Brendan Heiden, MD, MPHS

For early-stage non-small cell lung cancer (eNSCLC) surgical resection with possible adjuvant chemotherapy for tumors with certain high-risk features remains the preferred treatment, according to Brendan Heiden, MD, MPHS. “It is commonly cited that such treatments confer a meager 5% 5-year survival benefit compared with observation alone,” Dr. Heiden wrote. “We sought to reassess the benefit of adjuvant chemotherapy using modern, real-world datasets.”

Dr. Heiden and colleagues presented their research at the 2023 American Society for Clinical Oncology annual meeting recently held in Chicago and online.

Patients With eNSCLC and At Least One High-Risk Feature Selected

The study team conducted a retrospective cohort study using data from the National Cancer Database. They selected patients with eNSCLC (tumor size, 3-5cm, node-negative) eligible for adjuvant chemotherapy based on NCCN guidelines, which included the presence of at least one high-risk feature, defined as

  • tumor size 4cm or greater,
  • non-anatomic wedge resection,
  • poor differentiation,
  • inadequate lymph node evaluation,
  • vascular invasion, and
  • visceral pleural involvement.

To match patients with similar tumor, demographic, and treatment-related factors to compare outcomes between observation groups versus chemotherapy, researchers assessed average treatment effect on the treated (ATT) weighting. Overall survival was the primary outcome.

A total of 10,812 patients were included in the investigation. Poor differentiation (87.4%) was the most frequent high-risk feature, according to Dr. Heiden, followed by inadequate nodal sample (58.3%), tumor size of 4cm or greater (30.3%), visceral-pleural invasion (23.5%), vascular invasion (16.11%), and non-anatomical wedge resection (7.2%).

Only 13.2% of patients received adjuvant chemotherapy, despite the presence of high-risk features.

More Robust Treatment Options for Early-Stage Disease May Improve Outcomes

In the ATT weighted analysis, 50.3% of patients received observation and 49.7% of patients received adjuvant chemotherapy.

The 5-year overall survival was 62.0% (95% CI, 60.2-63.7%) in the observation group versus 70.0% (95% CI, 67.1-72.7) in the chemotherapy group (absolute 5-year survival difference, 8.0%).

In an independent cohort from the US Veterans Health Administration, a total of 11.3% of patients received adjuvant chemotherapy. Similarly, the 5-year overall survival was 56.2% (95% CI, 48.3-63.4) in the observation group versus 64.0% (95% CI, 51.4-74.2) in the chemotherapy group (absolute 5-year survival difference 7.8%).

“These data suggest a notably larger benefit of adjuvant chemotherapy in eligible patients with high-risk clinical pathologic features compared [with] commonly cited statistics,” Dr. Heiden and colleagues wrote. “With the addition of more robust treatment options in early-stage disease, adherence to adjuvant and neoadjuvant treatment guidelines may disproportionately improve early-stage NSCLC outcomes following curative-intent resection.”