Prolonged survival in a 57-year-old female with RB1-wildtype transformed small-cell lung cancer treated with immunochemotherapy and antiangiogenic combined therapy: a case report.

Abstract

Background: The transformed small-cell lung cancer (T-SCLC) has a dismal prognosis, yet there remains a lack of standardized therapeutic guidelines. While this transformation is predominantly driven by concurrent loss of TP53 and RB1, retaining wild-type RB1 is exceptionally rare. We report a rare case of RB1-wildtype T-SCLC with prolonged survival to highlight its diagnostic challenges, potential biological mechanisms, and therapeutic management.

Case description: A 57-year-old non-smoking woman with no significant prior medical history presented with persistent dizziness, headaches, and vomiting. She was diagnosed with EGFR-mutant stage IV lung adenocarcinoma (LADC; EGFR L858R/R776H, PIK3CA E542K, TP53 C176F; RB1 wild-type) following surgical resection of brain metastases. Primary lung biopsy was not feasible due to deep tumor location and marked vascularity. She received sequential dacomitinib [progression-free survival (PFS): 14 months] and osimertinib (PFS: 9 months), monitored by serial imaging and dynamic serum neuron-specific enolase (NSE). Rising NSE prompted re-biopsy of a liver metastasis, confirming small-cell lung cancer (SCLC) transformation at 35 months. She then received serplulimab, anlotinib, etoposide, and carboplatin; significant tumor regression was observed after two cycles, though grade 3-4 hematologic toxicities after the third cycle resolved with supportive care. Liver progression after six cycles prompted second-line nab-paclitaxel plus serplulimab and anlotinib, achieving renewed disease control for over 3 months. Treatment adherence was generally good throughout the clinical course. Overall survival (OS) was 5 years and 4 months, with post-transformation survival of 14 months.

Conclusions: This case highlights a rare RB1-wildtype transformation from EGFR-mutant LADC to SCLC, suggesting a distinct mechanism of lineage plasticity. Dynamic NSE elevation may serve as an early clinical indicator of transformation when tissue re-biopsy is challenging. The durable response achieved with serplulimab-based chemoimmunotherapy combined with anlotinib provides preliminary support for immunotherapy-based strategies in selected patients with T-SCLC.