Colorectal adenocarcinomas diagnosed following a negative faecal immunochemical test show high‐risk pathological features in a colon screening programme

Abstract

Aims The faecal immunochemical test (FIT) is used every 2 years to screen average‐risk British Columbians aged 50–74 years, with follow‐up colonoscopy for positive results. Non‐screen‐detected colorectal adenocarcinomas are defined as those detected within 25 months following a negative FIT. We aimed to more clearly characterise these malignancies. Methods and results A medical chart and focused pathology review of colorectal malignancies from 926 individuals who completed FIT in the British Columbia Colon Screening Program in 2014, and whose pathology reports were available for review, was conducted. This cohort was divided into two groups: individuals with colorectal adenocarcinomas diagnosed following a positive FIT (screen‐detected) and individuals with colorectal adenocarcinoma diagnosed within 25 months of a negative FIT (FIT‐interval cancers). Rates of clinically relevant pathological parameters, as outlined in the American Joint Committee on Cancer (AJCC), 8th edition, were compared between the screen‐detected and FIT‐interval cancer groups. A total of 876 screen‐detected and 50 FIT‐interval cancers were identified. FIT‐interval cancers exhibited higher rates of high‐grade differentiation (including poorly differentiated and undifferentiated cases; P < 0.01) and aggressive histotype (signet ring cell and mucinous carcinomas; P < 0.01) than did screen‐detected cancers after Bonferroni correction. Colorectal adenocarcinoma diagnosed after a negative FIT may therefore be associated with worse prognostic determinants than screen‐detected cancers. Conclusion FIT‐interval cancers are associated with high‐risk pathological features; the possibility that more aggressive, fast‐growing lesions which arise in the interval after truly negative FITs cannot be ruled out. Further study of a larger cohort of FIT‐interval cancers controlling for interaction among the different pathologic parameters will be undertaken.

Optimizing the colorectal cancer screening programme using faecal immunochemical test (FIT) in Flanders, Belgium from the “interval cancer” perspective

“…The FIT-IC proportion in Flanders during 2013–2018 was 13%, which lies within the range of FIT-IC proportion of 7–23% in other screening programmes using a FIT cut-off between 10 and 20 µg Hb/g [ 8 – 12 ]. Our study also supports previous findings that ICs after a negative faecal occult blood test are more common in women, [ 9 , 13 , 16 – 19 ] older people [ 16 , 20 , 36 ], in the right side of the colon [ 8 , 9 , 11 , 16 – 19 , 22 ] or in the rectum [ 10 , 17 , 37 ], at a more advanced stage [ 8 – 14 , 16 , 22 , 31 , 37 ] and with a higher grade [ 14 , 31 ], compared to screen-detected CRCs. Prior literature has proposed several explanations for these associations but definitive conclusions have not been reached.…”

“…Compared to screen-detected CRCs, FIT-ICs exhibited a higher grade and aggressive histotype (signet ring cell and mucinous carcinomas) [ 14 ]. However, it is still unclear to what degree FIT-ICs are due to FIT false-negative tests or a faster growth pathway of high-grade and aggressive histotype tumours.…”

“…However, it is still unclear to what degree FIT-ICs are due to FIT false-negative tests or a faster growth pathway of high-grade and aggressive histotype tumours. A recent study by Steel et al reported a mean time of 10.9 ± 2.9 months from FIT screening to diagnoses of all ICs and 11.6 ± 7.2 months from FIT screening to diagnoses of high-grade and aggressive histotype ICs [ 14 ]. The more advanced stage of FIT-ICs compared to screen-detected CRCs might be because FIT is known to be less sensitive for flat, right-sided and poorly or undifferentiated lesions, [ 14 , 46 – 48 ] tumours with these characteristics may be missed more often by FIT.…”

“…Tumour location was classified as right side (from the cecum to the transverse colon), left side (from the splenic flexure to the sigmoid colon) or rectum [ 8 , 9 , 18 ]. Differentiation grade was classified as well-differentiated (grade 1), moderately differentiated (grade 2) and poorly/undifferentiated (grade 3–4) [ 8 , 14 , 31 , 32 ].…”

“…The proportion of FIT-ICs ranged from 7 to 51% in previous studies with a FIT cut-off between 10 and 80 µg Hb/g (2-year screening interval) [ 8 – 13 ]. In addition, FIT-ICs have been shown to be associated with more advanced stage, higher grade and more aggressive histotype, resulting in reduced survival compared to screen-detected CRCs [ 8 , 12 , 14 , 15 ]. The European guidelines recommend monitoring interval cancers as a parameter of programme effectiveness [ 3 ].…”