Final Research Plan
Lung Cancer: Screening
August 16, 2018
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.
The draft Research Plan was available for comment from May 3 until May 30, 2018 at 8:00 p.m., ET.
* The evaluation of evidence on treatment will be limited to studies of surgical resection or stereotactic body radiotherapy for stage I non-small cell lung cancer.
1. a. Does screening for lung cancer with low-dose computed tomography (LDCT) change the incidence of lung cancer and the distribution of lung cancer types and stages (i.e., stage shift)?
b. Does screening for lung cancer with LDCT change all-cause mortality, lung cancer mortality, or quality of life?
c. Does the effectiveness of screening for lung cancer with LDCT differ for subgroups defined by age, sex, race/ethnicity, presence of comorbid conditions, or other lung cancer risk factors?
d. Does the effectiveness of screening for lung cancer with LDCT differ by the number or frequency of LDCT scans (e.g., annual screening for 3 years, the protocol used in the National Lung Screening Trial [NLST], vs. other approaches)?
2. Does the use of risk prediction models for identifying adults at higher risk of lung cancer mortality improve the balance of benefits and harms of screening compared with the use of trial eligibility criteria (e.g., NLST criteria) or the 2013 USPSTF recommendations?
3. a. What is the accuracy of screening for lung cancer with LDCT?
b. Does the accuracy of screening for lung cancer with LDCT differ for subgroups defined by age, sex, race/ethnicity, presence of comorbid conditions, or other lung cancer risk factors?
c. Does the accuracy of screening for lung cancer with LDCT differ for various approaches to nodule classification (i.e., those based on nodule size and characteristics)?
4. a. What are the harms associated with screening for lung cancer with LDCT?
b. Do the harms of screening for lung cancer with LDCT differ with the use of Lung-RADS™, I-ELCAP, or similar approaches (e.g., to reduce false-positive results)?
c. Do the harms of screening for lung cancer with LDCT differ for subgroups defined by age, sex, race/ethnicity, presence of comorbid conditions, or other lung cancer risk factors?
5. a. What are the harms associated with workup or surveillance of nodules?
b. Do the harms of workup or surveillance of nodules differ with the use of Lung-RADS, I-ELCAP, or similar approaches (e.g., to reduce false-positive results)?
c. Do the harms of workup or surveillance of nodules differ for subgroups defined by age, sex, race/ethnicity, presence of comorbid conditions, or other lung cancer risk factors?
6. a. What is the effectiveness of surgical resection or stereotactic body radiotherapy (SBRT) for the treatment of early (stage I) non-small cell lung cancer?
b. Does the effectiveness of surgical resection or SBRT differ for subgroups defined by age, sex, race/ethnicity, or presence of comorbid conditions?
7. a. What are the harms associated with surgical resection or SBRT for the treatment of early (stage I) non-small cell lung cancer?
b. Do the harms of surgical resection or SBRT differ for subgroups defined by age, sex, race/ethnicity, or presence of comorbid conditions?
8. What is the magnitude of change in all-cause and lung cancer mortality that results from a specified change in lung cancer incidence (and change in distribution of lung cancer stages [i.e., stage shift]) after screening?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
1. What are the barriers to implementing lung cancer screening and surveillance in clinical practice in the United States (e.g., barriers to shared decisionmaking, systematically eliciting and documenting a detailed smoking history, systems for tracking nodules and followup, and availability of appropriate LDCT protocols)?
2. a. Are the participants of randomized, controlled trials of lung cancer screening (e.g., NLST) that reported a reduction in all-cause or lung cancer mortality representative of screening-eligible U.S. adults (based on NLST criteria or USPSTF recommendations)?
b. How do the 5-year survival rate and life expectancy of persons eligible for lung cancer screening in the United States (based on NLST criteria or USPSTF recommendations) compare with those of NLST participants?
c. Are the settings and providers in randomized, controlled trials of lung cancer screening (e.g., NLST) that reported a reduction in all-cause or lung cancer mortality representative of U.S. health care settings and providers?
3. Does screening for lung cancer with LDCT have unintended benefits from detecting incidental findings (e.g., coronary artery calcium, chronic obstructive pulmonary disease, or extrapulmonary nodules) leading to interventions that improve health outcomes?
4. What is the effectiveness of smoking cessation interventions among patients receiving LDCT screening?
The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).
| Category | Include | Exclude |
|---|---|---|
| Populations | KQs 1–5, 8: Asymptomatic adults (age ≥18 years)
KQs 6, 7: Adults (age ≥18 years) with early (stage I) non-small cell lung cancer |
KQs 1–5, 8: Children; persons with symptoms or prior diagnosis of lung cancer
KQs 6, 7: Children; persons with nonprimary lung cancer or other than stage I lung cancer |
| Risk prediction | KQ 2: Externally validated models including demographic variables, clinical variables, or biomarkers intended for identifying persons at increased risk who are more likely to benefit from screening | KQ 2: Models including a single variable or biomarker; models not considering smoking and age (known risk factors for lung cancer) |
| Screening | KQs 1, 3, 4, 8: LDCT* | KQs 1, 3, 4, 8: No screening, chest x-ray, sputum cytology, and other screening modalities |
| Workup or surveillance | KQ 5: Computed tomography, biopsy, positron emission tomography, or other tests used after screening | |
| Interventions | KQs 6, 7: Surgical resection or SBRT | KQs 6, 7: Chemotherapy, natural therapies, immunotherapy, or targeted molecular therapy |
| Comparisons | KQs 1, 3, 8: Chest x-ray, no screening, or usual care
KQ 2: 2013 USPSTF recommendations or criteria used by trials showing benefit (e.g., NLST) KQ 3:
KQs 4, 5: Chest x-ray, no screening, usual care, or no comparison group KQs 6, 7: No comparison group is required; although the review will not assess comparative effectiveness of treatments, comparative effectiveness studies are eligible if they provide data for eligible populations, interventions, and outcomes and meet the other eligibility criteria |
KQs 1–3, 8: Studies without a comparison group |
| Outcomes | KQ 1a: Incidence of lung cancer (all stages); distribution of lung cancer types and stages
KQ 1b: All-cause mortality, lung cancer mortality, quality of life, or functional status KQ 2: Estimated number of deaths from lung cancer or all-cause mortality that can be prevented by screening, estimated screening effectiveness (e.g., number needed to screen), or estimated screening harms KQ 3: Sensitivity, specificity, and predictive value KQ 4: Radiation exposure, false-positive results, overdiagnosis†, smoking cessation rates, psychosocial harms, incidental findings leading to additional tests and subsequent harms, and unnecessary treatment (e.g., surgical resection for a benign nodule) KQ 5: Radiation exposure, false-positive results, overdiagnosis†, smoking cessation rates, psychosocial harms, incidental findings leading to additional tests and subsequent harms, unnecessary treatment (e.g., surgical resection for a benign nodule), and harms of workup (e.g., biopsy leading to an adverse event) KQ 6: 5- and 10-year incidence of advanced disease and mortality (survival rates) KQ 7: Harms of treatment, including mortality, infection, bleeding, bronchopleural fistula, and respiratory failure KQ 8: All-cause and lung cancer mortality |
Costs |
| Study designs | All KQs: Controlled trials
KQ 2: Modeling studies are also eligible; clinical prediction tools must include multiple factors KQ 3: Studies evaluating accuracy are also eligible KQs 4, 5, 7: Prospective cohort studies and case-control studies are also eligible KQ 6: Prospective cohort studies are also eligible |
All other study designs‡
KQ 2: Models including a single variable or biomarker; models not considering smoking and age (known risk factors for lung cancer) KQs 1–5, 8: Studies with a sample size less than 1,000 KQs 6, 7: For surgery (established standard treatment), studies with a sample size less than 500; for SBRT, no limit on sample size |
| Study duration | KQs 1–5, 7, 8: Any length of time
KQ 6: At least 5 years of followup |
KQ 6: Less than 5 years of followup |
| Settings | Published in or after 2001 | |
| Countries | Studies conducted in countries categorized as “Very High” on the 2016 Human Development Index (as defined by the United Nations Development Programme) | Studies conducted in countries that are not categorized as “Very High” on the 2016 Human Development Index |
| Language | English | Languages other than English |
| Study quality | Good or fair quality | Poor quality (according to design-specific USPSTF criteria) |
* The review will focus on computed tomography but will also search for and include new trials (published since the search cutoff dates of the last review) of other screening modalities. Older studies (before 2013) of other screening modalities will not be carried forward to this update.
† Defined as detection of disease that would never progress to produce symptoms or death.
‡ Systematic reviews are excluded from the evidence review. However, separate searches will be conducted to identify relevant systematic reviews and the citations of all studies included in those systematic reviews will be reviewed to ensure that database searches have captured all relevant primary studies.
Abbreviations: LDCT=low-dose computed tomography; NLST=National Lung Screening Trial; SBRT=stereotactic body radiotherapy; USPSTF=U.S. Preventives Services Task Force.
The USPSTF has commissioned a comparative decision modeling analysis to supplement the systematic evidence review on screening for lung cancer, as it did for the previous topic update in 2014. The decision models are mathematical simulations that project the health outcomes resulting from alternative interventions for screening, diagnosis, and treatment. In conjunction with the evidence review, the decision models will help the USPSTF examine the benefits and harms of screening for lung cancer at the population level, reflecting current nodule management and followup guidelines, while accounting for the variability in implementation patterns across the United States. The decision models will also evaluate different start and stop ages, screening intervals, and screening strategies based on individual lung cancer risk, particularly for population subgroups at higher risk for lung cancer.
For more information about how the USPSTF uses decision models in formulating its recommendations, please refer to the USPSTF procedure manual, available at https://www.uspreventiveservicestaskforce.org/Page/Name/procedure-manual.
The draft Research Plan was posted for public comment on the USPSTF Web site from May 3, 2018, to May 30, 2018. In response to comments, the USPSTF clarified that the screening test under consideration is LDCT, not computed tomography, and that KQ 1a covers stage shift (where more cancer cases are detected at an earlier stage). The USPSTF revised the eligibility criteria for KQ 3 to clarify the reference standards for accuracy assessment, revised KQs 4 and 5 to make it clear that I-ELCAP protocols are eligible, revised KQs 6 and 7 to include SBRT as an eligible treatment, and added subgroup questions to KQs 6 and 7. The USPSTF also added a contextual question about smoking cessation interventions among patients receiving LDCT screening. Lastly, the USPSTF added unnecessary treatment (e.g., surgical resection for a benign nodule), bronchopleural fistula, and respiratory failure to the list of eligible harms.