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

Abstract

Importance: 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.

Objective: 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.

Design, setting, and participants: 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.

Exposures: Endoscopic therapy, LC, and OC.

Main outcomes and measures: The primary outcomes were unadjusted life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) between competing treatment strategies.

Results: 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.

Conclusions and relevance: 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.

Figure 1.. Simplified Model Schematic

Strategy 1 is therapy A (endoscopic therapy) and therapy B (emergency colectomy). Strategy 2 is therapy A (laparoscopic colectomy) and therapy B (emergency open colectomy). Strategy 3 is therapy A (open colectomy) and no therapy B. CRC indicates colorectal cancer.

Figure 2.. Ten Most Important Variables for Each of the Biomarker Profiles

A and B, Figures demonstrate the univariate change on the incremental cost-effectiveness ratio (ICER) of laparoscopic colectomy (LC) vs endoscopic therapy (ET) for classes 0 and 4 in the order of decreasing sensitivity. The dividing line between the two different shades of blue bars denotes the base-case ICER. The darker blue bar represents the ICER range when the parameter is lower than its base-case value. The lighter blue bar represents the ICER range when the parameter is higher than its base-case value. ∞ indicates ICER when values for utility of recurrent cancer after endoscopic therapy (ET) are varied; EV, expected value (baseline); ICER, incremental cost-effectiveness ratio; LC, laparoscopic colectomy; and QALY, quality-adjusted life-year.