CRC Treatment Delays Linked to Higher Metastasis Risk, Supporting Pathway-Specific Benchmarks

Delays in initiating colorectal cancer (CRC) treatment are associated with increased metastatic progression risk, according to a cohort study published in JAMA Network Open, but clinically meaningful thresholds vary by treatment pathway, suggesting that pathway-specific benchmarks may better identify clinically significant delays than a universal standard.¹

Assessing the Impact of Treatment Timing on CRC Outcomes

CRC remains one of the most commonly diagnosed cancers and a leading cause of cancer-related mortality worldwide. Outcomes are strongly influenced by disease stage at diagnosis and timely access to effective treatment.² Patients who develop metastatic CRC often require more intensive therapies, experience worse survival outcomes, and contribute to substantially higher health care expenditures compared with those treated for localized disease.³

Although timely cancer treatment is widely recognized as an important component of high-quality oncology care, defining when a delay becomes clinically meaningful remains challenging.¹ Prior research across cancer types has demonstrated that prolonged treatment delays may be associated with increased mortality risk, highlighting the importance of reducing avoidable disruptions in care.⁴

CRC treatment pathways vary substantially based on tumor characteristics, disease location, and treatment goals.¹ Some patients undergo surgery first, whereas others receive neoadjuvant therapy followed by surgery or adjuvant therapy after resection. As a result, a single treatment-delay threshold may not accurately reflect appropriate care timelines across all patients.

To address this, researchers conducted a retrospective cohort study using Optum’s Clinformatics Data Mart to evaluate whether treatment delays were associated with metastatic progression across different CRC treatment pathways. The analysis included 11,927 adults aged 40 years or older with newly diagnosed nonmetastatic CRC who underwent curative-intent surgery within 1 year of diagnosis between 2017 and 2021.

Patients were grouped into 4 treatment pathways: surgery with or without radiation; neoadjuvant therapy followed by surgery; surgery followed by adjuvant therapy; and trimodality therapy consisting of neoadjuvant therapy, surgery, and adjuvant therapy.

The primary outcome was development of metastatic disease within 3 years of diagnosis. Researchers evaluated time-to-treatment initiation (TTI), defined as the number of days between diagnosis and the first cancer-directed treatment, and assessed whether clinically meaningful delay thresholds differed by treatment pathway.

Treatment Delay Thresholds Differed Across Pathways

Over the 3-year follow-up period, 1438 patients (12.1%) developed metastases. The researchers determined that longer treatment intervals were associated with increased metastatic risk, but the impact of delays varied according to treatment sequence.

Among patients receiving surgery followed by adjuvant therapy, delays were associated with increased metastatic risk even at relatively short intervals. Compared with patients who initiated treatment within 0 to 3 days, those with a TTI of 4 to 46 days had a 27% higher risk of metastasis (subdistribution HR [sHR], 1.27; 95% CI, 1.04-1.55), whereas those with delays of 47 days or longer had a 55% higher risk (sHR, 1.55; 95% CI, 1.08-2.23).

For patients receiving neoadjuvant therapy followed by surgery, treatment initiation delays of 68 days or longer were associated with increased metastatic risk compared with shorter delays (sHR, 2.66; 95% CI, 1.02-6.94).

Among patients undergoing surgery alone, only prolonged delays of 223 days or more were associated with a potential increase in metastatic risk; however, this finding was not statistically significant. No significant association between TTI and metastatic progression was identified among patients receiving trimodality therapy.

Implications for Care Coordination and Value-Based Oncology

The authors flagged that treatment timing must be interpreted within the context of each care pathway, as longer intervals may reflect appropriate treatment sequencing, particularly among patients receiving multimodal therapy, rather than delays in care delivery. As a result, the findings highlight the importance of developing CRC quality measures that account for differences in treatment approach. Pathway-specific benchmarks could help health systems identify avoidable delays while avoiding penalties for clinically appropriate treatment timelines.

Treatment delays may result from multiple factors, including fragmented communication among specialists, insurance authorization processes, scheduling challenges, and other barriers that affect timely access to cancer care.⁵ Improving coordination among oncology teams may help reduce preventable delays and support earlier initiation of appropriate therapy.

Because metastatic CRC is associated with greater treatment complexity and higher costs, preventing disease progression through timely care may have important implications for both patient outcomes and health care resource utilization.³

Study Limitations Highlight Need for Pathway-Specific Care Benchmarks

The researchers acknowledged several limitations, including that claims data lack detailed tumor characteristics and rely on claims-based capture of treatment data, which may introduce potential TTI misclassification and unmeasured residual confounding despite pathway stratification. In addition, the cohort consisted primarily of commercially insured and Medicare Advantage beneficiaries, which may limit generalizability to underserved populations.

Still, they concluded that CRC treatment timeliness should be evaluated using pathway-specific thresholds rather than a universal standard. Such an approach may provide a more accurate measure of care quality and help health systems target interventions where delays are most likely to affect outcomes.

“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,” the authors wrote. “Ensuring prompt access to CRC treatment remains an evidence-based priority for improving patient outcomes and advancing equitable, cost-effective care.”

References

1. 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
2. Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA. 2021;325(7):669-685. doi:10.1001/jama.2021.0106
3. McGarvey N, Gitlin M, Fadli E, Chung KC. Increased healthcare costs by later stage cancer diagnosis. BMC Health Serv Res. 2022;22(1):1155. doi:10.1186/s12913-022-08457-6
4. Hanna TP, King WD, Thibodeau S, et al. Mortality due to cancer treatment delay: systematic review and meta-analysis. BMJ. 2020;371:m4087. doi:10.1136/bmj.m4087
5. Neal RD, Tharmanathan P, France B, et al. Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review. Br J Cancer. 2015;112(Suppl 1):S92-S107. doi:10.1038/bjc.2015.48