Christian Schulz, Sarah Swart, Karolina Müller, Denise Bernhardt, Seyer Safi, Amanda Tufman, Niels Reinmuth, Björn Hackanson, Stephan Raab, Florian Fuchs, Kai Hildner, Daniel Heudobler
Multimodal therapy combining systemic and local ablative treatment was associated with improved outcomes compared with systemic therapy alone. A sequential approach, with systemic therapy followed by local ablative treatment, appeared to provide the greatest benefit. Prospective studies are warranted to define the optimal treatment sequence and refine patient selection.
BACKGROUND: Synchronous oligometastatic non-small cell lung cancer (sOMD) is a heterogeneous subgroup of stage IV disease in which multimodal treatment may improve outcomes.
METHODS: Patients with sOMD (≤5 metastases in ≤ 3 organs) diagnosed between July 2015 and May 2020 at five lung cancer centers were retrospectively analyzed. Patients receiving systemic therapy alone or multimodal therapy consisting of systemic therapy plus local treatment (surgery and/or radiotherapy) were included; those treated with local therapy alone were excluded. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method according to treatment modality and treatment sequence. Multivariable Cox regression identified independent prognostic factors.
RESULTS: Among 293 patients (median follow-up, 33.5 months), 74% received multimodal therapy. Median PFS was 9.9 months overall and was significantly longer with multimodal therapy than with systemic therapy alone (10.2 vs. 8.4 months; p = 0.02). Median OS was 26.4 months and numerically favored multimodal therapy (31.1 vs. 20.0 months). Among patients receiving local treatment, surgery was associated with longer PFS and OS than radiotherapy. Complete local treatment of all metastatic lesions was associated with improved OS compared with incomplete treatment (31.6 vs. 16.3 months). In multivariable analysis, omission of local therapy independently predicted worse PFS (HR 1.55) and OS (HR 1.52). Older age and poorer ECOG performance status were also independently associated with inferior outcomes.
CONCLUSIONS: Multimodal therapy combining systemic and local ablative treatment was associated with improved outcomes compared with systemic therapy alone. A sequential approach, with systemic therapy followed by local ablative treatment, appeared to provide the greatest benefit. Prospective studies are warranted to define the optimal treatment sequence and refine patient selection.