Racial disparities in interval colorectal cancer

A recent study looked at the racial/ethnic disparities in the development of interval colorectal cancer, defined as cancers that developed in a screened population but either were missed of the time of screening or developed de novo within the recommended screening/surveillance intervals (see colon ca screening inc interval ca in black pts AIM2017 in dropbox, or DOI: 10.7326/M16-1154).

Details:

-- a population-based cohort study of  Medicare enrollees aged 66-75 who had colonoscopy between 2002 and 2011, followed through 2013, with  linkage to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program

-- total study population 61,433: 51,313 white/4196 black/2696 Asian/1164 Hispanic

-- median age at index colonoscopy 70, 60% female (though higher in black and Hispanic persons), poverty level as defined by the ZIP Code of the patient's residence was high in 32% white/69% black/36% Asian/67% Hispanic, urban 83% white/89% black/ 98% Asian/98% Hispanic, Charlson Comorbidity Index>= 2 in 2.5% white/6.5% black/3% Asian/6% Hispanic (reflects higher rate of comorbidities)

-- similar screening colonoscopy rates between black and white persons (79.5% versus 80.7%), as well as similar polypectomy rates at the index colonoscopy (23.4% versus 24.7%)

-- 2735 cases of interval colorectal cancer (CRC) were identified over 235,146 person-years of follow-up

    -- proximal 66% white/56% black/46% Asian/62% Hispanic

    -- rectum 18% white/25% black/35% Asian

    -- other data not provided because numbers too low/concerns about protecting patient confidentiality

-- interval CRC was defined as a diagnosis 6-59 months after colonoscopy

-- interval CRC, when found, was mostly within three years of prior screening: 66% white/71% black/72% Asian/65% Hispanic

-- the study also evaluated whether any variation in incidence was related to the quality of the colonoscopy, as measured by the physicians' polyp detection rate (PDR), with higher rate suggesting higher quality colonoscopy performed (a validated instrument)

Results:

-- the probability of an interval CRC by the end of the follow-up was 7.1% in black persons and 5.8% in white persons, a 32% increase, HR 1.32 (1.15-1.51), after adjusting for age, sex, and year of colonoscopy (this ratio did not change with further adjustment by ZIP Code, comorbidity, or whether polypectomy was done at the index colonoscopy). The probability was lower in Hispanic (4.4%) and in Asian persons (3.8%)

-- 52.8% of black persons versus 46.2% of white persons received colonoscopy from physicians who had a lower PDR. This PDR rate was significantly associated with interval CRC risk. Overall, the risk for an interval CRC was higher in patients whose colonoscopy was performed by physicians in the lowest quartile of PDR, with a dose-response curve

-- However, adjustment for PDR did not alter the above HRs, decreasing the HR minimally from 1.32 to 1.31. Black persons still had a 35% increased interval cancer risk in those seeing physicians in the third-highest PDR quartile and 74% increase in those in the highest quartile. Also adjustment for colonoscopy by indication did not affect the results (see below).

-- the disparity was more pronounced for cancer of the rectum, with a 70% increased risk [HR 1.70 (1.25-2.31)] and a 25% increase in the distal  colon [HR 1.45 (1.00-2.11)], but a nonsignificant difference in proximal cancer [HR 1.17 (0.96- 1.42)]

-- Black persons also had a significant 60% higher risk of distant diseaseassociated with an interval CRC, but not for regional or local disease

Commentary:

-- background: CRC is the third most common type of cancer in men and women, and the second leading cause of cancer-related deaths in the US. Interval CRC accounts for 3-8% of the CRC cases.

--There are important ethnic/racial disparities: black persons have the highest incidence of and mortality from CRC, 22 to 27% higher than white persons, as well as earlier mean age of CRC onset/higher % of cancers under age 50

-- It is difficult to pinpoint the causes for these racial differences. Other studies have suggested that approximately 40% of the disparities in CRC incidence are from lower utilization of screening among black persons (though not found in this study). The above study looked at quality of screening, using PDR as a surrogate measure, and did find that black persons had more colonoscopies by physicians with lower PDR suggesting lower quality screening (though adjusting for this did not find any difference). This study did not look at other potential quality measures such as cecal intubation rates, colonoscopy withdrawal times, adequacy of bowel preparation, or completeness of polyp resection. In addition, there are no data about the characteristics/aggressiveness of cancers found, such as microsatellite instability. Also, as a large data-mining study, they do not have the actual specific indications for the colonoscopy itself though they did use patient characteristics and gastrointestinal conditions/symptoms within the prior 12 months to stratify screening versus non-screening. There was also no specific data about adenoma detection rate in the data, though other studies have suggested that PDR is well-correlated in other studies

-- there may well be genetic differences in colon cancer predisposition among the groups, see blog  http://gmodestmedblogs.blogspot.com/2017/06/nature-vs-nurture-studies-on-lipids-and.html  for a discussion of the interplay between nature and nurture

-- it was notable that black persons had more interval cancers in the distal colon, though still more than half of the interval cancer lesions were still in the proximal colon in general. These distal lesions are easier to reach endoscopically and have fewer difficult to-detect sessile polyps, so are more effectively assessed/treated by colonoscopy. Estimates of 10 to 16% of proximal colon tumors are missed; and about 37% of interval rectal cancers are missed (? If there are racial/ethnic differences in these numbers). Though, the efficacy of detecting proximal lesions in preventing CRC deaths is much lower than distal lesions. However, despite the fact that distal lesions are easier to detect on colonoscopy, the important shift in pickup for black persons is the 60% higher incidence of distant disease in the interval cancers.

-- another caveat is that black persons in this study were more likely to be poorer, urban, female and have more medical comorbidities, so there might well have been uncontrolled biases in the above observational study

-- Asian persons have similar polyp detection rates as compared to white persons in prior studies. The lower incidence of interval cancers found in the current study is consistent with slower progression to cancer in this group.

So, the study does find a pretty dramatic increase in interval colon cancers in black persons. And, at the time of these diagnoses, the cancers were more aggressive and had more distant spread. It therefore does raise the question of whether there should be different criteria for colonoscopy screening based on race.

-- for example, some guidelines suggest that black persons have colonoscopy beginning at an earlier age, with a recent suggestion of age 45 (this will be commented on further in an upcoming blog on new colorectal screening guidelines).

-- the study also raises the question of whether there should be shorter surveillance intervals in black persons (and perhaps longer intervals in Asian patients). I would caution here that we do not have the important clinical outcome data to support this conclusion. And, the fact that these tumors often manifested themselves within three years, many already with distant spread in black persons, may suggest that increased screening would not be useful.

--so, we really need a large prospective RCT to assess the appropriate interval for CRC screening for different racial/ethnic groups, with granular data about the quality of the colonoscopy preparation, the adequacy of polyp resection, more specifics about the aggressiveness of polyps resected, etc., prior to submitting a large number of people do a pretty difficult, invasive and not-entirely-benign screening test, as well as potentially very aggressive treatment regimens depending on the outcome. There might also be a role of FIT testing versus colonoscopy in this group, or perhaps colonoscopy at the usual intervals but more annual FIT testing in between.