FIT Screening Not a Good Fit for Proximal Colon Cancer

Liam Davenport

October 01, 2018

Colorectal cancer screening programs that rely on fecal immunochemical testing (FIT) are less able to detect proximal, or right-sided, colon cancers in comparison to distal, or left-sided, colon cancers.

This limits the efficacy of FIT screening over the longer term, owing to the fact that right-sided tumors are more prevalent in ageing populations, say Italian researchers reporting a large population-based study published online October 1 in the Annals of Internal Medicine.

FIT forms the basis of numerous colorectal cancer screening programs in Europe. It has been found to have high sensitivity, and adherence by the target population has been good.

However, colorectal cancer biology changes with increasing age of patients. The Italian team set out to determine detection rates for long-term advanced adenomas and colorectal cancers, by anatomic location, in a retrospective analysis of a population-based colorectal cancer screening program in the Veneto region of Italy.

Manuel Zorzi, MD, Veneto Tumour Registry, Azienda Zero, Padova, Italy, and colleagues analyzed data on more than 120,000 participants in the screening program.

They found that the detection rate of proximal colorectal cancers with FIT was less than two thirds of those in the distal colon, at 0.45 vs 0.73 per 1000 people screened.

The study also revealed that the proportional rate of tumors detected between screening rounds, known as interval cancers, in the proximal colon was more than four times that in the distal colon.

In an accompanying editorial, Chyke A. Doubeni, MD, MPH, University of Pennsylvania, in Philadelphia, and Theodore R. Levin, MD, Kaiser Permanente Medical Center, Walnut Creek, California, note that the study has several limitations, not least the lack of comparison with other screening tests and a relatively high attrition rate.

There was also a lack of adjustment for age and sex, and the findings may not be generalizable to more diverse populations.

Discussing the results, they argue that the lower effectiveness of FIT in the proximal colon may be due to lesions growing more rapidly and bleeding less than in the distal colon, as well as a longer transit time, which can lead to degradation of hemoglobin.

"Thus, enhancing detection of right colon lesions is now a crucial priority for the field of CRC screening," Doubeni and Levin write. "This requires new technologies or approaches, such as high-performing biomarkers that complement FIT or supplementing FIT with one-time colonoscopy to enhance detection of right-sided lesions, but these options need further study."

Noting that FIT nevertheless has many advantages, they add: "Ultimately, the effectiveness of FIT is determined not by yield, but by the ability to prevent premature death from CRC, which requires well-designed, adequately powered observational studies or trials.

"For now, increasing the uptake of CRC screening is a public health priority, to reduce disease burden and eliminate disparities in the population," they write.

Study Details

The retrospective study conducted by Zorzi and colleagues included individuals aged 50 to 69 years who completed six rounds of FIT screening, which was offered every 2 years if the previous FIT result was negative. Individuals were excluded from the analysis if their attendance was irregular.

With 123,347 individuals agreeing to participate in the first round of FIT, the total number of FITs across six rounds available for analysis was 441,647. The overall participation rate in subsequent rounds was 92.7%. Nevertheless, only 29,891 individuals took part in the sixth round.

Across all screening rounds, the rate of positive FIT results was 4.1%, and the adherence to post-FIT colonoscopy was 93.3%.

The team reports that 1704 cases of advanced adenomas and 200 cases of colorectal cancer were detected in the proximal colon. The corresponding numbers for the distal colon were 3703 and 324, respectively; those for the rectum were 1220 and 209, respectively.

The detection rate for colorectal cancer across six rounds of screening was 0.73 per 1000 persons screened in the distal colon, compared with 0.45 in the proximal colon (P < .001) and 0.47 in the rectum (P < .001).

In the proximal colon, the detection rate dropped sharply between the first and second screening rounds, from 0.63 to 0.36 per 1000 people screened.

In contrast, the rate in the distal colon decreased steadily across the six rounds, from 1.65 to 0.17 per 1000 people screened, a pattern that was also seen in the rectum, where the decline was from 0.82 per 1000 in the first round to 0.17 per 1000 in the sixth.

A similar trend was seen for advanced adenoma.

The results also show that 150 cases of interval cancer were diagnosed within 2 years of a negative FIT result, with the proportional interval cancer rate higher in the proximal colon, at 25.2%, than in the distal colon (6.0%) and rectum (9.9%).

No funding for the study was reported. Cesare Hassan, MD, has received personal fees from Fujifilm, Norgine, and Sonoscape and nonfinancial support from Olympus outside the submitted work. Douglas Rex, MD, has received personal fees from Olympus and Boston Scientific outside the submitted work. Dr Doubeni is a member of the US Preventive Services Task Force. No other relevant financial relationships have been disclosed.

Ann Intern Med. Published online October 1, 2018. Abstract, Editorial

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