589P - Impact of landmark point selection on molecular residual disease detection in stage I-IV resectable colorectal cancer

Background

Circulating tumor DNA (ctDNA) based molecular residual disease (MRD) detection has been shown to predict prognosis and guide individualized management of colorectal cancer (CRC). The landmark point is usually set at 4-12 weeks post resection in consideration of the disturbance to cell-free DNA (cfDNA) by surgery. This study aimed to evaluate the feasibility of moving the landmark point to 1-week post resection.

Methods

The study prospectively and consecutively enrolled stage I-IV CRC patients who received R0 resection. Blood samples at baseline, post-operative day (POD) 7, POD30 and subsequent every 3-6 months surveillance were collected. The MRD status of all the samples were evaluated by the Burning Rock Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (brPROPHET^TM) approach. The cfDNA level, mean tumor mutant (MTM), positive predictive value (PPV) and negative predictive value (NPV) were compared between POD7 and POD30.

Results

In total, 164 eligible patients were enrolled. The median follow-up duration was 311 days (95% CI, 296-351) up to date. The brPROPHET displayed a high sensitivity of 95.1% (155/163) for detecting ctDNA preoperatively, with 88.5%, 96.1%, 96.2%, 100% in stage I to IV, respectively. Post-resection ctDNA positive rates were decreased to 15.2% (25/164) at POD7 and 12.8% (21/164) at POD30. The cfDNA levels of POD7 were significantly higher than those of baseline and POD30 (P<0.001). However, the MTMs were similar between POD7 and POD30 (P = 0.55). The accordance between POD7 and POD30 was 91.5% (150/164). For 6-month recurrence, the PPV was 13.6% vs 15.8% for POD7 and POD30, respectively, with NPV of 100% vs 98.2%. Of the 25 ctDNA positive patients at POD7, 9 turned negative at POD30 and had significantly lower ctDNA levels at POD7 than those who didn’t (P<0.001). Patients with decreased ctDNA from POD7 to POD30 had a higher ctDNA clearance rate during surveillance than those without decreased ctDNA (100% vs 30%, P = 0.02).

Conclusions

The performance of ctDNA detection in POD7 and POD30 was similar. Shift of the landmark time to 1-week post resection may provide an easier way to evaluate MRD status for prognostic stratification.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.