Value of pretreatment DPYD genotyping in gastrointestinal oncology: An analysis of cost avoidance and healthcare utilization.

Abstract

39 Background: Fluoropyrimidines are foundational agents in GI oncology, however they can cause severe toxicity in patients with reduced dihydropyrimidine dehydrogenase (DPD) activity due to pathogenic DPYD variants. Pretreatment DPYD genotyping enables identification of at-risk patients and supports genotype-guided dose modification. Despite growing evidence of clinical benefit, adoption of DPYD testing in the United States remains limited. The costs of implementing routine pharmacogenomic screening and its impact on downstream healthcare expenditures have not been well elucidated. We evaluated the economic impact of pretreatment DPYD genotyping in a large ambulatory oncology practice, with a focus on healthcare utilization, cost avoidance, and value-based cancer care. Methods: We conducted a retrospective analysis of 250 consecutive patients initiating fluoropyrimidine-based therapy between 1/2024-12/2025. Patients were categorized according to receipt of upfront DPYD genotyping (n=126) or standard care (n=124). Clinical outcomes included fluoropyrimidine-related adverse events (AEs), hospitalization for treatment-related toxicity, and treatment discontinuation. A healthcare utilization analysis was performed to estimate costs associated with toxicity-related hospitalizations and compare these with institutional costs of DPYD testing. Between-group differences were assessed using chi-square or Fisher's exact tests, as appropriate. Results: DPYD testing identified pathogenic variants in 4.8% of patients, all of whom underwent genotype-guided dose modification prior to treatment initiation. The tested cohort experienced fewer clinically significant AEs (18 vs 28, p=0.0453), and fewer treatment discontinuations (1 vs 11, p=.0024). No hospitalizations occurred in the tested cohort compared to 6 in the untested cohort (p=0.0162). The number needed to test to prevent one hospitalization was 21 patients. Pretreatment DPYD testing was associated with a net cost avoidance of $257,178, reflecting $303,528 in hospitalization costs avoided at an implementation cost of $46,350. This represents a return of $6.55 for every $1 invested in DPYD testing. Conclusions: Pretreatment DPYD genotyping was associated with reduced healthcare utilization and substantial cost avoidance in patients receiving fluoropyrimidine-based therapy. Despite actionable variants being identified in only a minority of patients, implementation of genotype-guided dosing yielded meaningful clinical and economic benefits. These findings support pretreatment pharmacogenomic testing as a value-based strategy to improve patient safety while reducing downstream costs of cancer care.