Stage 4 lung LCNEC: major response to chemotherapy plus immunotherapy

What happened, in summary

A 45-year-old man was evaluated after a pulmonary mass was found during a routine medical examination in March 2023. He had smoked about 30 cigarettes per day for 30 years and had lost about 5 kg over 3 months. Chest CT showed a small mass in the left lower lobe with enlarged left hilar and mediastinal lymph nodes. PET-CT also showed a hypermetabolic nodule in the left adrenal gland. Brain MRI was unremarkable. A first mediastinal lymph node biopsy was insufficient, and hyperthyroidism increased anesthesia risk, so thiamazole was used before a thoracoscopic mediastinal lymph node biopsy. Pathology confirmed lung large-cell neuroendocrine carcinoma, positive for TTF-1, cytokeratin, chromogranin A, and synaptophysin, and negative for PD-L1. Targeted marker testing did not detect ALK, ROS1, RET, EGFR, KRAS, BRAF, PIK3CA, HER2, or MET alterations. The cancer was Stage IV, cT1N2M1, with left adrenal metastasis. Because the patient strongly wanted surgery and the primary lesion progressed slowly, the team started neoadjuvant immunochemotherapy: nab-paclitaxel, cisplatin, and serplulimab every 3 weeks for 3 cycles. CT then showed disappearance of the lung nodule, smaller lymph nodes, and shrinkage of the adrenal lesion. He underwent left lower lobectomy and mediastinal lymphadenectomy, with pathologic complete response. Three more cycles of the same regimen were followed by serplulimab maintenance. As of July 2024, after 17 maintenance cycles, PET-CT showed complete metabolic response of the adrenal metastasis and no pulmonary recurrence. Thyroid function fluctuated during treatment, but medication adjustments corrected the thyroid abnormalities, and no other major adverse effects were described.