Sigmoidoscopy Screening Reduces CRC, Mortality

A single sigmoidoscopy screening significantly reduced the long-term incidence of colorectal cancer (CRC), according to a new pooled analysis of four randomized trials.

Although endoscopic screening provides an opportunity for early identification and removal of premalignant polyps, data quantifying the long-term effects of sigmoidoscopy screening are lacking, corresponding author Frederik E. Juul, MD, said in an interview.

“Sigmoidoscopy screening have been shown to reduce colorectal cancer incidence and mortality, but it was unknown how long-lasting the effects were, and whether the effect differed by sex or age,” Juul said.

“For the first time, we were able to pool data from all four randomized sigmoidoscopy screening trials and include data from recent updates from two of the trials (U.S. and Italy), which means that we were able to answer these questions better than ever before,” he said.

In the pooled analysis, published in Annals of Internal Medicine, researchers from Norway, the United States, Italy, and the United Kingdom reviewed data from four studies with at least 15 years of follow-up. The analysis included 137,493 individuals randomized to at least one sigmoidoscopy screening and 137,459 randomized to usual care.

The primary outcomes were the incidence and mortality of CRC after sigmoidoscopy screening, compared with usual care, in adults with average CRC risk aged 55-64 years. Secondary outcomes included CRC incidence and mortality based on distal versus proximal colon, sex, and older versus younger age group (55-59 years vs. 60-64 years at study enrollment).

After 15 years’ follow-up, the pooled cumulative incidence of CRC was 1.84 cases per 100 persons in the screening group versus 2.35 cases per 100 persons in the usual-care group, representing a 21% reduction in incidence among those who were screened.

The pooled cumulative CRC mortality was 0.51 deaths per 100 persons in the screening group versus 0.65 deaths per 100 persons in the usual-care group, representing a 20% reduction in CRC mortality for those who were screened, the researchers noted. The all-cause mortality was reduced by 2% in the screening group compared with usual care; the pooled cumulative all-cause mortality was 14.3 deaths per 100 persons in the screening group versus 14.6 deaths per 100 persons in the usual-care group.

In terms of secondary outcomes, the significant reductions in CRC incidence and mortality were confined to the distal colon, with no significant differences observed in the proximal colon, the researchers noted. The reasons for this difference are unclear. Previous studies of three of the four trials showed a small reduction in CRC in the proximal colon, but may be related to the longer follow-up in the analysis of four trials.

The incidence of CRC varied by gender, with an incidence reduction of 25% for men versus 16% for women. The reasons for the gender difference are yet to be undetermined, but may include differences in the quality of bowel preparation, the greater technical challenge of screening women, and the higher incidence and proportion of proximal colon cancer versus distal colon cancer in women, the researchers noted.

“The long-term benefit of one single procedure was probably what surprised us the most,” Juul said in an interview. “Not only were the cumulative incidence and mortality lower in screened individuals 15 years after the procedure, but the yearly incidence was consistently lower in screened individuals compared to usual care, even at the end of the follow-up period.

“Although a previous study in Norway had indicated a sex difference in effect, we were surprised to see this in a pooled analysis across trials in four different countries,” he added.

Data May Drive Screening Guidelines

The main finding of the study is that sigmoidoscopy screening with investigation of the distal colon provides at least 15 years of protection against colorectal cancer; “this may have an impact on how often average-risk individuals needs to be screened,” Juul said in an interview.

As for additional research, ongoing studies are examining primary colonoscopy screening, including a study recently published in the New England Journal of Medicine, Juul said.”Our study investigating sigmoidoscopy screening has a longer follow-up and it will be interesting to see if primary colonoscopy screening is equally or more effective as sigmoidoscopy at 15-years follow-up.”

More research is needed on direct comparisons of different colorectal cancer screening methods such as sigmoidoscopy and colonoscopy, said Juul. In addition, “The optimal surveillance interval in individuals identified at screening to be low- or high-risk of developing colorectal cancer are unknown,” he said.

“Our research group is involved in trials [the EPoS trials] looking into this question, but there are still years until we have the final results,” he added.

The findings were limited by several factors including the variation in methodology among the four trials and the lower number of individuals referred for colonoscopy in the U.K. and Italian trials, lack of analysis of potential confounding variables, and less granular data from the U.K. trial because of privacy regulations, the researchers wrote.

However, the findings were strengthened by the large study population, long-term follow-up, and detailed data, and they indicate a “significant and sustained” effect of screening sigmoidoscopy for the long-term reduction of CRC incidence and mortality, the authors concluded.

Findings Can Inform Shared Decision-Making

“Colon cancer is the third-leading cause of death in the United States in men and women, and the second-leading cause of cancer deaths if we were to combine both genders,” Noel Deep, MD, said in an interview. “Sigmoidoscopy is more acceptable as a screening tool compared to a colonoscopy because of the lower risk of bowel injury, fewer side effects and less of a bowel prep, and also less need for sedation. This current study confirms prior data, including the 2012 PLCO trial, that it [sigmoidoscopy] reduces the incidence and mortality from colorectal cancer.”

The study findings were not surprising, given the prior knowledge and evidence of the benefits of sigmoidoscopy, Deep said, who was not involved in the study. However, “the fact that a single sigmoidoscopy led to decreased incidence and decreased mortality at 15 years was surprising to me, as current models suggest increasing incidence of proximal colon adenomas and cancers, which did not seem to be the case in this study.”

The current study can help primary care physicians and advance practice clinicians in patient counseling by supporting sigmoidoscopy as an option for patients who are unwilling to commit to a full colonoscopy, Deep said. However, “the patients should be advised that abnormal findings on the sigmoidoscopy would necessitate them being referred for a colonoscopy, and also the limitations of a sigmoidoscopy in detecting polyps or cancers in the cecum, ascending colon, transverse colon and descending colon.”

Looking ahead, “I would like to see research into the appropriate age for colorectal cancer screening using sigmoidoscopy and any benefit in offering this option at an earlier age,” Deep said. He also expressed a wish to know more about the reasons for the decreased benefit of screening sigmoidoscopy in women, and the reasons for the observed difference in all-cause mortality between genders.

“I would also like to see what the results of screening colonoscopies in a general population would reveal, and if it would reveal similar benefits, and also if there would be a gender difference or age-based difference in outcomes,” he said.

The study was supported by the Health Fund of South-East Norway. The researchers had no financial conflicts to disclose. Deep had no financial conflicts to disclose, but serves on the editorial advisory board of Internal Medicine News.

This article originally appeared on, part of the Medscape Professional Network.

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