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Shaikh T, Handorf EA, Meyer JE, Hall MJ, Esnaola NF
Mismatch Repair Deficiency Testing in Patients With Colorectal Cancer and Nonadherence to Testing Guidelines in Young Adults
JAMA Oncol (2018) 4:e173580.
Importance: Mismatch repair (MMR) deficiency of DNA has been observed in up to 15% of sporadic colorectal cancers (CRCs) and is a characteristic feature of Lynch syndrome, which has a higher incidence in young adults (age, <50 years) with CRC. Mismatch repair deficiency can be due to germline mutations or epigenetic inactivation, affects prognosis and response to systemic therapy, and results in unrepaired repetitive DNA sequences, which increases the risk of multiple malignant tumors. Objective: To evaluate the utilization of MMR deficiency testing in adults with CRC and analyze nonadherence to long-standing testing guidelines in younger adults using a contemporary national data set to help identify potential risk factors for nonadherence to newly implemented universal testing guidelines. Design, Setting, and Participants: Adult (age, <30 to >/=70 years) and, of these, younger adult (<30 to 49 years) patients with invasive colorectal adenocarcinoma diagnosed between 2010 and 2012 and known MMR deficiency testing status were identified using the National Cancer Database. The study was conducted from March 16, 2016, to March 1, 2017. Exposures: Patient sociodemographic, facility, tumor, and treatment characteristics. Main Outcomes and Measures: The primary outcome of interest was receipt of MMR deficiency testing. Multivariable logistic regression was used to identify independent predictors of testing in adult and/or young adult patients. Results: A total of 152993 adults with CRC were included in the study (78579 [51.4%] men; mean [SD] age, 66.9 [13.9] years). Of these patients, only 43143 (28.2%) underwent MMR deficiency testing; the proportion of patients tested increased between 2010 and 2012 (22.3% vs 33.1%; P<.001). Among 17218 younger adult patients with CRC, only 7422 (43.1%) underwent MMR deficiency testing; the proportion tested increased between 2010 and 2012 (36.1% vs 48.0%; P < .001). Irrespective of age, higher educational level (OR, 1.38; 95% CI, 1.15-1.66), later diagnosis year (OR, 1.81; 95% CI, 1.65-1.98), early stage disease (OR, 1.24; 95% CI, 1.18-1.30), and number of regional lymph nodes examined (>/=12) (OR, 1.44; 95% CI, 1.34-1.55) were independently associated with MMR deficiency testing, whereas older age (OR, 0.31; 95% CI, 0.26-0.37); Medicare (OR, 0.89; 95% CI, 0.84-0.95), Medicaid (OR, 0.83; 95% CI, 0.73-0.93), or uninsured (OR, 0.78; 95% CI, 0.66-0.92) status; nonacademic vs academic/research facility type (OR, 0.44; 95% CI, 0.34-0.56); rectosigmoid or rectal tumor location (OR, 0.76; 95% CI, 0.68-0.86); unknown grade (OR, 0.61; 95% CI, 0.53-0.69); and nonreceipt of definitive surgery (OR, 0.33; 95% CI, 0.30-0.37) were associated with underuse of MMR deficiency testing. Conclusions and Relevance: Despite recent endorsement of universal use of MMR deficiency testing in patients with CRC and well-established guidelines aimed at high-risk populations, overall utilization of testing is poor and significant underuse of testing among young adults persists. Interventions tailored to groups at risk for nonadherence to guidelines may be warranted in the current era of universal testing.
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Publication Date: 2018-02-08.
PMCID: PMC5838708
Last updated on Wednesday, February 05, 2020