In a groundbreaking analysis published in the upcoming issue of Annals of Internal Medicine, researchers from the German Cancer Research Center in Heidelberg have challenged the prevailing assumption that higher sensitivity in colorectal cancer screening tests always translates into better cost-effectiveness. Their study meticulously compares the economic feasibility of multitarget stool DNA tests (MSDT), along with their next-generation counterparts (N-G MSDT), against the traditional fecal immunochemical tests (FIT), which have been the cornerstone of non-invasive colorectal cancer (CRC) screening.

Colorectal cancer remains one of the leading causes of cancer mortality worldwide, and early detection through effective screening is crucial for improving patient outcomes. While MSDT and N-G MSDT, such as Exact Sciences’ Cologuard and Cologuard Plus, boast superior sensitivity in detecting advanced neoplasia and early-stage CRC compared to FIT, this heightened detection capability comes with significantly increased screening costs. The researchers have employed a robust cost analysis framework, factoring in Medicare reimbursement rates, test costs, and patient adherence to follow-up colonoscopies, to quantify the economic trade-offs.

Their findings reveal that the screening costs per early-detected CRC or advanced neoplasia case via MSDT-based methods are approximately seven to nine times higher than those associated with FIT-based screening. Strikingly, even if the prices for MSDT and N-G MSDT were slashed to 20% of their current levels, these methods would still not be more cost-effective than FIT. This critical insight underscores the need to balance test sensitivity with economic sustainability in public health strategies.

To deepen the analysis, the team modeled different scenarios of patient compliance with follow-up colonoscopy, ranging from 30% to 90%. Colonoscopy remains the definitive diagnostic and therapeutic procedure following a positive stool test. Lower colonoscopy uptake accentuated the cost disparity, with incremental costs soaring beyond $1.4 million for MSDT and $1.5 million for N-G MSDT per additional CRC case detected when compared with FIT. Even at the highest assumed follow-up rates, the additional costs remained over half a million dollars per early-detected case, highlighting persistent inefficiencies in MSDT approaches.

The investigators emphasize that although MSDT and N-G MSDT exhibit higher sensitivity, equivalent diagnostic performance could, in some cases, be achieved by adjusting the positivity threshold of FIT, thereby minimizing costs without compromising test efficacy. This finding challenges the perceived superiority of more expensive testing modalities and calls for recalibrating screening protocols to optimize both clinical outcomes and economic practicality.

Methodologically, the study synthesized data from two independent cohorts comparing the diagnostic accuracy of Cologuard and Cologuard Plus with a commercially available FIT. By integrating reimbursement rates and colonoscopy uptake metrics, the researchers calculated aggregate screening costs per diagnosis of advanced neoplasia or early CRC. This comprehensive approach provides a transparent and reproducible model for evaluating screening cost-effectiveness in real-world settings.

The implications of this research are multifold. Firstly, it questions the wholesale adoption of multitarget stool DNA testing as a superior alternative in population-based CRC screening programs. Given constrained healthcare budgets and the imperative for efficient resource utilization, FIT remains a compelling option for widespread screening initiatives. Secondly, the study points to the importance of patient adherence to follow-up procedures in determining the overall value of any screening regimen.

Moreover, the research reinforces the dynamic nature of screening strategies. Sensitivity and specificity rates are not immutable attributes of diagnostic tests but can be modulated through threshold adjustments. This flexibility in FIT performance offers pragmatic avenues for enhancing screening outcomes without incurring prohibitive costs associated with novel molecular assays.

These findings assume particular significance in the context of healthcare systems facing escalating cancer burdens combined with fiscal pressures. Policymakers and clinicians must weigh the marginal benefits of advanced diagnostic tests against their economic impact, ensuring that screening programs remain accessible, affordable, and scientifically justified.

Importantly, the study clarifies that while simplicity and accessibility favor FIT, it is not devoid of limitations. MSDT and N-G MSDT provide additional genetic and epigenetic information that might ultimately translate to clinical benefits in selected populations. However, such benefits must be validated against their cost implications in comparative effectiveness research.

The authors advocate for continued research aimed at refining screening algorithms, possibly incorporating risk stratification models that tailor test choice to individual patient profiles. Such precision screening could harness the strengths of both FIT and multitarget DNA tests, delivering personalized prevention strategies while safeguarding public health budgets.

In summary, this seminal work urges a reevaluation of the prevailing enthusiasm for expensive stool DNA-based diagnostics in colorectal cancer screening. It underscores the enduring value and cost-efficiency of FIT, advocating for evidence-based adjustments in screening thresholds to maximize benefit without disproportionate financial burden. The study serves as a clarion call for balancing technological innovation with economic realism in the fight against colorectal cancer.

Subject of Research: People

Article Title: Dollars needed to pay per early-detected colorectal cancer in stool-based screening

News Publication Date: 13-May-2025

Web References: http://dx.doi.org/10.7326/ANNALS-24-04026

Keywords: Colorectal cancer, Cost effectiveness, Cancer screening