IN advanced non-small cell lung cancer (NSCLC), progression by new lesions predicted shorter post-progression survival following first-line therapy.
Non-Small Cell Lung Cancer Progression Lesion Types
A secondary analysis of individual participant data from four first line randomized trials in advanced NSCLC evaluated whether the lesion type driving radiographic progression carries prognostic value after progression. Standard RECIST 1.1 criteria define progressive disease but do not distinguish whether progression is driven by growth of existing lesions, appearance of new lesions, or a combination of both.
Among 3,524 intention to treat participants, progressive disease occurred in 2,363 patients who formed the analytic cohort. Progression lesion types were common and distributed as existing lesions alone in 43% of cases, new lesions alone in 31%, and both existing and new lesions in 26%. The distribution of these progression lesion types did not differ meaningfully between patients treated with chemoimmunotherapy and those treated with chemotherapy.
Post-Progression Survival Differs by Lesion Pattern
Post-progression survival differed significantly by progression lesion type. Across treatment arms, patients whose progression involved new lesions had worse outcomes than those whose progression was limited to existing lesions. The poorest post-progression survival was observed when progression involved both existing and new lesions, suggesting a higher risk subgroup within RECIST 1.1 progressive disease.
The analysis also suggested that treatment modality modifies how strongly progression lesion type relates to survival outcomes. The survival impact of progression lesion type appeared greater in patients who received chemotherapy alone than in those treated with chemoimmunotherapy, indicating that the prognostic separation between lesion patterns may be attenuated when immunotherapy is included in first line treatment.
Clinically, these findings support documenting progression lesion patterns, not only the presence of progressive disease, when discussing prognosis after first line therapy in NSCLC. Lesion pattern at progression may help frame expectations around post-progression survival and may be useful for stratification in future analyses of outcomes after progression.
Reference: Gao Y et al. Progressive lesion type is predictive of post-progression survival in first-line chemoimmunotherapy for Non-Small Cell Lung Cancer. Cancer Letters. 2026;639:218191.
