As a potentially preventable cancer, CRC has been the target of recent public health campaigns and uptake of CRC screening tests is increasing. Individuals with a personal or family history of CRC or adenomatous polyps stand to benefit most from screening and current guidelines recommend different tests and surveillance intervals based on whether an individual’s cancer risk is estimated as average, moderately increased, or very high 18
. In a recent survey, 69% of Maryland residents aged ≥50 years were “up to date” with CRC screening, and 59% had undergone a colonoscopy in the last 10 years20
. In our study, 73% of individuals who met clinical criteria for LS had appropriate surveillance with colonoscopies every 1–2 years, which suggests there is room for improvement in cancer prevention among patients at highest risk for CRC.
Studies of CRC screening in U.S. populations have identified various factors associated with test uptake, such as level of education, income, having health insurance, participating in other cancer screening tests, and receiving a recommendation from their physician for CRC screening 21
. In this sense, the sociodemographic characteristics of the highly motivated subjects in our study cohort would predict they would be ideal participants in CRC screening and, indeed, 94% reported having had at least one colonoscopy. However, only 2 in 3 “cancer unaffected” individuals at highest risk for CRC had colonoscopies at intervals necessary to prevent Lynch-associated neoplasms.
These findings differ dramatically from reports from Finland and the Netherlands, where centralized cancer registries coordinate genetic testing and cancer screening for individuals with hereditary cancer syndromes and compliance with CRC surveillance among individuals with LS approaches 98% 22, 23
. In contrast, in the U.S. the responsibility for identifying and managing patients with hereditary cancer syndromes resides with individual primary care physicians, oncologists, surgeons, and gastroenterologists. Surveys have shown that a minority of clinicians are familiar with diagnosis and management of hereditary CRC 24,12
and simply referring patients for CRC screening because of “family history” may not be sufficient to ensure appropriate care of individuals at risk for hereditary CRC syndromes. In our cohort, half of subjects who had inadequate cancer surveillance reported having colonoscopies every 3–5 years, as recommended by their physicians. While this interval would be appropriate for patients categorized as at “increased familial risk” in CRC screening guidelines 18
, it is not frequent enough to prevent a significant number of Lynch-associated CRCs 7, 8
While it is not a surprise that individuals who had been diagnosed with CRC or who had a close relative with young-onset CRC were more likely to have appropriate surveillance, the finding that genetic evaluation is strongly associated with appropriate surveillance deserves attention. Current guidelines recommend genetic evaluation for individuals with personal or family histories that meet criteria for LS 10
and cost effectiveness analyses support MSI/IHC testing of selected CRC tumors 3
on the assumption that identifying high risk individuals will improve outcomes. To date, evidence that genetic evaluation for LS improves compliance with CRC surveillance has come from a few small studies: a Dutch study of 94 MMR gene mutation carriers found that the prevalence of colonoscopic screening increased from 31–88% following genetic testing 16
and two U.S. studies of 22 and 32 MMR gene mutation carriers each found that subjects increased their uptake of colonoscopy after receiving a positive genetic test result 14, 15
. Our large multicenter study of 181 individuals at risk for LS (including 105 MMR gene mutation carriers) found a strong association between genetic evaluation and appropriate CRC surveillance. Of those who underwent genetic evaluation, 63% reported that they subsequently increased cancer screening. CRC surveillance was appropriate in 80% of subjects who had undergone genetic evaluation compared with 51% in those who had not. The benefit of genetic evaluation was the same, regardless of the outcome of the genetic test (prevalence of appropriate CRC surveillance was 84% for subjects found to carry MMR gene mutations and 81% for those with indeterminate genetic test results). This suggests that the process of genetic evaluation (which at our centers includes genetic counseling, DNA testing, and a clinical visit with physicians with expertise in managing hereditary CRC), rather than just the result of the DNA test, may be an important intervention in educating patients and physicians about the need for specialized CRC surveillance and screening for other extracolonic cancers.
How can we improve CRC surveillance among those at highest risk? Our findings suggest that physician recommendations, rather than patient noncompliance, may be an important target for intervention. CRC screening should not be considered “one size fits all;” discussions about CRC screening should include a detailed review of the patient’s family history. Current CRC screening algorithms are stratified by cancer risk and include specific recommendations for individuals at high risk for genetic syndromes 18
. Although clinical diagnostic criteria for LS remain complex, a number of web-based models allow clinicians to enter a patient’s personal and family history and obtain a predicted probability that he/she carries an MMR gene mutation 25–27
. When individuals are referred for genetic evaluation, it is crucial that results of testing and recommendations for cancer surveillance be discussed with patients and communicated back to the referring physicians to ensure successful follow up.
We recognize that our study has certain limitations. Our study was conducted in a selected population of individuals who had direct or indirect contact with a cancer genetics clinic and agreed to spend 30-minutes completing a questionnaire. Consequently, these were highly motivated individuals who were aware of their family history of CRC. The primary outcome of appropriate cancer surveillance was assessed based on subjects’ self reports of colonoscopy frequency and we were unable to obtain medical record confirmation for many of these reports. However, previous investigations have validated the reliability of patient self reports of endoscopic exams 28–30
and a number of studies, including the U.S. National Health Interview Surveys (NHIS), collect information about CRC screening practices using subject interviews. In this cohort we expected that the frequency of colonoscopic exams was more likely to be over-reported, rather than under-reported. Consequently, we believe our finding that 73% of individuals had colonoscopies every 1–2 years is probably an overestimation of the true prevalence of appropriate CRC surveillance among individuals at risk for LS. We acknowledge that our finding of a strong association between genetic evaluation and appropriate CRC surveillance does not permit us to differentiate whether the effect is attributable to the DNA test itself or to the clinical consultation with specialists in management of hereditary CRC. The clinical genetic evaluations performed at our centers included pre and post test genetic counseling, as is recommended by multiple organizations 31, 5,32
. Because 90% of subjects in this study who had DNA testing for MMR gene mutations had also had genetic counseling, we cannot determine whether genetic testing in the absence of specialist consultation and genetic counseling would afford the same benefit.
Despite these limitations, our data from this large multicenter U.S. study demonstrate that many patients at highest risk for CRC are not screened at intervals necessary for cancer prevention. Among our highly motivated subjects, those who already had a CRC diagnosis, had a first degree relative with CRC diagnosed at age<50, and/or had undergone genetic evaluation were significantly more likely to have colonoscopies at intervals necessary to prevent Lynch-associated CRC. Physician recommendations for less frequent colonoscopies, rather than patient noncompliance, appeared to be an important reason why subjects had colonoscopies less frequently than every 1–2 years. With CRC screening strategies moving toward less-invasive testing at less frequent intervals, our findings reinforce the need for physician-patient discussions about CRC risk which incorporate a detailed family history. As more patients at risk for LS are identified through clinical and molecular testing, it is important to ensure that they and their physicians are aware of the specialized surveillance required for cancer prevention in hereditary CRC syndromes.