Case Report: Successful conversion surgery following chemo-antiangiogenic therapy in a lung adenocarcinoma patient with active rheumatoid arthritis and rare EGFR mutation after immunotherapy-triggered flare.

BACKGROUND: First-line treatment strategy for advanced non-small cell lung cancer (NSCLC) patients with concurrent driver mutations, high PD-L1 expression, and active autoimmune disease poses a significant challenge with limited guidance.

CASE PRESENTATION: A 41-year-old male with newly diagnosed active rheumatoid arthritis (RA) was found to have right lower lobe adenocarcinoma with ipsilateral interlobar pleural nodules (cT4N0M1a, stage IVA). Molecular profiling revealed a non-classical EGFR exon 18 mutation (E709_T710>del) with TP53 co-mutation and high PD-L1 expression (TPS 55%). Initial therapy with 'pemetrexed + carboplatin + tislelizumab' was administered. However, after only one cycle, the patient experienced a significant flare of RA symptoms and worsened serological markers, necessitating permanent discontinuation of immunotherapy. The RA flare was managed with methylprednisolone 1 mg/kg/day followed by a slow prednisone taper and sulfasalazine. Treatment was switched to 'pemetrexed + carboplatin + bevacizumab'. After six cycles, restaging by contrast-enhanced CT showed partial response (PR) of the primary lesion and pleural metastases. Preoperative PET-CT demonstrated complete metabolic response of pleural nodules. Following multidisciplinary team (MDT) assessment and adherence to a strict 6-week preoperative bevacizumab washout period (based on pharmacokinetic reasoning and NCCN guidelines, though prospective data are lacking), the patient underwent conversion from thoracoscopic to open right lower lobectomy with systematic lymph node dissection due to severe fibrosis and frozen hilar lymph nodes. Postoperative pathology confirmed downstaging to ypT2N1 (1 of 12 positive lymph nodes), with a tumor regression grade (TRG) of 1 according to IASLC 2020 criteria (residual tumor cells <10%, significant regression). Postoperative maintenance therapy with 'bevacizumab + pemetrexed' was continued for 12 cycles, and the patient remains disease-free with a progression-free survival (PFS) of 20 months at last follow-up (on a regular imaging surveillance schedule).

CONCLUSION: For advanced NSCLC patients with active autoimmune disease, immune checkpoint inhibitor therapy requires extreme caution even in the presence of high PD-L1 expression. Chemotherapy combined with antiangiogenic therapy can be an effective and safe induction strategy in this complex population. It may create a potential opportunity for conversion surgery in well-responding patients, enabling long-term disease control. This case underscores the critical importance of highly individualized, multidisciplinary treatment decision-making.