Single Negative Colonoscopy Predicts Low Colorectal Cancer Risk

Pam Harrison

May 26, 2020

A single negative screening colonoscopy is associated with long-lasting, significant reductions in the incidence of, and mortality from, colorectal cancer (CRC), but only if the colonoscopy is of high quality, a new study concludes.

The population-based study showed a durable reduction in CRC risk over 17.4 years of follow-up.

"Our findings confirm that a 10-year interval between high-quality screening colonoscopies [as is currently recommended] is safe and that there is no benefit from more frequent screening," lead author Nastazja Pilonis, MD, from the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, told Medscape Medical News.

"Furthermore, our findings suggest that this interval could even be prolonged, provided the baseline colonoscopy is of high quality," she added.

However, she emphasized that "only high-quality colonoscopy provided a durable reduction in mortality risk," and noted that "low-quality colonoscopy was associated with a significantly increased risk of CRC death after the first 5 years following the examination." 

The study was published online May 25 in the Annals of Internal Medicine.

Polish Colonoscopy Screening Program

The study included 165,887 average-risk patients enrolled in the Polish Colonoscopy Screening Program who had a single negative screening colonoscopy between October 2000 and December 2011.

Negative colonoscopy was defined as an examination where no evidence of any neoplastic lesion was found.

A high-quality screening colonoscopy was defined by three key properties: cecal intubation, adequate bowel preparation, and an endoscopist's adenoma detection rate (ADR) of 20% or greater calculated on a yearly basis.

A total of 505 different endoscopists performed the colonoscopies over a median follow-up of 10.1 years.

Compared with the general population, among individuals with a negative colonoscopy, the incidence of CRC was 72% lower and CRC mortality was 81% lower over a period of 5.1 to 10 years, Pilonis and colleagues report.

"This was mainly driven by long-lasting reductions in CRC incidence and mortality (by 84% and 90%, respectively) after high-quality screening colonoscopies," the investigators emphasize.

Beyond 10 years of follow-up, reductions in CRC incidence and mortality were similar to those observed for the earlier period of 5.1 to 10 years but only for participants who had had a high-quality screening colonoscopy, they emphasize.

Table. CRC incidence and mortality rates after negative colonoscopy

  Low-quality colonoscopy:


0-5.0 years

High-quality colonoscopy:


0-5.0 years

Low-quality colonoscopy:


5.1-10 years

High-quality colonoscopy:


5.1-10 years

CRC Incidence        
Incidence rate 23.22 12.30 41.04 20.66
Standardized incidence ratio (SIR) 0.28 0.15 0.35 0.18
CRC Mortality        
Mortality rate 4.96 2.69 15.71 6.88
Standardized mortality ratio (SMR) 0.13 0.07 0.25 0.11

Subgroup Analyses

In addition, subgroup analyses showed that high-quality colonoscopy — although not those of low-quality — effectively reduced the incidence of, and mortality from, CRC in women and in the proximal colon.

As Pilonis pointed out, previous studies have suggested that women may not benefit from screening colonoscopy to the same extent as men. Plus previous research suggests a reduced CRC risk in the proximal colon relative to that in the distal colon.

Overall, standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) significantly differed between men and women in the current study, but this difference was not observed after high-quality examinations, the investigators report.

"This is an extremely important finding because, for the first time, we showed that when you have high-quality colonoscopy, women benefit from screening colonoscopy as much as men," Pilonis emphasized.

Similarly, high-quality screening colonoscopy was associated with a 50% reduction in mortality in the proximal colon throughout the 17.4-year follow-up, whereas there was no decrease in mortality from CRC in the proximal colon with low-quality colonoscopies.

As Pilonis noted, lesions in the proximal colon are more subtle and are harder to detect."It's also easier to achieve good bowel preparation in the distal colon than in the proximal colon," she added.

Women are also more prone to develop lesions in the right (proximal) side of the colon and appear to have more pain with colonoscopy than men, all of which could have contributed to previous reports of colonoscopy not being very effective in women or for the detection of lesions in the proximal colon, as Pilonis suggested.

As the authors explain, current guidelines recommend a 10-year screening interval for the average-risk patient when colonoscopy results are negative.

This interval was partially based on the estimated time it was thought to take an adenoma to progress to a carcinoma and partially on the estimated sensitivity of screening colonoscopy.

"We showed that high-quality is a prerequisite for safe intervals between colonoscopies, Pilonis said. "So I would say that if, at a certain age, a patient has a negative colonoscopy of high-quality, a negative colonoscopy is highly predictive of a very low future risk of CRC," she added.

The study was funded by the Polish Ministry of Health.

Ann Intern Med. Published online May 25, 2020. Full text

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