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Am Fam Physician. 2022;105(5):487-494

Patient information: See related handout on lung cancer, written by the authors of this article.

Published online April 1, 2022.

Author disclosure: No relevant financial relationships.

Lung cancer is the second most common cancer in men and women in the United States; however, it remains the leading cause of cancer-related death in the United States and worldwide. The most common but nonspecific symptom of lung cancer is cough. Associated symptoms, including hemoptysis or shortness of breath, or systemic symptoms, including anorexia or weight loss, greatly increase the likelihood of having lung cancer. Referral to a multidisciplinary lung cancer team, imaging, and confirmation through sputum cytology, thoracentesis, fine-needle aspiration, or mediastinoscopy are recommended. If lung cancer is confirmed, treatment options vary based on staging, histology, immunotherapy biomarker testing, and patient health status. Treatments include surgical resection, immunotherapy, chemotherapy, and/or radiotherapy. Family physicians should focus on primary prevention of lung cancer by encouraging tobacco cessation and early recognition by screening at-risk individuals and following guidelines for pulmonary nodules. As of 2021, the U.S. Preventive Services Task Force recommends annual lung cancer screening using low-dose computed tomography starting at 50 years of age in patients with a 20 pack-year history.

Lung cancer remains the leading cause of cancer-related death in the United States and worldwide; in the United States, it is the second most common cancer among men and women.1,2 The majority of lung cancers are divided into two histologic types: non–small cell lung cancer (NSCLC; 84%) and small cell lung cancer (SCLC; 13%), which helps guide treatment.3 Smoking is closely linked to 80% to 90% of lung cancer deaths, whereas radon exposure is a leading cause of nonsmoking-related lung cancer.4 Several guidelines address the management of lung cancer, with the goal of improving patient outcomes.5 In the United Kingdom, the National Institute for Health and Care Excellence has developed clinical pathways that were last updated in 2019, whereas in the United States, the most recent comprehensive lung cancer guideline from the American College of Chest Physicians was last updated in 2013, with more recent treatment recommendations from the National Comprehensive Cancer Network.2,68

Clinical recommendation Evidence rating Comments
The initial evaluation for lung cancer begins with laboratory testing, including a complete blood count, serum chemistries, calcium levels, liver function tests, and chest radiography; CT of the chest with intravenous contrast media should be performed when there is a high level of suspicion, even if radiographic results are normal.2,9,10,1315 C Practice guidelines, expert opinion, disease-oriented studies
Adults 50 to 80 years of age who have a 20 pack-year smoking history and currently smoke or have quit smoking within the past 15 years should undergo annual low-dose CT screening.36,40,44 B USPSTF and AAFP guidelines and limited evidence from one large, randomized controlled trial showing moderate benefit
Patients with lung cancer should be offered smoking cessation interventions.45 B Cochrane review that shows reduction in morbidity and mortality; no randomized controlled trials to identify specific smoking cessation interventions are recommended
Patients with lung cancer can improve symptoms with exercise training and nurse counseling.46,47 B Cochrane reviews, with studies limited by heterogeneity, small sample sizes, and high risk of bias
RecommendationSponsoring organization
Do not perform CT screening for lung cancer among patients at low risk of lung cancer.American College of Chest Physicians/American Thoracic Society
Do not recommend screening for breast, colorectal, prostate, or lung cancers without considering life expectancy and the risks of testing, overdiagnosis, and overtreatment.American Geriatrics Society
Do not perform CT surveillance for evaluation of indeterminate pulmonary nodules at more frequent intervals or for a longer period of time than recommended by established guidelines.American College of Chest Physicians/American Thoracic Society

Clinical Presentation and Diagnosis

IN-OFFICE EVALUATION

When evaluating a patient for lung cancer, a detailed history and physical examination should be performed, including environmental and work exposures. Current smoking or history of smoking is the single most important risk factor for all types of lung cancer.9,10 Concomitant chronic lung disease or exposure to radon or asbestos may increase the risk of lung cancer.10

Patients with lung cancer typically present with symptoms,11 the most common of which is cough.9,11 Hemoptysis in combination with weight loss, loss of appetite, or shortness of breath increases the likelihood of lung cancer.11 Table 1 provides signs and symptoms of lung cancer due to local effects,12 and Table 2 and Table 3 show, respectively, advanced disease–displaying symptoms of distant metastases and paraneoplastic syndromes associated with lung cancer.12

Sign/symptom of the primary tumor*LR+LR–
Digital clubbing55.00.96
Hemoptysis13.20.81
Weight loss6.20.76
Loss of appetite4.80.84
Dyspnea3.60.52
Chest or rib pain3.30.68
Fatigue2.30.76
First visit for cough2.20.50
Second visit for cough3.20.66
Third visit for cough4.20.77
Sign/symptom of intrathoracic spreadClinical context

Decreased breath sounds and dyspneaMalignant pleural effusion
Decreased heart sounds and enlarged cardiac silhouetteMalignant pericardial effusion
DysphagiaEsophageal invasion
Elevated hemidiaphragmPhrenic nerve paralysis
Facial swelling, plethora, and upper extremity edemaSuperior vena cava syndrome
Hoarseness, weak coughRecurrent laryngeal nerve palsy
Pleuritic chest painChest wall invasion
Ptosis, miosis, facial anhidrosisHorner syndrome (sympathetic chain compression)
Shoulder pain and muscle wasting along C8-T3 nerve rootPancoast tumor (superior sulcus tumor)
SiteSign or symptomFrequency (%)
AnyAny sign or symptom33
LiverWeakness, weight loss, anorexia, hepatomegalyUp to 60
BonePain, fracture, elevated alkaline phosphataseUp to 25
LymphaticsLymphadenopathy15 to 20
BrainHeadaches, seizures, nausea and vomiting, mental status changesUp to 10
AdrenalsAdrenal insufficiencyRare
SkinSubcutaneous nodulesRare
SyndromeFrequency (%)Comments
Systemic (anorexia, cachexia, weight loss, fatigue, fever)0 to 68May be readily apparent and striking
Digital clubbing29More common with non–small cell lung cancer
Hypercalcemia10 to 20Ectopic production of parathyroid hormone–related peptide; may be life-threatening
Hyponatremia1 to 5Syndrome of inappropriate antidiuretic hormone or ectopic production of atrial natriuretic peptide
Paraneoplastic encephalitis0.2Mental status changes
Cushing syndromeRareEctopic production of adrenocorticotropic hormone
Hypertrophic osteoarthropathyRareTriad of clubbing, arthralgias, and ossifying periostitis
Muscular weaknessRareLambert-Eaton myasthenic syndrome

The initial evaluation for patients with a suspicion for lung cancer begins with laboratory testing, including a complete blood count, serum chemistries, calcium levels, and liver function tests, with chest radiography.2,9 A normal chest radiograph alone should not be used to rule out lung cancer because just under 20% to 25% of normal chest radiographs may miss the disease.13,14 Patients who have a high level of suspicion for lung cancer based on clinical assessment or initial chest radiography findings should receive computed tomography (CT) of the chest with intravenous contrast media, ideally to include the liver and adrenals.2,15

PULMONARY NODULE FOLLOW-UP

Among patients presenting with incidental nodules found on radiographic imaging, follow-up for those older than 35 years is assessed based on features and risk categorization, as recommended by the Fleischner Society, updated in 2017 (Table 4).16,17 New studies are emerging on the use of genomic classifiers and artificial intelligence to help facilitate clinical management of incidental nodules.18,19 For patients meeting high-risk criteria and undergoing lung cancer screening, appropriate follow-up recommendations should be determined by the 2019 Lung-RADS guidelines20 (eTable A).

Solid nodules*

Nodule typeSizeComments

< 6 mm (< 100 mm3)6 to 8 mm (100 to 250 mm3)> 8 mm (> 250 mm3)
Single
 Low riskNo routine follow-upFollow-up CT at 6 to 12 months, then consider follow-up CT at 18 to 24 monthsConsider PET/CT, tissue sampling, or follow-up CT at 3 monthsNodules < 6 mm do not require routine follow-up in low-risk patients (recommendation 1A)
 High riskOptional follow-up CT at 12 monthsFollow-up CT at 6 to 12 months and at 18 to 24 monthsConsider PET/CT, tissue sampling, or follow-up CT at 3 monthsCertain patients at risk with suspicious nodule morphology, upper lobe locations, or both may warrant 12-month follow-up (recommendation 1A)
Multiple
 Low riskNo routine follow-upFollow-up CT at 3 to 6 months, then consider follow-up CT at 18 to 24 monthsFollow-up CT at 3 to 6 months, then consider follow-up CT at 18 to 24 monthsUse most suspicious nodule to guide management; follow-up intervals may vary according to size of nodule and risk (recommendation 2A)
 High riskOptional follow-up CT at 12 monthsFollow-up CT at 3 to 6 months and at 18 to 24 monthsFollow-up CT at 3 to 6 months and at 18 to 24 monthsUse most suspicious nodule to guide management; follow-up intervals may vary according to size of nodule and risk (recommendation 2A)
Category descriptorLung-RADS scoreFindingsManagementRisk of malignancyEstimated population prevalence
Incomplete0Prior chest CT examination(s) being located for comparison
Part or all of lungs cannot be evaluated
Additional lung cancer screening CT images and/or comparison to prior chest CT examinations is neededNA1%
Negative: no nodules and definitely benign nodules1No lung nodules
Nodule(s) with specific calcifications: complete, central, popcorn, concentric rings and fat-containing nodules
Continue annual screening with low-dose CT in 12 months< 1%90%
Benign appearance or behavior: nodules with a very low likelihood of becoming a clinically active cancer due to size or lack of growth2Perifissural nodule(s)*
 < 10 mm (524 mm3)
Solid nodule(s)
 < 6 mm total diameter (< 113 mm3)
 New < 4 mm (< 34 mm3)
Part-solid nodule(s)
 < 6 mm total diameter (< 113 mm3) on baseline screening
Nonsolid nodule(s) (ground-glass nodules)
 < 30 mm (< 14,137 mm3)
or
 ≥ 30 mm (≥ 14,137 mm3) and unchanged or slowly growing
Category 3 or 4 nodules unchanged for ≥ 3 months
Continue annual screening with low-dose CT in 12 months< 1%90%
Probably benign finding(s): short-term follow-up suggested; includes nodules with a low likelihood of becoming a clinically active cancer3Solid nodule(s)
 ≥ 6 mm to < 8 mm (≥ 113 mm3 to < 268 mm3) at baseline
or
 New 4 mm to < 6 mm (34 mm3 to < 113 mm3)
Part-solid nodule(s)
 ≥ 6 mm total diameter (≥ 113 mm3) with solid component < 6 mm (< 113 mm3)
or
 New < 6 mm total diameter (< 113 mm3)
Nonsolid nodule(s)
 Ground-glass nodule ≥ 30 mm (≥ 14,137 mm3) on baseline CT or new
6-month low-dose CT1% to 2%5%
Suspicious: findings for which additional diagnostic testing is recommended4ASolid nodules
 ≥ 8 mm to < 15 mm (≥ 268 mm3 to < 1,767 mm3) at baseline
or
Growing < 8 mm (< 268 mm3)
or
 New 6 mm to < 8 mm (113 mm3 to < 268 mm3)
Part-solid nodules
 ≥ 6 mm (≥ 113 mm3) with solid component
 ≥ 6 mm to < 8 mm (113 mm3 to 268 mm3)
or
 With new or growing < 4 mm (< 34 mm3) solid component
Endobronchial nodule
3-month low-dose CT; PET/CT may be used when there is a ≥ 8 mm (≥ 268 mm3) solid component5% to 15%2%
Very suspicious: findings for which additional diagnostic testing and/or tissue sampling is recommended4BSolid nodule(s)
 ≥ 15 mm (≥ 1,767 mm3)
or
 New or growing, and ≥ 8 mm (268 mm3)
Part-solid nodule(s) with:
 A solid component ≥ 8 mm (≥ 268 mm3)
or
A new or growing ≥ 4 mm (≥ 34 mm3) solid component
Chest CT with or without contrast media, PET/CT, and/or tissue sampling depending on the probability of malignancy and comorbidities. PET/CT may be used when there is a ≥ 8 mm (≥ 268 mm3) solid component.> 15%2%
4XCategory 3 or 4 nodules with additional features or imaging findings that increase the suspicion of malignancyFor new large nodules that develop on an annual repeat-screening CT, a 1-month low-dose CT may be recommended to address potentially infectious or inflammatory conditions
Other: clinically significant or potentially clinically significant findings (non-lung cancer)SModifier: may add on to category 0–4 codingAs appropriate to the specific findingNA10%

Diagnosis Confirmation

Patients with suspected lung cancer should be referred to a pulmonologist within a multidisciplinary thoracic oncology team to help guide workup.6 Confirmation of the diagnosis should be made by one or more of the following methods, with further testing if suspicion is high and findings are negative: sputum cytology, thoracentesis of pleural fluid, bronchoscopy (often with endobronchial ultrasonography and/or electromagnetic navigation with or without fine-needle aspiration), or mediastinoscopy depending on local availability and expertise.21

STAGING

Staging of lung cancer follows the eighth edition of the American Joint Committee on Cancer's staging manual.22 Staging revisions from the seventh edition were based on analysis of a database of 94,708 cases by the International Association for the Study of Lung Cancer Staging from 1999 to 2010.23 The tumor, node, metastasis (TNM) classification describes the anatomic extent of the disease, is based on clinical and pathologic staging, and guides eventual treatment and prognosis22 (eTable B). Clinical TNM is based on history and physical examination findings, imaging, and staging procedures, and a pathologic TNM based on postsurgical histopathologic classification. The composite of these composes the TNM stage with associated prognostic stage groups I to IV22 (eTable C). TNM staging is recommended for NSCLC and SCLC for prognostic and tumor stratification purposes.22 For NSCLC, brain imaging should be performed in stage IIA patients with consideration for stage IB patients; patients with stages III to IV disease should have magnetic resonance imaging of the brain to assess for metastases even in the absence of clinical disease.7,24 Patients with any stage of SCLC should have brain imaging performed, preferably using magnetic resonance imaging.8 In patients who may undergo curative treatment, positron emission tomography CT should be performed to assess intrathoracic lymph node involvement and guide subsequent sampling.2,10

Label
T (Primary)
T0No primary tumor
 TisCarcinoma in situ (squamous or adenocarcinoma)Tis
T1Tumor ≤ 3 cm
 T1a(mi)Minimally invasive adenocarcinomaT1a (mi)
 T1aSuperficial spreading tumor in central airways*T1a SS
 T1aTumor ≤ 1 cmT1a ≤ 1
 T1bTumor > 1 cm but ≤ 2 cmT1b > 1–2
 T1cTumor > 2 cm but ≤ 3 cmT1c > 2–3
T2Tumor > 3 cm but ≤ 5 cm
or
Tumor involving visceral pleura, main bronchus (not carina), or atelectasis to hilum
T2 Visc Pl
T2 Centr
 T2aTumor > 3 cm but ≤ 4 cmT2a > 3–4
 T2bTumor > 4 cm but ≤ 5 cmT2b > 4–5
T3Tumor > 5 cm but ≤ 7 cm
or
Tumor invading chest wall, pericardium, phrenic nerve
or
Separate tumor nodule(s) in the same lobe
T3 > 5–7
T3 Inv
T3 Satell
T4Tumor > 7 cm
or
Tumor invading mediastinum, diaphragm, heart, great vessels, recurrent laryngeal nerve, carina, trachea, esophagus, spine
or
Tumor nodule(s) in a different ipsilateral lobe
T4 > 7
T4 Inv
T4 Ipsi Nod
N (Regional lymph nodes)
N0No regional node metastasis
N1Metastasis in ipsilateral pulmonary or hilar nodes
N2Metastasis in ipsilateral mediastinal/subcarinal nodes
N3Metastasis in contralateral, mediastinal/hilar, or supraclavicular nodes
M (Distant metastasis)
M0No distant metastasisM1a Pl Dissem
M1aMalignant pleural/pericardial effusion or pleural/pericardial nodules
or
Separate tumor nodule(s) in a contralateral lobe
M1a Contr
Nod
M1bSingle extrathoracic metastasisM1b Single
M1cMultiple extrathoracic metastases (1 or > 1 organ)M1c Multi
TX, NXT or N status not able to be assessedNA
T/MLabelN0N1N2N3
T1T1a ≤ 1IA1IIBIIIAIIIB
T1b > 1–2IA2IIBIIIAIIIB
T1c > 2–3IA3IIBIIIAIIIB
T2T2 Centr, Visc PlIBIIBIIIAIIIB
T2a > 3–4IBIIBIIIAIIIB
T2b > 4–5IIAIIBIIIAIIIB
T3T3 > 5–7IIBIIIAIIIBIIIC
T3 InvIIBIIIAIIIBIIIC
T3 SatellIIBIIIAIIIBIIIC
T4T4 > 7IIIAIIIAIIIBIIIC
T4 InvIIIAIIIAIIIBIIIC
T4 Ipsi NodIIIAIIIAIIIBIIIC
M1M1a Contr NodIVAIVAIVAIVA
M1a Pl DissemIVAIVAIVAIVA
M1b SingleIVAIVAIVAIVA
M1c MultiIVBIVBIVBIVB

Treatment

NON–SMALL CELL LUNG CANCER

The treatment of NSCLC varies based on staging, nonsquamous (usually adenocarcinoma) vs. squamous histology, and genetic and immunotherapy biomarker testing. Treatment options presented here provide an overview; however, specific regimens will vary based on the availability of treatment options and clinical experience of the multidisciplinary treatment team. Patients with advanced disease should be offered early palliative care.7

Patients with stages I to II NSCLC are usually offered a combination of three treatments: surgery, which can include complete resection of the tumor (usually stages I and II), and mediastinal lymph node dissection or lymph node sampling; radiotherapy; and adjuvant platinum-based chemotherapy.25 Select patients who have stage III NSCLC but do not have disease progression after chemotherapy may benefit from immunotherapy.7,26 Video-assisted thoracic surgery has lower mortality and hospital length of stay compared with open thoracotomy.27 Nonsurgical candidates can be offered radiotherapy and platinum-based chemotherapy.28 For patients with stage IV disease, palliative care and immunotherapy with or without platinum-based chemotherapy are recommended.7 In patients with fewer than three brain metastases, stereotactic radiotherapy or surgery with stereotactic radiotherapy is recommended.29 With more than three brain metastases, whole brain radiation is recommended, although it may not improve neurocognitive symptoms or overall survival.28,29 Radiotherapy and bisphosphonates are recommended for bone metastases to reduce pain and risk of skeletal fractures.28,29

All patients who have NSCLC with nonsquamous NSCLC, mixed histology, or small-volume biopsies should be offered genetic and immunotherapy testing (e.g., broad-based, next-generation sequencing).7 Common driver mutations, preferred treatment options, and common adverse effects are listed in eTable D. Genetic testing can predict overall prognosis and responsiveness to targeted therapies; however, U.S. Food and Drug Administration–approved therapies depend on histologic subtype, disease progression, and timing with first-line systemic chemo-therapy.7 Standard first-line therapy for advanced NSCLC is immunotherapy with or without chemotherapy, based on PD-L1 (programmed death-ligand 1) status of expression on tumor cells.7

Genetic mutationNational Comprehensive Cancer Network preferred therapyCommon adverse effects (> 20%)
Anaplastic lymphoma kinaseAlectinib (Alecensa), brigatinib (Alunbrig), or lorlatinib (Lorbrena)Anemia, arthralgia, constipation, cough, diarrhea, edema, fatigue, headache, mood effects, myalgia, nausea, weight gain
BRAF V600EDabrafenib (Tafinlar) plus trametinib (Mekinist)Chills, cough, decreased appetite, diarrhea, dry skin, dyspnea, edema, fatigue, hemorrhage, nausea, pyrexia, rash, vomiting
Epidermal growth factor receptorOsimertinib (Tagrisso)Anemia, cough, diarrhea, dry skin, fatigue, leukopenia, lymphopenia, musculoskeletal pain, nail toxicity, neutropenia, rash, stomatitis, thrombocytopenia
MET ex 14 skippingCapmatinib (Tabrecta) or tepotinib (Tepmetko)Decreased appetite, diarrhea, dyspnea, fatigue, musculoskeletal pain, nausea, peripheral edema, vomiting
NTRK gene fusionLarotrectinib (Vitrakvi) or entrectinibArthralgia, cognitive impairment, constipation, cough, diarrhea, dizziness, dysesthesia, dysgeusia, dyspnea, edema, fatigue, increased AST/ALT, myalgia, nausea, pyrexia, vision disorders, vomiting, weight gain
PD-L1/ PD-1Pembrolizumab (Keytruda)Abdominal pain, constipation, cough, decreased appetite, diarrhea, dyspnea, fatigue, musculoskeletal pain, nausea, pruritus, pyrexia, rash
Atezolizumab (Tecentriq)Cough, decreased appetite, dyspnea, fatigue/asthenia, nausea
Durvalumab (Imfinzi)Cough, dyspnea, fatigue, pneumonitis/radiation pneumonitis, rash, upper respiratory tract infections
RETSelpercatinib (Retevmo) or pralsetinib (Gavreto)Constipation, decreased albumin, decreased calcium, decreased leukocytes, decreased lymphocytes, decreased platelets, decreased sodium, diarrhea, dry mouth, edema, fatigue, hypertension, increased alkaline phosphatase, increased AST/ALT, increased creatinine, increased glucose, increased total cholesterol, musculoskeletal pain, rash
ROS1Entrectinib (Rozlytrek) or crizotinib (Xalkori)Arthralgia, cognitive impairment, constipation, cough, decreased appetite, diarrhea, dizziness, dysesthesia, dysgeusia, dyspnea, edema, fatigue, increased AST/ALT, myalgia, nausea, neuropathy, pyrexia, upper respiratory infection, vision disorders, vomiting, weight gain

PD-L1 expression (listed as a percentage between 0 and 100) of 50% or more can change the recommended immunotherapy regimen7,29,30 (eTable E).

Non–small cell lung cancer first-line systemic therapy

Genetic mutationTypeFirst-line therapyResponse or stable disease*
PD-L1 ≥ 50%
Nonsquamous cellPembrolizumab (Keytruda)Pembrolizumab
Carboplatin (Paraplatin) or cisplatin
plus
Pemetrexed (Alimta)
plus
Pembrolizumab
Pembrolizumab
plus
Pemetrexed
Atezolizumab (Tecentriq)Atezolizumab
plus
Bevacizumab (Avastin)
Cemiplimab (Libtayo)Atezolizumab
Nivolumab (Opdivo)
plus
Ipilimumab (Yervoy)
Cemiplimab
Squamous cellPembrolizumabPembrolizumab
Carboplatin
plus
Paclitaxel or albumin-bound paclitaxel (Abraxane)
plus
Pembrolizumab
Atezolizumab
AtezolizumabNivolumab
plus
Ipilimumab
CemiplimabCemiplimab
PD-L1 ≥ 1% to < 50%Nonsquamous cellCarboplatin or cisplatin
plus
Pemetrexed
plus
Pembrolizumab
Pembrolizumab
Pembrolizumab
plus
Pemetrexed
Atezolizumab
plus
Bevacizumab
Atezolizumab
Nivolumab
plus
Ipilimumab
Squamous cellCarboplatin
plus
Paclitaxel or albumin-bound paclitaxel
plus
Pembrolizumab
Pembrolizumab
Nivolumab
plus
Ipilimumab
Small cell lung cancer first-line systemic therapy

StageFirst-line therapy (4 cycles)Subsequent systemic therapy

Limited stageCisplatin and etoposide (Etopophos)Topotecan (Hycamtin)
Lurbinectedin (Zepzelca)
Enroll in clinical trial
Extensive stageCarboplatin and etoposide and atezolizumab, followed by maintenance atezolizumab
Carboplatin and etoposide and durvalumab (Imfinzi), followed by maintenance durvalumab
Cisplatin and etoposide and durvalumab, followed by maintenance durvalumab
-Topotecan
Lurbinectedin
Enroll in clinical trial

In 2017, five-year survival for localized NSCLC was 59%, with only 5.8% for five-year survival in patients with distant metastases; however, there have been reductions in mortality since 2013 likely due to a decrease in incidence and advancements in therapies, as described previously 31 (Table 522).

TypeIA1IA2IA3IBIIAIIBIIIAIIIBIIICIVAIVB
Clinical928377686053362613100
Pathologic908580736556412412

SMALL CELL LUNG CANCER

For patients with limited-stage SCLC, the standard of care is etoposide (Etopophos) plus cisplatin chemotherapy and concurrent thoracic radiotherapy, with surgical resection offered in select patients.8,32 Patients with significant comorbidities, including chronic kidney disease, may be offered an alternative carboplatin (Paraplatin)–based chemotherapy regimen with similar effectiveness.32 For patients with extensive-stage SCLC, four to six cycles of one of several combination chemotherapy/immunotherapy regimens should be offered with maintenance immunotherapy.8 Consolidative thoracic radiation may be considered for select patients with residual intrathoracic disease who have responded to systemic chemotherapy.8 In patients with limited-stage SCLC, prophylactic cranial irradiation for brain metastases reduces mortality.33 Localized palliative radiation for nonpulmonary sites, including whole brain radiotherapy for brain metastases, should be offered.28 Patients with relapse after initial therapy have overall poor prognosis; however, several second-line systemic therapy options are available. 8,34 Prognosis remains poor, with only 20% to 25% five-year survival for limited-stage SCLC and less than 10% two-year survival for extensive-stage SCLC35 (Table 522).

Screening

As of 2021, the U.S. Preventive Services Task Force (USPSTF) has recommended annual low-dose CT screening in adults 50 to 80 years of age who have a 20 pack-year smoking history and currently smoke or have quit smoking within the past 15 years.36 This replaces the 2013 recommendation of annual CT screenings for patients 55 to 80 years of age with at least a 30 pack-year history.37 The criteria for discontinuing screening are unchanged, including patients who have quit smoking for more than 15 years, have limited life expectancies (less than 10 years), or are not willing to undergo curative lung surgery.36

The updated recommendation is based on two major randomized controlled trials, the National Lung Screening Trial and the Dutch–Belgian lung-cancer screening trial (Nederlands–Leuvens Longkanker Screenings Onderzoek).38,39 Both of these trials found reductions in lung cancer mortality, with a number needed to screen to prevent one lung cancer death of 323 over 6.5 years of follow-up and 130 over 10 years of follow-up, respectively.3840 Through systematic review of these trials and modeling studies from the Cancer Intervention and Surveillance Modeling Network, the USPSTF updated its criteria for screening.36 Earlier screening recommendations are based on studies that suggest this may help address screening disparities for certain populations, including women and Black and Hispanic people.41,42 Compared with the previous USPSTF 2013 guideline, Cancer Intervention and Surveillance Modeling Network data suggest that earlier screenings would be associated with an increase in the reduction of lung cancer mortality, from a 9.8% reduction to 12.1% to 14.4%, and life-years gained, from 4,882 life-years to 6,018 to 7,596 per 100,000.37,43 The American Academy of Family Physicians supports the USPSTF's grade B recommendation of lung cancer screening in adults at increased risk; however, the harms of annual CT screenings are still not well documented, and further research is needed.44 Research gaps include evaluating potential harms associated with increased radiation exposure, identifying better technology to differentiate benign and malignant lung nodules to avoid overdiagnosis, and addressing the cost and availability of increased screening in economically disadvantaged populations.44

Smoking Cessation and Counseling

Smoking cessation reduces morbidity and mortality in patients with lung cancer; however, no randomized controlled trials have compared specific cessation interventions in this population.29,45 Exercise training may improve exercise capacity and quality of life.46 Nursing interventions can help patients with dyspnea, and a range of psychological interventions may improve coping skills and quality of life.47

Although all actively smoking patients should be offered cessation support, lung cancer screening for eligible patients coupled with cessation support may be associated with higher quitting rates.48 This combination is believed to serve as a teachable moment during a time when patients are the most receptive to quitting advice. Cessation assistance in combination with CT screening has been associated with a reduction in lung cancer–specific mortality and the potential to improve the cost-effectiveness ratio of screening.49,50 Patients who quit smoking have been shown to reduce their risk of lung cancer by 39.1% after five years.51 Patients should also be counseled that quitting smoking will reduce their risk of all second cancers by 3.5 times.52

This article updates previous articles on this topic by Latimer and Mott12 and Collins, et al.53

Data Sources: A PubMed search was completed in Clinical Queries using the key terms lung cancer, diagnosis, treatment, and screening. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. The Agency for Healthcare Research and Quality Effective Healthcare Reports, the U.S. Preventive Services Task Force, the Cochrane Database of Systematic Reviews, DynaMed, Essential Evidence Plus, the National Institute for Health and Care Excellence, and the National Comprehensive Cancer Network were also searched. Search dates: April and May 2021, and January 28, 2022.

The authors thank Hamid Mirshahidi, MD, associate professor of medicine, hematology and oncology, and Laren Tan, MD, associate professor of medicine, pulmonary and critical care, Loma Linda University School of Medicine, for thoughtful advice and review of the manuscript.

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