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Given high mortality risks, non-small cell lung cancer (NSCLC) requires timely treatment and persistent management to improve patient outcomes. Surgery is a standard treatment modality for stage I, II, and some IIIA NSCLC. Lobectomy is the gold standard for early-stage lung cancer, as it spares more respiratory function and offers a lower mortality rate compared to pneumonectomy. Nevertheless, despite the potential for considerable morbidity and mortality, pneumonectomy may be needed for some people with surgically resectable, early-stage, centrally located tumors when lobectomy or sleeve lobectomy can鈥檛 achieve negative resection margins.^1-4

Even with complete resection, however, more than 50% of patients with early-stage NSCLC will experience disease recurrence. Studies have shown that adding adjuvant or neoadjuvant chemotherapy to surgical resection in early-stage NSCLC鈥攍ong considered the standard of care for these patients鈥攊ncreases 5-year overall survival (OS) by 4% to 5%.⁵

Shifting treatment patterns

In recent years, however, immunotherapy has significantly changed the integration of systemic therapy in NSCLC. Initially studied and approved for unresectable locally advanced or metastatic NSCLC, immunotherapy is now used earlier in the disease state including in patients with early-stage NSCLC. Since 2021, the U.S. Food and Drug Administration has approved 3 immune checkpoint inhibitors for adjuvant or neoadjuvant therapy alongside platinum-doublet chemotherapy for early-stage NSCLC.

鈥淧atients who undergo a pneumonectomy have a higher stage of disease and should be considered for systemic therapy either before or after the procedure,鈥� says David R. Jones, MD, Professor and Chief of Thoracic Surgery at Memorial Sloan Kettering Cancer Center in New York. 

But despite the expanding range of options for systemic therapies in early-stage NSCLC, utilization of these treatments remains low. In a recently published study, Rodriguez-Quintero and colleagues suggest that the underutilization of neoadjuvant and adjuvant therapy in early-stage NSCLC may be particularly evident in those undergoing pneumonectomy, particularly in subsets of patients in which surgery may not be feasible or associated with high perioperative and subsequent risk.⁶ 

Defining the study cohort

To shed further light on this subject, Rodriguez-Quintero and colleagues evaluated the use of neoadjuvant and adjuvant therapy for patients with NSCLC undergoing pneumonectomy between 2006 and 2018, as identified in the National Cancer Database.⁶ A total of 2619 patients with IB to IIIA NSCLC underwent pneumonectomy with R0 resection for cure or complete remission. Among these patients, 45% had surgery alone (n=1189), while 12% received neoadjuvant therapy (n=314) and 43% received adjuvant therapy (n=1116).

Then, the authors identified factors associated with receipt of adjuvant and neoadjuvant therapy. In the analysis, the investigators also compared OS among patients who received systemic therapy to those receiving surgery alone after propensity score matching (1:1), based on age, sex, race, comorbidity index, year of diagnosis, type of facility, histologic type, grade, clinical T stage, and clinical N stage.

Results of the investigation

After analyzing the data, Rodriguez-Quintero and colleagues identified the following factors associated with receiving neoadjuvant therapy:

• Age younger than 65 years (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.10 to 2.11)

• Asian ethnicity (aOR 2.68, 95% CI 1.37 to 5.23)
• Treatment at a high-volume center (aOR 1.39, 95% CI 1.06 to 1.81)
• Having private insurance (aOR 1.42, 95% CI 1.05 to 1.94).

Factors associated with any type of systemic therapy (adjuvant or neoadjuvant) included:

• Age younger than 65 years (aOR 1.95, 95% CI 1.61 to 2.38)
• Comorbidity index 鈮�1 (aOR 1.66, 95% CI 1.29 to 2.16)
• Having private insurance (aOR 1.47, 95% CI 1.20 to 1.80).

In the matched cohort, receipt of systemic therapy (adjuvant or neoadjuvant) was associated with better survival than surgery (adjusted hazard ratio 0.67, 95% CI 0.58 to 0.78).

A new-and-improved standard of care?

Rodriguez-Quintero and colleagues suggest that their findings support neoadjuvant therapy as the standard of care for patients with surgically resectable, locally advanced NSCLC who may require pneumonectomy. They note that the favorable response rates seen in recent trials suggest that the need for pneumonectomy may be diminished after neoadjuvant therapy with combinations of immunotherapy and chemotherapy.

鈥淔or patients undergoing complex and more-involved surgeries like pneumonectomy, thinking about how to deliver systemic therapy to drive down the rate of distant metastases becomes critical to achieving cure,鈥� says Eric Brooks, MD, MHS, an assistant professor in the Department of Radiation Oncology at the University of Florida, in Gainesville. 鈥淎s we move toward an era of more-refined personalized medicine, the notion of the neoadjuvant approach in particular, especially for pneumonectomy-eligible patients, is attractive.鈥�

A limitation of this retrospective study is that it may not have fully accounted for selection bias in who received systemic therapy.

Published: October 12, 2023