Underutilization of Systemic Therapy in Patients With NSCLC Undergoing Pneumonectomy: A Missed Opportunity for Survival

Abstract

Introduction: Recent trials have reported promising results with the addition of immunotherapy to chemotherapy for patients with locally advanced NSCLC, but in practice, the proportion of patients who receive systemic therapy (ST) has historically been low. Underutilization of ST may be particularly apparent in patients undergoing pneumonectomy, in whom the physiologic insult and surgical complications may preclude adjuvant therapy (ADJ). We, therefore, evaluated the use of ST for patients with NSCLC undergoing pneumonectomy.

Methods: We queried the National Cancer Database, including all patients with NSCLC who underwent pneumonectomy between 2006 and 2018. Logistic regression was used to identify associations with ST and neo-ADJ (NEO). Overall survival was compared after propensity score matching (1:1) patients undergoing ST to those undergoing surgery alone using Kaplan-Meier and Cox regression methods.

Results: A total of 2619 patients were identified. Among these, 12% received NEO, 43% received ADJ, and 45% surgery alone. Age younger than 65 years (adjusted odds ratio [aOR] = 1.53, 95% confidence interval; [CI]: 1.10-2.11), Asian ethnicity (aOR = 2.68, 95% CI: 1.37-5.23), treatment at a high-volume center (aOR = 1.39, 95% CI: 1.06-1.81), and private insurance (aOR = 1.42, 95% CI: 1.05-1.94) were associated with NEO, whereas age younger than 65 years (aOR = 1.95, 95% CI: 1.61-2.38), comorbidity index less than or equal to 1 (aOR = 1.66, 95% CI: 1.29-2.16), and private insurance (aOR = 1.47, 95% CI: 1.20-1.80) were associated with any ST. In the matched cohort, ST was associated with better survival than surgery (adjusted hazard ratio = 0.67, 95% CI: 0.58-0.78).

Conclusions: A high proportion of patients who undergo pneumonectomy do not receive ST. Patient and socioeconomic factors are associated with the receipt of ST. Given its survival benefit, emphasis should be placed on multimodal treatment strategies, perhaps with greater consideration given to neoadjuvant approaches.

Keywords: Locally advanced tumor; Neoadjuvant therapy; Non–small cell lung cancer; Pneumonectomy; Systemic therapy.

Figure 1

Flowchart with patient inclusion criteria for the study. ADJ, adjuvant therapy; NCDB, National Cancer Database; NEO, neoadjuvant therapy; S, surgery only.

Figure 2

(A) Forest plot of multivariable logistic regression models for predictors of NEO. (B) Forest plot of multivariable logistic regression models for predictors of ST. CCI, Charlson-Deyo Comorbidity Index; CI, confidence interval; Dx, diagnosis; HR, hazard ratio; NEO, neoadjuvant therapy; ST, systemic therapy. ∗Statistically significant association.

Figure 3

Survival plot using the Kaplan-Meier method comparing patients with pIB to IIIA NSCLC that underwent pneumonectomy plus ST versus S. CI, confidence interval; HR, hazard ratio; S, surgery only; ST, systemic therapy.

Figure 4

Subgroup analysis assessing the differential risk of death from ST in different strata. CCI, Charlson-Deyo Comorbidity Index; CI, confidence interval; HR, hazard ratio; LVI, lymphovascular invasion; S, surgery only; SCC, squamous cell carcinoma; ST, systemic therapy.

Figure 5

Kaplan-Meier analysis comparing survival among those that received ST and surgery, stratified by pathologic stage. CI, confidence interval; HR, hazard ratio; S, surgery only; ST, systemic therapy.

Supplementary Figure