Association of pre-surgical circulating tumor DNA detection, use of sublobar resection with risk of recurrence in stage I non-small cell lung cancer

Background: Sublobar resection is increasingly recognized as an effective treatment for early-stage NSCLC. However, no studies to date have investigated the potential role of preoperative ctDNA detection in guiding surgical decisions, such as opting for sublobar resection, in stage I NSCLC.

Methods: Patients with solid-dominant (CTR>0.5), clinical stage I NSCLC were prospectively recruited between March 2014 and December 2020. Pre-surgical plasma samples were analyzed using a tumor-naïve, methylation-based cell-free DNA assay. The impact of sublobar resection versus lobectomy on recurrence-free survival (RFS) was assessed according to pre-surgical ctDNA status. Associations between pre-surgical ctDNA detection and clinicopathologic factors were also investigated.

Results: The analysis included 544 patients (178 women [33 %]; median age 66 [IQR, 60-71] years). Pre-surgical ctDNA was detected in 188 (35 %) patients. In patients without presurgical ctDNA, sublobar resection did not significantly increase the risk of relapse (adjusted HR, 1.01, p = 0.98). However, among ctDNA-positive patients, sublobar resection was associated with an increased risk of relapse (adjusted HR, 2.25; 95 % CI, 1.12-4.54; p = 0.024). Patients with presurgical ctDNA had higher rates of nodal upstaging (OR, 3.58; p < 0.001) and exhibited higher pathologic grade (p = 0.021), perineural invasion (p < 0.001), and lymphovascular invasion (p < 0.001).

Conclusions: Pre-surgical tumor-naïve ctDNA analysis holds promise in identifying patients with aggressive tumors that may not be sufficiently managed with sublobar resection. This approach can help personalize treatment strategies, potentially improving outcomes for patients with early-stage NSCLC.