Limitations of Current Timing and Frequency of Screening Colonoscopy and Possible Future Direction

Colonoscopy Guidelines of the ACS

The ACS first proposed in 1977 the idea that key to improving survival rates of colorectal cancer was to get an earlier diagnosis of the disease. ¹³ Later on in 1980, they followed up those suggestions by establishing the first recommendations of screening for colon cancer. They recommended a digital rectal exam for men and women over the age of 40 years along with using the gFOBT annually for all those over the age of 50 years combined with a sigmoidoscope examination every 3–5 years after an initial negative examination 1 year apart. ¹⁴ These recommendations provided a way to reduce risk, cost, and inconvenience in screening for colon cancer compared with any prior recommendations. ¹⁵

In a revision done in 1992, the ACS first mentioned the possibility of using a colonoscopy or a double-contrast barium enema every 5–10 years as a screening procedure, but because of the lack of clinical evidence regarding efficacy, availability, cost, and safety of the two procedures, neither was recommended at that time. ¹⁶

In 1997, the ACS first proposed a colonoscopy exam as a recommended screening procedure for men and women over the age of 50 years every 10 years, providing they were at average risk for developing colorectal cancer. The ACS also included that those patients who opted for a screening colonoscopy had no need for an annual gFOBT. The ACS based its recommendation on the guidelines of the Agency for Healthcare Policy and Research (AHCPR), which had released its rationale for colorectal cancer screening in February 1997. ⁸ The AHCPR used a 10-year interval in between each screening colonoscopy because (1) there was strong evidence to suggest that very few clinically important lesions are missed by a colonoscopy and (2) there was indirect evidence from the National Polyp Study that suggested very few polyps would turn into advanced colorectal cancer in less than 10 years. ¹⁷

In 2001, the ACS released an update on colorectal cancer screening and determined that colonoscopy was now the standard for colorectal cancer screening based on recommendations from the ACG, and the beginning age of screening remained 50 years of age as well as the 10-year increments. ¹⁸

In 2008, the current recommendations from the ACS, the U.S. MultiSociety Task Force on Colorectal Cancer, and the American College of Radiology came out in a joint guideline for the screening of colorectal cancer. The recommendation as it stands currently is for men and women over the age of 50 years at average risk for developing colorectal cancer should receive one colonoscopy every 10 years, and it still remained the preferential screening test. ⁶ However, the joint report did mention that there was a lack of randomized controlled trial data that supported that a colonoscopy every 10 years had reduced the incidence of mortality for colorectal cancer, although since a colonoscopy was used to evaluate other screening methods in randomized controlled trials, there was enough evidence to support their guideline. Also in the joint report it was mentioned that the appropriate interval between negative screening colonoscopy exams was uncertain because of lack of evidence providing support for the interval, although they concluded that it was still an acceptable option. ⁶

ACG

The ACG is a group of 7300 gastroenterologists and other healthcare professionals dedicated to clinical research and education in gastrointestinal medicine. In the year 2000, they released a report suggesting their guidelines for the screening of colorectal cancer. In their report, they mentioned that they previously had endorsed the AHCPR guidelines that were recommended in 1997, and they were now releasing a revised update based on two reasons: (1) their recommendations represented the trends and rapidly changing perceptions on how to properly and cost-effectively screen for colorectal cancer, and (2) that many studies on colorectal cancer screening are published frequently and they wanted to keep up with the new data. ⁷

In their report, they recommended that average-risk adults over the age of 50 years should receive a colonoscopy every 10 years. ⁷ They were the first organization to suggest that colonoscopy as the preferred screening option for colorectal cancer. Their evidence for this was based on multiple reasons. First, case-controlled studies on sigmoidoscopy and polypectomy had shown a 60%–70% decrease in colorectal cancer, and that data could be extrapolated to colonoscopy and polypectomy. This extrapolation was because the only major difference between sigmoidoscopy and colonoscopy was that colonoscopy could survey the colon past the splenic flexure. Second, cohort studies on colonoscopy screenings showed a 76%–90% decrease in colorectal cancer. Third, cross-sectional studies showed the prevalence of adenoma detection in screening colonoscopy that was twice that of the FSIG. ⁷ The ACG did, however, mention in their report that there had be no randomized controlled trials or case-controlled studies that demonstrated the effectiveness of colorectal screening by a colonoscopy. In addition to that, the ACG also stated that the interval at which a screening colonoscopy test should be administered had not yet been officially determined by any observational studies. ⁷

In 2008, the ACG released an update to their guidelines with the same age and interval of colonoscopy screening, although they also stressed that making colonoscopy the preferred screening option was better for compliance in patients rather than giving them a range of options as had been done in previous guidelines. ¹²

USPSTF

The USPSTF releases an annual report stating its current recommendations for cancer screening. Their current update made in their report on their recommendations for colorectal cancer screening was in 2008. They concluded in this report that a colonoscopy should be undergone for screening for all individuals at average risk over the age of 50 years every 10 years. They also concluded that those over 75 years of age should stop screening for colorectal cancer. ¹¹ Their rationale for lowering the age of stopping screening colonoscopy from the age of 85 years (which had appeared in earlier reports) to 75 years of age was based on the fact that there was only a small reduction in life-years gained with a relatively large reduction in colonoscopy screenings required. ¹¹ They used data from microsimulation screening analysis (MISCAN) and simulation model of colorectal cancer (SimCRC) to support their claims. In their report they also changed the interval of screening colonoscopy in both the MISCAN and SimCRC to 5 and 20 years. They found that in the MISCAN and SimCRC, when the interval was set to every 5 years that the amount of colonoscopy screenings per 1000 increased based on a 10-year interval and so did the life-years gained. When the interval was set to 20 years, both colonoscopy screenings performed and life-years gained per 100 decreased. ¹¹ They then concluded that their current recommendations struck a good balance between the two screening intervals and settled on men and women from 50 to 75 years of age at a 10-year interval.

AHCPR

In 1994, a panel of experts was assembled by the AHCPR to prepare clinical guidelines for screening of colorectal cancer based upon the best clinical evidence of that day. In 1997, they published their findings stating what they believed to be the best screening options for early detection of colorectal cancer. The significance of that report was that the AHCPR was the first organization to suggest using colonoscopy as a screening procedure. They suggested that a colonoscopy should be done every 10 years by men and women over the age of 50 years at average risk for getting colorectal cancer. ¹⁷ Their rationale was based on the following evidence. First, there was strong clinical evidence that few clinically important polyps were missed by a colonoscopy. Second, a controlled trial showed that surveillance follow-up after an initial negative screening for colorectal cancer showed very low incidence of any advanced adenomas. Third, estimates from pathologists and indirect evidence from the National Polyp Study indicated that very few polyps progress to advanced cancer in less than 10 years. ¹⁷ This suggestion of a 10-year interval proved to be very important because many of the other organizations that published guidelines in the following years would base their suggested interval on this study and all guidelines currently hold this time interval.^6,11,12 In 2003, they released a report again with no change in their recommended interval or starting age for colonoscopy screenings. ¹⁹

Limitations of the Proposed Guidelines

The main limitation that seems to be a common theme when reviewing the colorectal cancer guidelines from various organizations is the lack of a randomized controlled trial that compares a screening colonoscopy with no screening, examining the incidence and mortality of colorectal cancer from each group.^6,12 However, there has been a recent prospective randomized control trial comparing incidence and mortality of distal colorectal cancer in people screened with an FSIG compared with that of usual care. It was found that a FSIG screening every 3–5 years yielded a significant decrease in colorectal cancer incidence and mortality compared with those receiving usual care. ²⁰ Because the only major difference between FSIG and a screening colonoscopy is the amount of the colon surveyed (colonoscopy can observe the colon past the splenic flexure), this study adds to the notion that a screening colonoscopy can reduce the incidence and mortality of colorectal cancer, but still this evidence is not direct.

Another limitation to the proposed guidelines is that appropriate interval for screening colonoscopy has been uncertain because of the lack of long-term follow-up data. ⁶ The interval of every 10 years that was recommended by the AHCPR back in 1997 has still been used in many current guidelines, but again no direct evidence has been there to support it. Evidence showing a 5-year follow-up after a negative colonoscopy was published in 1996, concluding that the interval in between colonoscopy screenings could be expanded beyond 5 years, leading to the recommendation of a 10-year interval, but no studies have determined the specific optimal time.^17,21 This further warrants the need for a prospective randomized control trial to provide evidence for the proper interval.

Other concerns about screening colonoscopy are involved with what age is appropriate to stop routine colonoscopy screenings. The current recommendation offered by the USPSTF is to stop screening colonoscopy at 75 years of age, but this information is based solely off of simulation studies, and a randomized control study evaluating this issue would be preferred. ¹¹ In a study done in 2005 evaluating 178 patients comparing detection rates of colorectal cancer in patients >75 years of age with patients between 65 and 69 years of age, no significant difference was found in rate of detection of colorectal cancer, suggesting the continuation of screening of the elderly. ²² Studies in larger cohorts comparing the risk of screening colonoscopy past the age of 75 years with life-years gained by the patient would help in evaluating the proper stop time for colonoscopy screenings.

In a recent audit done in the United Kingdom evaluating the efficacy and safety of a colonoscopy it was found that out of 20,085 colonoscopies done during a 2-week time period, only 8 resulted in perforations and 52 in significant hemorrhages, accounting for a combined 0.003% chance of adverse outcomes in all colonoscopies performed. ²³ This indicates that there has been significant improvement in safety of colonoscopies and again warrants a study evaluating risk versus life-years gained by patients.

The start age of when to start screening colonoscopies is also in question. In 2005, a study looked at the incidence rate of average-risk patients between 40 and 49 years of age undergoing screening colonoscopies. Out of the 116 average-risk patients examined, the study found 16% of patients had evidence of colorectal cancer. It was concluded by this study that prospective studies of larger cohorts are needed to examine whether the starting age of screening colonoscopies should be lower than 50 years. ²⁴ There is a need for future trials to investigate these recommendations as the limitations of guidelines are also an issue. ²⁵

Then there are other recent developments of relation of colorectal cancer and other chronic diseases like diabetes mellitus. ²⁶ All in all it seems to be clear that more randomized controlled studies should be done to evaluate the efficacy and safety of screening colonoscopies for men and women over the age of 50 years at average risk for developing colorectal cancer with 10-year intervals. Once studies on this specific subject matter are conducted, it will better affirm the most efficacious age and time interval for colonoscopy screenings.

Recommendations for Future Screening Colonoscopy Guidelines

After review of much of the literature on colonoscopy screenings done for average-risk patients, we have come up with our own suggestions for screening colonoscopy. First, computed tomography colonography or virtual colonoscopy should be done at the age of 50 years. It has been documented that the computed tomography virtual colonoscopy with the three-dimensional approach is an accurate form of screening for detection of polyps and colorectal cancer. ²⁷ This form of screening is a lot less invasive than other forms and would help increase compliance with patients. According to some studies there is less than 50% compliance for screening colonoscopy, and more than 50% cancers are outside the guideline age range (i.e., they are either less than 50 or greater than 75 years of age). It should also be known that the cost of a virtual colonoscopy should be lower in the years to come to make it a cost-effective option for screening. ²⁸ In addition, it might assist in diagnosing other silent diseases/problems at the same time. Second, following computed tomography colonography at 50 years of age, a colonoscopy should be performed at 55 years of age, or an average-risk adult should have two colonoscopy screenings done at a 15-year interval between the ages of 50 and 75 years. Third, genetic testing should be done to identify those individuals with a higher risk of developing colorectal cancer and offering them a screening colonoscopy every 5 years, in order for them to undergo a more intense colorectal screening regimen. Although the technology and advancements in medicine have not been able to identify the all the determinants of mutations that directly cause colorectal cancer outside of genetic diseases such as familial adenomatous polyposis, when this technology does exist, it will be paramount to aid in screening for colorectal cancer. ²⁹ For those patients who have undergone a polypectomy, screening should be done for other polyps and colorectal cancer within a minimum of 5 years. ³⁰ We feel that these recommendations provide the best combination for detecting colorectal cancer, increasing patient compliance with screening, and decreasing mortality associated with colorectal cancer.