 patients with Pancoast tumors, Maggi et al found radiographic evidence of rib erosion in 50%; an almost equal percentage demonstrated involvement of the first or second rib, and 20% had involvement of the third rib. One patient had involvement of all 3 ribs.[9]

The tumor can also invade the first or second thoracic vertebral bodies or intervertebral foramina. From this point, it can extend to the spinal cord and result in cord compression. The subclavian vein or artery may also be invaded.

Involvement of the phrenic or recurrent laryngeal nerve or superior vena cava obstruction is not representative of the classic Pancoast tumor.

Etiology

The overwhelming majority of cases of Pancoast syndrome result from non–small cell lung carcinoma (NSCLC), with more than 95% located in the superior sulcus. The most common varieties are squamous cell carcinoma and adenocarcinoma; large cell carcinoma has also been reported. Small cell carcinoma accounts for fewer than 5% percent of cases in most series; more typically, small cell lung cancer manifests in a central rather than a peripheral location.[9]

Although NSCLC is by far the most common cause of Pancoast syndrome, the list of differential diagnoses is broad. Because of the wide variety of diseases that can produce Pancoast syndrome, a histologic diagnosis is mandatory before definitive treatment is initiated.

Rare causes include the following:

Risk factors are similar for almost all lung cancers and include the following:

Epidemiology

Overall, Pancoast tumors are much less common than other lung cancers, accounting for fewer than 5% of these cancers (1-3% in various previous series).[21, 22] Originally deemed universally fatal, Pancoast tumors are currently often amenable to curative treatment because of improvements in combined modality therapy and development of new techniques for resection.

Prognosis

The prognosis for patients with Pancoast syndrome is stage dependent. Adverse prognostic factors include the following:

Distant disease limits survival. Treatment failure is especially frequent in patients with involvement of the brain. The authors recommend careful surveillance for brain metastasis during and after the therapy. The authors also recommend obtaining brain imaging prior to surgery in patients receiving induction therapy for the primary tumor.

Mortality and survival

A 2007 study by Rusch et al in 110 patients with superior sulcus NSCLC treated with trimodality therapy reported 5-year survival of 44% for all patients and of 54% in patients with complete resection, with no difference between T3 and T4 tumors.[24] A Dutch study of 123 patients with superior sulcus NSCLC treated with trimodality therapy from 2002-2017 reported 10-year overall survival of 48.1% and disease-free survival of 42.6%.[25]

History

Patients with Pancoast syndrome (Pancoast-Tobias syndrome) may present with referred pain over the scapula to the shoulder as the result of damage to the afferent pain fibers of the sympathetic trunk. The symptoms are due to the location of the tumor in the superior sulcus or thoracic inlet adjacent to the eighth cervical nerve roots, the first and second thoracic trunk distribution, the sympathetic chain, and the stellate ganglion.

Initially, localized pain occurs in the shoulder and vertebral border of the scapula. Pain may later extend down the arm along an ulnar nerve distribution to the elbow and, ultimately, to the ulnar surface of the forearm and to the small and ring fingers of the hand (C8). If the tumor extends to the sympathetic chain and stellate ganglion, Horner syndrome and anhidrosis develop on the ipsilateral side of the face and upper extremity.

The pain is frequently relentless and unremitting, and adequate relief often requires administration of narcotics. The patient usually supports the elbow of the affected arm in the hand of the opposite arm, to ease the tension on the shoulder and upper arm.

The hand muscles may become weak and atrophic, and the triceps reflex may be absent. The first or second rib or vertebrae may be involved by tumor extension and intensify the severity of pain. The spinal canal and spinal cord may be invaded or compressed, with subsequent symptoms of spinal cord tumor or cervical disk disease.

Many patients are initially treated for presumed local musculoskeletal conditions such as bursitis and vertebral osteoarthritis with radicular pain. Symptoms may persist for many months before evaluation for progression reveals the cause. In a 1994 series by Maggi et al, symptoms lasted 2-36 months, with a mean of 9.7 months.[9] In 1997, Muscolino described plexopathy or radicular symptoms in 53% of 15 patients.[26]

Physical Examination

Physical examination of patients with Pancoast tumor may reveal findings consistent with Horner syndrome, such as ptosis and miosis, which result from paralysis of the dilating sympathetic fibers. Supraclavicular lymphadenopathy may also be observed.

Horner syndrome is the result of invasion of the lower cervical and first thoracic ganglia, which frequently fuse into a single ganglion, the stellate ganglion. Horner syndrome is observed in 20-50% of patients at presentation.[21, 9, 26, 27] Decreased sweating on the affected side and ptosis of the denervated lid may be observed. Application of topical cocaine to the miotic eye (contracted pupil) fails to cause pupil dilation, while appropriate dilation is noted in the unaffected eye.[28]  A more practical alternative is to use topical apraclonidine, which has little to no effect on a normal pupil but has a mydriatic effect on a pupil affected by Horner syndrome.[29]

Cough, dyspnea, and hemoptysis, which are signs often associated with lung cancer, are not as common in individuals with Pancoast syndrome because of the peripheral location of the tumor. When present, they are associated with a worse prognosis. Also uncommon but occasionally noted are more advanced tumors with involvement of the recurrent laryngeal nerve, phrenic nerve, or superior vena cava.

Infrequently, a patient with a Pancoast tumor may also have features of a paraneoplastic syndrome. Most of the metabolic manifestations are the result of the secretion of endocrine chemicals by the tumor. Manifestations encompass Cushing syndrome, excessive antidiuretic hormone secretion, hypercalcemia, myopathies, hematologic problems, and hypertrophic osteoarthropathy. The presence of paraneoplastic syndromes does not connote unresectability, but most of these are associated with small cell cancer.

Brain metastasis may be relatively common at the time of diagnosis and indicates an increased risk for treatment failure. Preoperative brain imaging studies are highly recommended in patients who are receiving induction therapy for the primary tumor in the superior sulcus.[30]

Approach Considerations

Imaging and biopsy are the cornerstones of evaluation of Pancoast syndrome. The apex of the lung can be difficult to investigate because it is bounded laterally by the first rib, posteriorly by the first rib and the vertebral bodies, and anteriorly by the costal cartilage of the first rib and the manubrium. Plain radiographs of the chest frequently show no change or an asymmetry or thickening of the apical cap. Apical lordotic films may be more revealing. Computed tomography (CT) and magnetic resonance imaging (MRI) have become standard. Liver, bone, and brain scans are performed to look for metastatic disease. For full discussion, see Pancoast Tumor (Pancoast Syndrome) Imaging.

Initially, most Pancoast tumors are diagnosed histologically on the basis of transthoracic needle biopsy results. Diagnosis via bronchoscopy is less helpful because most of these tumors are peripherally located. The flexible scope is more useful than the rigid scope in obtaining bronchoscopic aspirates and brush biopsy specimens. In very rare cases, sputum cytology has been helpful.

Although more than 90% of lung apical tumors can be correctly diagnosed on the basis of clinical and radiologic findings alone, open biopsy for pathologic validation may be performed through a supraclavicular incision. Results from a needle biopsy through the supraclavicular or posterior triangle can also be successful in confirming the diagnosis and in delineating the cell type before treatment. Even though clinical diagnosis is relatively simple, performing a tissue biopsy is still necessary.

Laboratory Studies

The blood workup for patients with Pancoast tumors is not specific, and results are not diagnostic.

Lung cancers produce various substances. Elevated levels of carcinoembryonic antigen (CEA) and beta-2 microglobulins are associated with many lung cancers. Unfortunately, these findings are not diagnostic, because levels of these chemicals are also elevated by other nonspecific causes, such as smoking and bronchitis.

Tumor markers (eg, bombesin, neuron-specific enolase, and other peptides) are common with small cell cancers and are related to the stage of the disease. They may aid in distinguishing differentiated forms of lung cancer from undifferentiated forms.

Routine blood work in all patients with a lung cancer includes a complete blood cell count (CBC), blood urea nitrogen (BUN) and creatinine levels, and urinalysis. Measurement of coagulation parameters, such as prothrombin time (PT) and activated partial thromboplastin time (aPTT), is appropriate. Unless metastatic disease is evident, liver function tests are not regularly performed. Any patient deemed a surgical candidate has blood drawn for typing and crossmatching.

Urinalysis is performed in all patients before surgery. A catheter specimen is obtained in women if the initial urinalysis result suggests contamination.

Molecular testing for driver mutations has become a standard part of the workup for lung cancers. Such testing can identify gene alterations that affect the selection of therapy for advanced and metastatic disease.[31, 32]

Chest Radiography

Chest radiographs may reveal a small homogeneous apical cap or pleural thickening; they may show a thin plaque at the lung apex in the area of the superior sulcus or may reveal a large mass, depending on the stage of the tumor. Suggestive films should prompt the astute diagnostician to order apical lordotic views for better visualization of the area.

Bone destruction of the posterior 1-3 ribs may sometimes be apparent. Rib invasion or vertebral body infiltration may be evident on a plain chest radiograph. Mediastinal enlargement may be apparent.

CT, MRI, and PET

CT and MRI of the neck, chest, and upper abdomen have largely replaced older radiographic studies in the workup of Pancoast syndrome.

CT is less expensive than MRI and much more available. It can help assess bone destruction and is useful in general imaging of the lung for the evaluation of mediastinal adenopathy, other pulmonary nodules, and liver involvement. CT scanning helps identify invasion of the brachial plexus, chest wall, and mediastinum, as well as reveal involvement of the vena cava, trachea, and esophagus. Contrast CT scanning is useful for assessing subclavian vessel involvement. Three-dimensional (3D) CT-based simulation provides precise anatomic definition of the tumor, which facilitates planning of conformal radiation therapy, allowing higher radiation therapy doses to tumor and lower doses to surrounding normal tissues.[33]

MRI is useful for evaluating resectability. It may be more accurate in evaluating chest wall invasion, examining vascular structures, and assessing the brachial plexus for invasion.[34, 35, 36] It is more accurate than CT for assessing invasion of cervical structures and vertebral bodies.

MRI has no advantage over CT in the evaluation of the mediastinum. In fact, CT is much better than MRI for assessing the mediastinum for lymph node involvement. Rib or transverse process involvement is not a sign of inoperability; however, involvement of the vertebral body makes achieving an adequate margin of resection very difficult and reduces the odds for survival.

MRI of the vertebrae may help differentiate between tumor invasion and reactive inflammation in patients with Pancoast syndrome, and thus help avoid unnecessary vertebrectomy. A retrospective study of MRI signal intensity characteristics in 92 vertebrectomies found that the optimum cut-offs (P < 0.05) to distinguish invasion from reactive inflammatory changes were as follows[37] :

Additional staging studies should be considered. Mediastinoscopy should be performed to evaluate mediastinal nodes. The presence of N2 mediastinal lymphadenopathy has a significant adverse effect on survival. CT or MRI of the head to exclude occult metastasis should be performed if treatment with curative intent is planned. CT of the chest can be extended to include the liver and adrenal glands.

Positron-emission tomography (PET) scanning is approved by the US Food and Drug Administration for the staging of non–small cell lung cancer in general, and it is increasingly being used in the setting of Pancoast syndrome. PET/CT provides accurate delineation of the gross tumor volume, which is needed for planning radiation treatment.[38]

Bronchoscopy and Biopsy

Bronchoscopy helps evaluate the tracheal and bronchial lumens; however, because most Pancoast tumors are peripheral, the diagnostic yield is low. Fiberoptic bronchoscopy has a higher yield than sputum cytology, which has positive results in fewer than 15% of patients,[39] but bronchoscopy findings are positive in only 20-30% of patients.[40] Bronchoscopy, however, can be useful in excluding otherwise unsuspected concurrent endobronchial lesions.

Tissue diagnosis is obtained on the basis of results from percutaneous needle biopsy, performed under either fluoroscopy or CT guidance. Staging is based on results of scalene node biopsy from palpable nodes or mediastinoscopy findings. If a patient presents with supraclavicular lymph node enlargement, then a fine-needle aspiration (FNA) biopsy of enlarged supraclavicular lymph nodes or an ipsilateral supraclavicular fullness procedure is a fast, safe, and inexpensive means of confirming the diagnosis.

Transthoracic needle biopsy by CT guidance has a high yield, up to 95% in some series.[41, 39, 42] Some tumors may be evaluated only by thoracotomy, either open or video assisted.

Other Tests

Rarely, arterial or venous involvement of the subclavian artery or vein occurs; in those cases, arteriography or phlebography may be helpful. This is usually accomplished in a retrograde fashion, although it can be approached from the opposite extremity or from the leg.

Baseline electrocardiography (ECG) is performed on all patients for comparison to postoperative ECG tracings (if one is performed).

Staging

Pancoast tumors are staged using the tumor-node-metastasis (TNM) system of the International System for Staging Lung Cancer, adopted by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC).[43] This classification stages lung cancers in terms of tumor characteristics and tumor distribution.

The T designation describes the size and invasiveness of the primary tumor. T3 indicates a tumor of any size that invades the chest wall (the parietal pleura). T4 is a tumor of any size that invades the vertebral body, a neural or vascular structure, the mediastinum, the esophagus, or the trachea.

The N designation describes the distribution of positive lymph nodes. N1 indicates metastasis to ipsilateral peribronchial or hilar nodes. N2 indicates the spread to ipsilateral mediastinal or subcarinal nodes. N3 indicates metastasis to nodes of the contralateral hilar and mediastinal areas or to scalene or supraclavicular nodes, either ipsilateral or contralateral.

The M designation describes the extent of distant metastasis. M0 indicates no identifiable metastatic disease, and M1 designates the presence of distant metastasis (eg, to brain, bone, or liver). Any M1 findings indicate stage IV disease.

Staging is determined by the location of the lesion and its metastases. A true Pancoast tumor is usually T3, reflecting extension of the tumor through the visceral pleura into the parietal pleura and the chest wall; it is classified as T4 when mediastinal invasion, cervical invasion, or both have occurred (see the Table below). Peripheral metastases signal a poor prognosis, and surgery is contraindicated in such cases.

IIIB

Table. AJCC/UICC Stages for Pancoast Tumors.



View Table

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Mediastinoscopy is used for staging to delineate the metastases to mediastinal lymph nodes. Cervical mediastinoscopy is indicated for right pulmonary lesions; a Chamberlain procedure (left second interspace mediastinoscopy) is indicated for left pulmonary lesions. Generally, mediastinoscopy is performed if the lymph nodes appear larger than 1 cm in diameter on a CT scan because the accuracy of CT for predicting metastatic involvement in enlarged lymph nodes is only 70%.

Conversely, if the CT scan does not reveal any enlarged lymph nodes, the patient is deemed operable. If the nodes in the mediastinum are positive, the prognosis is poor. The exception to this rule is an upper-lobe lesion with positive nodes on the right side of the trachea only. If these are internodal, spread is considered local, and the tumor may still be resectable.

Attar et al, reviewing their experience with 105 patients treated from 1955 to 1997, found that 30% of patients presented with T3 N0 disease (stage IIB), 26% with T4 N0 (stage IIIA), and 25% with metastatic disease (M1, stage IV).[27] In their review of 124 patients, Ginsberg et al found that 58% of patients had T3 N0 disease, 16% had T3 N2, and only 1% had T3 N1; in addition, 6% of patients had T3 N3 disease, 18% had T4 N0, and 1% had T4 N.[21]

Approach Considerations

Patients with superior sulcus pulmonary carcinoma (Pancoast tumors) should be considered for surgery after appropriate diagnostic evaluation to exclude distant metastasis or local progression. The ideal surgical candidate has a carcinoma restricted to the chest with T3N0M0 staging. A rare exception is made for a right upper-lobe lesion with intranodal mediastinal metastases and T3N2M0 staging. Surgery alone may be appropriate for selected patients who have very localized early disease. However, surgery alone is not the prevalent course of treatment.

 For stage III superior sulcus non–small cell lung cancer (NSCLC), current guidelines recommend trimodality therapy with preoperative concurrent chemotherapy and radiation therapy (RT), then surgery; this is followed by adjuvant therapy.[31, 44, 45]  For unresectable tumors, treatment is typically with definitive chemoradiation therapy. For possibly resectable stage IV superior sulcus tumors, National Comprehensive Cancer Network (NCCN) guidelines recommend surgical re-evaluation after preoperative treatment, as responsive tumors may have been rendered resectable.[31]

Chemotherapy for superior sulcus NSCLC continues to rely on the traditional platinum doublet (eg, cisplatin plus pemetrexed for nonsquamous SNCLC, cisplatin plus etoposide for squamous NSCLC). Increasingly, systemic therapy also includes biologic agents selected on the basis of molecular studies that identify specific tumor mutations.[31, 44]  For full discussion of this steadily advancing field, see Non–Small Cell Lung Cancer (NSCLC).

The occasional inoperable patient with Pancoast syndrome who continues to experience severe pain after chemoradiation therapy may be selectively considered for palliative resection. Contraindications to surgery include the following:

Ultrasound-guided cervical nerve roots ablation can be considered for patients with intractable neuropathic pain secondary to Pancoast tumor. Anecdotal reports have described excellent pain relief as well as improvement in quality of sleep with this technique.[46] Dorsal root entry zone microsurgery (DREZotomy) has also proved successful for pain relief.[47]

Preoperative Evaluation

Patients with poor respiratory function and ischemic coronary artery disease need a proper workup before undergoing surgical therapy. Heart failure, recent myocardial infarction, and unstable angina are contraindications for surgery. Although many patients are elderly (the age group with the highest risk of complications), age alone is relatively unimportant if the patient is in otherwise good health. The presence of Horner syndrome or ipsilateral supraclavicular node involvement is not an absolute contraindication for combined preoperative chemoradiation therapy and surgery.

Most of the postoperative complications that follow lung resection are cardiopulmonary (eg, myocardial ischemia, pulmonary embolism [PE], and respiratory failure). To avoid these complications, patients selected for surgery must undergo an evaluation of pulmonary function. High-risk patients benefit from supervised pulmonary rehabilitation accompanied by bronchodilator therapy.

Prophylactic heparin and antiembolic stockings are used in all patients. Preoperative nutritional status is carefully assessed in all patients because a low albumin level has been correlated with a higher morbidity.

Patients who smoke are encouraged to stop smoking at least 2 weeks before surgery. Preoperative assessment of cardiac risk factors is critical in evaluating candidacy for lung resection. Perioperative cardiac complications can be reduced preoperatively in patients at high risk by instituting better perioperative monitoring, performing a lesser procedure, or achieving medical optimization. Consider preoperative angioplasty or coronary bypass in all patients with significant coronary disease.

Preoperative Chemoradiotherapy

In patients with a resectable Pancoast tumor, a trimodality approach involving concurrent chemotherapy and radiotherapy followed by surgical resection has become the standard of care.[48, 24, 31, 49]  However, the rarity of Pancoast tumors has impeded the development of standardized protocols.

Radiotherapy

The purpose of preoperative irradiation is to shrink the tumor and to temporarily block lymphatic spread. The radiation field includes the primary tumor, adjacent mediastinum, and ipsilateral clavicular area. Advanced radiologic techniques such as intensity-modulated radiation therapy (IMRT) are used to conform the treatment field to the tumor, which maximizes tumor control and minimizes treatment toxicity.[2, 31]  

In older studies, administration of 30-40 Gy of radiation over 2-3 weeks appeared to yield the best results. Currently, dose selection is guided by disease stage and typically ranges from 45 to 54 Gy, although 60 Gy and above has been used in some studies.[31, 45]  An interval of 2-4 weeks after radiation therapy allows the radiation to have maximal effect. After 4 weeks, all patients are reassessed for surgery. If no distant disease spread has occurred, then surgery is offered. The tumor is then resected en bloc with the chest wall.

Clinical studies demonstrate that preoperative irradiation in doses not sufficient to cause gross regression of the tumor is still beneficial, as it decreases local recurrences, prevents the growth of disseminated tumor cells, and increases survival. Studies in selected patients have shown complete eradication of local growth, pain relief, and improved survival rates.

Chemotherapy

Since the 2007 study by Rusch et al,[24] preoperative chemotherapy for superior sulcus tumors has involved platinum doublets. For NSCLC (which constitutes the vast majority of Pancoast tumors), current NCCN guidelines recommend several preoperative chemotherapy regimens.[31]  For nonsquamous tumors, preferred regimens are as follows:

For squamous NSCLC, referred regimens are as follows:

Surgical Resection

In many centers, the current practice is to individualize a treatment plan for each patient. Treatment decisions should be made by a multidisciplinary thoracic oncology group with attention to adverse prognostic factors.

The use of neoadjuvant or induction chemoradiotherapy has become standard for patients with potentially resectable superior sulcus tumors[49, 31]  Surgery is generally undertaken 2-4 weeks after the completion of neoadjuvant therapy.

Pancoast tumors that are directly invading the parietal pleura and chest wall should undergo surgery, provided that the following conditions are satisfied:

Involvement of mediastinal nodes is always associated with poor outcome after resection. At the time of surgery, a complete resection of all involved structures is recommended.

In most patients, the surgical treatment of choice is complete removal of the tumor by en bloc chest wall resection combined with lobectomy and node staging.[21] Depending upon the extent of local invasion, surgical treatment may require resection of the paravertebral sympathetic chain, stellate ganglion, lower trunks of the brachial plexus, subclavian artery, or portions of the thoracic vertebrae. For tumors that invade the brachial plexus, the spine, or both, a combined thoracic-neurosurgical approach is warranted.

A single-center Dutch study of 18 patients with superior sulcus tumors invading the spine reported that partial or complete vertebrectomy, as part of trimodality therapy, is safe and results in good survival. However, the authors advise that such patients should be referred to expert centers.[50]

Some patients may have apical tumors that are not attached to the chest wall but for which computed tomography (CT) findings are inconclusive. In such cases, evidence suggests that thoracoscopy can be used to assess for chest wall invasion. With this strategy, unnecessary neoadjuvant treatment and futile thoracotomy may be avoided.[51]

Video-assisted thoracic surgery (VATS) is increasingly used in the management of Pancoast tumors. By starting with thoracoscopy, the surgeon can assess for pleural dissemination and precisely define the tumor location as well as the extent of thoracic wall resection needed. Thus, VATS can reduce the magnitude of the operation, either by sparing the patient a useless thoracotomy or by optimizing the site of the thoracotomy; it may obviate rib retractor use and so minimize postoperative pain and post-thoracotomy syndrome.[52, 53, 54]

Technical approaches

A Pancoast tumor can be approached from either an anterior or a posterior incision. With the posterior approach, the incision is made along the contour of the scapula, and the pleural cavity is entered at the third or fourth intercostal space. Dissection from below prevents injury to the subclavian vessels and the brachial plexus.

Before any resection, the degree of tumor invasion must be assessed. The surgical technique for resection of a superior sulcus tumor is an extended en-bloc resection of the chest wall, including posterior portions of the first 3 ribs, part of the upper thoracic vertebrae (including the transverse process), the intercostal nerves, the lower trunk of the brachial plexus, the stellate ganglion, and a portion of the dorsal sympathetic ganglion, together with the involved lung portion. Determinants of unresectability include the following:

The other approach to a Pancoast tumor is an anterior transcervical approach.[55] Most authorities believe that injury to the subclavian vessels and the brachial plexus is much less common with this incision.

With the anterior transcervical approach, exposure of the jugular and subclavian veins is facilitated, and the thoracic duct is easily identified. Assessment of tumor invasion of the subclavian vessels is readily accomplished, and reconstruction of these vessels is easier. The anterior incision is not recommended for tumors that invade the posterior aspects of the ribs and their transverse processes, the stellate ganglion and sympathetic chain, and the vertebral bodies.

After the procedure is completed, 2 large pleural tubes are placed for drainage, one at the apex of the chest to drain any residual air and the other in the posterior gutter to drain fluid. All drainage tubes are fixed to the skin site with a suture.

Surgical principles for curative resection of a Pancoast tumor can be summarized as follows:

Patients are cared for in the intensive care unit (ICU) and then extubated. Routine care of the chest tubes is maintained. Mortality from surgical resection of a Pancoast tumor ranges from 2% to 5%. After arrival in the ICU, vital signs are monitored every 15-30 minutes until the patient is stable. Urinary output, chest tube drainage, and temperature are monitored hourly. Daily chest radiographs are obtained until the drainage tubes are removed.

Adjuvant Therapy

Adjuvant therapy for Pancoast tumors that are NSCLCs uses the same platinum doublets as are part of preoperative chemoradiation therapy. In addition, adjuvant therapy may include biologic agents selected on the basis of the tumor's mutation status.[31, 44, 56]  Some of these options include the following:

Targeted therapy for NSCLC is a steadily expanding field. For full discussion, see Non–Small Cell Lung Cancer (NSCLC).

Adjuvant radiotherapy

The role for postoperative radiotherapy in superior sulcus tumors is undetermined. Radiotherapy is not indicated for patients who undergo complete resection and have no nodal metastasis. Yet, in the past, postoperative radiotherapy was often used in response to an incomplete resection with residual disease. To date, postoperative radiotherapy has not improved survival in patients with lung cancer who underwent complete surgical resection without gross or microscopic residual tumor.

Some retrospective studies suggested that postoperative radiotherapy was beneficial for patients with nodal disease; however, several oncology trials found no survival benefit in patients who underwent complete resection. Postoperative radiotherapy does decrease the frequency of local (intrathoracic) recurrence.

Treatment of Unresectable Disease

Chemoradiotherapy is used for treatment of Pancoast tumors that are unresectable, and in patients who are not candidates for surgery but are sufficiently fit to receive chemotherapy. As in stage III NSCLC generally, chemoradiation can be followed with durvalumab, in patients with no EGFR exon 19 deletion or L858R mutation; or with osimertinib, in patients without those EGFR alterations.[31, 44, 56]

In patients with metastatic Pancoast tumors, or those unfit for chemotherapy because of poor performance status, radiation therapy alone can be used.[57] Unresectable brain metastases can be treated with stereotactic radiosurgery.[31, 57]

A German study in seven patients with unresectable superior sulcus tumors described the use of interstitial high-dose-rate brachytherapy in combination with external beam radiotherapy (EBRT). One patient died during the course of therapy as a result of systemic progression. On median follow-up of 38 months, five patients achieved local control and one patient showed local and general progression. No severe toxicity from the treatment was observed.[58]

Palliative Procedures

Poor local control of a Pancoast tumor leads to significant intractable pain. The pain is caused by tumor invasion of the brachial plexus and nerve root compression in the intervertebral foramina, which is difficult to control. Pain relief has been reported with the use of ultrasound-guided cervical nerve roots ablation and dorsal root entry zone microsurgery (DREZotomy).[4, 47]

Palliative surgery does not always provide relief from pain. However, when epidural compression is imminent, surgical maneuvers that alleviate this compression are of value. Techniques employed to interrupt pain pathways include the following:

Occasionally, radiotherapy is required for pain control.[39] Radiation in doses of 40-60 Gy is administered over a period of 3 weeks, eliciting relief of pain in 90% of patients and occasionally reversing hoarseness and Horner syndrome. However, most patients die within 2 years. The most common site of metastatic disease is the brain.

Complications

The morbidity arising from the operation is solely caused by the extent of chest wall and lung resection.

Atelectasis is very common with this operation and requires aggressive pulmonary toilet, incentive spirometry, and early ambulation. An adjunct to the treatment of atelectasis is bronchoscopy, which is frequently required to suction out mucous plugs and to drain secretions.

Almost all patients have severe chest wall pain, and epidural anesthesia is highly recommended. Patients who do not undergo thoracic epidural anesthesia usually report significant pain and require continuous narcotics, either intravenously or in patch form.

Cerebrospinal fluid (CSF) leaks occur but are rare; they usually subside with pleural drainage. If a CSF leak occurs in the presence of a pneumothorax, the air may enter the spinal cord and result in meningitis, which manifests as a severe headache. If the CSF leak persists, an exploratory thoracotomy is performed, and a muscle flap is used to close the area.

Most air leaks subside within a few days, and the drainage tubes are removed.

Permanent neurologic deficits are rare. They usually result from resection of the lower trunk of the brachial plexus, but they are not incapacitating. Horner syndrome may occur from resection of the stellate ganglion and the root of C8. Deficits are usually temporary, lasting a few months. To prevent the disabling symptoms from resection of the brachial plexus, some studies indicate that neurolysis and preservation of the brachial plexus by a neurosurgeon may improve surgical outcome and postoperative symptoms.[59]

What is Pancoast syndrome?What is the pathophysiology of Pancoast syndrome?What causes Pancoast syndrome?What are the risk factors for Pancoast syndrome?What is the prevalence of Pancoast syndrome?What is the prognosis of Pancoast syndrome?What are the mortality and survival rates for Pancoast syndrome?What is the prevalence of relapse in Pancoast syndrome?Which clinical history findings are characteristic of Pancoast syndrome?Which physical findings are characteristic of Pancoast syndrome?Why is the diagnosis of Pancoast syndrome often delayed?Which conditions are included in the differential diagnoses of Pancoast syndrome?What are the differential diagnoses for Pancoast Syndrome?How is Pancoast syndrome diagnosed?What is the role of lab testing in the workup of Pancoast syndrome?What is the role of chest radiography in the workup of Pancoast syndrome?What is the role of imaging in the workup of Pancoast syndrome?What is the role of biopsy in the workup of Pancoast syndrome?What is the role of arteriography or phlebography in the workup of Pancoast syndrome?What is the role of ECG in the workup of Pancoast syndrome?How is Pancoast syndrome staged?How is Pancoast syndrome treated?What is included in the preoperative workup for Pancoast syndrome?What is the role of chemoradiotherapy in the treatment of Pancoast syndrome?What is the role of radiation therapy in the treatment of Pancoast syndrome?What is the role of chemotherapy in the treatment of Pancoast syndrome?What is the role of surgery in the treatment of Pancoast syndrome?How are Pancoast tumors surgically resected?What is included in palliative care for Pancoast syndrome?What is the role of radiation therapy in the post-operative treatment of Pancoast syndrome?What are the possible complications of surgical resection of Pancoast tumors?

Author

Karl J D'Silva, MD, Assistant Clinical Professor of Medicine, Department of Hematology/Oncology, Lahey Clinic, Sophia Gordon Cancer Center

Disclosure: Nothing to disclose.

Coauthor(s)

Sarah K May, MD, Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital, Commonwealth Hematology-Oncology PC

Disclosure: Nothing to disclose.

Chief Editor

Nagla Abdel Karim, MD, PhD, Director of Early Therapeutics, Inova Schar Cancer Institute; Professor of Medicine, University of Virginia School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Shabir Bhimji, MD, PhD Locum Cardiothoracic and Vascular Surgeon, Saudi Arabia and Middle East Hospitals

Shabir Bhimji, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Chest Physicians, American Lung Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Shreekanth V Karwande, MBBS Chair, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Utah School of Medicine and Medical Center

Shreekanth V Karwande, MBBS is a member of the following medical societies: American Association for Thoracic Surgery, American College of Chest Physicians, American College of Surgeons, American Heart Association, Society of Critical Care Medicine, Society of Thoracic Surgeons, and Western Thoracic Surgical Association

Disclosure: Nothing to disclose.

Jeffrey C Milliken, MD Chief, Division of Cardiothoracic Surgery, University of California at Irvine Medical Center; Clinical Professor, Department of Surgery, University of California, Irvine, School of Medicine

Jeffrey C Milliken, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Thoracic Surgery, American College of Cardiology, American College of Chest Physicians, American College of Surgeons, American Heart Association, American Society for Artificial Internal Organs, California Medical Association, International Society for Heart and Lung Transplantation, Phi Beta Kappa, Society of Thoracic Surgeons, Southwest Oncology Group, and Western Surgical Association

Disclosure: Nothing to disclose.

Michael Perry, MD, MS, MACP Nellie B Smith Chair of Oncology Emeritus, Director, Division of Hematology and Medical Oncology, Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

Michael Perry, MD, MS, MACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Association for the Study of Lung Cancer, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

  1. Villgran VD, Chakraborty RK, Cherian SV. Pancoast Syndrome. 2025 Jan. [View Abstract]
  2. Pancoast HK. Superior pulmonary sulcus tumor: Tumor characterized by pain, Horner's syndrome, destruction of bone and atrophy of hand muscles. JAMA. 1932. 99:1391-1396.
  3. Munir M, Jamil SB, Rehmani S, Borz-Baba C. Pancoast-Tobias Syndrome: A Unique Presentation of Lung Cancer. Cureus. 2021 Feb 3. 13 (2):e13112. [View Abstract]
  4. Cunha A, Quintela M, Costa C, Quispe-Cornejo AA, Freitas-Silva M. Pancoast Tumor as the Initial Presentation of a Metastatic Colon Adenocarcinoma. Cureus. 2021 Feb 16. 13 (2):e13371. [View Abstract]
  5. Amin R. Bilateral Pancoast's syndrome in a patient with carcinoma of the cervix. Gynecol Oncol. 1986 May. 24(1):126-8. [View Abstract]
  6. Glassman LR, Hyman K. Pancoast tumor: a modern perspective on an old problem. Curr Opin Pulm Med. 2013 Jul. 19 (4):340-3. [View Abstract]
  7. Paulson DL. Carcinomas in the superior pulmonary sulcus. J Thorac Cardiovasc Surg. 1975 Dec. 70(6):1095-104. [View Abstract]
  8. Pitz CC, de la Rivière AB, van Swieten HA, Duurkens VA, Lammers JW, van den Bosch JM. Surgical treatment of Pancoast tumours. Eur J Cardiothorac Surg. 2004 Jul. 26(1):202-8. [View Abstract]
  9. Maggi G, Casadio C, Pischedda F, et al. Combined radiosurgical treatment of Pancoast tumor. Ann Thorac Surg. 1994 Jan. 57(1):198-202. [View Abstract]
  10. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 18-2000. A 45-year-old woman with a thoracic mass and Pancoast's syndrome. N Engl J Med. 2000 Jun 15. 342 (24):1814-21. [View Abstract]
  11. Chong KM, Hennox SC, Sheppard MN. Primary hemangiopericytoma presenting as a Pancoast tumor. Ann Thorac Surg. 1993 Feb. 55(2):9. [View Abstract]
  12. Hatton MQ, Allen MB, Cooke NJ. Pancoast syndrome: an unusual presentation of adenoid cystic carcinoma. Eur Respir J. 1993 Feb. 6(2):271-2. [View Abstract]
  13. Mills PR, Han LY, Dick R, Clarke SW. Pancoast syndrome caused by a high grade B cell lymphoma. Thorax. 1994 Jan. 49(1):92-3. [View Abstract]
  14. Rabano A, La Sala M, Hernandez P, et al. Thyroid carcinoma presenting as Pancoast's syndrome. Thorax. 1991 Apr. 46(4):270-1. [View Abstract]
  15. Vandenplas O, Mercenier C, Trigaux JP, et al. Pancoast's syndrome due to Pseudomonas aeruginosa infection of the lung apex. Thorax. 1991 Sep. 46(9):683-4. [View Abstract]
  16. Gallagher KJ, Jeffrey RR, Kerr KM, Steven MM. Pancoast syndrome: an unusual complication of pulmonary infection by Staphylococcus aureus. Ann Thorac Surg. 1992 May. 53(5):903-4. [View Abstract]
  17. Simpson FG, Morgan M, Cooke NJ. Pancoast's syndrome associated with invasive aspergillosis. Thorax. 1986 Feb. 41(2):156-7. [View Abstract]
  18. Mitchell DH, Sorrell TC. Pancoast's syndrome due to pulmonary infection with Cryptococcus neoformans variety gattii. Clin Infect Dis. 1992 May. 14(5):1142-4. [View Abstract]
  19. Dao I, El Mostarchid B, Onen J, Mandour C, El Asri CA, Boucetta M. Pancaost syndrome related to hydatid cyst. Pan Afr Med J. 2013. 14:118. [View Abstract]
  20. Rong SH. Carotid pseudoaneurysm simulating Pancoast tumor. AJR Am J Roentgenol. 1984 Mar. 142 (3):495-6. [View Abstract]
  21. Ginsberg RJ, Martini N, Zaman M, et al. Influence of surgical resection and brachytherapy in the management of superior sulcus tumor. Ann Thorac Surg. 1994 Jun. 57(6):1440-5. [View Abstract]
  22. Johnson DE, Goldberg M. Management of carcinoma of the superior pulmonary sulcus. Oncology (Huntingt). 1997 Jun. 11(6):781-5; discussion 785-6. [View Abstract]
  23. Tsitsias T, Yasufuku K, Pierre A, Leighl N, Cho J, Waddell TK, et al. Influence of anterior tumor location on survival after resection of lung cancer invading the thoracic inlet (Pancoast tumors). J Thorac Cardiovasc Surg. 2023 May. 165 (5):1710-1719.e3. [View Abstract]
  24. Rusch VW, Giroux DJ, Kraut MJ, Crowley J, Hazuka M, Winton T, 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 Jan 20. 25 (3):313-8. [View Abstract]
  25. Ünal S, Winkelman JA, Heineman DJ, Bahce I, van Dorp M, Braun JA, et al. Long-Term Outcomes After Chemoradiotherapy and Surgery for Superior Sulcus Tumors. JTO Clin Res Rep. 2023 Apr. 4 (4):100475. [View Abstract]
  26. Muscolino G, Valente M, Andreani S. Pancoast tumours: clinical assessment and long-term results of combined radiosurgical treatment. Thorax. 1997 Mar. 52(3):284-6. [View Abstract]
  27. Attar S, Krasna MJ, Sonett JR, et al. Superior sulcus (Pancoast) tumor: experience with 105 patients. Ann Thorac Surg. 1998 Jul. 66(1):193-8. [View Abstract]
  28. Balcer LJ, Galetta SL. Images in clinical medicine. Pancoast's syndrome. N Engl J Med. 1997 Nov 6. 337(19):1359. [View Abstract]
  29. Cooper-Knock J, Pepper I, Hodgson T, Sharrack B. Early diagnosis of Horner syndrome using topical apraclonidine. J Neuroophthalmol. 2011 Sep. 31 (3):214-6. [View Abstract]
  30. Shah H, Anker CJ, Bogart J, Graziano S, Shah CM. Brain: the common site of relapse in patients with pancoast or superior sulcus tumors. J Thorac Oncol. 2006 Nov. 1(9):1020-2. [View Abstract]
  31. [Guideline] National Comprehensive Cancer Network. Non-Small Cell Lung Cancer. NCCN.org. Available at https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Version 3.2025 — January 14, 2025; Accessed: April 15, 2025.
  32. [Guideline] Kalemkerian GP, Narula N, Kennedy EB. Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement Summary of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Oncol Pract. 2018 May. 14 (5):323-327. [View Abstract]
  33. Chen AB, Neville BA, Sher DJ, Chen K, Schrag D. Survival outcomes after radiation therapy for stage III non-small-cell lung cancer after adoption of computed tomography-based simulation. J Clin Oncol. 2011 Jun 10. 29 (17):2305-11. [View Abstract]
  34. Beale R, Slater R, Hennington M, Keagy B. Pancoast tumor: use of MRI for tumor staging. South Med J. 1992 Dec. 85(12):1260-3. [View Abstract]
  35. Patz EF Jr. Imaging lung cancer. Semin Oncol. 1999 Oct. 26(5 Suppl 15):21-6. [View Abstract]
  36. Heelan RT, Demas BE, Caravelli JF, et al. Superior sulcus tumors: CT and MR imaging. Radiology. 1989 Mar. 170(3 Pt 1):637-41. [View Abstract]
  37. Mihoubi Bouvier F, Thomas De Montpréville V, Besse B, Missenard G, Court C, Tordjman M, et al. Can MRI differentiate surrounding vertebral invasion from reactive inflammatory changes in superior sulcus tumor?. Eur Radiol. 2021 Dec. 31 (12):8991-8999. [View Abstract]
  38. Bruzzi JF, Komaki R, Walsh GL, Truong MT, Gladish GW, Munden RF, et al. Imaging of non-small cell lung cancer of the superior sulcus: part 1: anatomy, clinical manifestations, and management. Radiographics. 2008 Mar-Apr. 28 (2):551-60; quiz 620. [View Abstract]
  39. Anderson TM, Moy PM, Holmes EC. Factors affecting survival in superior sulcus tumors. J Clin Oncol. 1986 Nov. 4(11):1598-603. [View Abstract]
  40. Maxfield RA, Aranda CP. The role of fiberoptic bronchoscopy and transbronchial biopsy in the diagnosis of Pancoast''s tumor. N Y State J Med. 1987 Jun. 87(6):326-9. [View Abstract]
  41. Paulson DL, Weed TE, Rian RL. Cervical approach for percutaneous needle biopsy of Pancoast tumors. Ann Thorac Surg. 1985 Jun. 39(6):586-7. [View Abstract]
  42. Shaham D. Semi-invasive and invasive procedures for the diagnosis and staging of lung cancer. I. Percutaneous transthoracic needle biopsy. Radiol Clin North Am. 2000 May. 38(3):525-34. [View Abstract]
  43. International Association for the Study of Lung Cancer. Lung Cancer. Rami-Porta R, ed. Staging Handbook in Thoracic Oncology. Second Edition. North Fort Myers, FL: Editorial Rx Press; 2016. 55-118.
  44. [Guideline] Daly ME, Singh N, Ismaila N, Antonoff MB, Arenberg DA, Bradley J, et al. Management of Stage III Non-Small-Cell Lung Cancer: ASCO Guideline. J Clin Oncol. 2022 Apr 20. 40 (12):1356-1384. [View Abstract]
  45. [Guideline] Simone CB 2nd, Bradley J, Chen AB, Daly ME, Louie AV, Robinson CG, et al. ASTRO Radiation Therapy Summary of the ASCO Guideline on Management of Stage III Non-Small Cell Lung Cancer. Pract Radiat Oncol. 2023 May-Jun. 13 (3):195-202. [View Abstract]
  46. Gofeld M, Bhatia A. Alleviation of Pancoast's tumor pain by ultrasound-guided percutaneous ablation of cervical nerve roots. Pain Pract. 2008 Jul-Aug. 8 (4):314-9. [View Abstract]
  47. Leclerc A, Derrey S, Emery E. Microsurgical DREZotomy for pain related to Pancoast-Tobias syndrome: how I do it?. Acta Neurochir (Wien). 2023 Apr. 165 (4):953-957. [View Abstract]
  48. Tamura M, Hoda MA, Klepetko W. Current treatment paradigms of superior sulcus tumours. Eur J Cardiothorac Surg. 2009 Oct. 36(4):747-53. [View Abstract]
  49. Ünal S, Heineman DJ, van Dorp M, Winkelman T, Braun J, Dahele M, et al. Chest wall resections for sulcus superior tumors. J Thorac Dis. 2024 Feb 29. 16 (2):1715-1723. [View Abstract]
  50. Unal S, Feller R, Stadhouder A, Heineman DJ, Jiya TU, van Dorp M, et al. Superior Sulcus Tumors Invading the Spine: Multimodal Treatment Outcomes From the Preimmunotherapy Era. JTO Clin Res Rep. 2023 Dec. 4 (12):100582. [View Abstract]
  51. Hubbard MO, Schroeder C, Linden PA. Routine use of staging thoracoscopy for pancoast tumors without overt radiographic chest wall invasion. Surg Laparosc Endosc Percutan Tech. 2011 Apr. 21(2):111-5. [View Abstract]
  52. Caronia FP, Ruffini E, Lo Monte AI. The use of video-assisted thoracic surgery in the management of Pancoast tumors. Interact Cardiovasc Thorac Surg. 2010 Dec. 11(6):721-6. [View Abstract]
  53. Caronia FP, Fiorelli A, Ruffini E, Nicolosi M, Santini M, Lo Monte AI. A comparative analysis of Pancoast tumour resection performed via video-assisted thoracic surgery versus standard open approaches. Interact Cardiovasc Thorac Surg. 2014 Sep. 19 (3):426-35. [View Abstract]
  54. Rosso L, Palleschi A, Mendogni P, Nosotti M. Video-assisted pulmonary lobectomy combined with transmanubrial approach for anterior Pancoast tumor resection: case report. J Cardiothorac Surg. 2016 Apr 14. 11 (1):65. [View Abstract]
  55. Dartevelle PG, Chapelier AR, Macchiarini P, et al. Anterior transcervical-thoracic approach for radical resection of lung tumors invading the thoracic inlet. J Thorac Cardiovasc Surg. 1993 Jun. 105(6):1025-34. [View Abstract]
  56. [Guideline] Singh N, Früh M, Gubens MA, Ismaila N, Daly ME. Management of Stage III Non-Small Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update Clinical Insights. JCO Oncol Pract. 2025 Apr. 21 (4):463-466. [View Abstract]
  57. Van Houtte P, MacLennan I, Poulter C, Rubin P. External radiation in the management of superior sulcus tumor. Cancer. 1984 Jul 15. 54 (2):223-7. [View Abstract]
  58. Neu M, Kahl KH, Körner M, Walter R, Raab S, Jehs B, et al. Interstitial High-Dose-Rate Brachytherapy Combined with External Beam Radiation Therapy for Dose Escalation in the Primary Treatment of Locally Advanced, Non-Resectable Superior Sulcus (Pancoast) Tumors: Results of a Monocentric Retrospective Study. J Clin Med. 2024 Dec 11. 13 (24):[View Abstract]
  59. Davis GA, Knight SR. Pancoast tumors. Neurosurg Clin N Am. 2008 Oct. 19(4):545-57, v-vi. [View Abstract]
Stage T(Tumor) N (Nodes)
IIBT3N0
IIIAT3N1
IIIBT3N2
IIICT3, T4N3