Imaging predictors of pleural response in stage IV non-small cell lung cancer

The relationship between imaging and pathologic findings after systemic therapy in stage IV non-small cell lung cancer with pleural involvement remains unclear. Morphologic and metabolic imaging changes may predict pleural clearance and inform further treatment decisions.

We reviewed 24 patients with stage IV non-small cell lung cancer and initial pleural involvement who underwent subsequent pulmonary resection between 2016 and 2025. Baseline and preoperative computed tomography and positron emission tomography-computed tomography scans were assessed for primary, nodal, metastatic, and pleural disease. Residual pleural disease (RPD) was defined by pathologically or cytologically confirmed tumor; undetectable pleural disease (UPD) was defined by absence of gross disease or negative tissue/cytology when available. Major pathologic response (≤10% viable tumor) was assessed in the primary tumor.

Seventeen patients (70.8%) had UPD and 7 (29.2%) had RPD. Patients with UPD had greater rates of major pathologic response in the primary tumor (52.9% vs 0%), complete radiologic response of the primary tumor (64.7% vs 0%, P = .014), complete nodal radiologic response (94.1% vs 5.9%, P = .001), and complete metabolic response in both primary (88.2% vs 20.0%, P = .009) and nodal sites (88.2% vs 11.8%, P = .021). Radiologic improvement in pleural disease did not differ between patients with UPD or RPD (52.9% vs 42.9%, P = .652); however, complete metabolic response was more frequent in patients with UPD (64.7% vs 16.7%, P = .069).

Complete radiologic or metabolic response of the primary and nodal sites strongly correlates with UPD at surgery. Residual pleural disease on imaging should not preclude consideration for surgical consolidation. These findings underscore the potential utility of refined, evidence-based imaging criteria to guide multidisciplinary decision-making.