Two new modeling studies suggest that expanding lung cancer screening — to include more smokers or even lifelong nonsmokers — would save thousands more lives in the US every year. But not everyone is convinced the projected benefits would outweigh the harms.

In one study, published in JAMA, researchers at the American Cancer Society (ACS) found that only about 19% of currently eligible Americans underwent lung cancer screening in 2024.

That, the study projected, could translate to roughly 15,000 lung cancer deaths averted over 5 years. But 100% screening uptake would save three times as many lives.

“We estimated that about 62,000 deaths from lung cancer can be prevented [over 5 years] if everybody eligible for screening were to take it up,” said lead author Priti Bandi, PhD, scientific director of risk factors and screening research at the ACS.

She and her colleagues then took their projections a step farther, modeling what could happen if screening were expanded to everyone aged 50-80 years with a smoking history — or about 28 million Americans. Their conclusion: nearly 30,000 additional lung cancer deaths averted over 5 years.

According to Bandi, the findings underscore the importance of boosting the screening rate among Americans who meet current eligibility criteria — and argue for broadening eligibility.

Benefit-Risk Balance

Right now, the US Preventive Services Task Force (USPSTF) recommendsannual low-dose CT screening for adults aged 50-80 years who have a 20 pack-year smoking history and either currently smoke or quit within the past 15 years.

Those criteria are stricter than guidelines from the ACS, which dropped the 15-year rule in 2023. Earlier this year, the National Comprehensive Cancer Network did the same.

However, more screening is not necessarily better, cautioned H. Gilbert Welch, MD, of the Center for Surgery and Public Health at Brigham and Women’s Hospital in Boston.

Clinical trials, including the NLST in the US and NELSON trial in Europe, have proven that low-dose CT screening can reduce lung cancer mortality by about 20%. But those trials focused on people with a heavy smoking history.

Proof of a mortality benefit in lower-risk smokers is lacking, Welch pointed out, while the potential for harm is real.

“All of a sudden expanding to a whole new group of people — it’s just going to lead to a whole new set of procedures, a lot more false alarms, a lot more complications, and more overdiagnosis,” Welch told Medscape Medical News.

“I would say screening is not efficacious in the lowest-risk categories,” he said.

Screening Nonsmokers?

At the same time, interest in expanding lung cancer screening to patient populations other than heavy smokers is growing. That includes even lifelong nonsmokers, who account for between 10% and 20% of lung cancer cases in the US — partly due to other exposures such as secondhand smoke, air pollution, and radon.

The second modeling study, published on November 20 in JAMA Network Open, asked what could happen if lung cancer screening were strictly age-based. A team at Northwestern University in Chicago used data from published studies and 997 patients with lung cancer at their center — 65% of whom did not meet USPSTF screening criteria — to model the expanded scenario.

They calculated that universal screening of Americans aged 40-85 years would detect 94% of all lung cancers and prevent upward of 26,000 deaths annually.

“We moved to universal age-based screening for breast and colon cancer with tremendous success, and we need to move to the same approach for lung cancer,” study author Ankit Bharat, MBBS, professor of thoracic surgery at Northwestern, said in a press release.

However, the study also modeled the risks associated with age-based lung cancer screening: At 70% uptake (comparable to breast and colorectal cancer screening rates), there would be an estimated 16 million false positive results each year, leading to 1.2 million invasive procedures, with complications in 4900.

For context, breast cancer screening was estimated to yield 3.3 million false-positives, 33,000 biopsies, and 500 complications, while colorectal cancer screening yielded 2.1 million false positives, 420,000 polypectomies, and 3200 complications.

Real-World Issues

Welch pointed to the challenges of translating clinical trial findings to the real world, even to higher-risk smokers and former smokers. The NLST researchers “worked hard,” he said, to limit the harms of screening, including overdiagnosis.

“They had growth assessment protocols. They were careful about who they biopsied,” Welch said.

He believes those standards are too high a bar to be expected in routine clinical practice — meaning the benefits of screening may be less and the harms greater. And expanding eligibility to people who are at lower risk vs NLST participants would further shift the risk-benefit equation, according to Welch.

Bandi agreed that the potential for harm is a concern and said that clinicians need to provide patients with information about the risks of screening, in addition to the benefits.

As for why lung cancer screening rates remain low a decade on, Welch and Bandi agreed that heavy smokers often face barriers: They are disproportionately low-income and have less access to healthcare — and may be dealing with daily life issues that push lung cancer screening down on the priority list.

It’s possible, Welch said, that expanding screening eligibility to lower-risk groups would boost the screening adherence rate. But whether screening would be efficacious for those groups is another matter.

Better Data Needed

An editorial published with the ACS study said that as it stands, “lung cancer screening has realized only a fraction of its life-saving potential” — in part because of “overly restrictive” eligibility criteria.

However, worries about the harms of expanding screening — especially to nonsmokers — are valid, stressed Chi-Fu Jeffrey Yang, MD, and colleagues at Massachusetts General Hospital in Boston.

“It is unlikely,” they wrote, “that screening recommendations in the US will be expanded to include populations who have never used tobacco without high-quality randomized trial data.”

And while such trials have long been seen as prohibitively expensive, they noted, new risk-stratification tools may make them feasible by enabling researchers to enroll the highest-risk never-smokers.

The study was funded by the ACS Intramural Research Department. The authors disclosed having no conflicts of interest. Welch reported receiving royalties from books including Should I Be Tested For Cancer?

Ernie Mundell is a freelance medical journalist based in Los Angeles. He has more than 30 years of experience, including editorial positions at Reuters Health and HealthDay.

Statin therapy remains a cornerstone for primary and secondary prevention of major adverse cardiac events (MACEs), but prescribing based on patient phenotype identified through imaging may boost its effectiveness, according to a new study.

“While population-level primary-prevention trials have established the efficacy of statins, it remains unclear whether their benefit depends on the extent of underlying atherosclerotic disease. Our work addresses this evidence gap by assessing whether the treatment effect varies with disease characteristics,” lead investigator Bálint Szilveszter, MD, PhD, a researcher at the Semmelweis University Heart and Vascular Centre in Budapest, Hungary, wrote in an email to Medscape Medical News.

“Clarifying this relationship could enable more personalized and also intensified therapy,” Szilveszter added.

Each 10% increase in statin use was associated with a decreased risk for MACE, for example, among those with obstructive coronary artery disease (CAD), high-risk plaque, a calcium score of ≥ 400, or a segment involvement score > 4. In contrast, there was no link between patients with “any CAD” and lower risk for MACE.

By contrast, “in asymptomatic individuals, routine CT screening is not recommended,” Szilveszter said.

The study was published online on August 5, 2025, in JACC: Cardiovascular Imaging.

More Than 8 Years Follow-Up

Szilveszter and colleagues studied 11,026 consecutive adults with stable chest pain referred for clinically indicated coronary CT angiography to assess CAD between January 1, 2013, and December 31, 2020. The population had a mean age of 59 years and 55% were men.

The MACE composite endpoint included all-cause mortality, acute myocardial infarction, or revascularization for unstable angina.

Statin use was based on prescription fills in Hungary’s National Health Service database. Sixty-six percent of patients were treated with a statin during the study period. Median follow-up was 8.3 years from the date of first statin use to an event or end of the study.

Key Findings

MACE was detected in 4.4% of patients, myocardial infarction alone in 0.9%, and all-cause mortality in 3.1%. Following coronary CT angiography, 14% of total patients stopped using statins, 11% started statin therapy, and 40% continued their statin regimen. The remaining patients were not treated with statins.

With each 10% increase in statin use, the risk for MACE was lowered in the presence of:

• Obstructive CAD (adjusted hazard ratio [aHR], 0.91; 95% CI, 0.85-0.97; P = .006)
• High-risk plaque (aHR, 0.82; 95% CI, 0.68-0.98; P = .026)
• Calcium score of ≥ 400 (aHR, 0.93; 95% CI, 0.87-0.99; P = .024)
• Segment involvement score of ≥ 4 (aHR, 0.89; 95% CI, 0.84-0.95; P < .001)

In contrast, results revealed no significant MACE reduction for “any CAD” (aHR, 0.95; 95% CI: 0.85-1.07; P = .411).

“Our message is not to restrict therapy but to better target and support statin use when anatomic disease is demonstrated,” Szilveszter said.

Whether coronary CT angiography can guide therapy in asymptomatic individuals remains under investigation, he added.

“Given radiation and contrast exposure and costs, we need to define the true cost–benefit and select subgroups in whom use may be justified in the future,” he said.

The Protective Role of Fitness

“Statins are widely prescribed. While it is clear that statin users improved some aspects of their lipid profile, the effects of health outcomes are not so obvious and there are some gaps in the knowledge,” Claudio Gil Araújo, MD, PhD, dean of Research and Education at CLINIMEX — Clínica de Medicina do Exercício in Rio de Janeiro, Brazil, wrote in an email to Medscape Medical News.

There has never been a randomized controlled trial comparing statins, exercise, a combination of both, and controls, according to Abraço.

“And unfortunately, due to other interests, it will never happen. However, observational data suggest that those who are fitter will have modest or no benefit in reducing MACE from taking statins,” he said, citing a 2013 study in The Lancet by Peter Kokkinos, PhD, and colleagues that supports that finding.

“It’s better to be highly fit or at least fit than not being fit and taking a statin,” Kokkinos, lead author and director of the Center for Exercise and Aging and professor at Rutgers-New Brunswick School of Arts and Sciences in New Brunswick, New Jersey, said in an interview.

Kokkinos and colleagues classified 10,043 veterans with dyslipidemia into four strata of fitness. They found significant protective effects against MACE with greater fitness levels, and statins conferred the most benefit among those who were least fit. Median follow-up was 10 years, during which 2318 patients died. The risk for death was 18.5% among those taking statins vs 27.7% among those not taking statins (P < .0001).

Therefore, even though the research shows an interaction between statins and reduced MACE risk, “once you go up to fit or highly fit, I’m not sure it matters,” Kokkinos said.

One potential limitation of the study by Kokkinos and colleagues is that the median age of the veterans was 59 years, so the interaction of statins, exercise, and risk for MACE later in life was not addressed in this study.

“I think it would have been similar; we had some people in their seventies and eighties. But, yes, we do not know this — I don’t have that data,” Kokkinos said.

Not a ‘One-Size-Fits-All’ Therapy

Asked to comment on the findings by Szilveszter and colleagues, Kokkinos said, “If you have some degree of CAD or a higher calcium score, then statins increase your survival rate.”

Kokkinos added that screening patients using coronary CT angiography makes sense. “Of course, the more you know about the severity of disease, the better off you are as a physician. As we get more and more technology, more high-resolution results, we are able to do that better and discriminate the different phenotypes.”

Regarding the controversial public health proposal that statins are so beneficial that they should be added to public water supplies, Kokkinos said, “I’ve heard that, but my research shows that we should try to have everyone exercise instead of putting statins in the drinking water.”

“Statins are not for everyone and should not be used as one-size-fits-all therapy,” he added. Instead, prescription of statins “should be treated more skeptically when it comes to people with no symptoms, no major coronary artery disease, or other risk factors.”

The JACC: Cardiovascular Imagingstudy was independently supported. Szilveszter, Abraço, and Kokkinos reported no relevant financial relationships.

Damian McNamara is a freelance contributor to Medscape Medical News. He worked full-time for Medscape and WebMD from 2018 to 2024. McNamara has a BA in chemistry and an MA in science, health, and environmental reporting/journalism. He works out of a home office in Miami, with a 100-pound chocolate lab known to snore under his desk during work hours.

NEW ORLEANS — An evaluation of myocardial blood flow with stress perfusion cardiac magnetic resonance (CMR) imaging after a negative angiogram changed the presumed diagnosis and treatment in the majority of patients in a randomized double-blind trial.

“Endotyping-informed therapy in the MRI-guided intervention arm led to a reduction in angina burden and an improvement in health-related quality of life,” reported the principal investigator Colin Berry, MBChB, PhD, a professor of cardiology and imaging at the University of Glasgow, Glasgow, Scotland.

The results of the late-breaking CorCMR trial were presented at American Heart Association (AHA) 2025 Scientific Sessions 2025. The findings were simultaneously published in Nature Medicine.

CMR Reclassified Diagnosis in More Than Half of the Patients

For the study, Berry and colleagues enrolled 250 patients presenting with chest pain who did not have obstructed coronary arteries on angiogram at three centers in the UK. All underwent a stress perfusion CMR with myocardial blood flow mapping. The randomization took place after angiography ruled out obstructive disease.

In almost all patients (97.6%), the presumed diagnosis after the negative angiogram was noncardiac chest pain, but CMR led to a reclassification in 53% of them (95% CI, 46.6-59.3).

In the intervention group, the management team was provided with the CMR results to guide care. For the control group, the CMR results were withheld, and subsequent management was performed with usual care.

After CMR, the diagnosis of noncardiac chest pain was upheld in only 47% of them. Fifty-one percent of patients were diagnosed with microvascular angina and 0.4% had vasospastic angina. Cardiomyopathy and myocarditis were incidental findings in two patients in each group.

The change in the initial diagnosis was the primary outcome of this diagnostic study. The secondary outcomes included control of angina, measured by the Seattle Angina Questionnaire (SAQ), and change in quality of life, measured by the five-dimension EuroQoL-5 assessment, at 12 months relative to baseline and between study groups.

At 12 months, the SAQ score improved by a mean of 21.7 points in the intervention group but remained essentially unchanged, down 0.8 points, in the control group. Differences in medical therapy are the likely explanation, according to Berry.

For those in the intervention group relative to the control group, anti-anginal therapies (84% vs 64%; P = .001), aspirin (77% vs 56%; P < .001), and statins (82% vs 62%; P = .001) were all offered more frequently.

The high diagnostic yield of CMR for patients who otherwise would have been discharged with a diagnosis of noncardiac chest pain was consistent across patient groups, Berry said.

“These results apply equally by sex but are perhaps particularly relevant to women because microvascular angina associates more commonly with women presenting with chest pain,” he said.

Data Said to Have Immediate Clinical Relevance

The data from CorCMR have immediate clinical relevance, according to Robert A. Harrington, MD, a cardiologist currently serving as dean of Weill Cornell Medicine and provost for Medical Affairs at Cornell University in New York City. He noted the study employed a “clever study design” to address “a common and important clinical problem.”

“This is a strategy we can use routinely for those with INOCA [ischemia with nonobstructed coronary arteries],” Harrington said.

As the second most common reason for emergency department visits among adults, chest pain is an important target for better and more efficient diagnostic strategies, according to Berry. He cited data suggesting that only half of the patients with chest pain are diagnosed with a cardiac cause, but CorCMR data suggest many of these are likely sent home despite cardiovascular pathology.

Based on the CorCMR data, “coronary angiography should include a functional test either invasively or noninvasively” to capture these patients, he maintained.

Janet Wei, MD, co-director of the Stress Echocardiography Lab at Cedars-Sinai Medical Center in Los Angeles, suggested these data coupled with those from other studies are “changing the paradigm of how we manage patients who present with ischemia.”

The importance of separating patients with a negative angiogram who have cardiac disease from those who do not is that INOCA “is not a benign condition,” Wei said. “It is associated with increased major adverse cardiac events as well as increased healthcare costs related to repeat testing.”

Because there has been no systematic approach to identify causes of noncardiac chest pain, delays in identifying the true cause of INOCA can often be measured in years, Wei reported.

“INOCA is associated with significant impairments in quality of life, whether it is the physical health, mental health, or social health,” she said.

This study has not resolved which protocol is best for establishing INOCA and its cause in patients presenting with chest pain, according to Wei, but it does show that taking an extra step to look for INOCA results in improvements in angina symptoms and quality of life.

The CorCMR trial was an investigator-initiated study without industry funding. Berry reported financial relationships with Abbott Vascular, AskBio, AstraZeneca, Boehringer Ingelheim, CorFlow, Edwards Lifesciences, MAIA Pharmaceuticals, Merck, Novartis, Servier, Xylocor, and Zoll Medical. Harrington reported financial relationships with Atropos, Azuma, Basking Biosciences, Bitterroot Bio, Bristol-Myers Squibb, Bridge Bio, Chiesi, CSL Behring, Edwards Lifesciences, Element Science, Foresight, and Merck. Wei reported a financial relationship with Abbott Vascular.