Prognostic impact of MRD positivity at ultra-sensitive ctDNA levels using a WGS-based personalized assay: A pan-cancer analysis from MONSTAR-SCREEN-3.

3044 Background: While circulating tumor DNA (ctDNA) demonstrates promise as a molecular residual disease (MRD) biomarker, its clinical implementation has been primarily limited to tumors with favorable ctDNA shedding characteristics. The MONSTAR-SCREEN-3 evaluates a whole-genome sequencing (WGS)-based MRD assay to assess MRD positivity at ultra-sensitive level beyond conventional WES-based MRD, including traditionally low-shedding tumors. Methods: MONSTAR-SCREEN-3 is a prospective multicenter study targeting 1,100 patients with solid tumors undergoing curative-intent treatment. Personalized panels were constructed using Precise MRD (Myriad Genetics), incorporating up to 1,000 tumor-specific alterations identified through WGS of matched tumor tissue. Serial plasma samples were collected at baseline, post-neoadjuvant treatment (NAT) (when applicable), 1-month (1M) post-surgery, every 3 months in year 1, and every 6 months thereafter up to 2 years. Assay performance was evaluated across multiple cancer types for ctDNA detection and recurrence monitoring. Results: Between May 2024 and November 2025, 1,088 patients across over 20 cancer types were enrolled, including colorectal (n=250), breast (n=156), cervical (n=95), gastric (n=88), and pancreatic (n=69) cancers. Treatment strategies included upfront surgery (n=704), NAT (n=296), and definitive chemoradiotherapy (n=96). Median follow-up was 5.3 months (range, 0–18.1). Baseline ctDNA detection was achieved in 96.2% (684/711), with 16.4% at ultra-sensitive levels (tumor fraction