Approximately 5% of all non-small cell lung cancers (NSCLC) are located in the extreme apex of the lung, frequently with involvement of some combination of the first and second ribs, brachial plexus, subclavian vessels, and upper thoracic vertebral bodies. This phenomenon is referred to as a superior sulcus carcinoma, indicating tumor location in the uppermost portion of the costovertebral gutter within the chest. Pancoast syndrome refers to superior sulcus tumors along with the triad of (1) shoulder and arm pain, (2) wasting of the hand muscles, and (3) ipsilateral Horner syndrome (i.e., ptosis, miosis, and anhidrosis due invasion of the stellate ganglion). Henry Pancoast was a radiologist who described these findings in 1932 but failed to recognize the pulmonary origin of these tumors. Unaware of Pancoast report, Tobias, an Argentine physician, described similar clinical findings and ascribed them to the presence of peripheral lung tumors. Pancoast–Tobias syndrome is perhaps a more appropriate eponym for this entity. Anatomically, the superior pulmonary sulcus is the area on the superior surface of the lung traversed by the subclavian vessels and encircled by the first rib and spine (Fig. 80-1). It also may be described as the thoracic outlet or thoracic inlet.

For the next 25 years, these tumors were considered unresectable and uniformly fatal. In 1951, during irradiation therapy, a patient of Dr. Robert Shaw developed unbearable pain that precluded continuation of his irradiation therapy. With a threat of suicide, Dr. Shaw performed an en bloc resection of the cancer, with the chest wall, and lower trunk of the brachial plexus. Dr. Shaw did not expect him to live long; however, the patient survived over 40 years (outliving Dr. Shaw).

In 1961, Shaw et al.¹ described successful outcomes in 18 patients undergoing 30 Gy of radiation, followed by resection, and this became the standard of care for the next 20 to 30 years. In over 400 patients with N0 stage I, Urschel found that approximately 35% had a 5-year survival. The treatment of choice since these reports has been preoperative irradiation (3000 rads over 2–3 weeks) followed by surgical en bloc resection of the lung, chest wall, lower brachial plexus, and vertebrae at a 1- to 2-month interval. This effects approximately a 35% to 50% 5-year survival with N0 stage I patients. Recently, the Intergroup 0160 phase II trial demonstrated superior outcomes by using trimodality therapy for superior sulcus tumors, which now represents the standard of care.²

Dr. Shaw’s initial successful outcome caused our group to treat several other patients in similar fashion with 3000 rads to the tumor and mediastinal lymph nodes over a period of 2 to 3 weeks, followed by a waiting period of 2 to 4 weeks. This delay allows time for the benefits of irradiation, which theoretically include shrinking of the tumor, blocking of the lymphatics, and weakening of the cells that might be left after surgery because the margins are extremely close in such tumor resections. In 1961, 14 patients were reported, with approximately 40% 5-year survival shown.¹ Chardack and MacCallum^3,4 presented a patient in 1953 and 1956 who had been resected and treated successfully with postoperative irradiation therapy. This approach, however, has not been as reproducible in other centers.

Factors that predict a favorable outcome after resection of superior sulcus tumors include R0 resection, absence of N2 or N3 metastases,⁵ lobectomy rather than limited pulmonary resection,⁶ and a complete pathologic response after induction chemoradiotherapy.^7,8 Surprisingly, tumor stage (T3 vs. T4 status) may be less important prognostically in this subset of patients; in the Intergroup 0160 study, this criterion was not a significant determinant of survival. The need for vertebral or subclavian vessel resection should not be considered an absolute contraindication to surgical treatment. Fadel et al.⁹ reported 5-year survival rates after resection of 36% in the presence of subclavian artery invasion.

Limited survival benefit occurs with surgical resection alone. Local recurrences are common and extremely debilitating in terms of pain and limb function. Even with induction radiotherapy, complete resection is achieved in only 60% of patients, and overall 5-year survival is no better than 30%. Resectability, local control, and long-term survival have been positively affected by the addition of concurrent chemotherapy, as demonstrated by the long-term results of the phase II multicenter Intergroup 0160 trial.² Two cycles of chemotherapy (i.e., cisplatin and etoposide) concurrent with 45 Gy of radiation to the primary tumor, followed by surgical resection 3 to 5 weeks later, with two adjuvant cycles of chemotherapy was well tolerated in 110 patients. This regimen resulted in R0 resection rates of 94% for T3 lesions, 96% for T4 lesions, an overall complete pathologic response rate of 56%, and 5-year survival of 44% (54% for R0 resection). Relapse occurred predominantly in the brain, with local failure in only 10 patients, a significant pattern shift in this disease. Ongoing questions exist about the optimal dose of radiation; our group⁸ has used higher radiation doses (median dose 56 Gy) with good tolerance and concomitant increased rates of complete pathologic response. Ideally, higher-dose regimens should be studied in a multicenter study protocol to make sure that these excellent results are generalizable.

Most superior sulcus tumors are approached posteriorly through a posterolateral thoracotomy extending up to the base of the neck, which is appropriate for posteriorly located tumors (Shaw–Paulson posterior approach). Exposure of tumors above the thoracic inlet is suboptimal with a posterior approach, however, and this may explain why there have been incomplete resections in the past. The anterior approach of Dartevelle is preferable for more anteriorly and superiorly located tumors because it provides better access to the subclavian vessels and other cervical structures. Many surgeons favor an anterior exposure when there is a palpable supraclavicular mass, clinical involvement of the C7 or C8 nerve root, Horner syndrome, proven or suspected vascular invasion, or any involvement of the thoracic inlet (or Sibson fascia) and structures superior to it.¹⁰ It is important to be familiar with both the anterior and posterior exposures to permit maximum flexibility while operating.

Given the magnitude of the surgical resections, especially following concurrent chemoradiation, it is important to select patients with satisfactory performance status, as well as adequate cardiac, pulmonary, and renal function (especially for platinum-based regimens). Smoking cessation is also critical. Marginal respiratory status in conjunction with pulmonary and chest wall resection increases perioperative risk. Careful neurologic assessment is critical to determine the extent of brachial plexus involvement. Any neurologic dysfunction higher than the lower trunk of the plexus is likely to lead to significant limb dysfunction after resection; in some rare cases, forequarter amputation may be considered a better palliative option.^11,12 In addition, long-track neurologic symptoms may indicate extensive spinal cord involvement owing to vertebral invasion.

Initial assessment is similar to that for any lung cancer resection. Tissue is almost always obtainable by transthoracic needle aspiration.¹³ Of note, tuberculosis and lymphoma have been reported to mimic Pancoast tumors. Tissue diagnosis therefore is critical before commencing multimodality therapy. In addition to chest and upper abdomen CT scanning and CT/PET, it is often helpful to include a neck CT scan to better image the thoracic inlet. To better delineate involvement of the brachial plexus, subclavian vessels, vertebral bodies, or neural foramina, MRI with contrast enhancement is the preferred imaging modality for this region. Involvement of the lower trunks of the brachial plexus may be considered a contraindication to resection because of limb dysfunction; however, resection of the T1 and C8 nerve roots can be easily accomplished. Brain imaging, using CT scanning or MRI, is also recommended as part of a thorough metastatic assessment. Extrathoracic metastases or persistent N2 or N3 disease after induction therapy is considered an absolute oncologic contraindication by most. It is critical to perform a thorough mediastinoscopic evaluation as part of the initial workup¹⁴ or after induction chemoradiation.⁸ If persistent postoperative N2 or N3 disease is documented, surgery should be attempted when it is the only satisfactory way to palliate pain because cure cannot be achieved.¹⁵

Extensive involvement of the subclavian and carotid arteries is not an absolute contraindication to resection (Table 80-1). Doppler ultrasound of the neck vessels and great vessels, including the vertebral artery, is helpful not only for assessment of tumor invasion but also to look for atherosclerotic changes that may affect clamp placement or critical stenosis.¹⁵ Careful neurologic examination and, in some cases, electromyography can help to define brachial plexus involvement, phrenic nerve involvement, and cord involvement. Preoperative neurosurgical consultation is highly recommended if there is any question of brachial plexus involvement or vertebral invasion; a team approach can be very useful intraoperatively (Table 80-2).

Clinical Presentation

Most patients present with shoulder and elbow pain because of involvement of the lower trunk of the brachial plexus. The discomfort often follows the distribution of the ulnar nerve because of malignant invasion of T1 and C8 nerve roots and extension into the parietal pleura and first rib.¹⁶ Weakness and atrophy of the intrinsic muscles in the hand, along with pain and paresthesias in the medial aspect of the arm and fourth and fifth digits (distribution of the ulnar nerve), sometimes associated with a loss of the triceps reflex, also are caused by C8 and T1 nerve root involvement. Pain may radiate into the neck and head and posteriorly into the scapular area or anteriorly into the chest (Fig. 80-2).

Classically, the patient presents holding the elbow with the opposite arm to support the shoulder and take the pressure off the brachial plexus for symptomatic relief (Fig. 80-3).^16,17 Frequently, the diagnosis is missed because of concentration on cervical osteoarthritis, discs, or other differential diagnoses, often delaying recognition of the true etiology. Horner syndrome classically presents as an ipsilateral ptosis, with narrowing of the palpebral fissure, miosis, and anhidrosis. It is produced by involvement of the sympathetic chain in the area of C7 and C8, the upper two-thirds of the stellate ganglion (Fig. 80-4).¹⁸ Vertebral involvement and spinal cord compression with paralysis (paraplegia) are observed occasionally. Phrenic or recurrent laryngeal nerve invasion is present infrequently, producing diaphragmatic paralysis or hoarseness. Superior vena cava syndrome may result if anterior tumors are present. This syndrome leads to swelling of the face and distention of the neck and upper chest wall veins. Primary pulmonary tumors also may produce the usual symptoms of cough, hemoptysis, dyspnea, wheeze, and weight loss.

Radiographic Findings

Chest roentgenographs (posteroanterior and lateral) are the simplest methods of discerning an apical mass (Fig. 80-5A). Apical lordotic chest views are valuable after the screening procedure. CT scan of the chest provides additional information, particularly about bone invasion (including the first rib) and vertebral involvement (Fig. 80-5B). It also may be used to delineate lung and liver metastases. MRI is particularly helpful in soft tissue areas, such as invasion of the brachial plexus, vascular structures, and chest wall, as well as lymph node metastases in the mediastinum (Fig. 80-5C).¹⁹

Diagnosis Tests

The definitive diagnosis is established by a transthoracic needle biopsy, usually through the supraclavicular space or the posterosuperior chest between the scapula and spine. These small needles are guided by fluoroscopy, ultrasound, or CT in most cases. The first description of transcervical biopsy via the supraclavicular approach was reported by McGoon ²⁰ in 1964. Biopsy may be performed under local or general anesthesia. The diagnostic yield for needle biopsy is greater than 90%. Diagnostic yield from sputum cytology is less than 20%, and for bronchoscopy (fiberoptic or rigid), it is less than 30%.²¹ The diagnostic yield of these tests is low because most of these tumors are peripheral.

Staging and Perioperative Assessment

Cervical mediastinal lymph node exploration is necessary before treatment in these patients to establish whether the lymph nodes are positive. The suggestion of enlarged nodes on either the CT scan or MRI may be helpful, but the staging of actual metastases is critical.²² False positive and false negatives occur frequently and often only supraclavicular lymph nodes are involved. If the mediastinal nodes are positive for a right upper lobe lesion, it is still treated as an operable case because the lymph nodes are assumed to be “regional.” Metastasis to the contralateral mediastinal lymph nodes is a poor prognosticator and surgical therapy is less likely to be successful. Mediastinal pathologic staging is mandatory in these patients and can be achieved using TBNA/EBUS/VATS or routine mediastinoscopy. The timing of staging can be either at the time of initiation of induction therapy or after completion of neoadjuvant chemoradiation in order to decide whether to proceed if residual positive lymph nodes are found. Our current approach is sample the lymph node by needle and then use surgical restaging prior to resection (where we will not resect if there are persistent positive mediastinal lymph nodes).

Although invasion of the vertebral body (T4) demonstrated by CT usually renders a patient inoperable (because “no reported cures” have resulted with vertebral involvement in our experience¹⁹); recent reports from the French groups have suggested possible cures even in these cases. Distant metastases are suspected by history and physical examination, as well as retroperitoneum, liver, and adrenal glands. These lesions should be biopsied and metastasis confirmed before a decision to proceed with aggressive therapy is made. Cell types encountered are predominantly squamous cell carcinoma, with large cell the second, and adenocarcinoma the third most commonly observed.²³ Many begin as so-called “scar” carcinomas or are secondary to other malignancies.^24–28 Metastatic carcinoma from other organs may produce similar symptoms in this area. Various other etiologies include benign tumors and infections such as actinomycosis, tuberculosis, Allescheria infection, cryptococcosis, and hydatid cyst.^29–36 Vascular aneurysms³⁷ and amyloidosis³⁸ also may produce the Pancoast syndrome.

Differential Diagnosis

Differential diagnosis includes thoracic outlet syndrome (TOS) that may mimic the symptoms of ulnar paresthesias and pain. First rib resection has been carried out mistakenly for TOS in patients with superior sulcus tumor of the lung.¹⁶ Vascular, esophageal, and cardiac disease also can mimic symptoms of superior pulmonary sulcus tumors, and these areas should be ruled out in the differential diagnosis.¹⁶

Indications for Surgery

If the patient has a tumor in the area of the superior pulmonary sulcus with or without rib involvement and with or without lower brachial plexus involvement, and it is staged as a T3N0 or N1, he or she is operable. N2 disease is operable if it is in the upper lobe and the mediastinal nodes are considered to be ipsilateral metastases. Involvement of the vena cava and subclavian artery or vein is not an absolute contraindication for surgery. These patients should undergo neoadjuvant chemoradiation followed by reassessment of the extent of disease prior to planned resection.

In addition to chest and upper abdomen CT scanning and CT/PET, it is often helpful to include a neck CT scan to better image the thoracic inlet. To better delineate involvement of the brachial plexus, subclavian vessels, vertebral bodies, or neural foramina, MRI with contrast enhancement is the preferred imaging modality for this region. Involvement of the lower trunks of the brachial plexus may be considered a contraindication to resection because of limb dysfunction; however, resection of the T1 and C8 nerve roots can be easily accomplished. Brain imaging, using CT scanning or MRI, is also recommended as part of a thorough metastatic assessment.

Extrathoracic metastases or persistent N2 or N3 disease after induction therapy is considered an absolute oncologic contraindication by most. It is critical to perform a thorough mediastinoscopic evaluation as part of the initial workup¹¹ or after induction chemoradiation.⁵ If persistent postoperative induction N2 or N3 disease is documented, surgery should be attempted when it is the only satisfactory way to palliate pain because cure cannot be achieved.¹²

Although vertebral involvement traditionally has been a contraindication for surgical resection of superior sulcus carcinoma, recent advances in spinal instrumentation have permitted a more complete resection of vertebral body tumor. Gandhi et al. ³⁹ (Garrett Walsh & Associates at MD Anderson) have published good results in 17 patients with vertebral resection of carcinoma extension. Contraindications include extensive involvement of the brachial plexus, mediastinal perinodal involvement, significant invasion of the soft tissues of the neck, and distant metastasis. Palliative resection is performed occasionally for intractable pain.¹⁹ Recent reports by Dartevelle et al.^40,41 and Grunenwald et al.⁴² suggest a role for extensive resection with good outcomes in selected patients.