Stage III Non-Small Cell Lung Cancer

Publication Date: July 23, 2024
Last Updated: July 23, 2024

Diagnosis

Evaluation and Staging

Recommendation 1.1

For patients with suspected stage III NSCLC, an evaluation to exclude metastatic disease should include, at a minimum: history and physical exam and computed tomography (CT) scan of chest and upper abdomen (with contrast, unless contraindicated).

(IC, B, L, S)
Clinical interpretation: Any suspected metastatic site identified on CT should be confirmed pathologically with biopsy. In general, biopsy sites should be selected to confirm highest possible disease stage, and to maximize tissue yield.
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Recommendation 1.2

Following evaluation with CT scan as per Recommendation 1.1, fluorodeoxyglucose positron emission tomography (FDG PET) with CT scan and brain imaging should be performed.

(EB, B, H, S)
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Recommendation 1.3

For patients with suspected stage III NSCLC, who are candidates for curative-intent treatment, mediastinal lymph node status should be confirmed by pathologic assessment. (EB, B, M, S)
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Recommendation 1.4

For patients who require pathologic assessment of lymph node status, endoscopic techniques should be offered as the initial staging modality.

(EB, B, M, S)
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Recommendation 1.5

For patients who require pathologic assessment of lymph node status but for whom endoscopic staging is either unavailable or inconclusive, surgical confirmation of mediastinal stage should be performed.

(EB, B, M, S)
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Recommendation 1.6

For patients who have suspected or confirmed stage III NSCLC, multidisciplinary discussion should occur prior to the initiation of any treatment plan.

(EB, B, M, S)
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Good Practice Point

Biopsy should generally be performed from the site that would establish the highest stage when feasible. Potential tissue yield for pathologic analysis and molecular sequencing should also be considered.

(, , , )
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Surgery

Recommendation 2.1

For patients with stage IIIA (N2) NSCLC, induction therapy followed by surgery (with or without adjuvant therapy) may be offered if all of the following conditions are met:

  1. A complete resection (R0) of the primary tumor and involved lymph nodes is deemed possible.
  2. N3 lymph nodes are deemed to be not involved by multidisciplinary consensus.
  3. Perioperative (90-day) mortality is expected to be low (≤5%).
(EB, B, M, W)
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Recommendation 2.2

For selected patients with T4N0 disease (by size or extension), surgical resection may be offered if medically and surgically feasible following multidisciplinary review.

(EB, B, M, W)
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Good Practice Points

Patients with stage III NSCLC generally should not be excluded from consideration for surgery by nonsurgical physicians.

(, , , )
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Presence of oncogenic driver alterations, available therapies, and patient characteristics should be taken into account.

(, , , )
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Patients and providers should consider enrollment on clinical trials when appropriate.

(, , , )
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Treatment

Neoadjuvant Therapy

Recommendation 3.1

Patients who are planned for a multimodality approach incorporating surgery as defined in Recommendation 2.1 should receive systemic neoadjuvant therapy.

(EB, B, M, S)
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Recommendation 3.2

Patients with stage III NSCLC who are planned for surgical resection should receive neoadjuvant chemoimmunotherapy, neoadjuvant chemotherapy, or neoadjuvant concurrent chemoradiation. (EB, B, H, S)
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Recommendation 3.3

For patients with resectable superior sulcus disease, neoadjuvant concurrent chemoradiation should be administered.

(EB, B, M, S)
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Adjuvant Therapy

Recommendation 4.1

Patients with resected stage III NSCLC who did not receive neoadjuvant systemic therapy should be offered adjuvant platinum based chemotherapy.

(EB, B, H, S)
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Recommendation 4.2

Patients with resected stage III NSCLC with EGFR exon 19 deletion or exon 21 L858R mutation should be offered adjuvant osimertinib after platinum-based chemotherapy.

(EB, B, H, S)
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Recommendation 4.3

For patients with completely resected NSCLC with mediastinal N2 involvement without extracapsular extension who have received neoadjuvant or adjuvant platinum-based chemotherapy, postoperative radiation therapy should not be routinely offered.

(EB, B/H, M, W)
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Unresectable Disease

Recommendation 5.1

Patients with stage III NSCLC who are medically or surgically inoperable and good performance status should be offered concurrent instead of sequential chemotherapy and radiation therapy.

(EB, B, H, S)
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Recommendation 5.2

Concurrent chemotherapy delivered with radiation therapy for definitive treatment of stage III NSCLC should include a platinum-based doublet, preferably cisplatin plus etoposide, carboplatin plus paclitaxel, cisplatin plus pemetrexed (non-squamous only), or cisplatin plus vinorelbine.

(EB, B, H, S)
Qualifying statement: Carboplatin may be substituted for cisplatin in patients with contraindications to or deemed ineligible for cisplatin.
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Recommendation 5.3

Patients with stage III NSCLC who are not candidates for concurrent chemoradiation but are candidates for chemotherapy should be offered sequential chemotherapy and radiation therapy over radiation alone. (EB, B, H, S)
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Recommendation 5.4

Patients with stage III NSCLC receiving concurrent chemoradiation should be treated to 60 Gy.

(EB, B, H, S)
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Recommendation 5.5

Doses higher than 60 Gy and up to 70 Gy may be considered for selected patients, with careful attention to doses to heart, lungs, and esophagus. (EB, B, L, S)
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Recommendation 5.6

Patients with stage III NSCLC receiving definitive radiation without chemotherapy in standard fractionation may be considered for radiation dose escalation and for modest hypofractionation from 2.15–4 Gy per fraction.

(EB, B, L, W)
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 Recommendation 5.7

Patients with stage III NSCLC receiving concurrent chemoradiation without disease progression during the initial therapy should be offered consolidation durvalumab for up to 12 months.

(EB, B, H, S)

Qualifying statement: There is insufficient evidence to alter the recommendation for consolidation durvalumab following concurrent chemo-radiation for molecularly defined subgroups (namely patients with an oncogenic driver alteration or those with low/no expression of programmed death-ligand 1 [PD-L1]).

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Recommendation 5.8

(Update): Patients with unresectable stage III NSCLC with an EGFR exon 19 deletion or exon 21 L858R mutation may be offered consolidation osimertinib after definitive chemoradiotherapya.

(, , M, S)

a Platinum based chemotherapy and thoracic radiation given concurrently or sequentially.

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Recommendation Grading

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 Death Ligand 1

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.

Overview

Title

Management of Stage III Non-Small Cell Lung Cancer

Authoring Organization

American Society of Clinical Oncology

Publication Month/Year

July 23, 2024

Last Updated Month/Year

November 7, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

The purpose of this guideline is to provide evidence-based recommendations to practicing clinicians on management of patients with stage III non–small-cell lung cancer (NSCLC), and to help clinicians involved in the diagnosis and treatment of lung cancer accurately confirm the presence of stage III non–small-cell lung cancer (NSCLC) and offer the most appropriate treatments. 

Target Patient Population

Patients with stage III NSCLC

Target Provider Population

Medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, pathologists, radiologists, primary care physicians, nurse practitioners, physician assistants, pharmacists, nurses, and other providers

PICO Questions

For patients with stage III NSCLC, does prescribing osimertinib as a consolidation therapy versus a placebo group have increased adverse events?

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant, radiology technologist

Scope

Assessment and screening, Treatment, Management

Diseases/Conditions (MeSH)

D002289 - Carcinoma, Non-Small-Cell Lung, D017024 - Chemotherapy, Adjuvant, D020360 - Neoadjuvant Therapy, D059248 - Chemoradiotherapy, D059186 - Chemoradiotherapy, Adjuvant

Keywords

lung cancer, non-small cell lung cancer, non-small-cell lung carcinoma (NSCLC), NSCLC, Stage III, stage IIIA

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

Supplemental Methodology Resources

Data Supplement, Evidence Tables

Methodology

Number of Source Documents
212
Literature Search Start Date
January 21, 1990
Literature Search End Date
August 21, 2021
Description of External Review Process
The draft recommendations were released to the public for open comment from May 18, 2021, through June 2, 2021. Response categories of “Agree as written,” “Agree with suggested modifications,” and “Disagree. See comments” were captured for every proposed recommendation with 62 written comments received. There were 14 respondents in total.
External Review Process Start Date
May 20, 2021
External Review Process End Date
June 4, 2021
Description of Public Comment Process
The public comment process coincided with the external review process, and the details are the same.
Public Comment Process Start Date
May 20, 2021
Public Comment Process End Date
June 4, 2021
Specialties Involved
Oncology, Pulmonology, Thoracic Surgery, Clinical Pathology, Medical Oncology, Radiation Oncology, Radiation Oncology, Pathology, Oncology, Oncology, Radiology
Description of Funding Source
All funding for the administration of the project was provided by ASCO
Company/Author Disclosures
The Expert Panel was assembled in accordance with ASCO's Conflict of Interest Policy Implementation for Clinical Practice Guidelines (“Policy,” found at https://www.asco.org/guideline-methodology/). In accordance with the Policy, the majority of the members of the Expert Panel did not disclose any relationships constituting a conflict under the Policy.