In the Journals

Genetic Testing Underused in Colon Cancer, Especially Young Patients

Genetic testing for mismatch repair deficiency in patients with colorectal cancer remains underused, especially in young adults, according to new research published in JAMA Oncology.

Nestor F. Esnaola, MD, MPH
Nester F. Esnaola

Considering growing support for universal mismatch repair (MMR) deficiency testing in CRC, and established guidelines recommending routine testing in patients younger than 50 years, these findings led investigators to call for interventions targeting groups at risk for guideline nonadherence.

“Mismatch repair (MMR) deficiency of DNA is a characteristic feature of Lynch syndrome and has been observed in up to 15% of sporadic CRCs,” Nestor F. Esnaola, MD, MPH, professor of surgical oncology at Fox Chase Cancer Center in Philadelphia, and colleagues wrote.

While MMR deficiency testing was historically recommended for individuals at risk for high microsatellite instability (MSI-H) tumors based on personal or family history, including younger patients, “most national consortiums [now] recommend universal screening for MSI-H tumors in all patients with newly diagnosed CRC,” they added.

To evaluate the use of MMR deficiency testing amid growing endorsement of universal testing, Esnaola and colleagues identified 152,993 adults within the National Cancer Database, who were diagnosed with invasive colorectal adenocarcinoma between 2010 and 2012 (51.4% men; mean age, 66.9 years).

Overall, only 28.2% received MMR deficiency testing, although the percentage of patients who received testing increased from 22.3% to 33.1% between 2010 and 2012 (P < .001).

Among the 17,218 patients younger than 50 years, just 43.1% were tested, and again the percentage of those tested increased from 36.1% to 48% throughout the study period (P < .001).

Multivariable analysis showed independent predictors of testing among patients of any age included female sex, higher education level, later year of diagnosis, a previous cancer diagnosis, early stage disease, and a higher number of regional lymph nodes examined. Further, factors associated with underuse of MMR deficiency testing included older age, black race, Medicare, Medicaid or no insurance, nonacademic or research facility, late stage disease, rectosigmoid or rectal tumor location, histology (non-mucin-producing adenocarcinoma), unknown or lower tumor grade, and nonreceipt of definitive surgery or colectomy. Among patients aged younger than 50 years, Hispanic ethnicity, nonmetropolitan residence and facility location emerged as additional predictors of testing underuse.

“Of particular concern, our study noted significant independent associations between patient socioeconomic and insurance status as well as cancer program location and type and utilization of MMR deficiency testing, suggesting that patient and health care system-level interventions tailored to groups at risk for nonadherence are warranted to ensure optimal and uniform implementation of newly endorsed, universal testing guidelines,” Esnaola and colleagues concluded.

While this is “a sobering study” of the state of MMR deficiency testing, “some of the reported associations ... are potentially actionable,” Stanley R. Hamilton, MD, of University of Texas MD Anderson Cancer Center in Houston, wrote in a related editorial. “The higher frequency of testing in individuals with higher educational levels and underuse of testing associated with older age, residence in a nonmetropolitan county, origin of the patient from a nonacademic/research facility, and geographic location suggest that expanded education of physicians and patients about MSI-H/dMMR testing could improve adherence to the current guidelines. The lower frequency of testing in association with African American race or Hispanic ethnicity and with Medicare/Medicaid or no medical insurance suggests that addressing underserved and underresourced patient populations is needed.” – by Adam Leitenberger

Disclosures: The researchers report no relevant financial disclosures. Hamilton reports he is a member of the Fred Hutchinson Cancer Research Scientific Advisory Committee, a consultant for LOXO-Oncology, a member of the Halio DX Scientific Advisory Committee, and has a financial relationship with The Johns Hopkins University School of Medicine and Merck & Company.

Genetic testing for mismatch repair deficiency in patients with colorectal cancer remains underused, especially in young adults, according to new research published in JAMA Oncology.

Nestor F. Esnaola, MD, MPH
Nester F. Esnaola

Considering growing support for universal mismatch repair (MMR) deficiency testing in CRC, and established guidelines recommending routine testing in patients younger than 50 years, these findings led investigators to call for interventions targeting groups at risk for guideline nonadherence.

“Mismatch repair (MMR) deficiency of DNA is a characteristic feature of Lynch syndrome and has been observed in up to 15% of sporadic CRCs,” Nestor F. Esnaola, MD, MPH, professor of surgical oncology at Fox Chase Cancer Center in Philadelphia, and colleagues wrote.

While MMR deficiency testing was historically recommended for individuals at risk for high microsatellite instability (MSI-H) tumors based on personal or family history, including younger patients, “most national consortiums [now] recommend universal screening for MSI-H tumors in all patients with newly diagnosed CRC,” they added.

To evaluate the use of MMR deficiency testing amid growing endorsement of universal testing, Esnaola and colleagues identified 152,993 adults within the National Cancer Database, who were diagnosed with invasive colorectal adenocarcinoma between 2010 and 2012 (51.4% men; mean age, 66.9 years).

Overall, only 28.2% received MMR deficiency testing, although the percentage of patients who received testing increased from 22.3% to 33.1% between 2010 and 2012 (P < .001).

Among the 17,218 patients younger than 50 years, just 43.1% were tested, and again the percentage of those tested increased from 36.1% to 48% throughout the study period (P < .001).

Multivariable analysis showed independent predictors of testing among patients of any age included female sex, higher education level, later year of diagnosis, a previous cancer diagnosis, early stage disease, and a higher number of regional lymph nodes examined. Further, factors associated with underuse of MMR deficiency testing included older age, black race, Medicare, Medicaid or no insurance, nonacademic or research facility, late stage disease, rectosigmoid or rectal tumor location, histology (non-mucin-producing adenocarcinoma), unknown or lower tumor grade, and nonreceipt of definitive surgery or colectomy. Among patients aged younger than 50 years, Hispanic ethnicity, nonmetropolitan residence and facility location emerged as additional predictors of testing underuse.

“Of particular concern, our study noted significant independent associations between patient socioeconomic and insurance status as well as cancer program location and type and utilization of MMR deficiency testing, suggesting that patient and health care system-level interventions tailored to groups at risk for nonadherence are warranted to ensure optimal and uniform implementation of newly endorsed, universal testing guidelines,” Esnaola and colleagues concluded.

While this is “a sobering study” of the state of MMR deficiency testing, “some of the reported associations ... are potentially actionable,” Stanley R. Hamilton, MD, of University of Texas MD Anderson Cancer Center in Houston, wrote in a related editorial. “The higher frequency of testing in individuals with higher educational levels and underuse of testing associated with older age, residence in a nonmetropolitan county, origin of the patient from a nonacademic/research facility, and geographic location suggest that expanded education of physicians and patients about MSI-H/dMMR testing could improve adherence to the current guidelines. The lower frequency of testing in association with African American race or Hispanic ethnicity and with Medicare/Medicaid or no medical insurance suggests that addressing underserved and underresourced patient populations is needed.” – by Adam Leitenberger

Disclosures: The researchers report no relevant financial disclosures. Hamilton reports he is a member of the Fred Hutchinson Cancer Research Scientific Advisory Committee, a consultant for LOXO-Oncology, a member of the Halio DX Scientific Advisory Committee, and has a financial relationship with The Johns Hopkins University School of Medicine and Merck & Company.