Continuing Education Activity

Pancoast or superior sulcus tumor consists of a wide range of tumors invading the apical chest wall and producing a characteristic syndrome named Pancoast-Tobias syndrome. Not all superior sulcus tumors are in this precise anatomic location, but the term signifies any tumor that presents in the apices of the lungs with the associated clinical symptoms that are the hallmark of this disease. Treatment of Pancoast tumors involves interprofessional care coordinated among a thoracic surgeon, a radiation oncologist and a medical oncologist. This activity reviews the evaluation and management of Pancoast tumors and reviews the role of the interprofessional team in managing patients with this condition.

Objectives:

• Outline the presentation of a Pancoast tumor.
• Describe the typical imaging findings associated with Pancoast tumors.
• Outline the treatment considerations for patients with Pancoast tumors.
• Review the importance of improving care coordination by an interprofessional team to improve the outcomes for patients affected by Pancoast tumor.

Introduction

Pancoast or superior sulcus tumor consists of a wide range of tumors invading the apical chest wall and producing a characteristic syndrome named “Pancoast -Tobias syndrome.” The superior sulcus is an anatomical pleuro-pulmonary groove that is formed by the subclavian artery when it curves in front of the pleura and runs upward and lateral immediately below the apex.[1] Not all superior sulcus tumors are in this exact location, but this term signifies any tumor that presents in the apices of the lungs associated with clinical signs and symptoms that are the hallmark of Pancoast syndrome.

The combination of severe shoulder/arm pain along with the distribution of the C8, T1, T2 nerve trunks, Horner syndrome (ipsilateral ptosis, miosis, and anhidrosis; caused due to interruption of sympathetic nerve chain running to the head) and atrophy of the intrinsic hand muscles is termed “Pancoast-Tobias syndrome.”[2]

The overall prognosis of patients with this disease is poor, although recent advancements in the treatment regimen showed significant improvement. Treatment of Pancoast tumors involves interprofessional care coordinated among a thoracic surgeon, a radiation oncologist, and a medical oncologist.[2]

Etiology

Primary tumors in superior sulcus/apex of the lung are generally considered Pancoast tumors, which account for 3% to 5% of lung cancers. The vast majority being bronchogenic cancers. Non-small cell lung cancer account for more than 95% of all the cases of Pancoast tumors.

A wide variety of diseases can cause Pancoast syndrome, like lung and pleural neoplasms, secondary metastases (thyroid malignancies, lymphomas), inflammatory and infectious processes (Pseudomonas, Staphylococcus, Actinomyces).[3][4][3][5]

Epidemiology

According to the World Cancer Research Fund (WCRF) statistics, 12.8% of all the newly diagnosed cancers (excluding non-melanoma skin cancer) in 2018 were lung cancers (about 2093876 cases). Pancoast tumors account for roughly 3 to 5% of all lung cancers.[6] The average age of presentation of Pancoast tumor is in the sixth decade, and it occurs more commonly in men than women.

Histopathology

Clinical symptoms and imaging findings can diagnose more than 90% of the cases. But still, a biopsy is necessary for histologic confirmation and planning therapy before starting treatment. Now, close to 95% is done by CT guided or ultrasound-guided percutaneous transthoracic needle biopsy.[7] Video-assisted thoracoscopy (VAT) or sometimes thoracotomy may be necessary when a percutaneous biopsy is inconclusive.[2]

Overall, the majority of Pancoast tumors are non-small cell lung carcinomas. The possibility of a small cell carcinoma at this site is very rare (only up to 5%). Close to 50% of the cases are adenocarcinoma, and the rest are squamous cell carcinomas (historically squamous cell carcinoma was predominant, but increasing cases of adenocarcinoma are now seen).[8][9]

History and Physical

Most of the presenting symptoms are due to the local invasion of the tumor. Due to anatomical proximity, Pancoast tumors may cause symptoms secondary to neurological involvement (brachial plexus, Horner syndrome) and musculoskeletal symptoms (shoulder pain, vertebral, or rib pain).[1]

Shoulder pain is present in up to 96% of patients and is the most common initial presenting symptom.[10][11][12] The pain could potentially be secondary to the invasion of brachial plexus, pleural invasion, extension into ribs or vertebral bodies, and is generally progressive. It may radiate to head and neck, axilla, scapula, anterior chest, or arm (weakness in the ulnar nerve distribution and intrinsic muscles of hand).

Horner syndrome is a combination of ipsilateral ptosis (drooping or falling of upper eyelid), miosis (persistent constricted pupil), and anhidrosis (inability to sweat on the ipsilateral side). Pancoast tumor causes second-order or pre-ganglionic Horner syndrome (i.e., affecting the second-order neuron, traveling from the sympathetic trunk, through the brachial plexus, over the lung apex).[13] Ipsilateral flushing and sweating of the face can occur before developing full-blown Horner syndrome likely due to tumor irritation of the sympathetic chain before the invasion of the sympathetic trunk.[1]

In approximately 5 percent of patients, the tumor may extend into the intervertebral foramina causing paraplegia and spinal cord compression.[1] Tumor extension into surrounding nerve roots, especially ulnar nerve roots (C8 and T1) occurs in approximately 8 to 22 percent of Pancoast tumors, which may result in weakness and atrophy of the intrinsic muscles of the hand, paresthesia over the distribution of 4th and 5th digits of hand and medial aspect of arm and forearm. In some cases, the patient may exhibit a loss of the triceps reflex.[14]

Evaluation

Pancoast tumor constitutes a group of malignancies (as it is classified based on location), which means there is no specific laboratory diagnosis to diagnose Pancoast tumor.

Initial plain radiological test with a chest x-ray is generally used to screen a patient with suspected or as an incidental finding showing soft tissue opacity at the apex of the lung (unilateral) or just an asymmetry in the apices greater than 5 mm can be noted. Local rib extension can sometimes be appreciated. Lordotic chest views may be helpful. In the early stages, it is difficult to appreciate these findings in the PA view of chest x-ray because of difficulty in interpreting the overlying shadows at apices (clavicle, scapula, acromion, and 1st rib).

CT scan provides more information on the extent of the primary tumor, mediastinal lymphadenopathy, and satellite tumors, which are essential in staging the tumor.[15] CT scan has poor sensitivity and specificity for accurate local staging but is excellent at identifying bony involvement.

MRI is far more sensitive and specific for local staging due to its superior delineation of the extent of involvement in lung tissue, surrounding blood vessels, spinal cord involvement, brachial plexus invasion.[15] Careful assessment of the brachial plexus is needed as the involvement of extending beyond the lower trunk, or C8 nerve root is deemed inoperable.[16]

Positron emission tomography-computed tomography (PET-CT) is useful in assessing nodal and distal metastasis, and accurate delineation of gross tumor volume at baseline staging; this is helpful for radiation treatment planning.[17]

Chest CT and PET-CT scans are considered mandatory before and after preoperative therapy, but recommendations vary whether mediastinoscopy or endobronchial/esophageal ultrasound is necessary.[18]

Treatment / Management

In the late 1950s, bimodality therapy (external beam radiation therapy before surgery) was the standard of care. In the 1980s, Dartevelle et al.[19] described an 'anterior transcervical approach,' which allows access to the anterior part of the thoracic inlet and subclavian vessels. There was a concurrent evolution of this technique.[20][21][22] In the 1990s, induction chemoradiotherapy, which was followed by resection, was proven effective regimen for stage III NSCLC.[23] Since then, the standard treatment for superior sulcus tumors included a combination of induction chemotherapy/radiotherapy followed by radical resection of the tumor.[24][25][26][27][28][29]

Induction chemotherapy includes combination chemotherapeutic drugs like cisplatin/etoposide or cisplatin/mitomycin or cisplatin/vindesine.[15][30][31][32][33] Thoracic radiotherapy is given at 45 Gy in 25 fractions over 5 to 6 weeks, followed by surgery 3 to 5 weeks after completion of chemoradiotherapy.[15][34]

Absolute contraindications to surgery include[15][35][10][36][37]:

1) Extensive invasion of brachial plexus, especially above T1 nerve root

2) Involvement of intervertebral foramina

3) Involvement of soft tissue at the base of the neck

4) Mediastinal perinodal or contralateral supraclavicular nodal involvement

5) Venous obstruction

Relative contraindications to surgery may include[38][19][39]:

1) Involvement of vertebral bodies

2) Involvement of subclavian artery

3) Spread to ipsilateral supraclavicular lymph nodes

Differential Diagnosis

Differential diagnosis of superior sulcus tumors include[40][41][42][43][44][45][46][47][48][49]:

• Mesothelioma
• Pulmonary metastases from cervix, larynx, liver, thyroid.
• Primary chest wall tumors (e.g., Ewing sarcoma)
• Adenoid cystic carcinoma
• Hemangiopericytoma
• Lymphoma
• Plasmacytoma

Prognosis

The main factors affecting prognosis in patients with Pancoast tumor who are undergoing trimodal treatment (surgery, chemotherapy, and radiotherapy) are[50]:

1. T-status of the tumor (worse for T4 tumors)

2. Response to induction treatment (better for complete responders)

3. Completeness of resection (dependent on T-status of tumor and response of the tumor to induction treatment)

Longer duration of disease, the presence of Horner syndrome, the extension of tumor into the base of neck/vertebral bodies/great vessels, the involvement of mediastinal lymph nodes, and resection of the tumor by a wide wedge resection are all associated with a worse prognosis.[51][52][1][53]

Tumor burden control by surgery and chemo-radiation, pain relief after treatment, and weight loss of less than 5% are suggestive of a better prognosis.[8]

Complications

Complications occur from the disease itself and the treatment.

Neurological complications involving upper extremity[1][14]:

1. Extension of the tumor to C8 and T1 nerve roots results in weakness and atrophy of the intrinsic muscles of the hand or pain and paresthesia of the fourth and fifth digits and the medial aspect of the arm and forearm

2. Extension to T2 causes abnormal sensation and pain in the axilla and medial aspect of the upper arm - triceps reflex may be lost

3. In approximately 5% of patients, tumors may invade intervertebral foramina early in the course of the disease, causing spinal cord compression and paraplegia - approximately 25% of patients ultimately develop spinal cord compression

4. In roughly 5% to 10% of patients, tumors may produce a phrenic or recurrent laryngeal neuropathy or superior vena cava syndrome

Treatment complications include[54][55][56]:

1. Surgical removal of lung tumors may result in chylothorax, ulnar nerve paralysis (seen in resection of the C8 nerve root), Horner syndrome (resection of the stellate ganglion and sympathetic chain),  cerebrospinal fluid leak and meningitis (Post-surgical complications); surgical mortality rates are 4% to 10%

2. Common side effects from radiotherapy include:

• Localized lung fibrosis, fatigue, esophagitis, and skin irritation
• Less commonly patients develop symptomatic pneumonitis
• Rare complications include skin fibrosis (leathery skin) with shoulder immobility
• Myelitis and brachial neuritis may cause weakness and pain in the hand, arm or shoulder

3. Chemotherapy-related complications like diffuse interstitial pneumonitis, nephrotoxicity (renal impairment, hypomagnesemia, Fanconi like syndrome, etc.), and peripheral neuropathy, to name a few.

Deterrence and Patient Education

The prognosis for most patients with Pancoast tumors is poor as they are diagnosed late in the course of the disease and generally present after the local spread of disease. Less than 30% are alive at five years. Chemoradiotherapy has shown minimal benefit in locoregional recurrence and long-term survival. After surgery, the quality of life is very poor, and patients often have debilitating pain.[57][58]

Patients should receive education regarding the prognosis, success, and recurrence of disease post-treatment and side effects/complications of treatment; to decide on the further course of the treatment plan.

Enhancing Healthcare Team Outcomes

Initially, patients get misdiagnosed with bursitis and osteoarthritis (due to presenting complaints of pain in neck and shoulder) and may lead to persistence of symptoms and delay in diagnosis up to 5 to 10 months in some cases.[12][59][36][60] High suspicion is necessary to diagnose these patients as early as possible for a better prognosis.

Adequate pain control measures are important when taking care of patients with superior sulcus tumors, as pain is the most debilitating symptoms about which patients complain.

The overall prognosis of the disease is quite poor, and so the interprofessional team should focus on prevention measures and educating the population at risk (primarily smokers). An interprofessional approach to this disease is best, involving physicians in multiple specialties, nursing, and pharmacy, as well as other ancillary personnel (respiratory and other therapists). Primary prevention education should start at the level of pharmacists, nurses, and primary care physicians. Smokers should be encouraged to quit smoking and have regular guidelines determined, age-appropriate screening (annual low dose CT scan in smokers age 55 to 80 years of age as per USPSTF recommendations). Early diagnosis and treatment have a better prognosis.

Review Questions

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• Comment on this article.

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Disclosure: Sai Giridhar Gundepalli declares no relevant financial relationships with ineligible companies.

Disclosure: Prasanna Tadi declares no relevant financial relationships with ineligible companies.