Pathological Complete Response after Immune-Checkpoint Inhibitor Followed by Salvage Surgery for Clinical Stage IV Pulmonary Adenocarcinoma with Continuous Low Neutrophil-to-Lymphocyte Ratio: A Case Report

Abstract

Immune-checkpoint inhibitors (ICIs) play a crucial role in the treatment of advanced nonsmall cell lung cancer (NSCLC); however, most patients fail this treatment after a limited period. We here report a patient with a pathological complete response after treatment with ICI for stage IV pulmonary adenocarcinoma. A 73-year-old man was referred to our hospital because of hoarseness. A roentgenogram and chest CT scan revealed a huge (78-mm diameter) pulmonary tumor in the right upper lobe and a tumor with cavitation in the left lower lobe. A CT scan also showed enlarged upper mediastinal lymph nodes (LNs). Transbronchial lung biopsy of the tumors showed adenocarcinomas in both. The tumor in the right upper lobe was considered to be the primary with mediastinal LNs metastasis and that in the left lower lobe a pulmonary metastasis. The disease was determined to be cT4N2M1a stage IVA. He was treated with first-line chemotherapy comprising cisplatin, pemetrexed, and bevacizumab for 6 cycles. However, 6 months after initial treatment, the primary and metastatic tumors enlarged, and he was treated with second-line anti-programed death 1 therapy for 7 months with a partial response. 18-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed weak accumulation of FDG in the primary tumor only with no accumulation in the left pulmonary metastasis or mediastinal lymph node (LNs), despite the LNs still being enlarged. He was diagnosed as having ycT1bN0M0 stage IA2 disease and underwent right upper lobectomy. Postoperative pathological findings revealed that cancer tissues had been replaced by scar tissue and that CD4-positive T cells, rather than CD8-positive T cells, were predominant. It was also noted that he had a lower neutrophil-to-lymphocyte ratio (NLR) during immunotherapy than before immunotherapy and after surgery. He was diagnosed to be ypT0N0M0 stage 0 (Ef.3). His postoperative course was uneventful, and he remained well for 12 months after surgery with no further treatment. Neoadjuvant chemotherapy with ICIs for advanced NSCLC may be a promising modality, even for clinical stage IV disease, in the near future. Furthermore, NLR during immunotherapy may be a promising biomarker of ICIs treatment.

Keywords: Immune-checkpoint inhibitor; Neutrophil-to-lymphocyte ratio; Nonsmall cell lung cancer; Pathological complete response; Salvage surgery.