Published December 2023
Authors: Yunan Nie, MD1
Section Editor: Chris Geiger, MD2
Executive Editors: Yilin Zhang, MD3; Brandon Fainstad, MD4
1Resident, Department of Medicine, University of Colorado
2Assistant Professor, Department of Medicine, Division of Medicine-Hematology, University of Colorado
3Assisstant Professor, Department of Medicine, University of Washington – Valley Medical Center
4Associate Professor, Department of Medicine, University of Colorado
- Select the appropriate lung cancer screening or diagnostic imaging based on age, tobacco use, and symptoms.
- Identify the preferred biopsy site and procedural service to establish accurate staging while minimizing risk.
- After a lung cancer diagnosis is confirmed, obtain additional studies to fully stage the disease and determine eligibility for surgical options and targeted therapies.
- Compare indications and side effects of major categories of oncologic treatments for lung cancer: chemotherapy, immunotherapy, and targeted therapy.
Plan to spend at least 30-60 min preparing for this talk by reviewing the teaching script and clicking through the graphic animations on the Interactive Board to become familiar with the flow and content of the talk. Print out copies of the Learner’s Handout so learners may take notes as you progress through the talk. All clickable elements are denoted by a rounded shaded rectangle and mouse cursor. There are questions that serve as prompts to engage the audience.
The anticipated time to deliver this talk is about 30-45 minutes.
Begin with reviewing the objectives for the session. We recommend progressing in order, though the modular nature of the teaching content gives you the flexibility to deliver more focused teaching.
Ask your learners “Where does lung cancer fall in the spectrum of malignancy-related deaths?” and click to reveal the answer.
Lung cancer is the #1 cause of cancer-related deaths worldwide, #1 cause of cancer in men and #2 cause of cancer in women. It is therefore very likely that an internist will diagnose and/or treat a patient with this diagnosis at some point in their career.
Objective 1: Review framework for risk stratification of patients for lung malignancy and screening (Diagnosis & Screening – Asymptomatic, Symptomatic, Biopsy)
Click on “Diagnosis and Screening” to reveal the first box in the flowchart in the diagnostic and screening pathway. Ask your learners what signs and symptoms are concerning lung cancer. Click “Symptoms?” to reveal the answer.
Clinically, lung cancer is often asymptomatic or displays relatively mild respiratory symptoms in the early stages, but when advanced can present with weight loss, malaise, hemoptysis, and symptoms associated with metastases such as bone pain due to bone metastases or headaches/seizures due to brain metastases.
No/Asymptomatic: If there are no symptoms, assess whether patients may be eligible for lung cancer screening. Current guidelines from USPSTF for lung cancer takes into account high risk vs low risk patients. Ask learners to discuss and name the screening recommendations. Click “Screening” followed by “Risk Assessment” to reveal high risk vs low risk.
- High risk: Patients who are greater than or equal to 50 yo AND have greater than or equal to 20 py should have a low dose CT scan annually.
- Low risk: Patients who do not meet the screening criteria should be reassessed annually for risk factors.
- Other risk factors: Other risk factors include exposures to radon, chemicals, occupational exposures, and secondhand smoke as well as a family history of cancer (e.g., Lynch syndrome, known mutations), personal history of COPD and underlying lung disease as well as prior cancer and cancer treatment.
Yes/Symptomatic: For patients with symptoms concerning for underlying lung cancer, an initial screening CXR should be performed.
- Not concerning: If the CXR was not concerning (as shown in the right upper hand corner with CXR that is clear), perform a risk assessment to help decide whether further imaging is needed. This assessment should consider overall clinical picture, risk factors, and persistence of symptoms. For example, hemoptysis should prompt a CT chest even if CXR is not concerning.
- Concerning: If the CXR imaging is concerning (as shown in the right upper hand corner with CXR that shows a R lung mass), patients should undergo further evaluation with they should proceed to a CT. While CT chest without contrast can give a better view of the lung fields, CT with contrast is preferred for initial malignancy workup given better visualization of structures such as lymph nodes.
- CT chest +/- abdomen and pelvis: Spiculated lesions, solid component in ground glass, irregular shape, thick-walled, necrosis, and extrapulmonary or satellite lesions are all concerning for malignancy. An increase in size of lesions over time should also prompt further workup.
- Biopsy is imperative for diagnosis, can mention the phrase “tissue is the issue.” Click “Biopsy” to proceed to the next page.
Where and How to Biopsy:
Ask learners how they decide where to biopsy. Click “Which lesion would you biopsy?” to reveal the answer.
It is preferable to biopsy the farthest lesion (assuming that it is safe) from what is believed to be the primary lesion, as this gives you both diagnosis and staging i.e. if there is a distant metastasis, this is considered Stage IV disease automatically. Core or excisional biopsies are preferred over fine needle aspiration (FNA) when possible to preserve the architecture of the sample (though this is generally more important for lymphomas as opposed to solid tumors) and will help ensure there is enough tissue for genetic testing. Depending on location of the lesion, different services will perform the procedures which can be institution dependent.
Objective 2: Develop a strategy for work up of a suspected lung cancer (Testing & Counseling – SCLC, NSCLC, Summary)
After a biopsy returns with pathology consistent with lung cancer, the next step would be to perform staging, which will guide assessment of surgical candidacy and treatment options.
- Staging: CT chest/abdomen/pelvis with contrast or a PET scan are helpful for determining any intrathoracic or extrathoracic non-CNS metastases. PET-CT is not ideal for intracranial assessment as the brain always lights up on a PET. MRI brain w/ contrast is helpful for assessing for intracranial metastases and should be part of the staging. A bronchoscopy and/or mediastinoscopy is helpful to clarify lymph node involvement, the “N” in TNM staging, especially if the patient does not have distant metastatic disease. If there are distant metastases, regardless of size of primary tumor or regional lymph node involvement, a patient has stage IV lung cancer
- Assessment of surgical candidacy: If the patient is a potential surgical candidate, PFTs are needed to assess baseline lung function. This is helpful in predicting whether a patient can tolerate a lobectomy or pneumonectomy. If a patient has metastatic lung cancer, they are usually not a surgical candidate and thus do not require PFTs.
- Additional labs: CBC, BMP+Ca, and LFTs, as well as molecular testing. PD-L1 percentage is important in determining candidacy for immunotherapy, such as pembrolizumab. Molecular testing looks for specific gene mutations such as EGFR mutations or ALK rearrangements, as targeted therapies may be an option. There is an estimated 50% chance that a patient who is a never-smoker with lung cancer has a mutation – emphasize that this dramatically changes treatment and prognosis.
The next section reviews the two predominant classifications of lung cancer (small cell lung cancer and non-small lung cancer). Click on the left-hand table of contents to navigate to each page. Reviewing the “SCLC” and “NSCLC” pages individually will take ~ 5-7 min. Reviewing the “Summary” page for a broad overview will take ~ 3 min.
- Overview – Small cell lung cancer comprises of 10-15% of all lung cancers and is associated with smoking as a major risk factor. This particular type of lung cancer tends to be rapidly progressive and aggressive, with high likelihood of progression to brain metastases. They are also associated with paraneoplastic syndromes. While they tend to respond well initially to chemotherapy and radiation, recurrence is common.
- Staging – SCLC is limited stage if the tumor is confined to the ipsilateral chest and can be treated with a single radiation field. Extensive stage means the cancer has spread beyond the ipsilateral chest and potentially involves distant metastases. In these patients, brain MRI is essential given propensity for SCLC to spread to the brain. In patients with limited stage and no brain metastases, prophylactic cranial irradiation is frequently performed.
- Treatment – The learning point here is that limited stage SCLC can potentially be resected – but otherwise mainstays of therapy are chemotherapy and radiation. The scalpel represents surgery, the radiohazard sign represents radiation, the infusion bag represents systemic therapy (chemotherapy, immunotherapy, targeted therapy).
- Prognosis – 5-year survival rates tend to be low for both limited and extensive stage small cell lung cancer, 10-13% vs 1-2%, with a median survival of 15-20 months vs 8-13 months.
- Overview – NSCLC is the most common type of lung cancer, comprising 80-85% of all lung cancers and can be divided into histological subtypes, which direct treatment. Can make a plug for NCCN guidelines here. Molecular testing also changes therapy options.
- Staging – Staging is dependent on size of tumor, lymph node involvement, and distant metastases.
- Treatment – Early-stage NSCLC can potentially be resected or treated definitively with radiation, but as you progress towards more advanced stages, systemic treatments are the standard of care. If the disease is not curable, treatment is considered “palliative” which is different from a patient following with palliative care.
- Prognosis – 5-year survival rates are very high for Stage I at 73-90% as compared to Stage IV at 0-10%. 5-year-survival rate decreases dramatically with each stage. Lung cancer screening is important in helping to capture these cancers early.
Summary – Click through Characteristics, Staging, Treatment, and Prognosis to compare SCLC vs NSCLC. The major learning point here is that in both SCLC and NSCLC, early diagnosis is key.
Objective 3: Compare indications and side effects of major categories of oncologic treatments for lung cancer (Systemic Tx)
Ask learners what the difference is between adjuvant, neoadjuvant, and palliative therapy.
- Neoadjuvant therapy is given prior to surgery to attempt to shrink the tumor and make the resection safer/easier.
- Adjuvant therapy is given after resection to kill any remaining tumor cells that were either not resected (margins not clear) or are microtumors not visible on a scan or gross examination during surgery.
- Palliative therapy is given with the goal of preventing progression of disease and shrinking the tumor, but that these patients are not considered “curative intent.”
Click on “Indication”, “Examples”, and “Toxicities” of each class of therapy. Internists are not expected memorize the names of therapies, but it can be helpful to be familiar with a couple of commonly used drugs. The most common type of targeted therapies are tyrosine kinase inhibitors or TKIs, but targeted therapies are broader category. As a bonus, you can mention that there are now other therapies in trials for novel mechanisms such bispecific T-cell engagers (BiTE) therapy, tumor infiltrating lymphocytes (TILs), and antibody drug conjugates (ADC).
- Chemotherapy –
- Indication: Used as neoadjuvant, adjuvant, and palliative therapy for NSCLC and SCLC.
- Examples: cisplatin, carboplatin, etoposide, paclitaxel, docetaxel, lurbinectedin are common therapies used in lung cancer
- Toxicities: Vary depending on the specific chemotherapy, but common side effects include nausea/vomiting, diarrhea, mucositis, cytopenias, kidney and renal dysfunction, neuropathy.
- Immunotherapy –
- Indication: Used as neoadjuvant, adjuvant, and palliative therapy for NSCLC and SCLC.
- Examples: pembrolizumab, nivolumab, ipilimumab, durvalumab, atezolizumab
- Toxicities: The “-itises,” which can affect any organ and can present early or late in the treatment course. These complications can present even after therapy has stopped for some time.
- Targeted Therapy –
- Indication: Used as adjuvant and palliative therapy for NSCLC, trials in progress for neoadjuvant settings
- Examples: Tend to end with -tinib (e.g., simertinib, alectinib, lorlatinib, entrectinib). The most common type of targeted therapies are tyrosine kinase inhibitors or TKIs, but targeted therapies are broader category. As a bonus, you can mention that there are now other therapies in trials for novel mechanisms such bispecific T-cell engagers (BiTE) therapy, tumor infiltrating lymphocytes (TILs), and antibody drug conjugates (ADC).
- Toxicities: Side effects are more specific to the pathway that is targeted, and they are generally quite well tolerated, but common side effects include rash (for the EGFR inhibitors in particular), diarrhea, anemia, fatigue. More rare but serious side effects include pneumonitis and QTc prolongation.
- Case 1: Lung cancer screening in an asymptomatic patient. Review the prior framework for symptomatic and asymptomatic patients. Remind the audience about the guidelines for screening and importance of smoking cessation counseling for any patient.
- Case 2: Patient with newly metastatic lung adenocarcinoma. Walk through framework for symptomatic patients and for deciding site of biopsy – diagnosis and staging.
Take Home Points
- Lung cancer screening is important due to the difference in mortality between early vs advanced lung cancer at time of diagnosis. Asymptomatic patients should undergo risk assessment to determine need and frequency of screening.
- Biopsy confirmed lung cancer should be followed with imaging studies to determine the stage of cancer. Early-stage lung cancer can be treated with curative intent using modalities such as surgery, radiation, and systemic medications.
- Molecular studies can help direct treatment with immunotherapies or targeted therapies.