The 10-year repeat after a negative colonoscopy

Screening for colorectal cancer (CRC) reduces CRC incidence and mortality [1] [2] [3] [4] [5]. Screening is robustly cost-effective, in part because cancer treatment is so expensive [6] [7]. Physicians can reliably inform patients that CRC screening is effective, and CRC screening is one of the few cancer preventive measures that have been endorsed worldwide [8] [9].

“The benefit of the 10-year follow-up colonoscopy is not limited to cancers found at the next colonoscopy.”

Once CRC screening efficacy was established, a logical next frontier question was: “Doc, when should I get the next examination?” For patients with 1 – 2 nonadvanced adenomas, randomized trials including the EPOS study in Europe and the soon-to-be-initiated FORTE trial in the United States, will address the recommended timing for surveillance [10]. Low-risk adenomas are a focus of interest as they are so prevalent and because the recent emphasis on adenoma detection is accelerating their identification.

But, what if you have a negative examination – is it necessary to return in 10 years?

In support of the need to return is the fact that CRC incidence rises with increasing age. In long-term follow-up from the United Kingdom’s flexible sigmoidoscopy screening trial, the rate per 1000 persons for diagnosis of CRC over the 17 years of follow-up was 24.7 in randomized control individuals aged 55 – 59 years and 33.0 in randomized controls aged 60 – 64 years [11]. The corresponding numbers for the group invited to screen were 18.2 for ages 55 – 59 years and 24.8 for ages 60 – 64 years.

Furthermore, CRC incidence increases over time, even in individuals with an initial negative examination. When comparing CRC incidence at 11 vs. 17 years of follow-up, the incidence of colon cancer in the intervention group rose from 114 cases per 100 000 person years of observation (PYO) to 137/100 000 PYO [11]. In the control group, the incidence of CRC rose from 149/100 000 at 11 years to 184/100 000 PYO at 17 years. Although the incidence of colon cancer in the intervention group remained statistically significantly lower than the control group, it is apparent that cancer incidence rises the further one is removed from the last screening examination. The increase in incidence between 11 and 17 years was especially relevant to right-sided cancers. In the intervention group, proximal CRC incidence rose from 50/100 000 PYO at 11 years to 68/100 000 at 17 years of follow-up.

Similarly, in the US PLCO flexible sigmoidoscopy cancer screening trial, cancers appeared postscreening, and not to a trivial degree [12]: in the cohort randomized to screening, 977 CRCs were diagnosed in 77 447 individuals over a mean follow-up of 11.5 years. A retrospective analysis determined that even if colonoscopy had been used as the initial screening modality, and even if it were perfectly implemented with complete compliance and accuracy, only 507 or 51.9 % of cancers would have been detected at the time of initial screening. Thus, over 11 years of follow-up, the initial colonoscopy would have only identified about half of the cancers that eventually occurred. A substantial number of cancers will not be prevented by one-time only screening.

A cohort study in nearly 36 000 individuals in Manitoba, Canada, compared CRC incidence in those who had undergone a negative colonoscopy with CRC incidence in the general population. The standardized incidence ratio for the development of CRC in the cohort with a negative examination over 10 years was 0.28, or a 72 % relative reduction [13].

Surely, if you have a negative examination, you are at lower risk; but is it low enough that you need do nothing more?

In this issue of Endoscopy, Murthy et al. use an administrative database in Ontario, Canada, to explore whether a repeat colonoscopy at 10 years after a negative examination is necessary [14]. They assembled a cohort of individuals who had a negative colonoscopy examination between 1996 and 2001, matched people with and without a subsequent colonoscopy in the subsequent 8 – 12 years, and compared cancer incidence. They found no difference in cancer incidence between those who did and those who did not have a repeat, follow-up colonoscopy, demonstrating that the 10-year repeat examination is of limited benefit. In effect, they are arguing that the initial examination identified a low-risk cohort, whose risk is not sufficient enough to require follow-up testing.

Studies that use administrative data have considerable inherent limitations. In this study, only about a tenth of the initial cohort was included in the matched analysis. The matching is necessarily crude, given the limited amount of information known about each patient. Of concern, the majority of the subsequent cancers in the cohort were identified before 8 years of follow-up and thus were not included in the analysis. The concern was that early-onset, symptomatic cases might bias the ascertainment of cancer, and hence inflate the association and thus the “benefit” of repeat colonoscopy and detection of cancer. But, excluding the majority of the cancers that occurred during follow-up raises concern about the accuracy of the findings. Finally, the cohort had a relatively abbreviated length of follow-up. The benefit of the 10-year follow-up colonoscopy is not limited to cancers found at the next colonoscopy. The 10-year follow-up may identify precancerous lesions, which, when removed, would potentially offer the patient another 10 or more years of protection.

Alternatively, a negative colonoscopy when combined with demographic or other risk factors might identify patients at low risk who do not require more testing, or perhaps could be tested with less-invasive, less-expensive methods, such as stool tests.

For additional guidance, we must look to studies of large cohorts with comprehensive follow-up to better understand both the application and optimal timing of subsequent CRC screening tests.

• References

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