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Background Non‐small cell lung cancer (NSCLC) patients with ipsilateral pleural dissemination (M1a) are generally contraindicated for surgery. Recently, several studies have demonstrated that these patients might benefit from primary tumor resection (PTR). However, whether PTR is beneficial for driver oncogene‐positive patients treated with targeted therapy, remains unclear. Here, we investigated the effects of PTR on survival in the era of targeted therapy. Methods In total, 105 NSCLC patients with ipsilateral pleural dissemination were identified. The mode of systemic treatment was assessed in this study. Survival analysis was performed with the Kaplan‐Meier method and Cox proportional hazards regression. The overall survival (OS) of patients with or without PTR was compared between propensity score‐matched groups (caliper: 0.02). Results In the entire cohort, PTR was associated with improved OS in both unmatched (median survival time [MST]: 50.0 vs. 29.6 months, P = 0.019) and matched (MST: 50.0 vs. 34.4 months, P = 0.052) cohorts. Multivariate regression models showed that surgery was an independent favorable prognostic factor for OS. A total of 70 patients underwent genetic testing, and targeted therapies, such as EGFR‐TKIs or ALK‐TKIs, were used in the driver oncogene‐positive patients. Subgroup analysis showed that PTR did not improve OS in the targeted therapy group (MST: 57.1 months vs. 50.4 months, P = 0.840). However, surgery significantly prolonged survival in the nontargeted therapy group (MST: 39.8 vs. 14.2 months, P = 0.002). Conclusions The results of this study indicated that PTR could prolong OS in stage IV NSCLC patients with ipsilateral pleural dissemination, especially in patients who are not candidates for targeted therapy. Key points Non‐small cell lung cancer patients with ipsilateral pleural dissemination can benefit from primary tumor resection. Primary tumor resection could prolong overall survival (OS) in non‐small cell lung cancer patients with ipsilateral pleural dissemination who are not candidates for targeted therapy.

BackgroundNon-small-cell lung cancer (NSCLC) patients with ipsilateral pleural dissemination are defined as M1a in the eighth of American Joint Committee on Cancer (AJCC) TNM staging. We aimed to build a nomogram to predict lung cancer specific survival (LCSS) of NSCLC patients with ipsilateral pleural dissemination and to compare the impact of primary tumor resection (PTR) on LCSS among patients with different features.MethodsA total of 3,918 NSCLC patients with ipsilateral pleural dissemination were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We selected and integrated significant prognostic factors based on competing risk regression to build a nomogram. The model was subjected to internal validation within SEER cohort and external validation with the cohort of 97 patients from Peking University People’s Hospital.ResultsAge (P < 0.001), gender (P = 0.037), T stage (P = 0.002), N stage (P < 0.001), metastasis pattern (P = 0.005), chemotherapy (P < 0.001), and PTR (P < 0.001) were independent prognostic factors. The calibration curves presented a good consistency and the Harrell’s C-index of nomogram were 0.682 (95%CI: 0.673–0.691), 0.687 (95%CI: 0.670–0.704) and 0.667 (95%CI: 0.584–0.750) in training, internal, and external validation cohort, respectively. Interaction tests suggested a greater LCSS difference caused by PTR in patients without chemotherapy (P < 0.001).ConclusionsWe developed a nomogram based on competing risk regression to reliably predict prognosis of NSCLC patients with ipsilateral pleural dissemination and validated this nomogram in an external Chinese cohort. This novel nomogram might be a practical tool for clinicians to anticipate the 1-, 3- and 5-year LCSS for NSCLC patients with pleural dissemination. Subgroup analysis indicated that patients without chemotherapy could get more benefit from PTR. In order to assess the role of PTR in the management of M1a patients more accurately, further prospective study would be urgently required.

Non-small cell lung cancer (NSCLC) with ipsilateral pleural dissemination (pM1a) is generally contraindicated for surgery owing to the extremely poor survival. However, some studies have demonstrated that primary tumor resection (PTR) may prolong the survival of these patients. Besides, with the development of systemic therapy, it is still hard to decide the best therapy model for pM1a patients. Thus, we reviewed essential studies about NSCLC with pleural disease and summarized the progress of new techniques in recent years, trying to provide promising new horizons about the management of pM1a patients. Firstly, we suggest performing PTR for highly selected pM1a patients, combined with appropriate systemic therapies and follow-up strategies. Secondly, hyperthermic intrathoracic chemotherapy (HITHOC) can control the symptoms and prolong the survival of NSCLC patients with malignant pleural effusion (MPE). It could also combine with PTR together. Finally, application of genetic testing and circulating tumor DNA (ctDNA) monitoring may furthermore make it possible for personalized management of pM1a patients in the future.

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