Lung Cancer Overdiagnosis Rate 67% in Danish Low-Dose CT Trial

CT Screening vs No Screening

Megan Brooks

August 14, 2018

Roughly two thirds of lung cancers detected with low-dose CT (LDCT) represent overdiagnosis (ie, detection of indolent cancers), report investigators from the Danish Lung Cancer Screening Trial (DLCST).

This rate of overdiagnosis is far higher than that found in two other major studies, the National Lung Screening Trial (NLST), which estimated that 18.5% of screen-detected lung cancers represented cases of overdiagnosis, and the Italian Lung Cancer Screening Trial (ITALUNG), which found no evidence of overdiagnosis.

But the Danish investigators are not certain about the meaning of their own findings.

"We think that the estimate drawn from the DLCST needs to be interpreted with caution, and we do not advise changing current clinical practice," lead DLCST investigator Bruno Heleno, MD, PhD, NOVA Medical School, Universidade Nova da Lisboa, Portugal, told Medscape Medical News. "The estimates of overdiagnosis with LDCT published so far are inconsistent," he noted.

The data from the DLCST were reported in a research letter published online August 13 in JAMA Internal Medicine.

This article adds to the confusion on this important topic. Dr David Yankelevitz

In the DLCST, 4104 current or former smokers (mean age, 57.3 years; 55.3% male) were randomly assigned to undergo five annual LDCT screenings or to undergo no screening. At the end of follow-up, 96 participants were diagnosed with lung cancer in the screened group (64 cancers were detected by screening), as were 53 participants in the control group. There was a 2.10–percentage point increase (95% confidence interval, 1.0 - 3.2 percentage points) in the absolute risk for lung cancer in the LDCT arm.

But the team estimated that 67.2% of screen-detected lung cancers in this trial could represent overdiagnoses.

"The estimate for overdiagnosis is quite high" compared to the estimates in the ITALUNG and NLST, David Yankelevitz, MD, professor of radiology, Icahn School of Medicine at Mount Sinai in New York City, noted in email to Medscape Medical News.

"This article adds to the confusion on this important topic. Based on this study, over half of the screen-detected cancers are overdiagnosed, which would have major implications for a person considering screening," said Yankelevitz, who was not involved in the study.

The Danish investigators say the differences among the results of the three trials are not adequately explained by differences in participants, interventions, or comparators.

Some Important Differences

However, the authors of an accompanying commentary say there are several possible explanations for the differing rates of overdiagnosis in the NLST and the DLCST.

First, in the DLCST, baseline risk for lung cancer was higher for the patients who underwent screening than for the control group. Second, participants in the DLCST underwent five rounds of screening, compared with three in the NLST. Also, in the NLST, results for patients who underwent LDCT were compared with results for patients who underwent chest radiography, whereas in the Danish trial, results for patients who underwent LDCT were compared with results for patients underwent no screening.

"All three of these factors could potentially have contributed to a higher estimate of overdiagnosis in the Danish study," write editorialists Mark Ebell, MD, of the University of Georgia, Athens, and Kenneth Lin, MD, of Georgetown University Medical Center, Washington, DC.

The study authors say practice "should not be changed immediately" on the basis of the DLCST data. "However, it is crucial that the remaining trials report their estimates of overdiagnosis, because this is a critical outcome for screening participants."

"We need the data from the other RCTs [randomized controlled trials] assessing lung cancer screening to clarify the extent of overdiagnosis in lung cancer screening," Heleno told Medscape Medical News.

For clinicians involved in shared decision making about lung cancer screening, Heleno said it may be interesting to consider the DLCST results when applied to a population of 1000 participants who meet the NLST criteria. "At this moment, we have high-quality evidence that screening reduces overall mortality (five deaths per 1000 screened participants, of which three deaths are due to lung cancer)," he said about that scenario.

"The evidence about overdiagnosis is of moderate quality due to inconsistency," Heleno added. "With lung cancer screening, five participants (NLST estimate) may be diagnosed with a cancer that does not progress to symptoms or death. This number may be as high as 16 participants (DLCST estimate) or as low as 0 participants (ITALUNG estimate)."

"Overdiagnosis is an often underappreciated harm of screening," write Ebell and Lin in their commentary. The US Preventive Services Task Force recommends shared decision making with high-risk patients who are eligible for annual LDCT screening. However, a study published this week suggests that physicians often fail to explain the pros and cons of lung cancer screening to those who are eligible.

As reported by Medscape Medical News, qualitative analysis of 14 audio-recorded physician-patient conversations about screening revealed that on average, both primary care physicians and specialists spent less than 60 seconds discussing the harms and benefits of LDCT screening.

Editorialists Ebell and Lin say, "Patients can make informed choices about LDCT only if practitioners fully disclose all the potential harms of screening, including the risk of overdiagnosis. It will be important for researchers to continue to refine estimates of lung cancer overdiagnosis, allowing physicians to provide more accurate information to our patients."

The study received no funding. The study authors, commentary writers, and Dr Yankelevitz have disclosed no relevant financial relationships.

JAMA Intern Med. Published online August 13, 2018. Abstract, Commentary

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