Author(s): Marc Ramos Emos, MD
Originally published: January 6, 2020 Last updated: April 9, 2026
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Disease/Disorder

Definition

Lung cancer is a malignant neoplasm arising in the lung or bronchus. It may represent a primary pulmonary malignancy or pulmonary involvement from metastatic disease. Primary lung cancers are broadly classified into small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC).

Etiology

Lung cancer develops through accumulated genetic and epigenetic alterations, most commonly in the setting of tobacco smoke exposure. Cigarette smoking remains the dominant risk factor, although secondhand smoke, radon exposure, occupational carcinogens, ionizing radiation, and air pollution also contribute to risk. In recent years, a growing proportion of lung cancers particularly adenocarcinomas have been recognized in never-smokers, underscoring the heterogeneity of disease biology and exposure history.1

Epidemiology including risk factors and primary prevention

Lung cancer remains the second most common cancer and the leading cause of cancer death in the United States. The American Cancer Society estimates approximately 229,410 new cases and 124,990 deaths in 2026. Most patients are diagnosed at older age; the average age at diagnosis is about 70 years. Important risk factors include cigarette smoking, secondhand smoke, radon exposure, occupational exposure to carcinogens such as asbestos and heavy metals, ionizing radiation, and air pollution. Primary prevention includes smoking avoidance and cessation, reduction of secondhand smoke exposure, and mitigation of radon and occupational risks where relevant.1

Patho-anatomy/physiology

Lung cancers are broadly classified into SCLC and NSCLC. SCLC accounts for a minority of cases and is typically characterized by rapid growth and early dissemination. NSCLC accounts for the majority of cases and includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. In modern practice, treatment selection and prognosis are influenced not only by histology and stage but also by molecular alterations and biomarkers, particularly in NSCLC.2

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

NSCLC is staged by the TNM classification system. In SCLC, clinicians commonly use both TNM staging and the traditional limited-stage versus extensive-stage framework. Limited-stage disease is generally confined to one hemithorax and regional lymph nodes whereas extensive-stage disease includes distant metastatic spread (often stage IV such as the brain, bone, liver, or adrenal metastases). Stage strongly influences prognosis, survival and treatment options. Recent ACS data reports an overall 5-year relative survival of about 27%, compared with approximately 64% for localized disease. Lung cancer mortality remains high in part because many patients present with advanced disease.2

Specific secondary or associated conditions and complications

Iatrogenic complications from cancer treatments (surgery, radiation, and chemotherapy) result in significant morbidity and mortality. 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.

PTPS is a pain condition defined as lasting more than two months after a thoracotomy. 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.3

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.4 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.4

Radiation pneumonitis may present with dyspnea two to three months after high-dose external beam radiation in up to 15% of irradiated patients. Exudation of fluid into alveoli causes decreased compliance and gas exchange, with eventual development of restrictive lung disease.5

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.5 The pathogenesis of this condition is described to occur in three phases.5

  • The prefibrotic phase is characterized by endothelial cell dysfunction. Local inflammation increased vascular permeability, and edema resulting 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 within years to decades following radiation therapy. As a result, affected tissue may become poorly vascularized, friable, and fragile.

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

Systemic therapy complications now extend beyond traditional chemotherapy related toxicities. Physiatrists must also recognize immunotherapy-related adverse events, including checkpoint inhibitor pneumonitis, endocrinopathies, myositis, neuropathies, myocarditis, and inflammatory arthritis, as well as targeted therapy related toxicities that may impair function and exercise tolerance. Additional complications highly relevant to rehabilitation include bone metastases, pathologic fracture risk, spinal cord compression, brain metastases, venous thromboembolism, and malignant pleural effusions.6

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 should include a standard oncologic review of symptoms including cough, hemoptysis, dyspnea, chest pain, fever, night sweats, weight loss, smoking history, family history, prior malignancy, and environmental or occupational exposures. Review of systems should also screen for signs of metastatic disease, including new bone pain, focal weakness, sensory change, headaches, seizures, gait dysfunction, dizziness, jaundice, or new lymphadenopathy.

From a rehabilitation perspective, the history should also characterize baseline and current functional status, including mobility, stair negotiation, endurance, use of assistive devices, oxygen requirement, falls, self-care, instrumental activities of daily living, swallowing, cognition, and communication. Prior activity level, home environment, caregiver support, occupation, return-to-work goals, and symptom burden should be documented. Weight loss, poor appetite, and reduced reserve may suggest frailty or cachexia and influence prognosis and treatment tolerance.

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 important in evaluating focal pain and possible musculoskeletal contributors to dysfunction. A comprehensive neurological exam should be performed including mini-mental state examination which may clue into neurocognitive deficits. Further examination should evaluate the cranial nerves, coordination and proprioception, 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 Therapy consultation may be appropriate to evaluate the patient for impairments in ADLs, strength, coordination, speech, swallowing, hearing, and cognition.

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

Observing transfers, gait, and self-care tasks remains one of the most practical ways to identify functional impairment. Useful functional assessment instruments include the timed up and go, 6-minute walk test, functional reach test, gait speed, and sit-to-stand measures. Symptom-based tools such as dyspnea ratings can complement performance testing. Clinical assessments of exercise capacity include the shuttle walk test, six-minute walk test, and cardiopulmonary exercise testing. Standardized performance scales such as ECOG and Karnofsky Performance Status are also valuable for describing disability, estimating treatment tolerance, and tracking change over time.

Laboratory studies

Laboratory evaluation is directed by the oncology and medical teams and may include complete blood count, comprehensive metabolic panel, and other testing relevant to treatment tolerance or complications. In contemporary lung cancer care, diagnosis and treatment planning rely heavily on tissue pathology and biomarker testing, particularly in NSCLC, because molecular alterations and PD-L1 expression influence treatment selection and anticipated toxicity profile.7,8

Imaging

Chest radiography is often an initial study in symptomatic patients, followed by CT for characterization and staging. PET/CT and Magnetic Resonance Imaging (MRI) are commonly used when metastatic disease is suspected. The USPSTF recommends annual low-dose CT screening for adults aged 50 to 80 years with a 20 pack-year smoking history who currently smoke or who quit within the past 15 years.9

Supplemental assessment tools

Symptoms including new focal pain, neurologic deficits, worsening dyspnea, or marked functional decline should prompt reassessment for disease progression or treatment toxicity. Imaging may be necessary to evaluate suspected recurrence, brain metastases, cord compression, pleural disease, or osseous metastases, especially when rehabilitation planning may be altered by fracture risk or neurologic compromise. PET imaging can distinguish between persistent or recurrent tumor from post-treatment scarring or fibrosis.10 CT imaging can demonstrate osteolytic and osteosclerotic lesions.11 MRI can demonstrate metastatic lesions to soft tissue, bone marrow cavity, or suspected cord compression secondary to pathologic vertebral compression fractures. Skeletal scintigraphy (bone scan) is commonly used to detect skeletal metastasis.

Early predictions of outcomes

TNM staging influences treatment and predicts survival. From a rehabilitation perspective, poor performance status, unintentional weight loss, frailty, and reduced exercise capacity often predict lower treatment tolerance, more complex discharge needs, and diminished physiological reserve. Conversely, preservation or improvement of function may support broader treatment options and quality of life.2 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.12 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.13 Dietary factors may reduce the risk of lung cancer, these include antioxidants, cruciferous vegetables and phytoestrogens.

Social role and social support system

Lung cancer can substantially disrupt family, community, and work roles. Evaluation should include caregiver burden, transportation barriers, financial toxicity, home support, and psychological distress. Depression, anxiety, and adjustment disorder may complicate treatment adherence and rehabilitation participation and should be considered during assessment.

Professional issues

Lung cancer survivors experience high rates of work disruption and reduced earnings. Early attention to vocational concerns, disability paperwork, work accommodations, and graded return-to-work planning may help preserve participation for selected patients.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Rehabilitation for lung cancer should be individualized across the disease continuum and may include prehabilitation, pulmonary rehabilitation, physical therapy, occupational therapy, speech-language pathology, and palliative rehabilitation. A recent clinical practice guideline supports rehabilitation interventions to improve function in patients with lung cancer, with evidence particularly supporting combined aerobic, resistance, and breathing exercise approaches in the prehabilitation and early post-treatment phases.14

Pulmonary rehabilitation remains a useful framework for many patients with lung cancer, particularly those with dyspnea, underlying COPD, reduced endurance, or postoperative pulmonary limitation. Exercise prescription should be individualized according to baseline function, symptoms, oxygenation, treatment phase, and metastatic burden.

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

Prehabilitation is increasingly important for patients preparing for thoracic surgery or multimodality treatment. Exercise-based and multimodal prehabilitation may improve functional reserve and reduce postoperative complications.15

During active treatment, common disability drivers include dyspnea, fatigue, anxiety, weakness, and deconditioning. Exercise and rehabilitation may still be appropriate during systemic therapy when medically safe, including supervised, home-based, or hybrid models. The physiatrist should understand the patient’s current regimen because toxicities differ substantially between cytotoxic chemotherapy, immunotherapy, and targeted therapy.

Cancer-related fatigue is common across the disease continuum. Contributing factors may include anemia, sleep disturbance, mood disorder, low activity, malnutrition, endocrine toxicity, cardiopulmonary compromise, or progressive disease. Management is multidisciplinary and may include exercise, pacing, energy conservation, treatment of reversible contributors, nutritional support, and psychosocial intervention.16

The chemotherapeutic agent bleomycin is a known cause of pulmonary fibrosis. Patients with prior bleomycin exposure warrant caution with high-concentration supplemental oxygen, particularly in perioperative and acute care settings, but oxygen should not be considered an absolute lifelong contraindication. clinical decisions should be individualized in conjunction with their pulmonologist.17

Pain may result from tumor invasion, osseous metastases, systemic therapy, surgery, radiation, neuropathy, or myofascial dysfunction. Management is multimodal and may include analgesics, neuropathic pain agents, therapy, bracing, interventional procedures, and palliative radiotherapy when indicated.

Palliative rehabilitation may be appropriate at any stage when the goal is to optimize mobility, self-care, comfort, caregiver support, communication, and participation despite progressive disease. This is distinct from hospice-only care and may coexist with disease-directed treatment. Dyspnea management, pressure injury prevention, positioning, contracture prevention, and caregiver training are especially important in advanced illness.

Coordination of care

Effective care requires coordination among oncology, physiatry, nursing, physical and occupational therapy, speech-language pathology, respiratory therapy, nutrition, social work, and, when indicated, palliative care and vocational services. Efficient communication is essential to align rehabilitation with disease status, precautions, prognosis, and patient goals.

Patient & family education

Education should address smoking cessation, symptom monitoring, fall prevention, pacing and energy conservation, exercise expectations, oxygen safety when applicable, recognition of urgent neurologic or respiratory changes, and understanding of the overall disease course and treatment effects.

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. Two commonly used scales for measuring performance status include the Eastern Cooperative Oncology Group (ECOG) scale and the Karnofsky scale. 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. 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.18

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

Pulmonary and rehabilitation interventions should be tailored to disease phase, symptom burden, metastatic risk, and treatment toxicity. New focal bone pain, severe back pain, or neurologic deficits should prompt consideration of metastasis, fracture, or cord compression before advancing mobility. Exercise prescriptions should account for oxygenation, fatigue, cardiopulmonary reserve, cytopenias, and fracture risk. Early referral particularly before surgery or significant functional decline, may improve outcomes.

Cutting Edge/Emerging and Unique Concepts and Practice

Emerging areas in lung cancer rehabilitation include multimodal prehabilitation, home-based and hybrid rehabilitation delivery, and rehabilitation integrated throughout active treatment and survivorship. The growing use of immunotherapy and targeted therapy has also created a need for rehabilitation models that account for novel toxicities and for patients living longer with advanced disease. Less invasive thoracic surgical approaches including, sublobar resection and single-port video-assisted thoracoscopic surgery may reduce some postoperative morbidity, however pain, shoulder dysfunction, fatigue, and exercise intolerance remain clinically significant.19,20 With the advance of less invasive surgical techniques, the change in incidence and severity of PTPS should be studied.

Gaps in the Evidence-Based Knowledge

Although the evidence base for lung cancer rehabilitation has expanded, important gaps remain. Recent clinical practice guidance now supports selected interventions to improve function in patients with lung cancer, but further study is needed to define optimal timing, intensity, duration, setting, and long-term follow-up of rehabilitation across disease phases. More data is needed for patients with advanced/metastatic disease, those receiving immunotherapy or targeted therapy, and those participating in tele-rehabilitation or home-based programs. Additional study is also needed on chronic pain syndromes, fatigue, frailty, cachexia, and the long-term functional consequences of modern multimodality treatment.

References

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  7. Marmor HN, Zorn JT, Deppen SA, Massion PP, Grogan EL. Biomarkers in Lung Cancer Screening: a Narrative Review. Curr Chall Thorac Surg. 2023;5:5. doi:10.21037/ccts-20-171
  8. Yu H, Boyle TA, Zhou C, Rimm DL, Hirsch FR. PD-L1 Expression in Lung Cancer. J Thorac Oncol. 2016;11(7):964-975. doi:10.1016/j.jtho.2016.04.014
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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

Previous Revision(s) of the Topic

Anam Purewal, MD, Marc Ramos Emos, MD, Ashish Khanna, MD. Lung Cancer. 5/18/2023

Author Disclosures

Marc Ramos Emos, MD
Nothing to Disclose