Author(s): Anam Purewal, MD, Marc Ramos Emos, MD, Ashish Khanna, MD
Originally published: January 6, 2020 Last updated: May 18, 2023
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Disease/ Disorder

Definition

Lung cancer is a malignant tumor of the lungs or bronchus. It originates as a primary pulmonary carcinoma or as metastasis from another malignancy. Primary lung carcinomas are a heterogeneous group of tumor subtypes, including small cell and non-small cell carcinoma.

Etiology

While cancer in general arises from mutated genes, lung cancer is most notably associated with cigarette smoke exposure, with reports of cigarette-use in up to 90% of lung cancer cases.1 Radon is the second leading cause of lung cancer, followed by occupational exposures to carcinogens and air pollution.2

Epidemiology including risk factors and primary prevention

Lung cancer is the second most common cancer, with American Cancer Society (ACS) estimating 238,340 new cases in 2023.3 However, lung cancer is the leading cause of cancer death in both men and women, with ACS estimating 127,070 deaths in 2023 from lung cancer alone.4 The median age at which diagnosis is made is 71 years.4 Risk factors associated with increased risk of lung cancer development include cigarette smoking (dose-dependent), secondhand smoke, radiation exposure, occupational exposure to carcinogens including asbestos, arsenic, beryllium, cadmium, chromium, and nickel, and air pollution.5 Primary prevention measures include smoking avoidance, smoking cessation, and reduced exposure to secondhand smoke and radon.

Patho-anatomy/physiology

Lung cancers are classified by their histopathology as one of two subtypes: small cell lung carcinoma (SCLC) or non-small cell lung carcinomas (NSCLC). SCLC are about 10-15% of all lung cancers. The other 80% are NSCLC, which are of multiple subtypes. The most prevalent are adenocarcinoma (40%), squamous cell carcinoma (30%), and large cell carcinoma (10%).

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

SCLC and NSCLC are staged by the TNM classification system, which designates stages 0 to IV based on location (localized, spread to regional lymph nodes, or metastasis to other parts of the body).6 This staging system helps prognosticate disease severity in addition to inferring treatment regimens. The National Cancer Institute estimates a 22.9% 5-year survival rate based on 2012-2018 data. Early staged cancers have a significantly better prognosis. For example, stage 1 lung and bronchus cancer have a 61.2% 5-year relative survival.7 Lung cancer is the leading cause of cancer death in the United States, likely due to case detection at late stage; only 19.9% of cases are diagnosed at an early stage.7

Specific secondary or associated conditions and complications

Iatrogenic complications from cancer treatments (surgery, radiation, and chemotherapy) result in significant morbidity and mortality. The most common complications include post-thoracotomy pain syndrome (PTPS), drug-induced infiltrative lung disease (DILD), radiation pneumonitis, radiation fibrosis syndrome, in addition to a broad spectrum of systemic chemotherapy-associated side effects. Thoracotomies are sometimes performed as a surgical intervention in the treatment of lung cancer, and a common and difficult to treat complication is pain.

PTPS is a pain condition defined as lasting more than two months after a thoracotomy, and its prevalence is reported to be as high as 83%.8 Its pathogenesis is poorly understood but is thought to be related to injury of the skin, muscle, joint, nerve, fascia, and parietal pleura. It is characterized by neuropathic and nociceptive pain. Neuropathic pain symptoms include hyperalgesia, allodynia, paresthesia, hypoesthesia, dysesthesia, burning pain, and shock-like pain. Treatment is generally conservative including physical therapy, pharmacological management including anti-inflammatory drugs, tricyclic antidepressants, anticonvulsants, selective serotonin noradrenaline reuptake inhibitors, and opioids when indicated. Other options exist including transcutaneous electrical nerve stimulation, botulinum toxin injections, and acupuncture. However, in cases of severe pain, interventional procedures may be explored. Some options include intercostal nerve blocks, thoracic paravertebral blocks, thoracic sympathetic blocks, epidural injections, interpleural blocks, spinal cord stimulation, and dorsal root ganglion pulse radiofrequency application.8

DILD is described as a spectrum of clinical manifestations, from mild to severe, including asymptomatic infiltrates to acute respiratory distress syndrome. The pathophysiology is related to dose-dependent toxicity or immune-mediated injury. It may develop within days of treatment initiation or may have delayed presentation until months or years later.9,10 Common drugs that are associated with development of drug-induced infiltrative lung disease include anti-inflammatory agents, chemotherapeutic agents, and biologic agents. Some drugs which are commonly used to treat non-small cell lung cancer that are associated with the development of radiation pneumonitis or subsequent interstitial lung disease include paclitaxel, docetaxel, gemcitabine, and etoposide. Cisplatin and gemcitabine have been shown when co-administered with bleomycin to increase the risk of development of DILD.11

Radiation pneumonitis may present with dyspnea two to three months after high-dose external beam radiation in up to 15% of irradiated patients.12 Exudation of fluid into the alveoli causes decreased compliance and gas exchange, with eventual development of restrictive lung disease..

Radiation fibrosis syndrome is characterized by radiation injury sequalae to affected tissues. Complications may include neuromuscular damage, myelopathy, radiculopathy, neuropathy, fatigue, dysphagia, radiation pneumonitis and fibrosis, and radiation dermatitis.13 The pathogenesis of this condition is described to occur in three phases.14

  • The prefibrotic phase is characterized by endothelial cell dysfunction. Local inflammation increased vascular permeability, and edema result in necrosis of the microvasculature and subsequent local ischemia. In this phase patients are usually asymptomatic.
  • The constitutive organized phase is characterized by active fibrosis with myofibroblasts in a poorly organized extracellular matrix and senescent fibrocytes in an already fibrotic extracellular matrix.
  • The late fibroatrophic phase is characterized by successive remodeling of the extracellular matrix resulting in dense radiated tissue. This stage may develop and progress years to decades following radiation therapy. As a result, affected tissue may become poorly vascularized, friable, and fragile.13

Chemotherapy is associated with a broad range of systemic side effects that can severely impact quality of life. Some common side effects include:

  • Chemotherapy-induced nausea and vomiting
  • Hematologic toxicity (manifesting as anemia and neutropenia)
  • Nephrotoxicity
  • Neurotoxicity (especially with cisplatin and taxanes)
  • Fatigue
  • Anorexia and weight loss

The role of the physiatrist is to monitor for signs of symptoms, work with the multidisciplinary oncology care team to alter treatment regimens to minimize significant side effects and prescribe treatments that will maximize a patient’s functionality to preserve quality of life.

Essentials of Assessment

History

History-taking for a patient with lung cancer includes a thorough review of  history and systems, including cough, hemoptysis, dyspnea, chest pain, fever, night sweats, weight loss, smoking history, family history, prior malignancy, and environmental exposures.15 Review of symptoms should be expansive and include all organ systems because new symptoms can indicate metastatic disease.16 Some key things to inquire about include new bone pain (associated with bone metastasis), neurological symptoms including headaches, weakness, sensory changes, dizziness, balance problems, seizures (associated with brain metastasis), jaundice (associated with liver metastasis), and lymphadenopathy (associated with regional metastatic spread).

The physiatrist participating in the care of a patient with cancer should also inquire about a patient’s functional status including ability to perform activities of daily living (ADLs) and instrumental ADLs (iADLs). It is crucial to inquire about whether the patient ambulates with or without an assistive device and if he has a home health aide. An exhaustive social history including occupation, living situation, prior activity level, and family and community support.

Physical examination

Examination should begin with vital signs, including orthostatic blood pressure, pulse oximetry and respiratory rate. Inspection should be performed, and signs of chest excursion, asymmetry, cyanosis, finger clubbing, venous distension of neck, facial edema and plethora, muscle atrophy, edema, and scapular winging should be noted. Palpation is a key part of examination especially if there is a complaint of focal pain. A comprehensive neurological exam should be performed including mini-mental state examination which may clue into neurocognitive deficits. Further examination should be done to evaluate the cranial nerves, coordination and propioception, sensation (light touch, vibration, pinprick, and temperature), deep tendon reflexes, tone, and gait. Active and passive range of motion should be done, with special attention paid to deficits and pain. Motor strength is evaluated for localized or generalized weakness. Physical therapy, occupational therapy, and speech therapy should also be consulted when indicated to evaluate the patient for impairments in ADLs, strength, coordination, speech, swallowing, hearing, and cognition.16

Clinical functional assessment: mobility, self-care cognition/behavior/affective state

Observing the patient ambulating, transferring, and performing ADLs is the easiest way to characterize functional impairments. There are a number of rehabilitation instruments which are useful in assessing a patient’s clinical status including functional capacity and cardiorespiratory performance. The Functional Reach Test is a simple assessment for measuring dynamic balance. The Timed Up and Go Test is an assessment which involves rising from an armchair, walking three meters, turning, walking back, and sitting. Both of these tests have been shown to predict the likelihood of a fall.17 Clinical assessments of exercise capacity include the shuttle walk test, six-minute walk test, and cardiopulmonary exercise testing.18,19 It has been shown that distances less than 350 meters in the shuttle walk test are associated with increased mortality.

Laboratory studies

Laboratory studies in the diagnosis and work-up of lung cancer would be performed by the medicine and oncology care team. Preliminary studies may include complete blood count and comprehensive metabolic panel.19 Further assessment may include testing for tumor markers including carcinoembryonic antigen, squamous cell carcinoma antigen, neuron-specific enolase, cytokeratin 19 fragment and pro-gastrin-releasing peptide.20

Imaging

A chest x-ray is used for initial evaluation of symptoms of lung cancer,21 followed by further characterization with computed tomography (CT) imaging. The US Preventative Services Task Force recommends annual screening for lung cancer with low-dose CT in adults 55-80 years of age with a smoking history of 30 pack-years who currently smoke or are in remission for 15 years.22,23 For investigating metastases, positron emission tomography (PET) imaging may be utilized.

Supplemental assessment tools

Signs and symptoms suspicious of new metastasis or cancer recurrence requires investigation by the primary oncology team, and may include imaging.24 PET imaging can distinguish between persistent or recurrent tumor from post-treatment scarring or fibrosis.25 CT imaging can demonstrate osteolytic and osteosclerotic lesions.25 Magnetic resonance imaging (MRI) can demonstrate metastatic lesions to soft tissue, bone marrow cavity, or suspected cord compression secondary to pathologic vertebral compression fractures.26 Skeletal scintigraphy (bone scan) is commonly used to detect skeletal metastasis, with the added benefit that whole body scan can be performed.27

Early predictions of outcomes

TNM staging influences treatment and predicts survival. Poor performance status and/or weight loss have been associated with shortened survival. Staging of SCLC usually uses the Veterans Administration Lung Study Group designations of limited (one hemithorax) or extensive (beyond one hemithorax) disease.28 Poorly differentiated tumors and lymphatic invasion are associated with worse prognosis. A tumor’s metabolic activity can be measured using the standardized uptake value (SUV) to assess the tumor uptake of fluorodeoxyglucose (FDG); high SUV was associated with a poor prognosis, and a lower FDG uptake was associated with a better prognosis.29 PET (or PET-CT) may also be useful in predicting response to chemotherapy.

Environmental

Smoke exposure is the primary risk factor for lung cancer. Other factors include exposure to asbestos, radon, metals (arsenic, chromium and nickel), ionizing radiation and polycyclic aromatic hydrocarbons.30 Dietary factors may reduce the risk of lung cancer, these include antioxidants, cruciferous vegetables and phytoestrogens.

Social role and social support system

Cancer survivors have specific cancer-related impairments that impact their roles in their families, communities, and workplace.31 This can lead to difficulty in adjusting to newly defined versions of social life. Therefore, a basic psychological evaluation for mood changes is important in evaluating for depression, anxiety, and adjustment disorder.

Professional issues

Lung cancer survivors are two to three times more likely to be unemployed and have the strongest decline in earnings compared to those affected by other cancers due to an observed higher median duration of sickness.32 Involving a vocational therapist early in treatment may help patients navigate occupational options.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Lung cancer rehabilitation is unique and tailored to a patient’s individual needs. This may include physical therapy, occupational therapy, speech therapy, and pulmonary rehabilitation. Pulmonary rehabilitation is defined by the American Thoracic Society as a “comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors.33 Pulmonary rehabilitation is a comprehensive treatment program focused on improving quality of life, and may in turn be considered a form of palliative care.

All prescriptions for pulmonary rehabilitation should be based on outcomes observed from exercise capacity testing. A therapy prescription should be defined in terms of exercise intensity, duration, frequency, type (interval or continuous), mode (e.g., walking, cycling, arm exercise), and progression recommendations.

Home oxygen may be indicated if:

  • Arterial oxygen tension (PaO2) is less than or equal to 55 mmHg or a pulse oxygen saturation (SpO2) less than or equal to 88%, or,
  • PaO2 less than or equal to 59 mmHg or a SpO2 less than or equal to 89% and there is evidence of cor pulmonale, right heart failure, or erythrocytosis.34

In addition, if there is dyspnea or ventilatory abnormalities during exercise, supplemental O2 may be given during exercise without evidence of desaturation demonstrated by a decrease in SpO2.

At different disease stages

In the acute phase of cancer treatment deconditioning, anxiety, and weakness are common contributors to disability. Dyspnea is highly prevalent as well, which may have been present pre-morbidly due to COPD since the vast majority of lung cancer patients have a history of smoking. This compounds the symptoms burden.

The majority (>75%) of cancer patients experience cancer-related fatigue, which can occur at any point along the cancer continuum.35 Paraneoplastic phenomena can occur at any time as well. Treatments include addressing the underlying malignancy, immunosuppression, and correction of electrolyte and hormonal derangements as indicated.

The chemotherapeutic agent bleomycin is a known cause of pulmonary fibrosis. Any patient treated with this agent at any time should not be exposed to supplemental oxygen. Oxygen is a mainstay of pulmonary rehabilitation but if provided to these patients it may trigger acute-onset pulmonary edema, even decades later.

Pain is a sequalae of lung cancer local invasion, or a consequence of therapeutic management including surgery, chemotherapy, or radiation. Management of pain is multimodal including pharmaceutical therapy including non-steroidal anti-inflammatory drugs, neuropathic pain medications, opioids, physical therapy, and modalities. When these options are inadequate in controlling pain, interventional pain management options may be explored including joint injections, nerve blocks, and neuromodulation.36

Palliative, or end-of-life care, is important to consider in the treatment of lung cancer. It involves minimizing complications associated with debility including the development of pressure ulcers and contractures, pain management, and psychosocial counseling.

Coordination of care

A quality comprehensive intervention would necessitate coordination among physicians, nurses, physical and occupational therapists, respiratory therapists, and social workers. Efficient coordination is key to integrating the expertise of all these providers into a cohesive program individually tailored to each patient.

Patient & family education

Patient and family education is critical in rehabilitation of lung cancer. Educational topics should include smoking cessation, awareness of disease process, promotion of self-management skills, and recognition of signs and symptoms that warrant medical attention and evaluation.

Measurement of treatment outcomes including those that are impairment-based, activity participation-based and environmentally-based

Survival of patients with lung cancer can be prognosticated by outcome measures which estimate performance status. Performance status is described as a patient’s ability to perform ADLs, instrumental ADLs (examples: cleaning, cooking), and ambulation. Two commonly used scales for measuring performance status include the Eastern Cooperative Oncology Group (ECOG) scale and the Karnofsky scale.37 The ECOG scale ranges from zero to five. Zero indicates a patient is fully active and able to carry out all activities without any restrictions. Increasing scores describe levels of increased disability, with four describing a level of complete disablement defined by the state of being wheelchair or bedbound. Contrasting to this, the Karnofsky scale ranges from 100 to zero in increments of 10. A score of 100 on the scale describes normal performance, and decreasing numbers indicate increasing amounts of disability. Both the ECOG and Karnofsky scales assess functional statuses of patients, and can be used to describe their functional impairment, track the effectiveness of their treatments, and grade their prognosis.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Pulmonary rehabilitation in the lung cancer patient often requires modification of standard practices to adhere to the individual’s unique disease process. This may be dependent on where in the cancer continuum the patient lies. A knowledge of the cancer type, severity, and prognosis is required, in addition to a patient’s individual needs and functional limitations. A thorough baseline evaluation is important prior to starting any program.

Cutting Edge/ Emerging and Unique Concepts and Practice

New and less invasive surgical procedures including, sublobar resection and single-port video-assisted thoracoscopic surgery (VATS) for NSCLC are being developed; these advances are promising in reducing post-operative complications. Notably with the advance of less invasive surgical techniques, the change in incidence and severity of PTPS should be studied.38 

Gaps in the Evidence-Based Knowledge

Major gaps and needs in the treatment of oncology exist and are influencing the development and practice of lung cancer rehabilitation. As a result, the field of lung cancer rehabilitation is growing and warrants further study to improve treatment outcomes. Areas of interest include research of complications from treatment including post-thoracotomy pain syndrome and further study of rehabilitation therapy procedures.

For example, there are currently there are no society guidelines for lung cancer rehabilitation including pulmonary rehabilitation regimens.39 Ongoing research is being conducted on the benefits and details of these therapies, which so far have been promising. Future studies should emphasize measuring the effects of therapy dosing, in terms of number of sessions, length of sessions, and intensity. Additionally future studies should emphasize long-term follow-up so that the long-term effects of pulmonary rehabilitation of lung cancer can be better understood.

Treatment of lung cancer is invasive and is constantly evolving—it may include chemotherapy, radiation, and surgery. As a result, new iatrogenic complications are being discovered and are poorly understood including post-thoracic pain syndrome. There is no there is still no consensus on its management. Improvements in the understanding of its etiology has led to repertoire of treatment options.8 Future studies should investigate the etiopathogenesis of this pain condition and further study the outcomes of different treatments.8

References

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Original Version of the Topic

Ashish Khanna, MD, Zachary Fallon, MD, Tanya DiFrancesco, MD, Mohammad Aalai, MD. Lung Cancer. 1/6/2020

Author Disclosures

Anam Purewal, MD
Nothing to Disclose

Marc Ramos Emos, MD
Nothing to Disclose

Ashish Khanna, MD
Nothing to Disclose