Million-Strong Study Supports CRC Screening Every 10 Years

Liam Davenport

December 24, 2018

Clinicians following guideline recommendations to screen for colorectal cancer once every 10 years can reassure their patients that the time interval is effective and does not put them at increased risk, conclude US investigators.

Researchers evaluated more than 1.2 million Californians aged 50 to 75 years who were enrolled in a health plan. They compared unscreened individuals with those who had a negative colonoscopy result over a 10-year period.

The results showed that the relative risk of developing colorectal cancer in people with a negative result at 10 years was 46% lower than that for unscreened individuals; the relative risk of colorectal cancer death was 88% lower.

The research was published online December 17 in JAMA Internal Medicine.

Lead author Jeffrey K. Lee, MD, Division of Research, Kaiser Permanente Northern California, Oakland, said in a press release: "Our study shows that, following a colonoscopy with normal findings, there is a reduced risk of developing and dying from colorectal cancer for at least 10 years."

These findings suggest, said Lee, that physicians "can feel confident" about the guideline-recommended 10-year rescreening interval after a negative colonoscopy in which no colorectal cancer or polyps were found.

"There is now solid evidence supporting that recommendation," he said.

Senior author Douglas A. Corley, MD, PhD, MPH, also of Kaiser Permanente Northern California, added: "This large study is the first with a high enough number of average-risk individuals to evaluate cancer risks after colonoscopy examinations, compared with no screening."

The study provides "greater certainty regarding the appropriate timing for rescreening after a negative colonoscopy," he said.

Asked for comment, Robert A. Smith, PhD, vice president of cancer screening, American Cancer Society in Atlanta, Georgia, said that "the new data show that a 10-year interval is pretty effective."

Approximately 63% of eligible individuals in the United States undergo colorectal cancer screening, Smith told Medscape Medical News. In the majority of cases, screening is opportunistic, with patients referred as a result of another encounter, he explained.

The current study, said Smith, "probably reinforces in people's minds the importance of screening.... It's widely accepted that colorectal cancer screening is a good thing."

On the other hand, some patients either do not undergo colonoscopy or do not prepare for the procedure properly and end up having to cancel.

"A concern is raised that we have uneven quality of colonoscopy in this country," he said.

"Just because you've had a normal examination doesn't mean that there aren't some lesions in there that were overlooked but could potentially grow to become malignancies in the interval before your next examination is due," Smith continued.

Echoing previous suggestions that "a reasonable and safe thing to do is a fecal immunochemical test, say, at 5 years," Smith argued that "a high-sensitivity stool test would have the opportunity to pick those [malignancies] up."

Study Details

Although current guidelines recommend that individuals with a negative colonoscopy result be rescreened after 10 years, the California investigators say the evidence supporting this is "modest" and that that recommendation is based on estimates of colonoscopy sensitivity and the time it takes for adenoma to progress.

Colorectal cancer is, however, a heterogeneous disease, and the few studies that have been conducted on long-term risk for colorectal cancer have suggested that a 10-year screening interval might either be too short or too long.

To investigate further, the team conducted a retrospective cohort study of members of Kaiser Permanente Northern California, an integrated healthcare delivery organization serving approximately 4 million individuals.

They included health plan members enrolled between 1998 and 2015 who were aged 50 to 75 years, had been continuously enrolled ≥1 years, and were at average risk for colorectal cancer.

This yielded a total of 1,251,318 eligible participants, for whom 9,339,354 person-years of follow-up information was available. The mean age of the participants was 55.6 years at entry, and 50.9% were men.

During 4,639,809 person-years of unscreened follow-up, 5743 colorectal cancer cases were diagnosed, of which 1821 (31.7%) were proximal and 2588 (45.1%) were of advanced stage.

Among 99,166 individuals who contributed 417,987 person-years of negative colonoscopy follow-up, 184 colorectal cancer cases were diagnosed, of which 94 (51.1%) were proximal and 91 (49.5%) were of advanced stage.

In the unscreened cohort, colorectal cancer incidence rates increased from 62.9 per 100,000 person-years in year 1 to 224.8 per 100,000 person-years in year 12. The mortality rate increased from 10.5 per 100,000 person-years to 192.0 per 100,000 person-years over the same period.

Among individuals with a negative colonoscopy result, the incidence of colorectal cancer increased from 16.6 per 100,000 person-years to 133.2 per 100,000 person-years from year 1 to year 10. The mortality rate increased from 6.8 per 100,000 person-years in year 1 to 92.2 per 100,000 person-years in year 12.

A negative colonoscopy result was associated with a marked reduction in the risk for colorectal cancer compared with not undergoing screening, at an adjusted hazard ratio of 0.05 at year 1 or less and 0.54 at year 10, with all reductions significant.

The team also calculated that there was significant reduction in colorectal cancer mortality with a negative screening result vs not undergoing screening, at an adjusted hazard ratio of 0.04 at year 1 or less and 0.12 at year 10. All reductions were significant.

Looking more widely at the research program conducted by Lee and colleagues, Smith said: "This group has now had a series of articles that are providing us with some outstanding data on the protective effects of colorectal cancer screening, but also explaining what accounts for the deaths that we still see.

"For example, there was a recent one that showed that failure to follow up adults who have a positive stool test accounts for a significant fraction of the deaths from colorectal cancer.... They are a completely avoidable cause of death, if people had just been properly followed up after a positive test."

Moreover, he believes that more is to come from the dataset.

"For example, if they were to examine individual characteristics for what factors are associated with a colorectal cancer appearing before the next colonoscopy, that means that you could potentially at some point refer some patients to a wider screening interval and some patients to a narrower one," Smith said.

"Another question that's on everybody's mind is, let's say you start screening at the age of 50, and your first colonoscopy shows that you don't have any polyps, you have a normal examination."

He explained that, if results of the second examination 10 years later are identical to the first, "that tells us you've just not the kind of person that grows polyps.

"At that point, could we safely say you're done with screening? That would be great if we could."

Smith added: "I don't think anyone would be sad about not having to have another colonoscopy."

The study was conducted within the National Cancer Institute–funded Population-Based Research Optimizing Screening Through Personalized Regimens consortium and was supported by the National Cancer Institute, an American Gastroenterological Association Research Scholar Award, and the Sylvia Allison Kaplan Foundation. One study author is a member of the US Preventive Services Task Force. The other authors have disclosed no relevant financial relationships.

JAMA Intern Med. Published online December 17, 2018. Full text

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