Pancoast Syndrome Treatment & Management

Pancoast tumors were once considered universally fatal. However, improvements in combined modality therapy and the development of new techniques for resection have made curative treatment possible for these tumors. ^{[7, 38]} For example, in 1993, Dartevelle et al presented their experience with an anterior transcervical thoracic approach that permitted greater exposure and control of the vascular structures of the thoracic inlet, which facilitated resection in cases in which vascular structures were invaded. ^[39]

Patients with superior sulcus pulmonary carcinoma should be considered for surgery after appropriate diagnostic evaluation. The ideal 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. However, surgery alone is not the prevalent course of treatment.

Surgery is indicated in patients who have very localized early disease. The occasional inoperable patient with severe pain after radiation therapy may be selectively considered for palliative resection. Contraindications to surgery include the following:

• Extensive invasion of the neck, brachial plexus, or vertebrae
• Perinodal mediastinal extension
• Peripheral metastases

These include extrathoracic metastatic disease and positive mediastinal nodes. Complete upper and lower brachial plexus invasion is a relative contraindication, provided that complete surgical excision can be performed. Vertebral body involvement should not be a contraindication unless invasion of the cortex is confirmed.

In general, medical management plays only a secondary role in the treatment of lung cancers. In patients with disseminated lung cancer, medical treatment is required for palliation and treatment of symptoms arising from paraneoplastic syndromes.

Data indicate that the best survival rate is obtained with preoperative chemoradiotherapy followed by surgical resection in carefully selected patients. ^{[33, 40, 41, 42]} Preoperative radiotherapy followed by surgery is a reasonable alternative in some patients. Involvement of the subclavian vessels or the vertebral column is associated with poor survival. ^[41] However, a few centers have obtained decent experience with better surgical approaches to these structures and have published reasonable survival rates after surgery.

In a study of 56 patients in stage IIB to IIIB who were treated with a trimodal approach (2-3 cycles of a platinum-based chemotherapy associated with radiotherapy (30–44 Gy) followed by surgical resection of eligible patients 2 to 4 weeks post-radiation), a 5-year survival rate of 38% was achieved. ^[43]  

To date, no data describe appropriate treatment for patients with unresectable tumors who may be curable. However, extrapolation from the data for non-Pancoast stage III non–small-cell lung cancer (NSCLC) suggests that chemoradiotherapy is the best approach. In patients whose disease is believed incurable, radiotherapy offers good palliation of pain.

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.

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.

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 are required to 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.

All patients 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.

In patients with a Pancoast tumor, a multimodality approach involving chemoradiotherapy and surgical resection seems to be optimal, provided that appropriate staging has been conducted. Patients with central T4 tumors that do not have mediastinal node involvement are uncommon. Such patients, however, seem to benefit from resection as part of the treatment as opposed to chemoradiotherapy alone when carefully staged and selected.

Currently, in accordance with the findings of the trial conducted by Rusch et al, most centers use cisplatin-based chemotherapy with etoposide and concurrent radiotherapy as neoadjuvant treatment, followed by surgical resection, as the standard of care for this group of patients. ^[38] One cautionary note is that this trial mandated a negative mediastinoscopy result. The preoperative radiotherapy dose was 45 Gy in 25 fractions.

Radiotherapy

Radiation therapy is used as the sole treatment only for patients with unresectable tumors or for those who are not surgical candidates. It provides excellent pain relief, but no long-term survival occurs if the primary tumor is not controlled. The most common site of recurrence after resection is the central nervous system (CNS), especially if the primary tumor is an adenocarcinoma or large cell cancer. In these situations, prophylactic cerebral radiotherapy should be administered if local control has been achieved.

Previously, superior sulcus tumors were considered inoperable and were not often successfully palliated with radiation therapy alone. The best results seem to occur when the tumor and the localized adjacent area, including the superior mediastinal nodes, are preoperatively treated with 30-40 Gy of radiation administered over 2-3 weeks. The radiation field includes the primary tumor, adjacent mediastinum, and ipsilateral clavicular area. The purpose of the preoperative irradiation is to shrink the tumor and to temporarily block lymphatic spread.

Preoperative treatment with more than 40 Gy may lead to poor healing after surgery. 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.

The presence of Horner syndrome or ipsilateral supraclavicular node involvement is not an absolute contraindication for combined preoperative radiation and surgery. In current practice, interstitial implantation of radioisotopes (brachytherapy) is performed in association with external radiation therapy.

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 compared with irradiation or surgery alone. Studies in selected patients have shown complete eradication of local growth, pain relief, and improved survival rates.

Whereas preoperative irradiation followed by complete en bloc resection represented an advance over previous treatment paradigms, ^[44] the high frequency of local recurrence despite aggressive measures, coupled with the eventual development of distant disease and death, prompt continued exploration of novel approaches.

Some evidence indicates that a multidisciplinary approach using neoadjuvant chemotherapy and radiation (see below) may improve resectability. However, such an approach is also associated with increased incidence of postoperative distress syndrome. ^[45]

Chemotherapy

The introduction of chemotherapy into the treatment plan, along with the development of newer modes of radiation therapy, brings the possibility of additional progress. Because Pancoast tumors are an uncommon subset of lung cancer, the number of cases has been insufficient to justify conclusions; however, further approaches to the general treatment of patients with regionally advanced disease (T3, chest wall invasion) are undergoing evaluation with chemotherapy, both with and without radiation therapy.

Data indicate that traditional treatment of Pancoast tumors with local approaches (surgery, radiotherapy, or a combination thereof) yields poor outcomes because of the high recurrence rate and the lack of systemic control. A trimodality treatment approach may improve local control and even survival.

There is evidence to suggest that induction chemotherapy combined with hyperfractionated accelerated radiotherapy before surgery may be effective in improving long-term survival and lowering recurrence rates. An empirical approach involving preoperative chemotherapy and radiation followed by surgical resection is being used in some centers, but no standardized protocols are available at present.

Several early trials demonstrated survival benefits in small groups of patients (not Pancoast patients) with locally advanced lung cancer treated with preoperative chemotherapy. ^{[46, 47]} The largest study of this kind, reported by Albain et al, reported complete pathologic responses in 21% of surgical patients after preoperative concurrent chemotherapy and radiation therapy. ^[48] The optimal chemotherapeutic regimen has not yet been identified, and newer agents may improve responses. ^[49]

Although present-day management of Pancoast syndrome is largely based on the published retrospective experience of large single institutions, 2 prospective multicenter phase 2 studies that used a trimodality approach of induction concurrent chemoradiotherapy followed by surgery (followed by 2 additional cycles of adjuvant chemotherapy in 1 study), reported 5-year survival rates of 44-56%. These studies support the idea that a trimodality approach may be the ideal approach in the management of Pancoast tumors. ^[50]

A lung intergroup trial (Southwest Oncology Group 0220) using induction therapy with cisplatin, etoposide, and radiotherapy with 45 Gy, followed by resection (if possible) and postoperative docetaxel, reported 5-year survival rates increasing to 44-56%, suggesting that this approach could be considered a new standard of care in the management of Pancoast tumors.

In various series, irrespective of local control of the tumor, a considerable number of patients died of distant metastases rather than of local disease. The microscopic presence of distant metastatic disease is not presently discernible by available conventional screening methods, which suggests that more potent chemotherapy might be necessary to control the disease. ^[51]

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

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

• No distant metastases are present
• The patient’s cardiopulmonary status allows surgery
• No preoperative evidence of extensive mediastinal adenopathy is present

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. ^[20] 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.

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. ^[52]

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. ^{[53, 54, 55]}

Radiation and chemotherapy may benefit local and systemic control by addressing individual adverse findings. In many centers, neoadjuvant or induction chemoradiotherapy is administered to patients with potentially resectable tumors (see above). Important factors include T category, nodal status, presence of Horner syndrome, and completeness of resection. ^{[20, 21, 22, 23, 24, 26]} Surgery is generally undertaken 2-4 weeks after the completion of radiation therapy.

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:

• Involvement of the subclavian artery
• Involvement of the vertebral body with or without cord compression
• Widespread invasion of the brachial plexus

The other approach to a Pancoast tumor is an anterior transcervical approach. ^[39] 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. Fix all drainage tubes to the skin site with a suture.

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

• Excise the entire first rib and posterior segments of the second and third ribs
• Excise corresponding thoracic nerve roots up to the intervertebral foramen
• Excise portions of the upper thoracic vertebrae, including the transverse process if necessary
• Excise the lower trunk of the brachial plexus
• Excise part of the stellate ganglion and the thoracic sympathetic chain
• The lung resection can be either a wedge resection or a lobectomy
• Radical mediastinal lymph node dissection can be performed

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.

The adjuvant 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, many people were treated with postoperative radiotherapy 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.

Postoperative radiotherapy following immediate operation and brachytherapy has been as effective as preoperative radiation therapy and brachytherapy in achieving complete resection, locoregional control, and, ultimately, cure. No studies document the usefulness of chemotherapy in the treatment of this disease.

Surgical 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. ^[56]

The 5-year postoperative survival rate is approximately 30%. Intraoperative brachytherapy has had no influence on locoregional recurrence or survival in patients with completely resected tumors. In the presence of positive mediastinal lymph nodes, the median survival rate is less than 9 months.

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.

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:

• Cervical cordotomy
• Selective posterior rhizotomy
• Stereotactic thalamotomy
• Commissural myelotomy

Occasionally, radiotherapy is required for pain control. ^[33] 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.