Although cancer screening yields a reduction in cancer deaths, this prevention method isn’t perfect, and screening tests have been linked to both benefits and harms. All of these factors must be considered when establishing guidelines and communicating value to patients. 

In 2011, results of the landmark National Lung Screening Trial (NLST) proved pivotal in bolstering the use of low-dose CT (LDCT) to lower cancer-specific mortality in smokers.

The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.

 

 

The NLST and its aftermath

 

In the 2011 NLST, the number needed to screen to prevent a single death was found to be 320.  

In total, 53,000 current and former smokers were randomized to receive annual lung cancer screening for 3 years with either LDCT or conventional chest x-ray (CXR). During a median follow-up of 6.5 years, lung cancer-specific mortality was significantly lower in the CT group vs the CXR group, or 1.33% vs 1.66%, respectively.

 

False-positive screenings were common. Among the patients in the CT group, 39% had at least one positive screen, as did 16% of patients in the CXR group. Of these positive results, approximately 95% were false-positives. In the group with positive CT screening results, major complications secondary to invasive diagnostic procedures occurred in about 12% of patients in whom cancer was eventually diagnosed, compared with <1% of patients in whom cancer was not diagnosed. Positive results led to 8,800 standard CTs; 2,500 chest x-rays; 1,500 PET scans; 320 percutaneous biopsies; 670 bronchoscopies; and 710 surgeries.

Publication of these results raised many questions, captured in the NEJM Journal Watch commentary. 

 

 

This study demonstrates that CT screening can lower lung cancer-related mortality. However, many questions remain.

Because of the unknowns, the NLST study investigators concluded that “policymakers should wait for cost-effectiveness analyses and other information before endorsing screening.”

 

2024 study results: To screen or not to screen?

 

Follow-up procedures and complications associated with lung cancer screening were assessed in the 2024 real-world study of 9,266 patients.

Rendle KA, Saia CA, Vachani A, et al. Rates of downstream procedures and complications associated with lung cancer screening in routine clinical practice: a retrospective cohort study. Ann Intern Med. 2024;177(1):18–28.

This study demonstrated much higher rates of downstream procedures and complications than those observed in NLST, as previously noted. 

 

 

“The results indicate substantially higher rates of downstream procedures and complications associated with [lung cancer screening] in practice than observed in NLST,” the investigators wrote. “Diagnostic management likely needs to be assessed and improved to ensure that screening benefits outweigh potential harms.” 

 

USPSTF guidelines

 

The USPSTF recommends annual screening for lung cancer with LDCT in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued 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.

Lung Cancer: Screening. Final Recommendation Statement. USPSTF. March 9, 2021.

 

This recommendation is Grade B, meaning there is a high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial. The USPSTF recommends offering or providing this service.

Grade Definitions After July 2012. USPSTF.

 

 

Discussing benefits vs risks

 

Even considering the results of the 2024 real-world study, guidelines for recommended screening should be followed. 

 

The author of a commentary on the 2024 real-world study writes, “Much of the value from lung cancer screening is predicated on relatively low complication rates. This study's real-world experience might complicate discussions with patients regarding potential screening harms. Nevertheless, the high rate of long-term, cancer-free survival among patients with cancer detected by screening supports guideline-recommended screening that includes shared decision-making.”

Dressler DD. Lung cancer screening complications. NEJM Journal Watch. January 18, 2024.

 

According to the American Cancer Society, one of the benefits of screening is to reduce the risk of being diagnosed with an advanced cancer.

Wender RC, Brawley OW, Fedewa SA, et al. A blueprint for cancer screening and early detection: advancing screening's contribution to cancer control. CA Cancer J Clin. 2019;69(1):50–79.

Another is to possibly prevent cancer by detecting precursor lesions. There is also the peace of mind that comes from having a normal test result.

 

Potential harms include the fallout from false-positive and false-negative results, overdiagnosis, and injury or death due to subsequent interventions. 

False-positives can result in additional diagnostic workup and anxiety; overdiagnosis results in unnecessary diagnostic tests and procedures. In addition, physical and emotional harms from screening and tests may affect a small number of patients. 

The National Cancer Institute specifically addresses the risks of overdiagnosis in its 2023 guidance update:

PDQ® Screening and Prevention Editorial Board. PDQ Lung Cancer Screening. Bethesda, MD: National Cancer Institute. Updated June 9, 2023.

 

“A less familiar harm is overdiagnosis, which means the diagnosis of a condition that would not have become clinically significant had it not been detected by screening—that is, had the patient not been diagnosed with the cancer, the patient would have died of other causes. In the case of screening with LDCT, overdiagnosis could lead to unnecessary diagnosis of lung cancer requiring some combination of therapy (eg, lobectomy, chemotherapy, and radiation therapy). Autopsy studies suggest that a significant number of individuals die with lung cancer rather than die of lung cancer. In one study, about one-sixth of all lung cancers found at autopsy had not been clinically recognized before death.”

 

Advising patients

 

For various reasons, recommendations for screening should be approached carefully by the clinician.  

“Over time and multiple rounds of screening, a growing proportion of the target population will have experienced some of the downsides associated with screening,” per the American Cancer Society. “There is limited evidence on methods to reduce the stress associated with false-positive findings, but providing advance information about the possibility of false-positive findings and potential undesirable outcomes has been associated with lower stress levels associated with being recalled for further evaluation.”

If the balance of benefits and harms of LDCT is close, then a shared decision-making conversation should take place with the provider.