Outcomes of Lung Resection for M1 Non-Small Cell Lung Cancer in Modern Clinical Practice

Y. Suzuki¹, E. Ha², S. Mazur¹, N. Christie¹, O. Awais³, R. Levy⁴, J. Luketich⁵, A. Pennathur⁶, M. Schuchert^1
1University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania ²University of Pittsburgh, Pittsburgh, Pennsylvania ³UPMC Mercy Hospital, Pittsburgh, Pennsylvania ⁴UPMC, Pittsburgh, Pennsylvania ⁵UPMC Presbyterian, Pittsburgh, Pennsylvania ⁶University of Pittsburgh Medical Center - Department of Cardiothoraci, Pittsburgh, Pennsylvania

Purpose: Lung resection is rarely indicated in non-small cell lung cancer (NSCLC) with distant metastasis. However, with recent advances in systemic treatment, including targeted treatment and immunotherapy, there is an emerging interest in expanding the indication. This study aims to evaluate the outcomes after lung resection in patients with M1 NSCLC.

Methods: We performed a single-institution, retrospective study, including patients with synchronous metastases (M1/Stage IV) NSCLC who underwent anatomic lung resection from 2009 to 2022. Clinicopathologic and demographic characteristics were collected. The patients with M1a disease were further divided into M1aL (contralateral lung metastasis) and M1aP (pleural metastasis/malignant effusion). Oligometastatic disease was defined as metastasis to one organ with three or fewer metastases, except for pleural metastasis and malignant effusion (M1aP). Overall survival and progression-free survival from the date of surgery were analyzed using the Kaplan-Meier method. The log-rank test was used to analyze differences between the groups for each prognostic variable.

Results: During the study period, 75 patients underwent anatomic lung resection (56 lobectomies, 13 segmentectomies, and 6 pneumonectomies) as a component of a multimodal treatment strategy for M+ lung cancer. The median age was 63, and 37 patients (49.3%) were female. The cohort was predominantly adenocarcinoma (52 [69.3%]) and consisted of 4 M1aL, 14 M1aP, 36 M1b, and 21 M1c diseases. The most common metastasis site was the brain (35 [46.7%]), followed by pleura/effusion (14 [18.7%]) (Table 1). Fifty-five patients (73.3%) met the predefined criteria of oligometastasis. The median overall survival was 32.7 months, and the median progression-free survival was 9.0 months. There was a significant difference in overall survival between M stages (median, M1aL: 37.3 months, M1aP: 23.3 months, M1b: 56.0 months, M1c: 18.5 months; p=0.049; Figure 1A). Olignometastatic disease tended to have better overall survival than non-oligometastatic disease, but the difference was not statistically significant (median, 39.9 vs 23.1 months; p=0.08). In univariable analysis, pre- (n=43) or postoperative (n=13) local therapy to metastasis, postoperative chemotherapy (n=43), pre- (n=6) or postoperative (n=10) immunotherapy, or metastasis site was not associated with overall survival, while preoperative chemotherapy was associated with significantly better overall survival (median, 36.7 vs 23.1 months; p=0.048) (Figure 1B).

Conclusion: Despite the high disease progression rate, reasonably long overall survival was seen after lung resection for M1 NSCLC, especially in patients with non-pleural single metastatic disease. Pleural metastasis was associated with poor survival similar to multiple metastatic diseases, which warrants careful operative consideration. A period of preoperative systemic therapy should be strongly considered in this population, as it could allow for observation of disease biology and may help patient selection. The data on targeted therapy and immunotherapy were limited in our study, and a large multicenter study would be warranted to clarify the role of surgery in this population.

Identify the source of the funding for this research project: None