Clinical Stage II Non-Small Cell Lung Cancer: Can We “Just Give Adjuvant Therapy”?

R. Jindani¹, I. Loh¹, J. Rodriguez Quintero¹, A. Ghanie¹, J. Olivera², A. Dweck², B. Cohen¹, M. Vimolratana¹, N. Chudgar¹, B. Stiles^3
1Montefiore Medical Center/ Albert Einstein College of Medicine, Bronx, New York ²Albert Einstein College of Medicine, Bronx, New York ³Montefiore Health System / Albert Einstein School of Medicine, Bronx, New York

Purpose: Following recent advances in multimodal therapy, the sequence of treatment for clinical stage II disease is controversial. While some advocate for a neoadjuvant approach, others argue for upfront surgery with adjuvant therapy. We sought to investigate accuracy of staging and oncologic/survival outcomes of patients with clinical stage II lung cancer.

Methods: The National Cancer Database was used to identify patients diagnosed with clinical stage II non-small cell lung cancer (cII NSCLC) from 2015-2020 who underwent surgical resection. We stratified the cohort based on receipt of neoadjuvant therapy or upfront surgery and evaluated rates of adjuvant chemotherapy uptake and associated outcomes. Predictors of adjuvant delivery and upstaging to pathological stage III/IV in patients undergoing upfront surgery were studied using multivariable analysis. Cox regression and Kaplan-Meier curves were used to evaluate the associations of different treatment strategies with overall survival (OS) in propensity-score matched cohorts.

Results: Among 17,674 cII NSCLC patients who underwent surgical resection, 728 (4.1%) received neoadjuvant therapy and 16,946 (95.9%) underwent upfront surgery. In patients undergoing upfront surgical resection, 16.7% (N= 2,830) were downstaged to pathological stage (pStage) I (IA: 41.5%, N=1,174, IB: 58.4%, N=1,653), while 23.3% (N= 3,941) were upstaged to pStage III/IV. Of those who underwent upfront surgery with pStage IB-IV, only 54.3% (N= 8,556/15,769) received adjuvant therapy (p <.001). Within that cohort, there were various patient and clinical characteristics that were associated with decreased likelihood of receiving adjuvant therapy (Figure 1). Geographic variations were present in the utilization of adjuvant therapy (Figure 2A). Predictors of upstaging to pStage III/IV were more recent time-period (aOR 1.17, 95%CI 1.09-1.26), Asian race (aOR 1.34, 95%CI 1.08-1.67), lymphovascular invasion (aOR 3.33, 95%CI 2.95-3.75), higher grade (aOR 1.17, aOR 1.04-1.32), clinical T3 classification (aOR 1.91, 95%CI 1.51-2.42), and clinical N positivity (aOR 1.83, 95%CI 1.54-2.17). In well-balanced propensity-score matched cohorts (N= 7,951), receipt of adjuvant therapy after upfront surgery was associated with improved 5-year OS (60.3% vs. 55.2% in no-adjuvant group). This was particularly true in patients who were upstaged after surgical resection, with 5-year OS 47.3% vs. 34.4% (Figure 2B).

Conclusion: Despite lack of consensus around diagnosis and treatment of cII NSCLC, clinical staging is fairly accurate. More patients are upstaged than downstaged after upfront surgery and over 80% of patients meet indications for adjuvant treatment. Only 54% of eligible patients make it to adjuvant therapy and failure is associated with worse survival. A minority of clinical stage II NSCLC patients receive neoadjuvant therapy, suggesting that routine neoadjuvant chemo-immunotherapy delivery may be challenging. Processes should be put in place to help ensure return to intended oncologic therapy or to implement practice patterns incorporating neoadjuvant treatment protocols for patients with cII NSCLC.

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