Colorectal Cancer Treatment Delay Thresholds and Metastasis Risk

Timely treatment in colorectal cancer (CRC) may influence the disease course and, thus, outcomes, but optimal delay thresholds remain uncertain. Identifying pathway-specific time-to-treatment initiation (TTI) effects can guide benchmarks and policies for coordinated, timely care.

To evaluate the association between TTI and 3-year metastasis risk in patients with newly diagnosed nonmetastatic CRC undergoing curative-intent surgery, with attention to variation by treatment pathway.

This cohort study of insured US patients with nonmetastatic CRC used deidentified administrative claims from Optum's Clinformatics Data Mart. Eligible individuals were adults aged 40 years or older with incident nonmetastatic CRC diagnosed during January 1, 2017, to December 31, 2021, who underwent curative-intent surgery within 1 year of diagnosis and had continuous coverage 1 year before and after. Data were analyzed June 2025.

TTI was defined as days from CRC diagnosis to the first receipt of cancer-directed therapy (surgery, chemotherapy, or radiation). Patients were categorized into 4 treatment pathways: surgery with or without radiation, surgery followed by adjuvant therapy with or without radiation, neoadjuvant therapy followed by surgery with or without radiation, and trimodality therapy (neoadjuvant therapy, followed by surgery, followed by adjuvant therapy with or without radiation).

The outcome was 3-year cumulative incidence of metastasis. XGBoost identified optimal TTI thresholds, and Fine-Gray models with death as a competing risk evaluated these thresholds and estimated their associations with metastasis.

Among 11 927 patients (mean [SD] age, 70.7 [10.8] years; 6007 women [50.4%]; 1251 Black [10.5%], 7948 White [66.6%]), 4539 (38.0%) had moderate or severe comorbidity. Over 3 years, 1438 patients (12.1%) developed metastasis. Longer TTIs were associated with higher metastasis risk, varying by treatment pathway. For surgery plus adjuvant therapy, TTIs of 4 to 46 days (subdistribution hazard ratio [sHR], 1.27; 95% CI, 1.04-1.55) and 47 days or longer (sHR, 1.55; 95% CI, 1.08-2.23) were significantly associated with increased risk vs zero to 3 days. For surgery followed by radiation, delays of 223 days or longer showed higher risk (sHR, 2.00; 95% CI, 0.95-4.25) than TTI up to 222 days, although these results were not significant. For neoadjuvant therapy plus surgery, TTI of 68 days or longer were associated with higher risk (sHR, 2.66; 95% CI, 1.02-6.94) than TTI up to 67 days. For patients receiving trimodality therapy, there was no association between TTI and risk of metastasis.

In this cohort study, treatment delays were associated with higher, pathway-specific metastasis risk. These findings support pathway-tailored benchmarks for treatment initiation and highlight the importance of integrated care in reducing delays and improving timely, equitable, cost-effective CRC care.