Management of Stage III Non-Small Cell Lung Cancer: ASCO Rapid Guideline Update

Publication Date: July 23, 2024

Last Updated: November 20, 2024

Objective

The purpose of this patient summary is to provide guidance on the diagnosis and management of stage III non-small cell lung cancer (NSCLC) when evaluating adults with suspected or known stage III NSCLC.

Background

Lung cancer is categorized into two main types, Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer.
- Non-small cell lung cancer is different from small cell lung cancer by its microscopic appearance, immunochemistry and molecular profile.

The abbreviation NSCLC throughout this summary refers to non-small cell lung cancer.

The most common cause of lung cancer is years of smoking.

Air pollution and radon gas exposure are important risk factors for never-smokers.

Staging:

Staging considers things like:
- How large is the cancer?
- Where is it located?
- Is there more than one tumor?
- Has it spread beyond the original site to nearby tissue or to lymph nodes or to other parts of the body?
- Are lymph nodes involved? If so, where?

Stage III NSCLC refers to a stage of cancer where the cells from the tumor have spread to nearby tissues and possibly nearby lymph nodes called mediastinal lymph nodes (lymph nodes within the chest).

Diagnosis and Evaluation

For patients with suspected stage III NSCLC, evaluating for metastatic disease (cancer that has spread outside of the original tumor location) should include:
- A history and physical examination performed by the healthcare provider to assess your symptoms and current state of health.
- Computed tomography (CT) scan of chest and upper abdomen.
  - A CT scan uses X-rays to create detailed images of the lungs, helping healthcare providers see the size and spread of NSCLC.
  - CT scans require radiation exposure and typically contrast dye exposure (used to highlight areas on the imaging).
- Afterwards, additional imaging includes a fluorodeoxyglucose positron emission tomography (FDG PET), a CT scan and brain imaging with MRI.
  - An FDG PET scan uses a small amount of radioactive sugar to create images of the body, helping to look for cancer cells in the lungs and other areas.
- A brain MRI is used to see if the cancer has spread to the brain.
  - An MRI scan uses radio waves, a powerful magnet, and a computer to make a series of detailed pictures of areas inside the body.

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For patients with suspected stage III NSCLC who may be candidates for treatment aimed at curing the cancer (referred to as curative-intent):
- Mediastinal lymph nodes should be assessed to see if there has been a spread of the cancer to those areas.
  - Samplings from the tissue for these lymph node assessments should be offered through an endoscopic technique when initially staging the cancer.
  - If an endoscopic technique is not available or the results are inconclusive, a surgical biopsy should be done to confirm the staging.
    - An endoscopy (or endoscopic technique) uses a special tube with a camera to get detailed pictures and information. A surgical biopsy requires a procedure to get a sample of the tissue.

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At all stages of your treatment, you will be an active participant in discussions and treatment choices.

If clinical trials (studies) are available and convenient, you will be offered to participate in one. Ask your healthcare provider about clinical trials.

Support services are available to help you manage issues like cost, convenience, planning your future, family matters, and concerns or questions over what lies ahead.

Before starting any treatments, patients who have suspected or confirmed stage III NSCLC should have shared decision-making discussions with a team of various specialists involved in the treatment plan.

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Treatment

Treatment Terms:
Treatment types:

CRT (Chemoradiotherapy): A treatment approach that combines chemotherapy and radiation therapy.

RT (Radiotherapy/Radiation Therapy): A treatment that uses radiation to target and kill cancer cells.

Adjuvant Therapy: Additional treatment given after surgery with the goal of preventing the cancer from coming back.

Neoadjuvant Therapy: A treatment given before the main treatment (like surgery) to shrink the cancer.

Surgery: A treatment where doctors remove the tumor and possibly some surrounding tissue or lymph nodes to get rid of cancer.

Treatment Phases:

Induction: The initial phase of treatment aimed at quickly reducing the size of the tumor.

Consolidation: Follow-up treatment given after induction to ensure the cancer is fully eliminated and to prevent it from coming back.

Remission: A period during which cancer is undetectable, indicating a positive response to treatment.

Recurrence: The return of cancer after a period of remission, necessitating further treatment and management.

Treatment Goals:

Treatment goals for NSCLC overall can be focused on:
- Curative treatment:
  - Treatment aimed at eliminating the cancer completely, if possible, and curing the patient.
- Definitive treatment:
  - Treatment intended to be the main method to control or eliminate cancer, often with the goal of long-term success.
- Definitive and curative are used interchangeably, and the definitions sound the same.
If the cancer is not eliminated, the goal is to manage it like a chronic disease.

Palliative treatments:

Treatment focuses on relieving symptoms and improving quality of life without necessarily curing the disease.
Treatment for stage III NSCLC often involves several different kinds of treatment – surgery, radiation, chemotherapy, immunotherapy and targeted therapy:
Targeted therapy (also called precision medicine): Uses drugs that specifically target the cancer's unique genetic features while sparing as much normal tissue as possible.
Induction Therapy: You may first receive treatment, like chemotherapy, chemoimmunotherapy or chemoradiation, to shrink the tumor and make it easier to remove.
Surgery: After the initial treatment, surgery may be done to remove the tumor and affected lymph nodes.
Adjuvant and neoadjuvant therapy are often used in combination with surgery.

Surgery

After evaluating and staging the cancer, surgery may be offered for some patients.
- Surgeons should generally be the final decision-makers for who should have surgery.
- The presence of certain gene changes, available treatment options, and patient preferences should be taken into account when deciding treatment plans.
- Patients and healthcare providers should consider enrollment in clinical trials (studies) when appropriate.
The most important decisions are whether your cancer can be completely removed by surgery or treated with radiation, and whether you are generally healthy enough to undergo the needed procedure.
It is also important to discuss your current living situation and work to ensure that you have the support you need.

For patients with NSCLC stage IIIA (N2 [cancer-containing lymph nodes on only one side of the chest]), induction therapy followed by surgery (with or without adjuvant therapy) may be offered if all of the following conditions are met:
- A complete resection (full removal of the original tumor and lymph nodes it might have spread to) is possible.
- A partial resection combined with adjuvant and/or neoadjuvant therapy may also be an option.
- The team of various specialties has determined that cancer-containing lymph nodes are not on both sides of the chest.
- The chance of mortality within 90 days of the procedure is low (less than 5%).
- Note: Induction therapy refers to the initial phase of treatment aimed at quickly reducing the size of the tumor.

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For certain patients with stage T4N0 (large tumor, no spread to lymph nodes) NSCLC disease, surgical resection may be offered if the team of different specialties determines it to be medically and surgically appropriate.

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Neoadjuvant Therapy

For treatment plans that involve surgery for stage III NSCLC, patients should receive systemic (throughout the body) neoadjuvant therapy.
- This can come in the form of neoadjuvant chemoimmunotherapy, neoadjuvant chemotherapy, or neoadjuvant concurrent chemoradiation if surgical resection is planned.

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For patients with superior sulcus disease (where the tumor is located at the top part of the lung), neoadjuvant concurrent chemoradiation followed at an appropriate interval by surgery is recommended.

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Adjuvant Therapy

Patients with stage III NSCLC who did not receive neoadjuvant therapy before their surgery should be offered adjuvant therapy using platinum-based chemotherapy.
- Some patients may also benefit from immunotherapy following the completion of chemotherapy.
- If the resected tumor contains either an EGFR exon 19 deletion or an exon 21 L858R mutation, adjuvant therapy with a medication called osimertinib should be offered after platinum-based chemotherapy.

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If a tumor was completely removed during surgery, patients who received platinum-based chemotherapy before or after their surgery, who had a tumor that spread no further than lymph nodes on the same side of the chest as the tumor, should NOT routinely be offered radiation treatment after their surgery.

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Definitive Treatment for Unresectable Disease

Unresectable disease refers to lung cancer that cannot be removed with surgery due to its size, location, or spread.
- Definitive treatment for unresectable disease aims at controlling or eliminating cancer when surgical removal of the tumor is not possible.

Stage III NSCLC patients who cannot have surgery and are in good health should be offered treatment with chemotherapy and radiation given together, instead of one after the other.
- The chemotherapy given with the radiation therapy for definitive treatment in stage III NSCLC is preferably recommended to include the following medicine combinations:
  - Cisplatin and etoposide
  - Carboplatin and paclitaxel
  - Cisplatin and pemetrexed OR
  - Cisplatin and vinorelbine

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For stage III NSCLC patients receiving chemotherapy and radiation together, the recommended radiation dose is 60 Gy.
- Radiation is measured in Gy (Gray), which is a unit of measurement for radiation dose that tells the doctor how much radiation energy is absorbed by the body’s tissues. This helps them give enough to effectively treat cancer while minimizing protecting healthy tissue.
- The radiation dose is usually 60 Gy, but in some cases doses up to 70 Gy may be considered.

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Patients with unresectable disease who cannot have surgery and cannot receive concurrent chemoradiation but are able to receive chemotherapy should be offered a treatment with chemotherapy given first, then radiation, rather than treating with radiation alone.

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Patients with unresectable stage III NSCLC who did not receive chemotherapy but are receiving only radiation therapy with a standard fractionation approach may be appropriate for having increased doses (radiation dose escalation) over time.

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Patients with unresectable disease whose cancer did not get worse after receiving concurrent chemotherapy and radiation together should be offered durvalumab, an immunotherapy drug, for up to 12 months, with the goal of killing any remaining cancer cells and prevent the cancer from returning.

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Patients with specific genetic mutations (EGFR exon 19 deletion or exon 21 L858R) may be offered consolidation therapy with the medication osimertinib after definitive chemoradiotherapy.

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Abbreviations

CT: Computed Tomography
EGFR: Epidermal Growth Factor Receptor
FDG PET: Fluorodeoxyglucose-positron Emission Tomography
Gy: Gray
NSCLC: Non-small Cell Lung Cancer
PD-L1: Programmed Cell Death Ligand 1

Source Citation

Daly ME, Singh N, Ismalia N, et al. Management of Stage III NSCLC: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2024 July 23. doi:10.1200/JCO.24.01324

Singh N, Daly ME, Ismaila N, et al. Management of Stage III NSCLC: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2023 July 20. doi:10.1200/JCO.23.01261

Daly ME, Singh N, Ismaila N, et al. Management of Stage III NSCLC: ASCO Guideline. J Clin Oncol. 2021 Dec 22. doi:10.1200/JCO.21.02528

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.