Colonoscopy is considered the gold standard of colorectal cancer (CRC) screening because it is able to detect potential tumors at an early stage before any symptoms arise (e.g. blood in your stool), and because it can remove and biopsy polyps, i.e. pre-cancerous growths (QH). Over the last 10 years there has been an astounding drop in colon cancer rates in America: "[c]olon cancer rates have fallen by 30% over the past decade in people over age 50, and colonoscopies are getting much of the credit" (USA Today). Unfortunately, there has been a rise in CRC among those under 50 (QH), but this unfortunate trend is more than offset by the decline in CRC for those over 50 (which is when CRC is more prevalent).
But can we quantify more precisely the benefit from colonoscopy given that alternative diagnostics and better treatments also deserve credit in driving down CRC incidence and death rates? In particular, use of fecal screening (e.g. FIT) has become more common, although it does not quite approach colonoscopy in terms of accuracy.
Surprisingly, the impact of colonoscopy on colorectal cancer and related death risks is uncertain despite its widespread use for screening. The best evidence to support its use has been limited to data from observational cohort studies, which have estimated that this type of screening has been associated with a 40 to 69% decrease in the incidence of colorectal cancer and a 29 to 88% decrease in the risk of death from this disease. Unlike randomized, controlled trials (RCTs), observational cohort studies probably overestimate the real-world effectiveness of colonoscopy because of the tendency of healthier persons to seek preventive care.
In fact, a pooled analysis of four large, randomized sigmoidoscopy trials showed significant reductions in both the incidence of colorectal cancer and the risk of related deaths (22% and 26%, respectively).
sigmoidoscopy (which examines only lower part of the colon) or colonoscopy.
Examines the lower part of the colon: Specifically the rectum and sigmoid colon, the last part of the colon before the rectum. whereas colonosocopy examines the entire colon (large intestine).
The solution is to perform an RCT on colonoscopy effectiveness. A new study was published in The New England Journal of Medicine from a research group in Norway that recruited more than 84,000 healthy people aged 55 to 64 in Poland, Norway, and Sweden who had not previously undergone screening. The participants were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (the invited group, roughly 28,000) or to receive no invitation or screening (the usual-care group, roughly 56,000). The primary endpoints were risks of colorectal cancer and related death. The secondary endpoint was death from any cause.
With a median follow-up of 10 years, there were 259 colorectal cancer cases in the invited group and 622 in the usual-care group. Based on these numbers, risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group resulting in an 18% risk reduction (risk ratio 0.82, 95% CI 0.70-0.93). The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio 0.90, 95% CI 0.64-1.16; see Figure 1). A type of control (to ensure that the overall health in the two groups was approximately the same) was the risk of death from any cause, which was about the same: 11.03% in the invited group and 11.04% in the usual-care group (risk ratio 0.99, 95% CI 0.96-1.04).
Many in the medical community were surprised by the small benefit of colonoscopy i.e. CRC incidence risk ratio of 0.82 and death risk ratio of 0.9. But a major caveat was that only 42% of the invited group underwent screening. After adjusting the data to assume everyone assigned to screening actually got screened, the 10-year risk of colorectal cancer dropped by about a third, from 1.22% to 0.84%. This translates to a risk reduction of approximately 31%. The risk ratio for dying from CRC was even better with those who underwent the colonoscopy having a 0.15% chance of dying in the 10-year period compared to a 0.30% risk in the usual care group corresponding to a risk ratio of 0.5. The problem is that focusing only on those in the invited group who actually did get the colonoscopy raises the issue of confounding from selection bias of those more likely to seek medical care. This is why the "treatment" group in the primary analysis consisted of those invited for a colonoscopy, not those who actually received a colonoscopy.
Thus, interpreting this study is not straightforward. In a STAT piece describing the results, the lead researcher suggests that the real benefit of colonoscopy may lie in between the two estimates (primary analysis of invited group and secondary analysis of those who were screened), say in the range of 20 to 30% risk reduction for CRC incidence and death. These numbers are close to those from the randomized sigmoidoscopy trials, as well as at the lower end of the range of estimates from the observational studies.
The next step is a more rigorous comparison of colonoscopy to fecal diagnostics. Some argue that fecal tests might be equally effective, cheaper, and less invasive than colonoscopy. Indeed in Europe, the medical community seems to favor fecal tests over widespread colonoscopy screening. Large trials comparing colonoscopy with fecal tests are ongoing and should be informative. Regardless for now colonoscopy remains the gold standard for colorectal cancer screening.
Figure 1. "Cumulative Risk of Death from Colorectal Cancer at 10 Years." There was almost no difference between the invited group (red line, 0.28% at 10-year point) and the usual-care group (blue line, 0.31% at 10-year point) (from Figure 3 of Bretthauer et al. NEJM, 2022).
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