Subsequent risk of lung cancer in patients with positive low-dose CT screens and initial negative lung biopsy

Lung cancer screening with low-dose CT (LDCT) has been shown to reduce lung cancer mortality. There is a paucity of literature, however, describing the relationship between negative lung biopsy in individuals following a positive screen and ultimate lung cancer incidence. To assess this question, we analyzed data from the National Lung Screening Trial (NLST).

LDCT arm NLST participants receiving a negative biopsy after a positive screen were included in the negative biopsy cohort (NBC). Lung cancer incidence was calculated within this group overall, and by biopsy type (resection vs. non-resection). In individuals ultimately receiving a lung cancer diagnosis, the biopsy site (lobe) was compared to the cancer diagnosis site. A control cohort without lung biopsy was also compared to the NBC for lung cancer incidence.

Of 10,160 LDCT arm participants with positive screens, 410 were included in the NBC, 152 with resection biopsy and 258 with non-resection biopsy. Within the NBC, lung cancer incidence rates were elevated in the non-resection versus resection biopsy group (RR = 3.5; 95% CI:1.8-6.6). The majority of biopsy sites in the non-resection group were concordant with the sites of eventual cancer diagnosis, 62.7% (p < 0.001). Individuals in the NBC had greater lung cancer incidence than controls (RR = 1.6, 95% CI:1.2-2.2) but this relationship was driven by the non-resection biopsy group (RR = 2.2, 95% CI:1.5-3.3).

Clinicians should maintain a high index of suspicion for lung cancer in individuals with positive LDCT screens and negative non-resection biopsies and counsel patients accordingly.