In a cohort study of patients with nonmetastatic colorectal cancer, treatment delays were associated with a higher risk of metastasis, with the magnitude differing by treatment pathway. Nguyen et al published the findings in JAMA Network Open.
“These results suggest that pathway-specific thresholds for treatment initiation may be more effective than a single universal threshold in improving outcomes, promoting timely, cost-effective [colorectal cancer] care, and guiding clinical practice and performance benchmarks,” the investigators commented.
Study Details
Using deidentified administrative claims from the Optum Clinformatics Data Mart, the investigators evaluated the association between time to treatment initiation (TTI) and 3-year metastasis risk among insured U.S. adults with newly diagnosed nonmetastatic colorectal cancer who underwent curative-intent surgery within 1 year of diagnosis. The cohort included 11,927 patients aged at least 40 years who were diagnosed between January 1, 2017, and December 31, 2021, and had continuous insurance coverage for at least 1 year before and after diagnosis.
TTI was defined as the number of days from colorectal cancer diagnosis to the initiation of cancer-directed therapy, including surgery, chemotherapy, or radiation therapy. Patients were categorized into four treatment pathways: surgery with or without radiation therapy; surgery followed by adjuvant therapy with or without radiation therapy; neoadjuvant therapy followed by surgery with or without radiation therapy; and trimodality therapy consisting of neoadjuvant therapy, surgery, and adjuvant therapy with or without radiation therapy.
The primary outcome was the 3-year cumulative incidence of metastasis. The investigators used XGBoost to identify optimal TTI thresholds and Fine-Gray models, with death treated as a competing event, to evaluate these thresholds and estimate their associations with metastasis.
The mean patient age was 70.7 years, 50.4% were women, 66.6% were White, 10.5% were Black, and 38.0% had moderate or severe comorbidity.
Key Findings
Over 3 years, 12.1% of patients developed metastases.
Longer TTIs were found to be associated with an increased risk of metastasis, with the magnitude varying by treatment pathway. The investigators reported the following pathway-specific findings:
- Surgery followed by adjuvant therapy: TTIs of 4 to 46 days (subdistribution hazard ratio [sHR] = 1.27, 95% confidence interval [CI] = 1.04–1.55) and at least 47 days (sHR = 1.55, 95% CI = 1.08–2.23) were associated with a higher risk of metastasis than TTIs of 0 to 3 days.
- Surgery followed by radiation therapy: TTIs of at least 223 days were associated with a higher risk of metastasis than TTIs of up to 222 days (sHR = 2.00, 95% CI = 0.95–4.25), although the association was not significant.
- Neoadjuvant therapy followed by surgery: TTIs of at least 68 days were associated with a higher risk of metastasis than TTIs of up to 67 days (sHR = 2.66, 95% CI = 1.02–6.94).
- Trimodality therapy: No association was observed between TTI and metastasis risk.
“In this cohort study of patients with [nonmetastatic colorectal cancer] undergoing curative-intent surgery, treatment delays were associated with higher metastasis risk in a pathway-dependent manner,” the investigators concluded. “Six to seven weeks of delays were consequential for patients requiring surgery and adjuvant chemotherapy.”
They continued, “These findings underscore the importance of coordinated, timely care and support the development of pathway-specific quality benchmarks and integrated-care models to minimize avoidable delays. Ensuring prompt access to [colorectal cancer] treatment remains an evidence-based priority for improving patient outcomes and advancing equitable, cost-effective care.”
Chi M. Nguyen, PhD, of Indiana University School of Medicine, Indianapolis, is the corresponding author of the article in JAMA Network Open.
Disclosure: The study was funded by the Indiana University Cancer Prevention and Control Research Program, Community Outreach & Engagement Research Program, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Zerbe Chair in Pharmacoeconomics, and AnalytiXIN. The study authors reported no conflicts of interest.
