Cost-effectiveness Evaluation of Targeted Surgical and Endoscopic Therapies for Early Colorectal Adenocarcinoma Based on Biomarker Profiles

Se Ryeong Jang,Monika Laszkowska,Angela C Tramontano,Chin Hur,Jin Choi,Han Truong,Aaron Oh

doi:10.1001/jamanetworkopen.2019.19963

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. The prognosis for patients with CRC varies widely, but new prognostic biomarkers provide the opportunity to implement a more individualized approach to treatment selection. To assess the cost-effectiveness of 3 therapeutic strategies, namely, endoscopic therapy (ET), laparoscopic colectomy (LC), and open colectomy (OC), for patients with T1 CRC with biomarker profiles that prognosticate varying levels of tumor progression in the US payer perspective. In this economic evaluation study, a Markov model was developed for the cost-effectiveness analysis. Risks of all-cause mortality and recurrent cancer after ET, LC, or OC were estimated with a 35-year time horizon. Quality of life was based on EuroQoL 5 Dimensions scores reported in the published literature. Hospital and treatment costs reflected Medicare reimbursement rates. Deterministic and probabilistic sensitivity analyses were performed. Data from patients with T1 CRC and 6 biomarker profiles that included adenomatous polyposis coli (APC), TP53 and/or KRAS, or BRAFV600E were used as inputs for the model. Data analyses were conducted from February 27, 2019, to May 13, 2019. Endoscopic therapy, LC, and OC. The primary outcomes were unadjusted life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) between competing treatment strategies. Endoscopic therapy had the highest QALYs and the lowest cost and was the dominant treatment strategy for T1 CRC with the following biomarker profiles: BRAFV600E, APC(1)/KRAS/TP53, APC(2) or APC(2)/KRAS or APC(2)/TP53, or APC(1) or APC(1)/KRAS or APC(1)/TP53. The QALYs gained ranged from 16.97 to 17.22, with costs 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 the most effective strategy (with 16.45 and 16.61 QALYs gained, respectively) but was not cost-effective. Laparoscopic colectomy 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. This modeling analysis found that ET was the most effective strategy for patients with T1 CRC with less aggressive biomarker profiles. For patients with more aggressive profiles, LC was more effective but was costly, rendering ET the cost-effective option. This study highlights the potential utility of prognostic biomarkers in T1 CRC treatment selection.

Highlights

Colorectal cancer (CRC) is the fourth most prevalent cancer and the second leading cause of cancerrelated mortality in the United States.[1]
Laparoscopic colectomy cost $65 234.87 for adenomatous polyposis coli (APC)(2)/KRAS/TP53 and $71 250.56 for APCwt, resulting in incremental cost-effectiveness ratio (ICER) of $113 290 per qualityadjusted life-years (QALYs) and $178 765 per QALY, respectively. This modeling analysis found that endoscopic therapy (ET) was the most effective strategy for patients with T1 CRC with less aggressive biomarker profiles
CRC is a heterogeneous disease that is associated with multiple genetic factors, its tumor initiation and progression depend on mutations in a few key drivers, such as adenomatous polyposis coli (APC [OMIM 611731], found in 85% of CRC tumors), TP53 (OMIM 191170), KRAS (OMIM 190070), and BRAFV600E (OMIM 164757).[5,6]

Summary

Introduction

Colorectal cancer (CRC) is the fourth most prevalent cancer and the second leading cause of cancerrelated mortality in the United States.[1]. CRC is a heterogeneous disease that is associated with multiple genetic factors, its tumor initiation and progression depend on mutations in a few key drivers, such as adenomatous polyposis coli (APC [OMIM 611731], found in 85% of CRC tumors), TP53 (OMIM 191170) (found in 35%-55% of tumors), KRAS (OMIM 190070) (found in 35%-45% of tumors), and BRAFV600E (OMIM 164757) (found in 8%-12% of tumors).[5,6] Inactivation of APC initiates the adenoma-carcinoma pathway for microsatellite-stable tumors, with these adenomas advancing to CRC when additional mutations are present in TP53, KRAS, or both.[6,7,8,9] In contrast, wild-type APC (APCwt) and BRAFV600E mutations are associated with microsatellite instability–high (MSI-H) tumors.[7]

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Results

Discussion

Conclusion