Background: ctDNA Lung DETECT is a multicentre investigator initiated prospective study at 3 thoracic surgery centres in the Greater Toronto Area assessing ctDNA detection and association with recurrence free survival (RFS) in patients with early stage non-small cell lung cancer (NSCLC) (NCT05254782). Patients who have ctDNA detected perioperatively are offered ctDNA Lung RCT, a randomized trial investigating the benefit of adjuvant chemo-immunotherapy in patients where the standard of care is observation alone after surgery (NCT04966663). Herein, we report on ctDNA outcomes at 12 months for patients with resected early stage NSCLC. Methods: Patients with stage I (T1-2N0) or multifocal T3-4 < 4cm N0 NSCLC planned for resection at University Health Network consented to plasma ctDNA assessment before and after surgery, and at 12 months post-operatively or relapse using the tumor-informed RaDaR® assay, which detects up to 48 tumor-specific variants in plasma with a Limit of Detection (LoD₉₅) of 0.0011% variant allele fraction. Results: From July 2021 to January 2024, 178 patients were enrolled; 115 had sufficient tissue for assessment. Of these, 68/72 patients have 12 month post-resection ctDNA results available (3 withdrew, 1 sample failed). ctDNA was detected pre-operatively in 18 patients; 99% (71/72) had ctDNA clearance post-operatively, and 93% (62/67) remained ctDNA negative at 12 months. Median follow up time was 18.7 months (range 12.0– 28.3); 8/72 (11%) patients (5 stage I, 3 stage II) experienced lung cancer recurrence. Median time to recurrence was 13.9 months (range 6.2- 24.9). Of these, 3 had ctDNA detected on their preoperative and 12-month or recurrence sample, 1 had ctDNA detected at 12 months prior to relapse, 1 had ctDNA detected at 12 months and recurred around the same time, 2 had negative ctDNA samples and 1 missed sample collection preoperatively. The recurrence rate was 16.7% (3/18, 95% exact CI 3.6-41.4%) in patients with ctDNA detected pre-operatively vs. 7.5% (4/53, CI 2.1-18.2%) in those without. New lung cancers were diagnosed in 5/72 (median time to new primary 15.3 months, range 4.9-14.2) and 2/72 patients had new cancers diagnosed (ovarian/liposarcoma). For those with new lung primaries, 1 had ctDNA detected preoperatively but none had ctDNA detected at time of new primary diagnosis. Of 4 patients who have died, 2 were from recurrent lung cancer and 2 from new primaries (lung/sarcoma). Conclusions: This study represents one of the largest prospective cohorts of ctDNA kinetics in patients with resected lung cancer. Of patients with at least 12 months follow up, 8/72 experienced a lung cancer recurrence with a higher rate in those with pre-operative ctDNA detected (16.7% vs 7.5%). Pre-operative ctDNA detection may help identify patients with resected stage I NSCLC that could benefit from treatment intensification, currently under study in ctDNA Lung RCT (NCT04966663). Clinical trial information: NCT05254782.