Lung Pancoast Tumor

Etiology

Pancoast tumors are primary lung cancers arising in the apical region of the lung, also known as the superior sulcus, and account for approximately 3% to 5% of all lung cancers. Most Pancoast tumors are non–small cell lung cancers (NSCLC), which represent more than 95% of reported cases. Consequently, Pancoast tumors are best regarded as a distinct clinical and anatomical subset of NSCLC that warrants special consideration due to their proximity to the brachial plexus, sympathetic chain, and chest wall.

Pancoast syndrome, the characteristic constellation of shoulder and arm pain, Horner syndrome, and hand muscle weakness, is most commonly caused by apical lung cancer but is not exclusive to this etiology. Other etiologies include pleural mesothelioma, metastatic disease to the lung apex (such as from malignant neoplasms or lymphomas of the thyroid), and inflammatory or infectious processes involving the apical pleura or chest wall (for example, infections due to Pseudomonas, Staphylococcus, or Actinomyces spp). Recognizing this differential diagnosis is important, as nonmalignant conditions can occasionally mimic the clinical picture of a Pancoast tumor.[5]

Epidemiology

According to the American Society of Clinical Oncology, an estimated 234,580 new cases of lung cancer were diagnosed in 2024, making it the second most common cancer and the main cause of oncological mortality in both sexes. Lung cancer is also the most lethal cancer in the US, with approximately 125,070 deaths annually. Pancoast tumors account for roughly 3% to 5% of all lung cancers.[6] The average age of presentation of a Pancoast tumor is in the sixth decade, and it occurs more commonly in men than in women.

Pathophysiology

More than 95% of lung cancers are classified into 4 major histologic types: adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and small cell lung cancer. Approximately 80% to 85% of all lung cancers are non–small cell lung cancers, with adenocarcinoma now the most common subtype in many regions. Pancoast tumors represent a small subset of lung cancers, accounting for roughly 3% to 5% of cases and arising predominantly in the superior sulcus. More than 95% of Pancoast tumors are non–small cell lung cancers, most commonly adenocarcinoma and squamous cell carcinoma; small cell histology is distinctly uncommon, reported in up to 3% to 5% of cases. Historically, squamous cell carcinoma was the predominant histologic subtype in this location, but results from contemporary series demonstrate a shift toward adenocarcinoma predominance, mirroring broader trends in lung cancer epidemiology.[7]

Histopathology

Clinical symptoms and imaging findings can diagnose more than 90% of cases of Pancoast tumor. However, a biopsy is necessary for histologic confirmation and treatment planning before starting treatment. Currently, close to 95% of biopsies are performed via CT- or ultrasonography-guided percutaneous transthoracic needle biopsy.[8] Video-assisted thoracoscopy (VAT) or sometimes thoracotomy may be necessary when a percutaneous biopsy is inconclusive.[4]

Overall, the majority of Pancoast tumors are non–small cell lung carcinomas. Small cell carcinoma at this site is uncommon, accounting for no more than approximately 5% of cases. About half of Pancoast tumors are adenocarcinomas, with most of the remaining cases being squamous cell carcinomas. Historically, squamous cell carcinoma was the predominant histology, but results from contemporary series show adenocarcinoma to be more frequent, paralleling broader epidemiologic shifts in lung cancer.[9]

History and Physical

Most presenting symptoms are due to local tumor invasion. Given 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] The frequently deceptive nature of these symptoms poses a significant diagnostic challenge because pulmonary signs such as cough, dyspnea, and hemoptysis are often absent, especially in the early stages, prompting clinicians to consider orthopedic or neurological diagnoses first. Because of this, patients are often initially incorrectly diagnosed with cervical disc disease, rotator cuff pathology, or frozen shoulder.[10]

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

Horner syndrome is a combination of ipsilateral ptosis (drooping or falling of the upper eyelid), miosis (persistent constricted pupil), and anhidrosis (inability to sweat on the ipsilateral side). Pancoast tumor causes second-order (preganglionic) Horner syndrome (affecting the second-order neuron, traveling from the sympathetic trunk through the brachial plexus over the lung apex).[11] Ipsilateral facial flushing and sweating can occur before the development of full-blown Horner syndrome, likely due to tumor irritation of the sympathetic chain before invasion of the sympathetic trunk.[1]

In approximately 5% 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% of Pancoast tumors, which may result in weakness and atrophy of the intrinsic muscles of the hand, paresthesia over the distribution of the fourth and fifth digits of the hand, and the medial aspect of the arm and forearm. In some cases, the patient may exhibit a loss of the triceps reflex.[12]

Evaluation

Pancoast tumor constitutes a group of malignant neoplasms (as the tumor is classified based on location), which means no specific laboratory test exists to diagnose a Pancoast tumor. An initial plain radiological examination with a chest radiograph is generally used to screen a patient with a suspected Pancoast tumor or as an incidental finding showing soft tissue opacity at the apex of the lung (unilateral); an asymmetry in the apices greater than 5 mm can also be noted. Local rib extension can sometimes be appreciated (see Image. Pancoast Tumor). Lordotic chest views may be helpful. In the early stages, these findings are difficult to appreciate on the posteroanterior view of a chest radiograph because of difficulty in interpreting the overlying shadows at the apices (clavicle, scapula, acromion, and first rib).

CT scan provides more information on the extent of the primary tumor, mediastinal lymphadenopathy, and satellite tumors, which is essential for staging the tumor. CT scan has poor sensitivity and specificity for accurate local staging, but is excellent at identifying bony involvement. Furthermore, 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, and brachial plexus. Please see StatPearls' companion reference, "Pancoast Syndrome," for further information. Careful assessment of the brachial plexus is needed as the involvement extending beyond the lower trunk, or C8 nerve root, is deemed inoperable.[13]

Positron emission tomography–computed tomography (PET-CT) is valuable for baseline staging in patients with Pancoast tumors. PET-CT improves the detection of mediastinal nodal involvement and distant metastases, thereby altering resectability assessment and overall treatment strategy. Additionally, integrated PET-CT facilitates more accurate delineation of the gross tumor volume by distinguishing metabolically active tumor from adjacent atelectasis or normal tissue, thereby refining target definition for radiotherapy planning and potentially reducing interobserver variability.[14][15] Chest CT and PET-CT scans are considered mandatory before and after preoperative therapy, but recommendations vary on whether mediastinoscopy, endobronchial ultrasonography, or esophageal ultrasonography is necessary.[16]

Treatment / Management

In the late 1950s, bimodality therapy (external beam radiation therapy before surgery) was the standard of care. In the 1990s, induction chemoradiotherapy, which was followed by resection, was proven to be an effective regimen for pancoast tumors (stage III non-small cell lung cancer, NSCLC).[17] Since then, the standard treatment for superior sulcus tumors has included a combination of induction concurrent chemoradiotherapy followed by radical en bloc resection of the tumor, and then completion of the chemotherapy regimen. Please see StatPearls' companion reference, "Lung Pancoast Tumor," for further information.

Induction chemotherapy includes combination chemotherapeutic drugs such as cisplatin and etoposide, cisplatin and paclitaxel, or cisplatin and pemetrexed with concurrent radiotherapy. Usually, 2 cycles of chemotherapy are given with concurrent radiation, while 2 cycles are given after the surgical procedure in an adjuvant setting.[18] Thoracic radiotherapy is given at 45 to 50 Gy in 25 to 28 fractions over 5 to 6 weeks, followed by the surgical procedure 3 to 5 weeks after completion of chemoradiotherapy.[19](B2)

Differential Diagnosis

Several pathologies other than primary lung cancer may present as Pancoast tumors, including the following:

• Mesothelioma [20]
• Pulmonary metastases from the cervix, larynx, liver, thyroid [21]
• Primary chest wall tumors (eg, Ewing sarcoma) [22]
• Hemangiopericytoma [23]
• Lymphoma [24]
• Extramedullary plasmacytoma [25]

Surgical Oncology

Since the approval of induction chemoradiotherapy followed by a surgical procedure, en bloc resection of the chest wall lesion is recommended in all cases of pancoast tumors. [9] Determination of resectability, surgical staging, and pulmonary resection should be performed by thoracic surgeons who perform lung cancer procedures as a prominent part of their practice.[26]

Radiation Oncology

Previously, radiation therapy in the neoadjuvant or induction setting was delivered up to 45 Gy in 25 fractions, but beginning in 2018, technological advancements enabled the use of intensity-modulated arc therapy, allowing a dose escalation to 50.4 Gy in 28 fractions.[22]

Pertinent Studies and Ongoing Trials

Recently, medical oncologists have been evaluating the efficacy of immunotherapy as part of induction chemoradiotherapy for these patients.[27][28] So far, only early-phase 2 trials have been conducted due to the rarity of Pancoast tumors, and data are generally extrapolated from stage III lung cancer trials.

Medical Oncology

Treatment of Pancoast tumors is based on tumor, node, metastasis (TNM) staging and assessment of resectability. For resectable disease, standard treatment is induction concurrent chemoradiotherapy followed by surgical resection with negative margins.[29] Unresectable cases are treated with definitive concurrent chemoradiotherapy, with consideration of consolidation immunotherapy, as in the Patients With Unresectable Stage III Non–Small-Cell Lung Cancer (PACIFIC) trial.[30] Metastatic disease is managed with systemic therapy, including chemotherapy, immunotherapy, or targeted therapy based on molecular profile.[31] Interdisciplinary care and effective pain control are essential due to frequent chest wall and brachial plexus involvement.

Staging

Pancoast tumors are staged according to the standard TNM system for non–small cell lung cancer because they represent an anatomic subset of NSCLC. Pancoast tumors are most often classified as T3 or T4 owing to their apical location and propensity for local invasion into adjacent structures. T3 disease typically reflects invasion of the chest wall or parietal pleura, whereas T4 denotes more extensive involvement, such as invasion of the vertebral bodies, major subclavian vessels, or brachial plexus. Nodal status is categorized as N0 to N3 based on the presence and location of regional lymph node metastases, and distant metastatic spread is captured by the M category (M0 or M1). At presentation, most Pancoast tumors are stage 2B or stage 3, consistent with locally advanced disease driven by early involvement of chest wall and neurovascular structures.[4]

Prognosis

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

1. The 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)[32]

Longer duration of disease, the presence of Horner syndrome, the extension of tumor into the base of the neck, vertebral bodies, or 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.[33] Control of tumor burden by surgical procedure and chemoradiation, pain relief after treatment, and weight loss of less than 5% are suggestive of a better prognosis.[9]

Complications

Complications may occur from the disease itself or from the treatment. Neurological complications involving the upper extremity include:

• 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.[12]
• Extension to the T2 nerve root causes abnormal sensation and pain in the axilla and medial aspect of the upper arm, and the triceps reflex may be lost.
• 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.
• In roughly 5% to 10% of patients, tumors may produce a phrenic or recurrent laryngeal neuropathy or superior vena cava syndrome.

Treatment complications include:

• 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 (postsurgical complications). Surgical mortality rates are 4% to 10%.[34] After the surgical procedure, the quality of life is very poor, and patients often have debilitating pain.[35]

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

Chemotherapy-related complications include diffuse interstitial pneumonitis, nephrotoxicity, and peripheral neuropathy.