Treatment delays and risk of metastatic progression in colorectal cancer patients undergoing curative surgery: Real-world evidence from a national claims database.

453 Background: Timely treatment following diagnosis is essential in colorectal cancer (CRC) management to reduce the risk of progression from non-metastatic (non-mCRC) to metastatic disease (mCRC). This study examines the association between delays in initiating cancer treatment and the risk of metastatic relapse in patients newly diagnosed with non-mCRC. Methods: We conducted a retrospective cohort study using Optum’s de-identified Clinformatics® Data Mart, including CRC patients aged ≥40 years, newly diagnosed between January 1, 2017, and December 31, 2021. Eligible patients had no metastasis within six months, underwent curative surgery within a year, had ≥1 year of prior medical records, and ≥1 year of follow-up. Treatment delay was measured as time to treatment initiation (TTI), defined as days from diagnosis to first treatment. The primary outcome was 3-year cumulative incidence of metastatic relapse, with a primary endpoint of first mCRC diagnosis. TTI intervals were identify using machine learning that best differentiated the relapse risk. Competing risk models estimated TTI's effect on the relapse risk, adjusting for gender, race/ethnicity, diagnosis age, Charlson comorbidities, and first-year cancer treatments including gastrointestinal surgery, chemo/pharmacotherapy, and radiation. Results: Total cohort included 11,927 non-mCRC patients, of whom 12.1% experienced relapse and 6.7% died without relapse in the 3-year period. Four treatment patterns were observed during the first year: (1) upfront surgery ± radiation (78.2%), (2) surgery followed by adjuvant chemo ± radiation (18.2%), (3) neoadjuvant chemo followed by surgery ± radiation (2.0%), and (4) neoadjuvant therapy, surgery, and adjuvant chemo ± radiation (1.6%). The TTI was classified into four intervals: 0–3 days (67.8% of patients), 4–20 days (14.3%), 21–46 days (11.3%), and ≥47 days (6.5%). Compared to 0–3 days, a delay of 4–20 days was significantly associated with an 18% increased risk of metastatic relapse (HR = 1.18, p = 0.03). Delays of 21–46 days showed a non-significant 16% increase (HR = 1.16, p = 0.08), and ≥47 days showed a 22% increase (HR = 1.22, p = 0.06), suggesting potential clinical concern despite marginal statistical significance. Conclusions: Our findings highlight the importance of timely treatment initiation and suggest an optimal TTI window that can support oncologists in making informed decisions to improve outcomes for the non-mCRC patients.