From Detection to Delay: Real-World Gaps in Post-Cologuard® Colonoscopy Adherence

Background Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, underscoring the importance of early detection. Cologuard ®, a non-invasive stool-based DNA test, offers an alternative to traditional screening methods by detecting biomarkers linked to CRC and precancerous lesions. Despite its non-invasive nature, Cologuard® has limitations, including a reliance on follow-up colonoscopy for confirmation and a relatively high false positive rate. This study aims to assess whether patients with a positive Cologuard result undergo colonoscopy within a reasonable timeframe and to evaluate the diagnoses made following a positive test. Methods We conducted a retrospective cohort study using the TriNetX database, a global federated real-world data platform, to analyze patients aged ≥ 18 years who tested positive on Cologuard. The primary outcome was whether patients underwent an endoscopic procedure (colonoscopy) within 12 months of a positive result. The secondary outcome was the diagnoses made during follow-up colonoscopy, including malignant neoplasms (colorectal cancer) and benign neoplasms (polyps). Results A total of 3,916 patients underwent Cologuard® testing, with 61.3% being female, 35% male, and 3.7% other genders. Of the 385 patients who tested positive for Cologuard® (mean age 65 ± 8.75 years), 171 (44%) underwent follow-up colonoscopy within 12 months. Of these, 10 cases (5.8%) were diagnosed with malignant neoplasms, and 56 cases (32.7%) were diagnosed with benign neoplasms (polyps). Discussion The study demonstrates suboptimal adherence to follow-up colonoscopy, with only 44% of patients undergoing the procedure within 12 months after a positive Cologuard® result. Additionally, the results highlight a higher false positive rate than previously reported, with only 38.5% of positive tests resulting in the detection of malignant or benign lesions and 67.3% of patients did not have significant findings. The uncertainty surrounding a positive result can lead to significant patient anxiety, potentially affecting adherence to follow-up procedures. This underscores the need for improved patient education, more streamlined care pathways, and enhanced communication strategies to increase follow-up compliance. Study limitations include the retrospective design leading to potential biases in patient selection, variations in Cologuard® interpretation across healthcare settings, and the TriNetX platform which provides de-identified patient data, which limits the ability to assess individual behaviors.