The stage of lung cancer tells you the location of a tumor, its size, and whether the cancer has spread and to what extent. Imaging (MRIs, CT scans, PET scans) and biopsies can determine the stage of the cancer.
What the Numbers Mean: Understanding Staging for Non-Small Cell Lung Cancer
The staging of non-small cell lung cancer (NSCLC) plays a crucial role in determining the extent of the disease and guiding treatment options. NSCLC is staged using the TNM system, which assesses three key components:
- T (Tumor): This describes the size of the primary tumor and whether it has invaded nearby tissues. For instance, T1 means the tumor is smaller, while T4 indicates a larger tumor or one that has invaded surrounding structures.
- N (Nodes): This indicates whether the cancer has spread to nearby lymph nodes, which are part of the immune system. N0 means no lymph node involvement, while higher numbers, such as N2 or N3, mean cancer has spread to distant or more numerous lymph nodes.
- M (Metastasis): This determines whether the cancer has spread (metastasized) to distant organs, such as the liver, brain, or bones. M0 means no distant spread, while M1 indicates that metastasis has occurred.
These TNM values are combined to determine the overall stage of the cancer, expressed using Roman numerals I through IV. For example, Stage I NSCLC is localized and typically has a better prognosis, while Stage IV means the cancer has spread to distant parts of the body and is more challenging to treat.
In addition to the TNM system, molecular testing for genetic mutations and rearrangements, such as those involving the RET gene, is critical in the management of NSCLC. RET rearrangements and RET fusion (where the RET gene fuses with another gene, creating an abnormal protein that drives cancer growth) are specific genetic alterations that occur in a subset of lung cancers. Understanding if your cancer has a RET fusion can directly influence the treatment plan, as targeted therapies are available for patients with this specific genetic mutation.
The Higher the Stage, the More Advanced the Cancer
The stage number reflects how advanced the lung cancer is, with higher numbers indicating greater spread and severity. For instance, Stage I may involve a small tumor confined to the lung, while Stage III or IV indicates that the cancer has spread to lymph nodes or distant organs. In some stages, additional letters (A or B) further differentiate the cancer’s progression within the same stage. For example, Stage IIIA might indicate a less advanced spread compared to Stage IIIB.
Cancers with similar TNM stages generally have comparable characteristics and treatment strategies. In cases where a RET rearrangement or RET fusion is detected, treatments such as targeted therapies specifically designed to block the abnormal RET protein may be used, providing an option beyond traditional chemotherapy. The staging, along with genetic testing for mutations like RET, helps doctors tailor treatment plans for optimal outcomes.
Why Knowing Your NSCLC Stage and Genetic Mutation Status is Key to Treatment Planning
Before any treatment can begin, a complete understanding of the cancer’s stage and genetic makeup is essential. Accurate staging provides critical information about how far the disease has spread and helps doctors develop a personalized treatment plan that may include surgery, chemotherapy, radiation therapy, or newer targeted therapies.
If your NSCLC tests positive for RET rearrangements or RET fusion, your treatment may involve RET-targeted therapies, which are more effective and less toxic than conventional treatments for this genetic subtype. In addition to guiding treatment, the stage of NSCLC helps doctors estimate a patient’s prognosis by comparing it to outcomes in other patients with the same stage of lung cancer. Patients with RET-positive lung cancer may also be eligible for clinical trials testing the latest RET inhibitors or other innovative treatments.
Staging, along with molecular testing for mutations like RET fusion, helps determine eligibility for clinical trials, which can offer access to cutting-edge treatments. This is especially important for advanced-stage patients who may be seeking new therapies that are not yet widely available. Understanding both the stage and genetic characteristics of your NSCLC is not just about treatment decisions, but also about being informed and empowered to consider all available options, including clinical trials and emerging targeted therapies.
Stage 0
Stage 0: Early Signs of Lung Cancer
Stage 0 lung cancer are tumors that are only found in the lining layers of cells lining the air passages, but have not invaded deeper lung tissue. The cancer has not spread to nearby lymph nodes or to other parts of the body. Tumors at this stage are usually curable by surgery. No chemotherapy or radiation therapy is needed.
Stage I
Stage I: Tumor Size Matters
Stage I lung cancer tumors are smaller than 3 cm, and they are present in one lung only. Stage I lung cancer is divided into two substages, stage IA and stage IB, based mainly on the size of the tumor. Tumors, smaller than 3 cm are stage IA, and more than 3 cm but no more than 4 cm are stage IB.
Surgery is the treatment option for stage I lung cancer. If the doctor determines that there may be a risk of the tumor to come back, chemotherapy or immunotherapy based on immune checkpoint inhibitors after surgery may be viable lung cancer treatment options.
Stage II
Stage II: Larger Tumors Within the Lung
Stage II non-small cell lung cancer are bigger tumors located in the lung. They are divided into two stages: stage IIA are tumors are more than 4 cm but no more than 5 cm, and stage IIB lung cancer are tumors bigger than 5 cm but no more than 7 cm or tumors that are bigger than 5 cm and have spread to the peribronchial nodes and/or to the hilar and intrapulmonary nodes of the lung.
Stage II non-small cell lung cancer patients are usually treated with surgery followed by chemotherapy, immunotherapy, or targeted therapies if available.
Stage III
Stage III: Locally Advanced Lung Cancer
Stage III non-small cell lung cancer or locally advanced lung cancer has spread within the chest but has not metastasized to other organs of the body. They are divided in stage IIIA, IIIB and IIIC. Stage IIIA are tumors bigger than 7 cm that have not spread to the lymph nodes, but they may have spread to a different lung lobe or to other parts of the chest as the diaphragm, mediastinum, or the heart. They can also be tumors smaller than 5 cm that have spread to mediastinal lymph nodes. Stage IIIB lung cancer are tumors either bigger 5 cm that have spread to mediastinal lymph nodes or smaller than 5 cm and have spread to the mediastinal or hilar nodes near the lung without the primary tumor, or to any supraclavicular, or scalene, lymph nodes. Stage IIIC tumors are bigger than 5 cm and have spread to mediastinal or hilar nodes near the lung without the primary tumor, or to any supraclavicular, or scalene, lymph nodes.
Stage III lung cancer patients may receive different types of treatment including combination of surgery with chemotherapy or immunotherapy, radiation, or specific targeted therapy if available.
Stage IV
Stage IV: Metastatic Non-Small Cell Lung Cancer
Stage IV lung cancer has metastasized to distant parts of the body. It is divided into two stages: stage IVA and stage IVB. Stage IVA tumors may be of any size, may or may not have spread to any lymph nodes, and have metastasized, either from one lung into the other lung, into the chest area and/or have spead to one site outside the chest area. Stage IVB tumors may be of any size, may or may not have spread to any lymph nodes, and have metastasized to multiple sites outside the chest area.
Stage IV non-small cell lung cancer is treated depending on additional characteristics of the tumor. Treatment options include targeted therapy if available, immunotherapy, chemotherapy, or combinations.
What Do You Need to Know About the RET Lung Cancer Stages?
The majority of RET fusion non-small cell lung cancer patients (70%) had stage IV disease at the time of diagnosis (5-6). Knowing if you have RET fusion positive lung cancer is important no matter your stage, but it is key to determine treatment options for stage IV .
First-line treatment options for RET fusion positive stage IV lung cancer patients are targeted therapies with selective RET kinase inhibition including the FDA-approved RET inhibitors that target the RET molecule: selpercatinib (Retevmo) and pralsetinib (Gavreto). These RET inhibitors specifically target the RET protein and showed great benefit and durable responses in most RET positive non-small cell lung cancer patients. These RET inhibitors are preferred when compared with other cancer therapies such as multikinase inhibitors, chemotherapy, or immunotherapies based on immune checkpoint inhibitors.
For early-stage RET rearranged lung cancer patients, the treatment options may involve surgical resection and chemotherapy. Several ongoing clinical trials are currently evaluating the efficacy of selective RET inhibitors in early-stage RET-positive non-small cell lung cancer. The NAUTIKA1 study is a phase II clinical trial currently testing the selective RET inhibitor pralsetinib in patients with resectable stage II–III RET fusion positive NSCLC patients (NCT04302025). In addition to this study, the LIBRETTO-432 clinical trial is currently testing the selective RET inhibitor selpercatinib in patients with stage IB–IIIA RET fusion positive NSCLC (NCT04819100).
If you have any questions about RET lung cancer stages or would like to learn more about the latest advancements in RET lung cancer research, feel free to contact us for additional information.
Sources and References
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- Lungevity
- GO2
- Cancer.org (staging NSCLC)
- Cancer.org (by stage)
- Gautschi O, Milia J, Filleron T, Wolf J, Carbone DP, Owen D, Camidge R, Narayanan V, Doebele RC, Besse B, Remon-Masip J, Janne PA, Awad MM, Peled N, Byoung CC, Karp DD, Van Den Heuvel M, Wakelee HA, Neal JW, Mok TSK, Yang JCH, Ou SI, Pall G, Froesch P, Zalcman G, Gandara DR, Riess JW, Velcheti V, Zeidler K, Diebold J, Früh M, Michels S, Monnet I, Popat S, Rosell R, Karachaliou N, Rothschild SI, Shih JY, Warth A, Muley T, Cabillic F, Mazières J, Drilon A. Targeting RET in Patients With RET Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry. J Clin Oncol. 2017 May 1;35(13):1403-1410. doi: 10.1200/JCO.2016.70.9352. Epub 2017 Mar 13. PMID: 28447912; PMCID: PMC5559893.
- Aldea M, Marinello A, Duruisseaux M, et al. RET-MAP: An International Multicenter Study on Clinicobiologic Features and Treatment Response in Patients With Lung Cancer Harboring a RET Fusion. J Thorac Oncol. 2023;18(5):576-586. doi:10.1016/j.jtho.2022.12.018
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