NLST: Lung cancer growth rates differ by sex

2016 12 30 17 22 48 885 Gender Symbols 400

Lung cancers in men and women grow at sufficiently different rates that radiologists should consider managing them differently depending on the patient's sex, according to a presentation at the RSNA 2016 meeting in Chicago.

In a study that analyzed 200 lung cancer cases from the National Lung Screening Trial (NLST), men had significantly more fast-growing lung cancers than women. Men also had more solid nodules that turned out be malignant, whereas women had more part-solid nodules and slower-growing cancers, concluded researchers from the Mayo Clinic in Rochester, MN.

"Men had a significantly faster volume doubling times than women; in fact, the difference between the sexes was 572 days," said Dr. Phillip Boiselle.

Current thinking in lung cancer screening with low-dose CT reveals a renewed focus on the connection between clinical characteristics and nodule features to lung cancer risk, as well as to potential overdiagnosis, said Boiselle, who is a radiologist at Beth Israel Deaconess Medical Center and a professor of radiology at Harvard Medical School.

"Experience in early trials ... suggested the possibility that women may be at higher risk for overdiagnosis at lung cancer screening compared to men," he said. "However, the influence of patient sex on screening for lung cancers has yet to be fully elucidated in large, randomized trials."

Measured by sex, nodule type

For their study, Boiselle and colleagues measured tumor volume doubling times among CT-detected screened lung cancers that were also stratified by sex and nodule consistency in the NLST, which recruited more than 50,000 individuals at high risk for lung cancer and examined them annually for three years with low-dose CT or chest radiography.

Dr. Phillip Boiselle from Beth Israel Deaconess Medical Center.Dr. Phillip Boiselle from Beth Israel Deaconess Medical Center.

The investigators included a random sample of 89 men and 84 women who were diagnosed after the second (T1) or third (T2) screening rounds, yielding 290 lung cancers, 270 of which had a definitive finding. NLST data forms were used to identify the cancer by lobe on the latest screening CT obtained prior to diagnosis. The finding was then matched with the corresponding nodule on one or more previous scans, Boiselle said.

Two readers used segmentation analysis and tracking tools on a 3D workstation to identify nodule consistencies and volumes. Volume doubling time (VDT) was calculated for each lung cancer and categorized by growth rate in days, as very fast (101-400 days), intermediate (401-800 days), or slow (> 801 days). Nodule volumes were calculated at the first time they were retrospectively visible and again at the last time they were visible at screening before diagnosis.

"And we consider very slow-growing nodules as [having] a potential for overdiagnosis," Boiselle said.

Solid for men, part solid for women

Among men, the results showed intermediate to fast-growing solid nodules in 51 (57.3%) of 89 lung cancers, with a mean volume doubling time of 420 ± 515 days. Among women, there were intermediate to slow-growing part-solid nodules in 45 (53.6%) of 84 lung cancers, with a mean volume doubling time of 1,371 ± 2,590 days.

The men had a significantly faster VDT than women, with a difference of 572 days, Boiselle said. "That is comparable to early work from the Mayo Clinic CT trials showing nearly a 500-day difference between the sexes, but is higher than a previous study from Japan that showed a difference of about 170 days between the two sexes," he said.

Nodule growth rates by sex and nodule consistency
Nodule consistency No. of patients/cancers Average VDT in days ± standard deviation
All cancers
Men 89 536 ± 600
Women 84 1,108 ± 2,054
Part solid
Men 30 646 ± 677
Women 45 1,371 ± 2,590
Men 51 420 ± 515
Women 33 717 ± 1,148
Men 8 862 ± 687
Women 6 1,280 ± 995

Broken down by nodule consistency, growth rate differences were significant between the sexes only for part-solid nodules. Boiselle said.

"If you were to ask what was the most common presentation among men for the NLST, I would say it was the fast to intermediate-growing solid nodules," he said. "Typical for a woman, I would say, was an intermediate to slow-growing part-solid nodule."

Lung cancer mortality was significantly higher for men than women for both solid and part-solid nodules, he said. Not surprisingly, lung cancer mortality was higher for nodules that were growing fast or very fast, compared with those in the intermediate and slow-growing categories.

Fast-growing nodules more common in men

Importantly, men were overrepresented in the fast (56% of all men) and very fast-growing (7% of all men) categories, he added. Women were overrepresented compared to men in the intermediate nodule growth category.

"What we did find very interesting is that there was no real sex difference in those slowest growing nodules -- more than 800 days -- so our overdiagnosis rates of 20% for men and a little higher for women do not show a statistically significant difference," Boiselle said.

Study limitations included a small number of part-solid nodules, which limited their evaluation. Scans acquired a year apart led to a bias for slow-growing cancers, and the researchers were limited to the acquisition technique for the NLST. Finally, work to correlate findings with histology is ongoing.

"Screen-detected lung cancers differed by sex in the NLST, most commonly represented as fast or intermediate-growing solid nodules among men and intermediate to slow- growing part-solid nodules in women, and these differences suggest a potential need to consider sex when looking at management algorithms for screen-detected nodules," Boiselle said.

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