Potential for Prognostic Biomarkers in T1 Colorectal Cancer Treatment Selection

In this study, researchers found that endoscopic therapy was the most effective strategy for patients with T1 CRC with less aggressive biomarker profiles and laparoscopic colectomy was the most effective for patients with more aggressive profiles.

A study, published in JAMA Network Open, highlightedß the potential utility of prognostic biomarkers in T1 colorectal cancer (CRC) treatment selection.1

Researchers found that endoscopic therapy (ET) was the most effective strategy for patients with T1 CRC with less aggressive biomarker profiles. However, for patients with more aggressive profiles, laparoscopic colectomy (LC) was more effective but was also costly, making ET the cost-effective option. 

“Choice of therapy in class 0 or 4, which have a worse prognosis, may be dependent on patients’ long-term health outcomes, such as recurrent cancer rates and mortality rates, thus requiring further study,” the authors wrote. “Future prospective studies with adequate patient numbers and follow-up duration are needed to better define and validate targeted treatment approaches in T1 CRC based on tumor biomarker profiles.”

To assess cost-effectiveness in this economic evaluation study, researchers developed a Markov model. Risks of all-cause mortality and recurrent cancer after ET, LC, and open colectomy (OC) were estimated with a 35-year time horizon. Additionally, quality of life was based on EuroQoL 5 Dimensions scores and hospital and treatment costs reflected Medicare reimbursement rates. 

Researchers used data from patients with T1 CRC and 6 biomarker profiles that included adenomatous polyposis coli (APC), TP53 and/or KRAS, or BRAFV600E as inputs for the model. The data analyses were performed from February 27, 2019 to Mary 13, 2019. 

Overall, ET had the highest quality of life-adjusted life years (QALYs), the lowest cost, and was also the dominant strategy for T1 CRC with the following biomarker profiles: BRAFV600EAPC(1)/KRAS/TP53APC(2) or APC(2)/KRAS or APC(2)/TP53, or APC(1) or APC(1)/KRAS or APC(1)/TP53. Further, the QALYs gained ranged from 16.97 to 17.22, with costs found to be between $68,902.75 and $77,784.53 in these subgroups. 

For the 2 more aggressive biomarker profiles with worse prognoses (APC(2)/KRAS/TP53 and APCwt [wild type]), LC was suggested to be the most effective strategy (with 16.45 and 16.61 QALYs gained, respectively), but was not cost-effective. Moreover, LC cost $65,234.87 for APC(2)/KRAS/TP53 and $71,250.56 for APCwt, resulting in ICERs of $113,290 per QALY and $178,765 per QALY, respectively. 

In an editorial written by Timothy J. Yeatman, MD, of Intermountain Healthcare, Michael J. Schell, PhD, of Moffitt Cancer Center, and William Sause, MD, of intermountain healthcare, the authors wrote, “We applaud the authors for the novelty of basing their findings on biological data (i.e., somatic variants) rather than simply pathological data. The use of genetic data raises the hope that, with future research, nodal status could be more accurately predicted, reducing the chances of recurrent disease (and its associated costs) when only a local therapy is administered.”2

According to the study authors, the findings presented in the study underscore the need for long-term outcomes research in patients who have T1 CRC with specific biomarker profiles in order to more accurately predict optimal treatment strategies.

“A prospective comparison of genetic vs pathologic staging in predicting surgical pathologic staging will be necessary to determine whether genetic assessment can improve accuracy and lower costs when a less aggressive procedure is deemed appropriate,” the editorial authors wrote. “These approaches are consistent with the emerging population health model for sustainable and affordable health care.”


1. Jang SR, Truong H, Oh A, et al. Cost-effectiveness Evaluation of Targeted Surgical and Endoscopic Therapies for Early Colorectal Adenocarcinoma Based on Biomarker Profiles. JAMA Network Open. doi:10.1001/jamanetworkopen.2019.19963.

2. Yeatman TJ, Schell MJ, Sause W. Assessment of Treatment Cost-effectiveness Using a Colorectal Cancer Mutation Profile. JAMA Network Open. doi:10.1001/jamanetworkopen.2019.19991.