Brain metastasis in stage IV lung adenocarcinoma is frequently missed by symptom-based screening

TL;DR

This study finds that neurological symptoms are not reliable indicators of brain metastases in lung cancer patients, suggesting current screening practices may miss many cases.

Contribution

The study provides real-world evidence that symptom-based screening for brain metastases in stage IV lung adenocarcinoma is insufficient and may lead to under-detection.

Findings

Neurological symptoms do not reliably predict brain metastases in stage IV LUAD patients.

Asymptomatic patients who underwent brain imaging had brain metastases detected more frequently than expected.

Symptom-triggered imaging was associated with under-detection of asymptomatic brain metastases.

Abstract

Brain metastases (BM) are a major clinical challenge in metastatic lung adenocarcinoma (LUAD), affecting up to 50% of patients during disease progression. Current guidelines do not mandate brain imaging for all metastatic lung cancer patients at diagnosis unless there are neurological symptoms present. However, real-world data on the predictive value of neurological symptoms for BM detection remain scarce.

This retrospective multicenter study analyzed all consecutive patients diagnosed with stage IV LUAD with molecular assessment in western Sweden from 2016 to 2021 (n = 912). We extracted data from patient charts, imaging referrals, radiology reports and the Swedish National Lung Cancer Registry to determine diagnostic brain imaging (DBI) frequency and modality, presence of neurological symptoms, BM detection rates, size, number, location and overall survival (OS).

Among stage IV LUAD patients, 63% underwent DBI, and BM was detected in 23% of all patients (37% of those receiving DBI). Neurological symptoms prompted DBI in 63% of cases, yet 58% of these symptomatic patients had no BM on imaging. Conversely, 28% of asymptomatic patients who underwent DBI had BM. Patients with BM detected in the absence of neurological symptoms had smaller metastases. Neurological symptoms were associated with worse OS, irrespective of the presence of BM.

Neurological symptoms alone do not reliably predict the presence of brain metastases in stage IV LUAD. In this real-world cohort, symptom-triggered imaging was associated with under-detection of asymptomatic BM. Our findings support the need to re-evaluate current symptom-based screening practices and may inform future efforts toward more standardized brain imaging strategies in metastatic NSCLC.

The online version contains supplementary material available at 10.1007/s12672-025-04210-7.

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