Recurrence Risk and Its Impact on Current Treatment Strategies in Early and Locally Advanced NSCLC

Recurrence rates in early and locally advanced non-small-cell lung cancer (NSCLC) remain high despite curative treatment. Recently, the survival benefit of immune checkpoint inhibitors (ICI) in the (neo)adjuvant setting in patients with stage II-III NSCLC has been demonstrated. This study aimed to identify predisposing factors for disease recurrence to select patients who would benefit from multimodality treatment.

This retrospective observational study included patients with stage I-IIIA NSCLC discussed at the Thoracic Multidisciplinary Tumour Board of the University Hospital, Brussels, between 2017 and 2021.

Of the 167 patients, 34% had a recurrence, with a median time to recurrence of 9.1 months [272 (interquartile range=175-621.5) days]. The highest recurrence rate (56.5%) was observed in cTNM stage IIIA. Of surgical patients who were not eligible for (neo)adjuvant ICI according to current European reimbursement criteria, 21.7% developed disease recurrence. Twelve out of 20 patients eligible for ICI had no recurrence at a median follow-up of 34.1 months and would have been overtreated if they had received ICI therapy. Treatment modality and TNM stage were significantly associated with recurrence and worse progression-free survival (p<0.05). Stereotactic body radiotherapy, higher TNM stage and the presence of serine/threonine kinase 11 (STK11) mutation were significantly associated with worse overall survival.

European reimbursement criteria for (neo)adjuvant ICI in surgical patients are based on TNM stage (T≥4 cm or N1/N2 disease). However, TNM stage alone does not give the full picture. In patients undergoing surgery, the presence of the STK11 mutation was significantly associated with worse overall survival. We suggest the integration of analysis of circulating tumour DNA into perioperative strategies to reduce over- and undertreatment.