Multidisciplinary Management and Resectability of Locally Advanced Non-Small Cell Lung Cancer

Publication Date: October 16, 2024
Last Updated: October 18, 2024

Assessing Surgical Resectability and Management of Locally Advanced Lung Cancer

Patients with locally advanced NSCLC (clinical stage IIA-III) should be discussed by an MDT, including but not limited to board-certified thoracic surgeons experienced in lung cancer surgery and thoracic-focused medical and radiation oncologists to discuss optimal treatment options, including a determination of feasibility and appropriateness of resection, potential induction therapies, and alternative treatment options.
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Surgical resectability should be decided up-front. Until more data emerge, patients who are deemed unresectable at the outset should not be given neoadjuvant therapy in an attempt to convert unresectable to resectable disease.
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In medically operable patients with 4-7cm NSCLC without clinical nodal metastasis and without a driver mutation, neoadjuvant platinum-based chemotherapy with immunotherapy prior to surgical resection is preferred over adjuvant therapy, particularly in tumors with elevated PD-L1 expression; the data is less clear in 4-5cm tumors whether neoadjuvant chemoimmunotherapy is superior to adjuvant therapy.
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In medically operable patients with clinically involved single or multiple N1 nodes without driver mutations, neoadjuvant platinum-based chemotherapy with immunotherapy prior to surgery is preferred over adjuvant therapy, particularly in tumors with elevated PD-L1 expression.
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In medically operable patients with biopsy-proven NSCLC with single-station, non-bulky N2 disease without driver mutations, surgical resection is generally appropriate as part of a multimodality approach, and neoadjuvant platinum-based chemotherapy with immunotherapy prior to surgery is preferred over adjuvant therapy.
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In patients with NSCLC with pathologically proven single-station, bulky N2 disease, there is not enough data currently to guide whether surgical resection is superior to other treatment options. However, in select cases, particularly if lobectomy is considered likely, surgery may be considered as a part of multimodality therapy after MDT discussion. Inclusion of these patients in clinical trials is strongly encouraged.
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Patients with NSCLC with pathologically proven multi-station N2 disease are generally not considered candidates for surgical resection as they experience poor long-term outcomes after surgery, especially in bulky nodal disease. However, in select cases with non-bulky, 2-3 involved N2 stations, particularly if lobectomy is considered likely, surgery might be considered as a part of multimodality therapy after MDT discussion. Inclusion of these patients in clinical trials is strongly encouraged.
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For patients with resectable NSCLC and persistent N2 disease after induction therapy but without progression, it is generally appropriate to proceed with surgical resection.
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Patients with clinical T4 NSCLC represent a heterogeneous group of patients, and in selected patients with T4 N0-1 disease, surgical resection can be considered after induction therapy following MDT discussion at highly experienced centers. Clinical examples include:
  • Patients with NSCLC > 7 cm or satellite nodules in different lobes with N0 or N1 involvement
  • Patients with T4 N0-1 tumors invading the diaphragm, mediastinal structures, recurrent laryngeal nerve, vertebral body, or carina
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Patients with T4N2 tumors are generally considered poor candidates for surgery for curative intent and are ideally treated with non-surgical therapies.
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For patients with resectable Pancoast tumors without N2 node involvement, pre-operative concurrent chemoradiation followed by surgery remains the standard treatment over induction chemotherapy with immunotherapy, outside of clinical trials.
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Neoadjuvant Therapy

Patients may receive either neoadjuvant or perioperative (peri-adjuvant chemoimmunotherapy with stage IIA and higher NSCLC. It remains unclear which approach is superior, but the attainment of a pathological complete response after neoadjuvant therapy predicts event-free survival.
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In patients with surgically resectable stage II-III NSCLC eligible for neoadjuvant chemoimmunotherapy, tumor PD-L1 expression predicts response to neoadjuvant therapy, but lack of PD-L1 expression should not be used to exclude patients from consideration of neoadjuvant immunotherapy.
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In patients with stage II-III NSCLC that is surgically resectable, the addition of neoadjuvant immunotherapy to chemotherapy has minimal to no additional efficacy in tumors with mutations in EGFR, ALK, ROS1, RET, ERBB2 (HER2), and NTRK, leading to a recommendation against use in these molecular subtypes. These patients can be treated with neoadjuvant chemotherapy or chemotherapy with radiation therapy followed by surgical resection and, when approved, adjuvant-targeted therapy. Alternatively, when appropriate, surgery followed by adjuvant targeted therapy (with or without chemotherapy) is an alternative treatment paradigm.
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The investigation of neoadjuvant targeted therapies is in its early stages, and patients with stage II-III NSCLC (majority adenocarcinoma histology) with driver mutations should be considered for, and if available undergo active discussion about clinical trials that incorporate appropriate targeted therapies, including neoadjuvant therapy.
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Adjuvant Therapy

Although patients with persistent N2 disease after neoadjuvant chemoimmunotherapy have inferior oncologic outcomes, the role of additional adjuvant chemotherapy is unknown. Offering adjuvant immunotherapy to patients may be reasonable based on reported perioperative immunotherapy trials.
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Adjuvant immunotherapy may be continued if following a perioperative regimen with phase III data, and for EGFR mutant NSCLC, adjuvant osimertinib should be offered for 3 years (ideally without prior immunotherapy exposure in the neoadjuvant setting).
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In patients with NSCLC with N2 involvement who received neoadjuvant chemotherapy with immunotherapy followed by surgery, PORT is not routinely indicated. If significant persistent mediastinal nodal disease exists (for example, ypN2 > 1 nodal station), a small volume, highly conformal PORT may be considered as an option (versus additional systemic therapy) after MDT discussion. Enrollment in clinical trials is strongly encouraged, and if available, clinical trials should be discussed with the patient.
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PORT should be considered if the surgical pathology indicates an R1/R2 resection.
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Recommendation Grading

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

Multidisciplinary Management and Resectability of Locally Advanced Non-Small Cell Lung Cancer

Authoring Organization

Society of Thoracic Surgeons

Publication Month/Year

October 16, 2024

Last Updated Month/Year

October 18, 2024

Document Type

Consensus

Country of Publication

US

Document Objectives

The contemporary management and resectability of locally advanced lung cancer are undergoing significant changes as new data emerge regarding immunotherapy and targeted treatments. The objective of this document is to review the literature and present consensus among a group of multidisciplinary experts to guide the determination of resectability and management of locally advanced non-small cell lung cancer (NSCLC) in the context of contemporary evidence.

Target Patient Population

Patients with locally advanced non-small cell lung cancer

Target Provider Population

Oncologists, thoracic surgeons, and other allied providers caring for patients with locally advanced non-small cell lung cancer

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Hospital, Outpatient, Radiology services, Operating and recovery room

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D008175 - Lung Neoplasms

Keywords

non-small cell lung cancer, non-small-cell lung carcinoma (NSCLC), NSCLC, locally advanced non-small cell lung cancer

Source Citation

Kim SS, Cooke DT, Kidane B, Tapias LF, Lazar JF, Awori Hayanga JW, Patel JD, Neal JW, Abazeed ME, Willers H, Shrager JB, The Society of Thoracic Surgeons Expert Consensus on the Multidisciplinary Management and Resectability of Locally Advanced Non-Small Cell Lung Cancer, The Annals of Thoracic Surgery (2024), doi: https://doi.org/10.1016/j.athoracsur.2024.09.041.