Medically reviewed by C.H. Weaver M.D. updated 5/2022
In general treatment for non-small cell lung (NSCLC) may require surgery, radiation, and/or systemic therapy with chemotherapy, immunotherapy or precision cancer medicines. The specific treatment for each person is individualized and is based on the stage of the cancer and its genomic profile.1,2,3
The initial evaluation of NSCLC is designed to determine the role of surgery. Patients with early stage (I-III) NSCLC are typically treated with surgery and some patients will benefit from pre or post operative systemic therapy.
Staging of Lung Cancer
Cancer doctors need to determine the stage or the extent of the spread of the cancer in order to plan effective treatment. The focus of the staging evaluation is to determine if cancer is localized or metastatic. Metastatic disease is treated with systemic chemo-immunotherapy. Surgical resection however can be part of a curative treatment strategy if the cancer is localized.
A cancer’s stage is a key factor in determining the best treatment. Doctors will use the following tests to evaluate where a lung cancer is located both in the chest and the rest of the body.
- Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data.
- Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue. MRI gives better pictures of tumors located near bone than CT, does not use radiation as CT does, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the tumor.
- Positron emission tomography (PET): PET scanning has been used to improve the detection of cancer in lymph nodes and a combined PET/CT is often used to evaluate lung cancers. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that spontaneously emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons). The positrons react with electrons in the cancer cells, which creates the production of gamma rays that are detected by the PET machine, which transforms the information into a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.
- Bone Scan: A bone scan is used to determine whether cancer has spread to the bones. Prior to a bone scan, a surgeon injects a small amount of radioactive substance into a vein. This substance travels through the bloodstream and collects in areas of abnormal bone growth. An instrument called a scanner measures the radioactivity levels in these areas and records them on x-ray film.
Staging The Mediastinum
The mediastinum is the space behind the breastbone (sternum) in the middle of the chest, between the 2 lungs. It contains: Lymph nodes. The heart and its great vessels.
Determining the presence of cancer in the mediastinum is essential for NSCLC treatment planning. Incorrectly staged patients may undergo unnecessary surgery, not be offered systemic treatment that could prolong their survival or be unnecessarily exposed to the side effects of chemo-immunotherapy that offers no benefit.
In addition to PET/CT scanning physical examination of the mediastinum is required to arrive at the correct stage of NSCLC. There are two ways to evaluate the mediastinum.
- During a mediastinoscopy, a surgeon makes a small incision in the neck while a patient is under general anesthesia. Next, a thin scope, called a mediastinoscope, is inserted through the opening to provide access to the lungs and surrounding lymph nodes. This mediastinoscope allows the surgeon to examine the center of the chest (mediastinum) and nearby lymph nodes, as well as remove a tissue sample.
- Endobronchial ultrasound (EBUS) is a minimally invasive procedure used to evaluate the mediastinum that allows physicians to perform a technique known as transbronchial needle aspiration (TBNA) to obtain tissue or fluid samples from the lungs and surrounding lymph nodes without conventional surgery.
Benefits of EBUS
- Provides real-time imaging of the surface of the airways, blood vessels, lungs, and lymph nodes
- The improved images allow the physician to easily view difficult-to-reach areas and to access more, and smaller, lymph nodes for biopsy.
- The accuracy and speed of EBUS allows rapid onsite pathologic evaluation in the operating room.
- EBUS is performed under moderate sedation or general anesthesia
- Patients recover quickly and can usually go home the same day
For patients with NSCLC limited to the chest surgical resection is not only an important therapeutic modality, but in many cases, the most effective method of controlling the disease. Patients with stages I-II localized cancer without spread to lymph nodes are considered to have early stage lung cancer and are almost always treated with surgery to remove the cancer. Some individuals with stage IIIA NSCLC can be treated with surgery as well however surgery for stage IIIB and IV disease is ineffective because the lung cancer has already spread.1,2,3
Radiation therapy uses high-powered energy beams, such as X-rays or protons, to kill cancer cells. Radiation therapy may be used alone or with chemotherapy before surgery to shrink a tumor or after surgery to kill any remaining cancer cells.1-6
Systemic Therapy & MRD
Systemic therapy is any treatment directed at destroying cancer cells throughout the body. Many patients with NSCLC have small amounts of cancer that have spread outside the lungs or remain after surgery. These cancer cells are difficult to detect with currently available tests and are referred to as minimal residual disease (MRD). Their presence causes NSCLC recurrence following local treatment with surgery and/or radiation therapy alone. An effective systemic treatment is needed to cleanse the body of MRD in order to improve a patient’s duration of survival and potential for cure.
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Systemic Therapy For NSCLC: Precision Cancer Medicines, Chemotherapy & Immunotherapy
Precision cancer medicines, chemotherapy and immunotherapy are all forms of systemic treatment that circulate in the blood and can kill cancer cells throughout the body. Chemotherapy, once the only systemic therapy is increasingly being replaced by more targeted precision cancer medicines and immunotherapy for treatment of both early and later stage cancer. Their role is determined by performing biomarker tests that identify which therapy will be most effective. All NSCLC patients should undergo NGS testing to look for these markers and at a minimum have EGFR, PDL-1, and ALK evaluated.
Precision Cancer Medicines
The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
- Large-scale screening for epidermal growth factor receptor (EGFR) PD-1, ROS1, ALK, RET, BRAF, MET, TRK and other mutations in lung cancer is now considered standard of care because it allows for customization of treatment leading to improved outcomes. Genomic biomarker testing should be performed at the time of a new lung cancer diagnosis.7-11
Immunotherapy has become standard treatment for NSCLC and can be used alone or in combination with other systemic therapy. Immunotherapy works best when patients have a biomarker known as PDL-1. The higher the PDL-1 value, the better immunotherapy works.
Chemotherapy uses medications that can be taken orally as a pill or are injected into a vein to kill cancer cells. In some situations chemotherapy is combined with radiation therapy or other precision cancer medicines to achieve the best results.
Treatment of Non Small Cell Lung Cancer by Stage
Stage I: The cancer measures 5 centimeters or smaller and does not involve the lymph nodes.
Stage II: The cancer has not spread to the lymph nodes but is larger than 5 centimeters or involves structures near the lung such as the chest wall or diaphragm. NSCLC is also considered to be Stage II if it measures 7 centimeters or less and involves the lymph nodes within the lung or near the bronchus.
Stage IIIA: NSCLC is a single cancer mass that is not invading any adjacent organs and involves one or more lymph nodes away from the primary cancer. Stage IIIA cancers are further subdivided into N1 and N2 subgroups. N1 cancers involve lymph nodes farther away from the mediastinum and are easier to remove with surgery. N2 cancers involve lymph nodes in the mediastinum and may be difficult to remove surgically.
Stage IIIB: NSCLC has already spread to more than one location in the chest, but cannot be detected outside the chest cavity with currently available diagnostic tests. Unfortunately, most of these patients have undetectable spread of cancer outside the chest. This undetectable cancer is the cause of relapse or recurrence of cancer in the majority of patients.
Stage IV: Cancer is found in both lungs, in the fluid that surrounds the lungs or heart, or has spread to other parts of the body such as the liver, brain, or bones.
Recurrent/Relapsed: Cancer has progressed or returned (recurred/relapsed) following an initial treatment with surgery, radiation therapy and/or chemotherapy.
Radiation therapy uses high-powered energy beams, such as X-rays or protons, to kill cancer cells. Radiation therapy may be used as part of an overall strategy to treat stage III disease, treat single metastases, or control the cancer in individuals unable to undergo surgery systemic chemotherapy treatment.
Some patients with NSCLC are not able to undergo the surgery to remove their cancer. Advanced age and other medical conditions such as heart disease and diminished lung capacity make it more difficult for these patients to withstand surgery. Studies have demonstrated that patients with stages IIIA NSCLC who are not able to, or do not wish to undergo surgery may be treated with radiation therapy alone. Results indicated that radiation therapy alone produced an average survival time of over 30 and 34 months, respectively.2,4
Prophylactic brain radiation: Researchers have found that the most common site for cancer to spread in patients is the brain.3 These patients may benefit from radiation treatment to the brain during their initial therapy, which is called prophylactic treatment. Results of a clinical trial indicate that prophylactic brain radiation reduced the rate of cancer recurrence in the brain from 30% to 8% and the overall chance of relapse in the brain from 54% to 13%. Researchers reported that patients who received prophylactic brain radiation did not experience impaired attention or visual memory after treatment.2,5,6
- Keep Current With The Lung Cancer Community Newsletter
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- American Cancer Society. Cancer Facts & Figures 2017.
- Jeremic B, Calssen J, Bamberg M. Radiotherapy alone in technically operable, medically inoperable, early-stage (I/II) non-small-cell lung cancer. International Journal of Radiation Oncology, Biology, Physics 2002;54:119.
- Stuschke M, Eberhardt W, Pottgen C, Stamatis G, Wilke H, Stuben G, Stoblen F, Wilhelm HH, Menker H, Teschler H, Muller RD, Budach V, Seeber S, Sack H. Prophylactic cranial irradiation in locally advanced non-small-cell lung cancer after multimodality treatment: long-term follow-up and investigations of late neuropsychologic effects. Journal of Clinical Oncology. 1999 Sep;17(9):2700-9.
- Mamon H, Yeap B, Jänne P, et al. High Risk of Brain Metastases in Surgically Staged IIIA Non–Small-Cell Lung Cancer Patients Treated With Surgery, Chemotherapy, and Radiation. Journal of Clinical Oncology. 2005; 23: 1530-1537.
- Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. New EnglandJournal of Medicine. [early online publication]. August 19, 2009.
- Quest Diagnostics Press Release. Quest Diagnostics Introduces Dako’s PD-L1 Complementary Diagnostic Test to Support Bristol-Myers Squibb’s OPDIVO® Anti-PD-1 Therapy for Non-squamous Non-small Cell Lung Cancer. The new Quest test service is based on the first FDA-approved complementary diagnostic. Available online at: . Accessed November 8, 2015.
- Keytruda (pembrolizumab) demonstrates superior progression-free and overall survival compared to chemotherapy as first line treatment in patients with advanced non-small cell lung cancer. [Press release.] mercknewsroom.com/news-release/oncology-newsroom/mercks-keytruda%C2%A0pembrolizumab-demonstrates-superior-progression-free- Accessed June 21, 2016.
- Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2015; 373:1627-1639.
- OSI Pharmaceuticals. FDA Approves Tarceva as a Maintenance Therapy for Advanced Non-small Cell Lung Cancer. Available at: investor.osip.com/releasedetail.cfm?ReleaseID=460783. Accessed April 19, 2010.
- Zhou C, Wu Y-L, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomized, phase 3 study. Lancet Oncology. Early online publication July 22, 2011.
- Shaw AT, Kim DW, Mehra R, et al: Ceritinib in ALK-rearranged non–small-cell lung cancer. New England Journal of Medicine. 2014; 370: 1189-1197.
- Leighl NB, Rekhtman N, Biermann WA, et al. Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Guideline. Journal of Clinical Oncology. 2014;32(32):3673-79. Available at: http://jco.ascopubs.org/content/32/32/3673. Accessed September 30, 2016.
- United States Food and Drug Administration (FDA). FDA expands use of Xalkori to treat rare form of advanced non-small cell lung cancer. Available at: FDA expands use of Xalkori to treat rare form of advanced non-small cell lung cancer. Accessed March 11, 2016.
- FDA grants regular approval to dabrafenib and trametinib combination for metastatic NSCLC with BRAF V600E mutation
- Gainor JF, et al. Abstract 9008. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
- Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children
- Entrectinib Granted Priority Review by FDA for NTRK+ Tumors and ROS1+ NSCLC
- US Food and Drug Administration. FDA approves third oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor. August 15, 2019.