Blood Tests Improve Efficiency of Lung Cancer Screening

BARCELONA, Spain — Screening patients for early lung cancer can be made far more effective by using ancillary blood tests, new research suggests.

"Screening by CT saves lives, reducing lung cancer mortality by at least 20%," noted Stephen Lam, MD, chair, provincial lung tumor group at the British Columbia Cancer Agency in Vancouver, Canada.

However, a key issue in lung cancer screening is how to identify those at high risk for lung cancer and who would benefit the most from low-dose CT screening, he added.

Lam spoke here at a press briefing at the IASLC World Conference on Lung Cancer.

Initial use of lung cancer screening has focused on individuals who are considered to be at high risk by using the United States Preventive Services Task Force (USPSTF) criteria based on age and smoking history.

However, this has led to many false positive results and unnecessary investigations, increasing the risk of potential harm for many while benefiting only a few, as previously reported by Medscape Medical News.

To improve the benefit vs harm ratio, researchers are exploring ways of identifying those individuals who are at highest risk and who would benefit most from screening.

Blood Test As a First Step, Followed by Imaging

One approach is to use a blood test as a first step. For example, using the novel, autoantibody EarlyCDT-Lung test. If this comes back positive, the next step is chest X-ray and CT scans.

This approach was investigated in the Early Detection of Cancer of the Lung Scotland (ECLS) study, and results were presented at the meeting by Frank Sullivan, MD, professor of primary care medicine at St. Andrews School of Medicine.

Scotland has one of the highest rates of lung cancer in the world, he noted, and the prognosis is grim: Fewer than 9% of patients diagnosed with lung cancer in the United Kingdom are still alive 5 years after diagnosis, due mostly to late-stage disease at diagnosis.

Sullivan pointed out during an interview with Medscape Medical News that slightly over half of all participants in the ECLS were in the most deprived areas of Scotland where smoking rates are especially high. The mean age at study enrolment was 60.5 years, and the mean number of pack-years smoked was 38.2.

The study was conducted in over 12,000 asymptomatic participants randomly assigned to either the intervention group, who had a blood test followed by chest X-ray and CT scan if the blood test was positive, or to a control group who received standard care.

"The principle outcome was the difference, at 24 months after randomization, between the two groups in the number of patients with stage 3 and 4 lung cancer at diagnosis," Sullivan noted.

In total, 127 lung cancers were diagnosed in the 2-year study period (56 in the intervention group and 71 in the control arm).

Approximately 10% of the intervention group tested positive on the EarlyCDT-Lung test and 3.4% of them were diagnosed with lung cancer.

Fewer participants in the intervention group were diagnosed at a late-stage (stages 3 and 4) compared with the control group (33 vs 52). The rate of late-stage lung cancer diagnosis in the intervention group was 58.9% and in the control group was 73.2%.

At the end of 2 years, there were 36% fewer late cancers in the intervention group compared with controls — "a worthwhile clinical gain," Sullivan commented.

The number of early-stage (stages 1 and 2) lung cancers diagnosed in the intervention group was higher than in the control group (23 vs 19).

The EarlyCDT-Lung test was positive for 12 of the 23 early cancers (sensitivity 52.2%) and for six of the 33 late-stage cancers (sensitivity 18.2%).

There was a nonsignificant trend suggesting fewer deaths in the intervention arm, but the study was not powered to look at mortality differences between the two groups.

One of the main points [of the study] is that the blood test on its own is not going to be enough — it has to be used with imaging. Dr Frank Sullivan

"One of the main points [of the study] is that the blood test on its own is not going to be enough — it has to be used with imaging, because imaging is quite sensitive so you need the two modalities together," he said.

Blood MicroRNA Test, Followed by Low-Dose CT Scan

Another approach to essentially individualizing lung cancer risk is to use a combination of a blood microRNA test plus low-dose CT scans.

This was the approach used in the Plasma microRNA Profiling as First Line Screening Test for Lung Cancer Detection (bioMILD) trial, conducted in Italy in 4119 current or former smokers (10 years or less) between 50 and 75 years of age.

All participants were tested with the microRNA test and low-dose CT at baseline.

A negative CT scan was defined as lesions under 113 mm³. This is a fairly high threshold, but which has been shown to be a good cut-point to distinguish negative from positive lesions, commented lead investigator Ugo Pastorino, MD, from the Istituto Nazionale dei Tumori Foundation in Milan, Italy.

The median age of the cohort was 60 years, the median number of pack-years was 42, and 79% of the group were current smokers.

Importantly, investigators selected a group of participants with the same exposure to smoking at baseline in order to try and individualize their personal risk over a median follow-up of 4.2 years.

Some 58% of the cohort were "double negatives," meaning they had a negative blood test and a negative CT scan.

Some 37% of the group tested positive to either the microRNA blood test or the CT scan (the "single positive" group), while only 5% of the overall cohort ended up in the "double positive" group, meaning both their blood test and their CT scans were positive.

A 3-year screening interval was deemed acceptable for double negative patients, while single positive patients at intermediate risk were rescreened annually. Those who tested positive on both tests were rescreened every 3 to 6 months.

Preliminary analyses showed that the incidence and overall mortality of lung cancer in participants who tested positive on either the microRNA blood test or on low-dose CT or on both were both significantly higher than those in the lowest-risk group.

"Of interest, the incidence of lung cancer and mortality from it was very low at 4 years in the double negative group," Pastorino emphasized.

	Double negative	Single positive	Double positive	P value
Lung cancer	0.6%	3.8%	20.1%	< .001
Lung cancer deaths	0.1%	0.6%	3.8%	< .001
Lung cancer within 3 years	0.1%	2.5%	19.1%	< .001
Stage 1 lung cancer	47%	67%	55%	NS

"The take-home message is that blood microRNA and CT together can improve screening, reducing unnecessary repeats," Pastorino concluded.

In addition, he said, "the knowledge of individual risk by microRNA and low-dose CT improves the efficacy of screening and allows us to personalize prevention measures such as smoking cessation."

Use of Risk Prediction Model

A third approach described at the meeting is the use of a risk prediction model — the so-called PLCOm2012 model — that has been shown in several studies to perform better than the USPSTF criteria in being able to select out individuals most likely to benefit from CT screening.

This was investigated in the International Lung Screen Trial (ILST), conducted in 4985 ever smokers between the ages of 55 to 80 years of age who met the screening criteria in both the PLCOm2012 model and the USPSTF recommendations.

The results were presented at the meeting by Lam from the British Columbia Cancer Agency in Vancouver, Canada, who also spoke at the press briefing.

"What we found is that screening the same participants [with both criteria] showed that the PLCOm2012 risk prediction model had an 18.2% higher sensitivity rate compared with age and pack-years alone," Lam reported.

More importantly, the risk prediction model was able to detect 21.8% more cancers in high-risk participants than the USPSTF criteria based on age and pack-years alone.

In addition, 80% of PLCOm2012-positive lung cancers that were negative on USPSTF criteria were early-stage cancers and potentially curable, Lam added.

"Our analysis of ILST data indicates that classification accuracy of lung cancer screening outcomes supports the PLCOm2012 criteria over the USPSTF criteria," Lam concluded.

The presenters have disclosed no relevant financial relationships.

IASLC 2019 World Conference on Lung Cancer: Abstracts PL02.02, PL02.03, PL02.04. Presented September 9, 2019.

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