Delay in Colorectal Cancer Treatment Increases Risk of Metastasis: JAMA
USA: A recent cohort study published in JAMA Network Open has revealed that delays in initiating colorectal cancer treatment were associated with a higher risk of metastasis, with the impact varying across different treatment pathways. The findings highlight the need for pathway-specific treatment timelines and integrated care strategies to minimize delays and improve timely, equitable, and cost-effective colorectal cancer care.
Although timely treatment is considered an important component of colorectal cancer (CRC) management, the duration of delay that may adversely affect outcomes has remained uncertain. To address this gap, researchers led by Chi M. Nguyen from the Department of Biostatistics & Health Data Science, Indiana University School of Medicine, evaluated whether time-to-treatment initiation (TTI) influenced the risk of metastatic progression in patients with newly diagnosed nonmetastatic CRC and whether this association differed according to treatment strategy.
The researchers analyzed deidentified administrative claims data from Optum's Clinformatics Data Mart, including 11,927 insured adults aged 40 years or older diagnosed with nonmetastatic colorectal cancer between 2017 and 2021 who underwent curative-intent surgery. Time-to-treatment initiation was defined as the interval between diagnosis and the first cancer-directed therapy.
Patients were categorized into four treatment pathways: surgery alone (with or without radiation), surgery followed by adjuvant therapy, neoadjuvant therapy followed by surgery, and trimodality therapy comprising neoadjuvant therapy, surgery, and adjuvant therapy.
The following were the key findings:
- During the three-year follow-up, 1,438 patients (12.1%) developed metastatic colorectal cancer.
- Longer time-to-treatment initiation was associated with a higher risk of metastasis, with the delay threshold varying according to the treatment pathway.
- In patients undergoing surgery followed by adjuvant chemotherapy, initiating treatment 4–46 days after diagnosis was associated with a 27% higher risk of metastasis compared with treatment within 3 days.
- Delays of 47 days or longer in the surgery plus adjuvant chemotherapy group were associated with a 55% higher risk of metastasis.
- Among patients receiving neoadjuvant therapy followed by surgery, treatment initiation after 68 days was significantly associated with an increased risk of metastasis compared with treatment within 67 days.
- In patients treated with surgery alone, only delays of 223 days or longer were linked to a higher risk of metastasis, although this association was not statistically significant.
- No significant association was observed between treatment delay and metastatic progression in patients receiving trimodality therapy.
The researchers suggested that a single treatment initiation benchmark may not be suitable for all colorectal cancer patients, recommending pathway-specific timelines to improve outcomes and optimize healthcare delivery.
They acknowledged limitations, including the lack of detailed tumor information, reliance on administrative claims data, limited representation of underserved populations, and the observational nature of the study, which precludes causal conclusions. They called for future studies incorporating clinical and genomic data to validate pathway-specific treatment thresholds.
Overall, the findings highlight the importance of minimizing avoidable treatment delays, particularly for patients undergoing surgery followed by adjuvant chemotherapy, to reduce metastatic progression and improve colorectal cancer outcomes.
Reference:
Nguyen CM, Skaar TC, Imperiale TF, et al. Colorectal Cancer Treatment Delay Thresholds and Metastasis Risk. JAMA Netw Open. 2026;9(7):e2623057. doi:10.1001/jamanetworkopen.2026.23057
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