Even after a clear scan, smokers face an elevated lung cancer risk

A “clean” lung cancer screening result may offer reassurance, but it doesn’t necessarily mean you’re in the clear. New research, published March 20, 2026, in JAMA Network Open, suggests that for people with a history of smoking, the risk of developing lung cancer can persist and even increase years after a negative scan. The findings highlight the need for ongoing, and potentially more personalized, screening strategies rather than a one-size-fits-all approach.

Lung cancer remains the leading cause of cancer-related death worldwide, and tobacco smoking is responsible for the vast majority of cases. Low-dose computed tomography (LDCT) screening has become a key tool for detecting lung cancer early, particularly in high-risk individuals such as current or former smokers. However, up to 80% of baseline screenings come back negative, leaving clinicians with limited guidance on how best to monitor patients over time.

A team of Chinese researchers, led by Yin Liu, Ph.D., of the Department of Cancer Epidemiology at the affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital in Zhengzhou, China, sought to better understand long-term lung cancer risk after a negative LDCT result. The team analyzed data from more than 30,000 participants enrolled in a population-based screening program in China. All participants were between ages 40 and 74 and had negative findings on their initial LDCT scan. They were then followed for lung cancer incidence through the end of 2023.

Over a median follow-up period of several years, 76 participants developed lung cancer. The researchers found that smoking history played a major role in shaping long-term risk. Compared with never smokers, individuals who smoked had nearly three times the risk of developing lung cancer. The risk was even higher among those with heavier smoking exposure, particularly those with 20 or more pack-years, a standard measure of cumulative smoking exposure.

Interestingly, the increased risk was not immediate. The study found no statistically significant difference in lung cancer risk within the first two years after a negative scan. However, by year three, risk rose significantly and continued to increase over time. This pattern aligns with the biological lag between tobacco-related damage and the development of detectable tumors.

The findings also revealed a nonlinear relationship between smoking exposure and cancer risk, with risk crossing clinically meaningful thresholds at around 20 pack-years. In addition, women appeared to have higher susceptibility to lung cancer than men at similar levels of smoking exposure, though the authors noted that further research is needed to better understand this difference.

Another notable finding: Quitting smoking for less than 15 years did not significantly reduce lung cancer risk among those with heavy prior exposure. This suggests that even former smokers may require long-term monitoring.

Taken together, the findings suggest that a single negative scan does not eliminate future risk, particularly for people with a substantial smoking history. Instead, the results support a more personalized approach to screening and follow-up, potentially including longer intervals after the initial scan but closer long-term monitoring based on individual risk factors.

The study raises important questions about how often individuals should undergo follow-up screening after a negative result.

In an invited commentary accompanying the study, Ashley Elizabeth Prosper, M.D., and Yannan Lin, M.D., M.P.H., Ph.D., of the Department of Radiological Sciences at the David Geffen School of Medicine at the University of California, Los Angeles, note that while low-dose CT screening has demonstrated clear mortality benefits, important questions remain about how to refine eligibility criteria and follow-up strategies over time.

The commentators emphasize that “a negative baseline screen did not preclude an eventual diagnosis of lung cancer,” noting that 76 cases were still identified during follow-up. They also highlight that lung cancer risk “increased significantly beginning at year 3 following a negative baseline screen,” underscoring the complexity of determining optimal screening intervals.

At the same time, Prosper and Lin caution against reducing screening frequency based on these findings alone. “Absent annual screening, there is potential for these de novo lung cancers to grow undetected and unchecked,” they write, pointing to concerns that less frequent screening could allow more aggressive tumors to progress.

Overall, the Prosper and Lin emphasize that lung cancer risk is dynamic and influenced by a range of factors beyond a single screening result. As screening strategies continue to evolve, the authors call for further research, particularly in more diverse populations, to better tailor both eligibility and surveillance while preserving the goal of early detection.