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Low rate of mismatch repair deficiency testing in colorectal cancer

Roshini Claire Anthony
18 Jan 2018

Despite guidelines advocating mismatch repair (MMR) deficiency testing in individuals with colorectal cancer (CRC), particularly in young adults, uptake of MMR testing remains low, according to a large study from the US.

“[MMR] deficiency testing in patients with [CRC] remains low, even in high-risk populations … [o]ur results demonstrate that, despite long-standing, national guidelines recommending MMR deficiency testing in young patients with CRC, there was significant and persistent underuse of testing during the study period,” said the researchers.

Using data from the National Cancer Database, researchers assessed 152,993 adults diagnosed with invasive colorectal adenocarcinoma between 2010 and 2012 (mean age 66.9 years, 51.4 percent male). Of these, 28.2 percent (n=43,143) underwent MMR deficiency testing, with the proportion increasing between 2010 and 2012 (22.3 and 33.1 percent, respectively). [JAMA Oncol 2017;doi:10.1001/jamaoncol.2017.3580]

Less than half of the 17,218 young adult patients (age 18–49 years) with CRC underwent MMR deficiency testing (43.1 percent, n=7,422), though, as with the overall population, the proportion increased between 2010 and 2012 (36.1 percent vs 48.0 percent; p<0.001). 

Female gender (odds ratio [OR], 1.04; p=0.002), later diagnosis year (OR, 1.48 and 1.81 for 2011 and 2012, respectively; p<0.001 for each comparison vs 2010), previous cancer diagnosis (OR, 1.07; p<0.001), earlier stage of disease (OR, 1.24; p<0.001 for stage 2 vs stage 1), and receipt of chemotherapy (OR, 1.11; p<0.001) were among the factors associated with a higher likelihood of undergoing MMR deficiency testing.

Conversely, factors associated with a lower likelihood of testing included older age (OR, 0.31 for age ≥70 years; p<0.001 vs age <30 years), rectosigmoid or rectal tumour location (OR, 0.92; p=0.01), nonmucin-producing adenocarcinoma (OR, 0.93; p=0.01), grade 2 or unknown grade tumour (OR, 0.93; p=0.04 and OR, 0.61; p<0.001), nonreceipt of definitive surgery (OR, 0.33; p<0.001), and nonreceipt of colectomy (OR, 0.89; p=0.001).

Among younger adults, later diagnosis year (OR, 1.52 and 1.74 for 2011 and 2012, respectively vs 2010) and stage 2 disease (OR, 1.29) were among the factors associated with receipt of MMR deficiency testing while older age (OR, 0.64 for age 40–49 vs <30 years), rectosigmoid or rectal tumour location (OR, 0.76), unknown tumour grade (OR, 0.64), and not undergoing definitive surgery (OR, 0.42; p<0.001 for all) were associated with nonreceipt of testing.

Patients who had ≥12 regional lymph nodes examined during colectomy were more likely to undergo MMR deficiency testing, regardless of age group (OR, 1.44; p<0.001), while those without insurance coverage (OR, 0.84; p=0.0307) or those admitted to a nonacademic or nonresearch facility (OR, 0.44 and 0.63 for comprehensive community cancer programme or community cancer programme, respectively; p<0.001) were less likely to undergo testing.

“[MMR] deficiency of DNA is a characteristic feature of Lynch syndrome and has been observed in up to 15 percent of sporadic CRCs. [MMR] deficiency can be due to germline mutations in DNA MMR genes [MLH1, MSH2, MSH6, or PMS2] or somatic epigenetic silencing of MLH1, which result in unrepaired repetitive DNA sequences,” said the researchers, highlighting that the results of MMR deficiency testing may have both prognostic and therapeutic implications.

“[U]nderuse of testing according to socioeconomic and insurance status potentially suggests that national guidelines are not being equitably applied across all sociodemographic groups … interventions tailored to groups at higher risk for nonadherence to testing guidelines may be warranted,” they said.

 

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Most Read Articles
Stephen Padilla, 6 days ago
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