In a new study published in JAMA Internal Medicine, the high rate of false-positive results identified in the VHA’s LCS demonstration project has caused concern about whether lung cancer screening (LCS) should be implemented in the population. By re-examining the data, researchers found that the high false-positive rate results in amore concerning harm-to-benefit ratio for those eligible persons at lower LC risk, but a much better harm-to benefit ratio for high-risk patients.

The Veterans Health Affairs (VHA) lung cancer screening (LCS) demonstration project identified a much higher false-positive rate following initial low-dose computed tomographic screening than did the National Lung Screening Trial (58.2% vs 26.3%).

Most false-positive results (nodules not confirmed to be lung cancer [LC] after follow-up) resulted in repeated imaging, but 2.0% of people screened also required non-beneficial downstream diagnostic evaluation to determine these nodules were not cancer.

The team sought to put these findings into context by examining how this high false-positive rate influences the harm-to-benefit ratio for higher- vs lower-risk patients. The team found that even given these very high false-positive rates, the overall balance of pros and cons among patients at high LC risk still surpasses those of most established cancer screening programs.

The results should be interpreted with several caveats in mind. The high rate of false-positive results found in the VA demonstration project may represent a substantial overestimate of future rates for 2 reasons: (1) initial screens likely have more false-positive results than recurrent screening, and (2) newer nodule management guidelines are showing great promise in lowering false-positive rates.

Reducing the rate of false-positive findings would improve the harm-to-benefit balance for all quintiles. However, the analysis did not include all potential harms of lung cancer screening (LCS), such as overdiagnosis and psychological effects from false-positive results.

In addition, effectiveness studies are still needed to confirm the extent to which the mortality benefit observed in the National Lung Screening Trial, a 20.0% reduction in lung cancer and a 6.7% reduction in all-cause mortality, applies in actual practice. These real-world findings reinforce the need to risk stratify patients for LCS and provide support for personalized, risk-based harm-benefit estimates for all eligible persons during LCS decision-making.