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Bringing fecal immunochemical test into play in symptomatic population: Exploring the feasibility of fecal immunochemical test‐symptom combined approach

The risk of having invasive colorectal cancer (CRC) in fecal immunochemical test (FIT) positive subjects is around 4% to 5% in asymptomatic populations aged 50 to 75 years, which is 20 times higher than that in the general population. It has therefore become a well-established tool to stratify risk of colorectal neoplasm and, more clinically relevant, risk of CRC, in asymptomatic general population and is widely used in population CRC screening due to its non-invasiveness, high-throughput, and low-cost characteristics. Its effectiveness in reducing CRC mortality has been demonstrated in several large-scale cohort studies. The utility of FIT in the symptomatic population is, however, unclear. In clinical settings, many patients are presented for some specific or non-specific symptoms of CRC, such as anemia or gastrointestinal symptoms (i.e. bleeding at defecation, bowel habit change, and abdominal pain or bloating), and some clinicians may order diagnostic colonoscopy, which was associated with rather low likelihood of detecting CRC. Some physicians may also choose FIT for investigating these symptoms and then arrange colonoscopy if the test result turns out to be positive. Such a practice of using FIT in the primary care setting is quite arbitrary and has yet been established as a standard way of practice. The symptomatic population is highly heterogeneous and composed of patients with functional gastrointestinal disorder, inflammatory bowel diseases, or CRC patients. Colonoscopy capacity is always constrained and providing universal colonoscopy examination for all symptomatic patients may put considerable workload on the endoscopy service of a health care system and may also ensue considerable cost therefore the demand for better triaging of such a population emerged. Some recent studies have demonstrated the usefulness of using FIT in symptomatic subjects. McDonald et al. further demonstrated that fecal hemoglobin concentrations (FHbCs), the quantitative measurements of FIT, was associated with the likelihood of detecting organic diseases especially CRC at colonoscopy and has the potential of reducing unnecessary colonoscopy. Cubiella et al. reported that a scoring system, combining several clinically easily obtainable variables such as FHbC, age, and sex, may simplify CRC diagnosis and its AUC for CRC detection was 0.88 (95% CI: 0.85–0.90) in the derivation and 0.91 (95% CI: 0.90–093) in the validation cohort. A recent meta-analysis has shown the usefulness of FIT in diagnosing CRC in symptomatic populations regardless of the prevalence of CRC but was not able to specify most relevant symptoms owing to heterogeneous populations among analyzed studies. The study by Harmaneh et al. in this issue of JGH presents a significant suggestion regarding triaging these FIT positive patients presented with symptoms and comorbidities. In the current study, similar to previous studies, only 33.4% of all colonoscopies in their study period were indicated by positive FIT, which means the majority of colonoscopies were possibly driven by symptoms. However, the incidence of important colorectal disease diagnosed after colonoscopy for patients with lower gastrointestinal symptoms and iron deficiency anemia (IDA) was only up to 37% and 25% respectively, and only a few were CRC. In other words, most of the colonoscopies in these symptomatic patients only found benign etiologies and which may possibly crowd out and delay the timing of colonoscopy for those who has significant colorectal diseases. Therefore, the utility of FIT as a triaging tool in selecting high risk patients for colonoscopy has attracted the attention of clinicians recently. With this commendable study, the author showed that, in comparison with FIT positivity alone, the subjects with concomitant gastrointestinal symptoms, such as abdominal pain or peri-anal bleeding, or non-gastrointestinal symptom such as IDA carries much higher risk (almost 10 fold) of CRC. This result could help for better triaging and prioritizing patients who are preparing to go for colonoscopy after positive FIT by which physicians are able to plan a more reasonable management for the patients, such as arranging esophagogastroduodenoscopy for FIT negative IDA patients, rather than arranging colonoscopy or concurrent esophagogastroduodenoscopy and colonoscopy, thereby remarkably reduce the cost required for work-ups and more importantly, to make timely diagnosis of CRC. Such an association is independent of age, and the risk of CRC in those aged 75 and greater was higher if there were IDA or GI symptoms together with FIT positivity. Though recent guidelines extend the upper age limit of CRC screening to 85 years in those who are otherwise healthy, most of the screening programs recommend stop screening at 75, and the findings from this study provide a compromise rule of practice in the elderly who are currently not included in the screening population. This study, however, showed several limitations. First, due to the retrospective nature, missing data are inevitable, and this might have led to inaccurate grouping of the cohort especially when categorizing those with or without IDA, since some IDA patients, especially those without relevant symptoms, might not have received hemogram check, and some of them would be misclassified into the non-IDA group. Second, owing to the study design and paucity of CRC cases, the stage distribution of those CRC was not demonstrated and compared therefore the benefit of combining FIT and symptoms is not clear. Third, the optimal FIT cutoff that should be used for such a FIT-symptom approach in the symptomatic population may be different from that used in screening settings and may vary across different age groups (<75 vs >75) or symptoms. Recent studies, including those from the Asia-Pacific, reported an increasing trend of young-onset CRC. Though American Cancer Society currently recommends starting CRC screening from 45, most of the existing screening programs still suggest 50 doi:10.1111/jgh.15100