Wait-and-See Treatment Strategy Could be Considered for Lung Adenocarcinoma with Special Pleural Dissemination Lesions, and Low Genomic Instability Correlates with Better Survival

Background This study aimed to evaluate the feasibility of a wait-and-see strategy for non-small cell lung cancer (NSCLC) patients with special pleural dissemination lesions (r-pM1a and s-pM1a). Furthermore, the study characterized genomic alternations about disease progression. Methods For this study, 131 NSCLC patients with a diagnosis of pM1a were retrospectively selected. Survival differences were evaluated among patients treated with three different initial postoperative treatments: chemotherapy, targeted therapy, and wait-and-see strategy. Whole-exome sequencing (WES) was performed on primary and metastatic tumors of 10 patients with dramatic progression and 13 patients with gradual progression. Results The wait-and-see group showed better progression-free survival (PFS) than the chemotherapy group ( p < 0.001) but PFS similar to that of targeted group ( p = 0.984). This pattern persisted in epidermal growth factor receptor (EGFR)-positive patients. For patients with EGFR-negative/unknown status, PFS was longer in the wait-and-see group than in the two treatment groups. Furthermore, better overall survival (OS) was observed for the patients who received chemotherapy or targeted therapy after the wait-and-see strategy than for those who received chemotherapy or targeted therapy immediately. Lymph node status was an independent prognostic factor for PFS and OS. Finally, WES analysis showed that a high genomic instability index (GIS) and chromosome 18q loss were more common in metastatic tumors, and low GIS was significantly associated with better PFS ( p = 0.016). Conclusions The wait-and-see strategy could be considered for special pM1a patients without lymph nodes metastasis, and patients with a low GIS may be suitable for this strategy.