Non-Small Cell Lung Cancer Guidelines 

Updated: Oct 20, 2015
  • Author: Winston W Tan, MD, FACP; more...
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Lung Cancer Screening

Guidelines on lung cancer screening have been issued by the following organizations:

  • American Cancer Society (ACS)

  • American College of Chest Physicians (ACCP)

  • National Comprehensive Cancer Network (NCCN)

  • U.S. Preventive Services Task Force (USPSTF)

The guidelines are in agreement that annual screening with low-dose, computed tomography (LDCT) scanning should be offered to patients aged 55 to 74 years (the USPSTF extends the recommended age range to 80 years) and who have at least a 30 pack-year smoking history and either continue to smoke or have quit within the past 15 years. [1, 2, 3, 4] The NCCN guidelines recommend beginning screening at age 50 and lowering the threshold to at least a 20 pack-year smoking history when a patient has one of the following additional risk factors:

  • Radon exposure (documented sustained and substantially elevated)
  • Occupational exposure to carcinogens (eg, silica, cadmium, asbestos, arsenic, beryllium, chromium, diesel fumes, nickel, coal smoke, soot)
  • Cancer history (eg, lymphomas, head and neck cancer)
  • Family history of lung cancer in first-degree relatives
  • Disease history (chornic obstructive pulmonary disease [COPD] or pulmonary fibrosis)

The groups also agree that the shared decision making is required and should include a discussion of benefits and risks. None of the guidelines recommend screening asymptomatic patients for lung cancer with chest radiograph or sputum cytology.

See Clinical Presentations of Lung Cancer: Slideshow, a Critical Images slideshow, to help efficiently distinguish lung carcinomas from other lung lesions, as well as how to stage and treat them. Also see the Lung Cancer Staging -- Radiologic Options slideshow for additional information on staging and treatment.


ACCP Diagnosis and Management Guidelines

The American College of Chest Physicians (ACCP) updated its comprehensive set of lung cancer guidelines in 2013. The guideline set of more than 275 recommendations includes an executive summary of current recommendations for diagnosis and treatment, along with additional recommendations for screening, chemoprevention and treatment of tobacco use in patients with lung cancer. [5]

Diagnosis of Pleural Abnormalities

The updated ACCP guidelines recommendations for diagnosis of pleural abnormalities include the following [5, 6] :

  • The least invasive and safest method (bronchoscopy with transbronchial needle aspiration, endobronchial ultrasound-guided needle aspiration, endoscopic ultrasound-guided needle aspiration, transthoracic needle aspiration, or mediastinoscopy) should be used to establish a diagnosis in individuals who have extensive infiltration of the mediastinum based on radiographic studies and no evidence of extrathoracic metastatic disease (negative positron emission tomography scan)

  • For individuals who have a solitary extrathoracic site suspicious of a metastasis, tissue confirmation of the metastatic site is recommended if a fine-needle aspiration (FNA) or biopsy of the site is feasible

  • In individuals in whom biopsy of a metastatic site would be technically difficult, it is recommended that diagnosis of the primary lung lesion be obtained by the least invasive method

  • In patients suspected of having lung cancer who have an accessible pleural effusion, ultrasound-guided thoracentesis is recommended to diagnose the cause of the pleural effusion

  • If pleural fluid cytology is negative, pleural biopsy (via image-guided pleural biopsy, medical or surgical thoracoscopy) is recommended as the next step

Diagnosis of Primary Tumor

The updated ACCP guidelines recommendations for diagnosis of primary tumor include the following [5, 6] :

  • If lung cancer is suspected and sputum cytology is negative for carcinoma, further testing should be performed

  • In patients who have a central lesion, bronchoscopy should be used to confirm the diagnosis; further testing should be performed if bronchoscopy results are non-diagnostic and suspicion of lung cancer remains

  • As an adjunct imaging modality when a tissue sample is required due to diagnostic uncertainty or poor surgical candidacy, radial endobronchial ultrasonography can confirm in real time the ideal location of bronchoscopic sampling and increase the diagnostic yield over conventional bronchoscopy for peripheral nodules

  • With peripheral lung lesions difficult to reach with conventional bronchoscopy, electromagnetic navigation guidance can be used if the equipment and the expertise are available; if electromagnetic navigation is not available, transthoracic needle aspiration (TTNA) is recommended

  • In patients who have a peripheral lesion, and who require tissue diagnosis before further management can be planned, TTNA is diagnostic option; however, further testing should be performed if TTNA results are non-diagnostic and suspicion of lung cancer remains

  • The diagnosis of non–small cell lung cancer (NSCLC) made on cytology (sputum, TTNA, bronchoscopic specimens, or pleural fluid) is reliable. However, adequate tissue must be obtained to accurately define the histologic type and to perform molecular analysis when applicable.

Treatment of Clinical Stage I and II NSCLC

The updated ACCP guidelines recommendations for treatment of clinical stage I and II NSCLC include:

  • Surgical resection is the primary and preferred treatment approach for patients with no medical contraindications and a lobectomy rather than sub-lobar resection is preferred; however, in patients with major increased risk of perioperative mortality or competing causes of death (due to age-related or other co-morbidities), an anatomic sub-lobar resection (segmentectomy) over a lobectomy is suggested

  • Patients should be evaluated by a thoracic surgical oncologist even if they are considered for nonsurgical therapies such as percutaneous ablation or stereotactic body radiation therapy

  • For clinical stage I patients, a minimally invasive approach such as video-assisted thoracoscopy surgery (VATS) is preferred over a thoracotomy for anatomic pulmonary resection

  • For patients with in whom a complete resection can be achieved, a sleeve or bronchoplastic resection is suggested over a pneumonectomy

  • For patients with clinical stage I NSCLC who cannot tolerate a lobectomy or segmentectomy, stereotactic body radiation therapy (SBRT) and surgical wedge resection are suggested over no therapy

  • The use of adjuvant chemotherapy for stage II NSCLC is recommended and has shown benefit

  • The use of adjuvant radiation or chemotherapy for stage I NSCLC is of unproven benefit

Treatment of Clinical Stage III NSCLC

The updated ACCP guidelines recommendations for treatment of clinical Stage III NSCLC include the following [5, 8] :

  • Combined chemoradiotherapy is preferred over radiotherapy alone in most subsets of patients and concurrent chemoradiotherapy is recommended over sequential chemoradiotherapy

  • Consolidation chemotherapy or targeted therapy following definitive chemoradiation is not recommended

  • Neoadjuvant therapy followed by surgery is neither clearly better nor clearly worse than definitive chemoradiation

  • Postoperative radiotherapy improves local control without improving survival

Treatment of Clinical Stage IV NSCL

The updated ACCP guidelines recommendations for treatment of clinical stage IV NSCLC include the following [5, 9] :

  • The treatment of stage IV NSCLC should be specific for particular histologic subtypes and clinical patient characteristics and according to the presence of specific genetic mutations.

  • Both erlotinib and gefitinib as first-line therapy in patients with stage IV NSCLC and documented EGFR mutations based on superior response rates, progression-free survival and toxicity profiles compared with platinum-based doublets

  • Pemetrexed should be restricted to patients with nonsquamous histology (adenocarcinoma)

  • Bevacizumab in combination with chemotherapy (and as continuation maintenance) should be restricted to patients with nonsquamous histology and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1

  • The use of maintenance therapy with either pemetrexed or erlotinib should be considered after four cycles of first-line therapy in those patients without evidence of disease progression

  • The use of second- and third-line therapy is recommended in those patients retaining a good PS (1-2)

  • In the elderly and in patients with a poor PS, the use of two-drug, platinum-based regimens is preferred.

  • Palliative care should be initiated early in the course of therapy for stage IV NSCLC

Palliative Care

The updated ACCP guidelines recommendations for palliative and end-of-life care include the following [5, 10] :

  • For patients with stage IV lung cancer and/or a high symptom burden, palliative care combined with standard oncology care should be introduced early in the treatment course

  • Begin conversations about the patient's prognosis and goals of care at the time of the diagnosis, and continue these throughout the course of the illness

  • All physicians caring for patients with advanced lung cancer should initiate conversations about the goals of care, the pros and cons of life-sustaining treatment and end-of-life care options


EGFR Testing and Targeted Treatment

International evidence-based guidelines jointly published by the College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) in 2013 recommend all lung cancer patients with adenocarcinomas should be tested for the genetic abnormalities that indicate suitability for treatment with targeted agents, irrespective of clinical variables such as sex, ethnicity, or smoking status. [11, 12, 13]

The 2015 National Comprehensive Cancer Network (NCCN) guidelines recommend using erlotinib, gefitinib, or afatinib as first-line therapy in patients with documented EGFR mutations. [14]


Video-Assisted thoracoscopy surgery (VATS)

NCCN 2015 practice guidelines recommend that VATS or minimally invasive surgery (including robotic-assisted approaches) be strongly considered for patients who have no anatomic or surgical contraindications, provided that standard oncologic and dissection principles of thoracic surgery are not compromised. The guideline notes that in high-volume centers with significant VATS experience, VATS lobectomy in selected patients results in improved early outcomes (ie, decreased pain, reduced hospital length of stay, more rapid return to function, fewer complications) without compromise of cancer outcomes. [14]


Chemotherapy for Stage IV Disease

American Society of Clinical Oncology (ASCO) 2015 guidelines on chemotherapy for stage IV disease recommend that patients with performance status (PS) 0 to 1 (and, in appropriate cases, patients with PS 2), and without an EGFR-sensitizing mutation or ALK gene rearrangement, receive combination cytotoxic chemotherapy, guided by histology. In addition, ASCO recommends early palliative care assistance for all patients with stage IV NSCLC, because it improves survival and well-being. [15]

First-line therapy recommendations include the following [15] :

  • Platinum-doublet therapy for patients with PS 0 to 1 (bevacizumab may be added to carboplatin plus paclitaxel if no contraindications)

  • Combination or single-agent chemotherapy or palliative care alone for patients with PS 2

  • Afatinib, erlotinib, or gefitinib for patients with sensitizing EGFR mutations

  • Crizotinib for patients with ALK or ROS1 gene rearrangement

  • Other recommended first-line regimens or platinum plus etoposide for patients with large-cell neuroendocrine carcinoma

Maintenance therapy recommendations include the following [15] :

  •  Pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens
  • Alternative chemotherapy
  • A chemotherapy break

Second-line therapy recommendations include the following [15] :

  • Docetaxel, erlotinib, gefitinib, or pemetrexed for patients with nonsquamous cell carcinoma
  • Docetaxel, erlotinib, or gefitinib for patients with squamous cell carcinoma
  • Chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib

For third-line therapy, treatment with erlotinib is recommended for patients who have not received erlotinib or gefitinib.

Patients with large-cell neuroendocrine carcinoma should receive platinum plus etoposide or the same treatment as other patients with nonsquamous carcinoma.