Biological predisposition for specific metastatic organs might differ between molecular subgroups of lung cancer. We aimed to assess the association between molecular status and metastatic organs at diagnosis in a nationwide stage IV non-squamous non-small cell lung cancer ((ns)-NSCLC) cohort.

All ns-NSCLC from 2013 that were stage IV at diagnosis were identified from the Netherlands Cancer Registry, which records information on metastatic organs at diagnosis. Tumors were matched to the Dutch Pathology Registry (PALGA) from which data on molecular status established in routine practice was extracted. Four molecular subgroups (EGFR+, KRAS+, ALK+, triple-negative) were identified. For each metastatic organ, proportions of tumors metastasized to this organ were, per molecular subgroup, compared to triple-negative tumors by multivariable logistic regression analyses (adjusted odds ratios (OR) with 95% confidence intervals (CI)), taking clinicopathological variables into account.

160 EGFR+ (exon 19 del, exon 21 L858R), 784 KRAS+, 42 ALK+, and 1008 triple-negative tumors were identified. Most frequent metastatic organs were the bone (34%), pleura (24%), lung (23%), and brain (22%). Compared to triple-negatives, EGFR+ tumors had more often metastases to the bone (31.5 vs 53.8%; OR 2.55 (95% CI 1.80-3.62)) and pleura (24.1 vs 37.5%; OR 2.06 (1.42-2.98)), and less often to the brain (22.0 vs 12.5%; OR 0.53 (0.32-0.88)) and adrenal glands (19.1 vs 7.5%; OR 0.46 (0.28-0.75)). Compared to triple-negatives, KRAS+ and ALK+ tumors had at diagnosis metastasized more often to the lung (20.3 vs 26.7%; OR 1.40 (1.12-1.76)) and the liver (13.1 vs 23.8%; OR 2.07 (1.00-4.32)), respectively.

NSCLC molecular status was associated with metastatic pattern at diagnosis. 54% of stage IV EGFR+ ns-NSCLC patients had bone metastases at diagnosis. These observational results are hypothesis generating, and call for a prospective study where EGFR+ patients are screened for bone metastases, and treated to prevent skeletal related events.