How to Improve CT Lung Cancer Screening

As the US grapples with low CT lung cancer screening rates, researchers and clinicians around the world are pressing ahead with ways to make the exam more effective – especially in countries with high smoking rates. Two new studies published this week show the progress that’s being made.

In Brazil, researchers in JAMA Network Open found that using broader criteria to determine who should get CT lung screening not only expanded the eligible population, but it also reduced racial disparities in screening’s effectiveness. 

Researchers compared three strategies for determining screening eligibility: two based on 2013 and 2021 USPSTF criteria, and one in which all ever-smokers ages 50-80 were screened, finding: 

  • Screening all ever-smokers generated the largest possible screening population (27.3M people) compared to USPSTF criteria for 2013 (5.1M) and 2021 (8.4M)
  • Number of life-years gained if lung cancer is averted due to screening was highest with all-screening (23 vs. 19 & 21)
  • But the all-screening strategy also had the highest number needed to screen to prevent one lung cancer death (472 vs 177 & 242)
  • The USPSTF 2021 criteria reduced (but did not eliminate) racial disparities; the USPSTF 2013 criteria produced the greatest disparity 

The authors said the results showed that CT lung cancer screening in Brazil could identify 57% of preventable lung cancer deaths if 22% of ever-smokers are screened. Their study should help the country decide which screening strategy to adopt. 

In a second paper in the same journal, researchers from China described how they performed CT lung cancer screening via opportunistic screening, offering low-dose CT scans to patients visiting their doctor for other reasons, such as a routine checkup or a health problem other than a pulmonary issue. Among 5.2k patients, researchers found that people who got opportunistic LDCT screening had:

  • 49% lower risk of lung cancer death by hazard ratio
  • 46% lower risk of all-cause mortality
  • 43% received their lung cancer diagnosis through opportunistic screening

The Takeaway

This week’s studies continue the positive progress toward CT lung cancer screening that’s being made around the world. Both offer different strategies for making screening even more effective, and add to the growing weight of evidence in favor of population-based lung screening.

Lung Screening’s Long-Term Benefits

CT lung cancer screening produced lung cancer-specific survival over 80% in the most recent data from the landmark I-ELCAP study, a remarkable testament to the effectiveness of screening. 

The findings were published this week in Radiology from I-ELCAP, one of the first large-scale CT lung screening trials, and are the latest in a series of studies pointing to lung screening’s benefits. The findings were originally presented at RSNA 2022

The I-ELCAP study is ongoing and has enrolled 89k participants at over 80 sites worldwide from 1992-2022 who have been exposed to tobacco smoke and who received annual low-dose CT (≤ 3mGy) scans. Periodic I-ELCAP follow-up studies have documented the survival rates of those whose cancers were detected with LDCT, and the new numbers offer a 20-year follow-up, finding: 

  • Primary lung cancers were detected on LDCT in 1,257 individuals who had lung cancer-specific survival of 81%, matching the 10-year survival rate of 81%
  • 1,017 patients with clinical stage I lung cancer underwent surgical resection and saw a lung cancer-specific survival rate of 87%
  • The I-ELCAP survival rate is much higher than another landmark screening study, NLST, in which it was 73% for stage I cancer at 10 years
  • Lung cancer-specific survival hit a plateau after 10 years of follow-up, at a cure rate of about 80%

I-ELCAP is unique for a variety of reasons, one of which is that it continues to screen people beyond a baseline scan and 2-3 annual follow-up rounds – perhaps the reason for its higher survival rate relative to NLST. 

  • It also has included people who were exposed to tobacco smoke but who weren’t necessarily smokers – an important distinction in the debate over how broad to expand lung screening criteria.  

The findings come as CT lung cancer screening is generating growing momentum. Studies this year from Germany, Taiwan, and Hungary have demonstrated screening’s value, and several countries are ramping up national population-based screening programs. 

The Takeaway

The 20-year I-ELCAP data show that CT lung cancer screening works if you can get people to do it. But achieving survival rates over 80% also requires work on the part of healthcare providers, in terms of defined protocols for working up findings, data management for screening programs, and patient outreach to ensure adherence to annual screening. Fortunately, I-ELCAP offers a model for how it’s done.

More Support for CT Lung Cancer Screening

Yet another study supporting CT lung cancer screening has been published, adding to a growing body of evidence that population-based CT screening programs will be effective in reducing lung cancer deaths. 

The new study comes from European Radiology, where researchers from Hungary describe findings from HUNCHEST-II, a population-based program that screened 4.2k high-risk people at 18 institutions. 

  • Screening criteria were largely similar to other studies: people between the ages of 50 and 75 who were current or former smokers with at least 25 pack-year histories. Former smokers had quit within the last 15 years. 

Recruitment for HUNCHEST-II took place from September 2019 to January 2022. Participants received a baseline low-dose CT (LDCT) scan, with the study protocol calling for annual follow-up scans (more on this later). Researchers found: 

  • The prevalence of baseline screening exams positive for lung cancer was 4.1%, comparable to the NELSON trial (2.3%) but much lower than the NLST (27%)
  • 1.8% of participants were diagnosed with lung cancer throughout screening rounds
  • 1.5% of participants had their cancer found with the baseline exam
  • Positive predictive value was 58%, at the high end of population-based lung screening programs
  • 79% of screen-detected cancers were early stage, making them well-suited for treatment
  • False-positive rate was 42%, a figure the authors said was “concerning”

Taking a deeper dive into the data produces interesting revelations. Overdiagnosis is a major concern with any screening test; it was a particular problem with NLST but was lower with HUNCHEST-II. 

  • Researchers said they used a volume-based nodule evaluation protocol, which reduced the false-positive rate compared to the nodule diameter-based approach in NLST.

Also, a high attrition rate occurred between the baseline scan and annual screening rounds, with only 12% of individuals with negative baseline LDCT results going on to follow-up screening (although the COVID-19 pandemic may have affected these results). 

The Takeaway

The HUNCHEST-II results add to the growing momentum in favor of national population-based CT lung screening programs. Germany is planning to implement a program in early 2024, and Taiwan is moving in the same direction. The question is, does the US need to step up its game as screening compliance rates remain low?

CT Lung Screening Saves Women

October may be Breast Cancer Awareness Month, but a new study has great news for women when it comes to another life-threatening disease: lung cancer. 

Italian researchers in Lung Cancer found that CT lung cancer screening delivered survival benefits that were particularly dramatic for women – and could address cardiovascular disease as well. 

  • They found that in addition to much higher survival rates, women who got CT lung screening after 12 years of follow-up had lower all-cause mortality than men. 

Of all the cancer screening tests, lung screening is the new kid on the block.

  • Although randomized clinical trials have shown it to deliver lung cancer mortality benefits of 20% and higher, uptake of lung screening has been relatively slow compared to other tests.

In the current study, researchers from the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan analyzed data from 6.5k heavy smokers in the MILD and BioMILD trials who got low-dose CT screening from 2005 to 2016. 

In addition to cancer incidence and mortality, they also used Coreline Soft’s AVIEW software to calculate coronary artery calcium (CAC) scores acquired with the screening exams to see if they predicted lung cancer mortality. Researchers found that after 12 years of follow-up …

  • There was no statistically significant difference in lung cancer incidence between women and men (4.4% vs. 4.7%)
  • But women had lower lung cancer mortality than men (1% vs. 1.9%) as well as lower all-cause mortality (4.1% vs. 7.7%), both statistically significant
  • Women had higher lung cancer survival than men (72% vs. 52%)
  • 15% of participants had CAC scores between 101-400, and all-cause mortality increased with higher scores
  • Women had lower CAC scores, which could play a role in lower all-cause mortality due to less cardiovascular disease

The Takeaway

This is a fascinating study on several levels. First, it shows that lung cancer screening produces a statistically significant decline in all-cause mortality for women compared to men.

Second, it shows that CT lung cancer screening can also serve as a screening test for cardiovascular disease, helping direct those with high CAC scores to treatment such as statin therapy. This type of opportunistic screening could change the cost-benefit dynamic when it comes to analyzing lung screening’s value – especially for women.

CT Detects Early Lung Cancer

A massive CT lung cancer screening program launched in Taiwan has been effective in detecting early lung cancer. Research presented at this week’s World Conference on Lung Cancer (WCLC) in Singapore offers more support for lung screening, which has seen the lowest uptake of the major population-based screening programs. 

Previous randomized clinical trials like the National Lung Screening Trial and the NELSON study have shown that LDCT lung cancer screening can reduce lung cancer mortality by at least 20%. But screening adherence rates remain low, ranging from the upper single digits to as high as 21% in a recent US study. 

Meanwhile, lung cancer remains the leading cause of cancer death worldwide. To reduce this burden, Taiwan in July 2022 launched the Lung Cancer Early Detection Program, which offers biennial screening nationwide to people at high risk of lung cancer.

The Taiwan program differs from screening programs in the US and South Korea by including family history of lung cancer in the eligibility criteria, rather than just focusing on people who smoke. 

Researchers at WCLC 2023 presented the first preliminary results from the program, covering almost 50k individuals screened from July 2022 to June 2023; 29k had a family history of lung cancer and 19k were people who smoked heavily. Researchers found …

  • 4.4k individuals receive a positive screening result for a positive rate of 9.2%
  • 531 people were diagnosed with lung cancer for a detection rate of 1.1%
  • 85% of cancers were diagnosed at an early stage, either stage 0 or stage 1

This last finding is perhaps the most significant, as part of the reason for lung cancer’s high mortality rate is that it’s often discovered at a late stage, when it’s far more difficult to treat. As such, lung cancer’s five-year survival rate is about 25% – far lower than breast cancer at 91%.

The Takeaway

Taiwan is setting an example to other countries for how to conduct a nationwide LDCT lung cancer screening program, even as some critics take aim at population-based screening. Taiwan’s approach is broader and more proactive than that of the US, for example, which has erected screening barriers like shared decision-making.

Although it’s still early days for the Taiwan program, future results will be examined closely to determine screening’s impact on lung cancer mortality – and respond to screening’s critics.

AI-Assisted Radiographers

A new European Radiology study provided what might be the first insights into whether AI can allow radiographers to independently read lung cancer screening exams, while alleviating the resource challenges that have slowed LDCT screening program rollouts.

This is the type of study that makes some radiologists uncomfortable, but its results suggest that rads’ role in lung cancer screening remains very secure.

The researchers had two trained UK-based radiographers read 716 LDCT exams using a computer-assisted detection AI solution (158 w/ significant pulmonary nodules), and compared them with interpretations from radiologists who didn’t have CADe assistance.

The radiographers had significantly lower sensitivity than the radiologists (68% & 73.7%; p < 0.001), leading to 61 false negative exams. However, the two CADe-assisted radiographers did achieve:

  • Good sensitivity with cancers confirmed from baseline scans – 83.3% & 100%
  • Relatively high specificity – 92.1% & 92.7%
  • Low false-positive rates – 7.9% and 7.3%

The CADe AI solution might have both helped and hurt the radiographers’ performance, as CADe missed 20 of the radiographers’ 40 false negative nodules, and four of their seven false negative malignant nodules. 

Even as LDCT CADe tools become far more accurate, they might not be able to fill in radiographers’ incidental findings knowledge gap. The radiographers achieved either “good” or “fair” interobserver agreement rates with radiologists for emphysema and CAC findings, but the variety of other incidental pathologies was “too broad to reasonably expect radiographers to detect and interpret.”

The Takeaway
Although CADe-assisted radiographer studies might concern some radiologists, this seems like an important aspect of AI to understand given the workload demands that come with lung cancer screening programs, and the need to better understand how clinicians and AI can work together. 

Good thing for any concerned radiologists, this study shows that LDCT reporting is too complex and current CADe solutions are too limited for CADe-equipped radiographers to independently read LDCTs… “at least for the foreseeable future.”

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