SynthesisBMC cancer2026
Histological transformation in lung cancer: a single-arm meta-analysis and systematic review.
Synthesis in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
backgroundHistological transformation represents an important mechanism of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant lung cancer; however, its incidence, timing, and post-transformation outcomes remain incompletely characterized.
methodsWe conducted a systematic review and meta-analysis in accordance with PRISMA guidelines and Cochrane recommendations. PubMed, Web of Science and Embase were searched up to November 2025 for studies reporting histological transformation in EGFR-mutant lung cancer following EGFR-TKI resistance. Eligible studies included prospective or retrospective studies and consecutive case series (sample size ≥ 10 or ≥3events). Random-effects models were applied to pool transformation proportions and survival outcomes, and Kaplan-Meier-based methods were used to synthesize time-to-event data.
resultsA total of 35 studies were included. Among patients with non-small cell lung cancer (NSCLC) who developed resistance to EGFR-TKIs, the pooled proportion of transformation to high-grade neuroendocrine carcinoma (HGNEC) was 6% (95% CI, 5%-8%), while transformation to non-neuroendocrine NSCLC occurred in 2% of cases (95% CI, 2%-3%). The pooled median time from EGFR-TKI initiation to histological transformation was 19.39 months (95% CI, 16.18-22.60). After transformation, the pooled median progression-free survival (mPFS) was 3.93 months (95% CI, 3.14-4.72), and the pooled median overall survival was 10.69 months (95% CI, 8.34-13.04).
conclusionsHistological transformation occurs in a clinically relevant proportion of EGFR-TKI-resistant EGFR-mutant lung cancer, and is associated with poor post-transformation outcomes.
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