Abstract 855: A systematic analysis on patients with NSCLC transformation to SCLC.

Abstract Background: Lung cancer is a leading cause of global cancer mortality. Histologic transformation to small-cell lung cancer (SCLC) is a clinically significant yet under-recognized resistance mechanism in non-small cell lung cancer (NSCLC). However, a systematic review encompassing all NSCLC subtypes is lacking. To address this gap, this study integrates published cases to define the clinicopathological features and prognosis of this transformation, thereby guiding clinical management. Method: We systematically reviewed the published literatures from 2015 to the present using PubMed database to summarize the characteristics and prognosis of cases with transformation from NSCLC to SCLC, included keywords like "transition from NSCLC to SCLC" and "NSCLC conversion to SCLC." Results: Analysis of 72 publications identified 82 T-SCLC patients (54.9% male; median age 61 (IQR: 52-68). Available data showed 53.97% were never-smokers (34/63) and 53.66% had stage IV disease (44/65). Initial histology was adenocarcinoma (87.80%). The EGFR mutation rate was 58.54% (48/53) pre-transformation, mostly exon 19 Del (40.24%), rising notably to 84.6% (11/13) post-transformation.For pre-transformation, the first-line treatment was targeted therapy (35.37%), combination therapy (29.3%), and chemotherapy (28.0%), with a median progression-free survival (PFS) of 12.1 months (7.0-24.0); the first-generation EGFR-TKIs (18.3%) were most common. Targeted agents were also the most frequent choice in second-line (50.9%). Post-transformation, the mPFS was 8.0 months (5.0-13.0) and platinum-etoposide was the backbone (70.8%). Subsequent lines saw increased targeted therapy use but a sharp patient decline beyond third-line.Survival data post-SCLC diagnosis was accessible for 53 patients. The median overall survival (mOS) was 47.0 months (95% CI, 30.0-66.0 months) . Longer survival was associated with male, adenocarcinoma, smoker, non-metastatic disease, and early-stage disease at initial diagnosis. The median time from the first diagnosis of NSCLC transforming to SCLC was 29.0 months(20.0-46.0). The mOS after the diagnosis of SCLC was 12.0 months (7.0-19.0). The mOS of never smoker was 36.0 months (20.0-78.0). In comparison to male, female had a shorter mOS after converting to SCLC (11 vs 12 ). Conclusion: This review systematically summarizes the pathological features of the transformation from NSCLC to SCLC, which primarily occurs in adenocarcinomas harboring EGFR mutations. Despite the availability of platinum-based combination chemotherapy with etoposide tailored for SCLC, patient prognosis remains poor, highlighting a critical therapeutic challenge. This underscores the urgent need for prospective clinical trials and investigations into the mechanisms of resistance to improve patient outcomes. Citation Format: Duo Xu, Xiaomei Wu, Bo Zhu. A systematic analysis on patients with NSCLC transformation to SCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 855.