2021 recommendations cut minimum age, lower years of smoking history

Updated recommendations from the U.S. Preventive Services Task Force (USPSTF) will lead to 86% more of the U.S. population meeting eligibility requirements for lung cancer screening (LCS).

The revised recommendations drop the eligibility age for low-dose CT-based screening to age 50 and lowers smoking history from 30 to 20 pack years; however, they still call for stopping annual screening in people who have not smoked for 15 years or have limited life expectancy because of comorbidities that also would restrict the ability to undergo lung surgery.

“This recommendation replaces the 2013 USPSTF recommendation on screening for lung cancer,” explained Alex H. Krist, MD, MPH, of Virginia Commonwealth University in Richmond, and co-authors in JAMA, although the 2021 version still carries a “B” grade (“moderate certainty” of a net benefit). “The USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancer–related deaths.”

The recommendations are based on an evidence report that includes data from the Dutch NELSON trial and updates to the study that started it all, the 2012 National Lung Screening Trial (NLST). The recommendations are also based on a microsimulation modeling study in which LCS was compared with no screening for harms and benefits.

Besides changes to eligibility criteria, other advice from the task force in the recommendations includes:

  • “A pack-year is a way of calculating how much a person has smoked in their lifetime. One pack-year is the equivalent of smoking an average of 20 cigarettes — 1 pack — per day for a year.”
  • After a discussion with a healthcare provider, if an individual opts in to LCS, they should be referred to for LCS with low-dose CT, “ideally to a center with experience and expertise in lung cancer screening.”
  • If the person is a current smoker, smoking cessation interventions should be offered, based on the 2021 USPSTF guidance on behavioral and pharmacotherapy interventions for quitting.

With regard to potential LCS harms, these include “false-positive [FP] results leading to unnecessary tests and invasive procedures, incidental findings, short-term increases in distress due to indeterminate results, overdiagnosis, and radiation exposure,” Krist and co-authors acknowledged. However, they maintained that there was “adequate evidence that the harms of screening for lung cancer with LDCT are moderate in magnitude.”

Several accompanying opinion articles augmented the pros and cons of the updated recommendations.

“This update is timely because many more studies regarding LCS have been published,” noted Christopher G. Slatore, MD, MS, of the VA Portland Health Care System in Oregon, and co-authors in a JAMA Oncology editorial.

Unfortunately, uptake and the infrastructure to provide LCS have not necessarily kept up with the science: “With this update…the population eligible for LCS will increase from an estimated 14.1% to 22.6%. Increasing the number eligible without increasing the means to do so will very likely perpetuate the problem of limited implementation,” they cautioned.

Future research should take on the task of pinpointing “effective strategies to reach and engage the target population and ensure implementation of each core element for high-quality LCS,” Slatore’s group advised.

In a JAMA editorial, Ethan Basch, MD, of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, and co-authors added to concerns about LCS’ reach by pointing out that neither NLST nor NELSON enrolled never-smokers, while minorities were underrepresented in NLST, and NELSON skipped a subgroup analysis of at-risk women.

Minorities and women “develop lung cancer at an earlier age and with lower smoking histories than the predominantly White and male populations enrolled in the original [NLST]… [t]he incidence of lung cancer in the U.S. is highest among Black individuals, and the highest mortality rate of all racial groups occurs in Black male individuals,” explained Yolonda L. Colson, MD, PhD, of Massachusetts General Hospital in Boston, and co-authors in a JAMA Surgery editorial.

Other barriers to undergoing LCS include lack of insurance or inadequate insurance, and geographical hardships, which are especially problematic because the updated recommendations drop the “screening-eligible age to 50 years… [w]hile expanded eligibility criteria are an important step toward equity… complex implementation issues [need] to be addressed,” Basch’s group noted, adding that the American Thoracic Society has taken a first step with strategies to broaden LCS’ purview.

Beyond these hurdles, Basch’s group emphasized that “the future of screening strategies lies in individualized risk assessment including genetic risk. The 2021 USPSTF recommendation statement represents a leap forward in evidence and offers promise to prevent more cancer deaths and address screening disparities. But the greatest work lies ahead to ensure this promise is actualized.”

Colson and co-authors backed the assertion that guidelines are good, but are not good enough, as it takes a village to build a thriving LCS program: “Success requires access and willingness to undergo screening and follow-up within a coordinated multidisciplinary lung cancer screening program composed of primary care physicians, diagnostic radiologists skilled at pulmonary nodule detection and management, and multidisciplinary specialists including thoracic surgeons, interventional radiologists, pulmonologists, radiation specialists, and medical oncologists experienced in lung cancer care,” they wrote.

Other key personnel include patient navigators, smoking cessation counselors, and community partners to overcome the aforementioned barriers, according to Colson’s group. Several studies have shared paths for improving LCS community outreach, particularly in underserved areas.

Then there’s the Medicare-mandated shared decision-making model (SDM) that requires “beneficiaries first undergo a billable counseling visit for shared decision-making using a patient decision aid,” explained Richard M. Hoffman, MD, MPH, of the Holden Comprehensive Cancer Center at the University of Iowa in Iowa City, and co-authors in a JAMA Viewpoint.

They advocated for continued coverage of LCS by CMS, and the mandated SDM model, as the latter “has been shown to increase knowledge of the tradeoffs between benefits and harms of screening decisions, improve perceptions of risk, improve communication with clinicians, reduce decisional conflict, and help clarify personal values.” Hoffman’s group cited a 2020 systematic review of SDM for LCS that “found that they increased patients’ knowledge, reduced decisional conflict, and were highly acceptable to patients and clinicians.

They also underscored that SDM “may also improve health equity around lung cancer,” but only if it can be “tailored for culturally diverse populations and those with low health literacy and numeracy,” such as an LCS program based in an Hispanic urban location near the University of Miami.

In a January 2021 study in JAMA Network Open, Utah-based researchers evaluated LCS eligibility criteria using the USPSTF revisions and stated that they would “likely increase lung cancer screening rates for female, Black, and Hispanic populations. However… lung cancer screening inequities may persist without tailored eligibility criteria.”

For the evidence report, Daniel E. Jonas, MD, MPH, of The Ohio State University in Columbus, and co-authors looked at 223 pieces of research, including seven randomized controlled trials. Besides the two major trials, others reviewed were DANTE and ITALUNG (Italy), DLCST (Denmark), and LUSI (Germany).

“For benefits of screening, the NLST demonstrated a reduction in lung cancer mortality and all-cause mortality with 3 rounds of annual LDCT screening compared with chest radiography, and the NELSON trial demonstrated a reduction in lung cancer mortality with 4 rounds of LDCT screening with increasing intervals,” they wrote in JAMA.

As for the other trials, “Taken together, there is moderate evidence to suggest that, compared with no screening, persons who receive LDCT screening do not have worse general HRQoL [health-related quality of life], anxiety, or distress over 2 years of follow-up,” the authors said.

While LCS was tied to FP results that could lead to a cascade of negative outcomes, “Most studies reviewed in this article (including the NLST) did not use current nodule evaluation protocols such as Lung-RADS… A study included in this review estimated that Lung-RADS would reduce false-positive results compared with NLST criteria and that about 23% of all invasive procedures for false-positive results from the NLST would have been prevented by using Lung-RADS criteria,” Jonas’ group wrote.

Review limitations included the fact that trials were primarily performed at large, academic centers, so application to community-based practice is uncertain. Also, studies with a sample size of >1,000 were excluded, and that research may have offered more data on LCS harms.

For the modeling study, Rafael Meza, PhD, of the University of Michigan in Ann Arbor, and co-authors, created comparative simulation modeling with four lung cancer natural history models, from the Cancer Intervention and Surveillance Modeling Network (CISNET), for people born in 1950 and 1960 who were followed from age 45 through age 90.

The main outcomes were “Estimated lung cancer deaths averted and life-years gained (benefits) compared with no screening. Estimated lifetime number of LDCT screenings, false-positive results, biopsies, overdiagnosed cases, and radiation-related lung cancer deaths (harms),” they wrote in JAMA.

They found that most of the efficient risk factor–based LS strategies started screening at ages 50 or 55 years and stopped at age 80. Meza’s group also reported that the 2013 USPSTF LCS recommendations — ages 55-80 and 30-pack years — “were not among the efficient strategies for the 1960 U.S. birth cohort.”

However, yearly strategies with a minimum criterion of 20 pack-years of smoking were efficient and, compared with the 2013 USPSTF-recommended criteria, were estimated to:

  • Increase screening eligibility: 20.6% to 23.6% vs 14.1% of the population ever eligible.
  • Avert more lung cancer deaths: 469 to 558/100,000 vs 38/100,000.
  • Increase life-years gained: 6,018 to 7,596 per 100 000 vs 4882/100,000.

On the other hand, these strategies were estimated to result in more FP test results at 1.9 to 2.5/person screened versus 1.9/person screened with the USPSTF strategy and lead to more overdiagnosis at 83 to 94/100,000 versus 69/100,000, as well as more radiation-related lung cancer deaths at 29.0 to 42.5/100,000 versus 20.6/100,000.

The authors added that risk model-based approaches — such as those from the 2013 recommendations — were estimated to be linked with more benefits and fewer radiation-related deaths but more overdiagnosed cases, versus risk factor-based strategies, such as the PLCOm2012 model and the BACH model.

Study limitations included the assumption of 100% uptake of, and adherence to, LCS, and lack of data on incidental findings or adverse events related to screening. Slatore and co-authors added LCS uptake/adherence in the real world, which is already dismally low at an estimated 5%/12%, respectively, is even lower in ethnic groups and those with mental health issues, so “these real-world issues will drastically reduce the benefits predicted by the model as well as the expected benefits and harms for different groups.”

As for how the new recommendations stack up against those from other professional groups:

  1. The U.S. Preventive Services Task Force (USPSTF) recommends annual low-dose CT lung cancer screening (LCS) in adults, age 50 to 80 years, who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.

  2. LCS should stop once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery.

Shalmali Pal, Contributing Writer, BreakingMED™

The USPSTF is funded by the Agency for Healthcare Research and Quality (AHRQ). The evidnce report was funded by AHRQ. The modeling study was funded by AHRQ and supported by the National Cancer Institute (NCI).

USPSTF members reported travel reimbursement and an honorarium for participating in USPSTF meetings. One member reported relationships with Healthwise.

Slatore reported support from the VA Portland Health Care System, the American Cancer Society and the U.S. Department of Veterans Affairs. Co-authors reported support from, and/or relationships with, the National Heart, Lung, and Blood Institute, the VA Boston Healthcare System, the American Thoracic Society/RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center/USPSTF, and the VA New England Lung Cancer Screening Council.

Basch reported relationships with AstraZeneca, CareVive Systems, Navigating Cancer, and Sivan Healthcare. Co-authors reported support from, and/or relationships with, NCI, Biodesix, bioAffinity, and Johnson & Johnson.

Colson and co-authors reported no relationships relevant to the contents of this paper to disclose.

Hoffmann reported support from, and/or relationships with, the Holden Comprehensive Cancer Center/NCI, the Shared Decision Making working group of the National Lung Cancer Roundtable (NLCRT), and the VA Office of Rural Health. Co-authors reported support from, and/or relationships with, the Cancer Prevention and Research Institute of Texas, the MD Anderson Cancer Center/NCI/Shared Decision Making Core, NLCRT Shared Decision Making Task Group, NCI, and the AHRQ.

Meza reported no relationships relevant to the contents of this paper to disclose. Co-authors reported support from, and/or relationships with, the European Union, the University of Zurich, Cancer Research UK, the International Association for the Study of Lung Cancer, the Russian Society of Clinical Oncology, Biomedical Research in Endstage and Obstructive Lung Disease Hannover, Erasmus University Medical Center, the Nederlands–Leuvens Longkanker Screenings Onderzoek trial, Siemens Germany, Grail, Merck Sharp & Dohme, Teva, and Ipsos MORI.

Jonas and co-authors reported relationships with AHRQ.

Cat ID: 24

Topic ID: 78,24,730,24,142,143,192,154,195,489,65,925