| Summary: | Surveyed Canadian laboratory managers and directors have identified DNA mismatch repair (dMMR) testing as a laboratory test that is potentially over-utilized. According to clinical experts, dMMR testing appears to be transitioning from an approach aimed at identifying patients and families with Lynch syndrome into a tumour phenotyping procedure that can be used to predict the prognosis of colorectal cancer (CRC) and to guide decisions for adjuvant chemotherapy. The use of a test with a prognostic and predictive value falls under the realm of "personalized medicine." According to oncology and pathology experts, this recent application of dMMR testing is the major driver of new test requisitions. This transition has led to an increased demand for the test, with unclear benefits for the patient or family members. In general, there is a lack of clarity regarding when the tests should be ordered and the impact of dMMR status on CRC outcomes in the current era of oxaliplatin- and irinotecan-based chemotherapy. The central question, however, is whether universal dMMR testing of primary CRC tumours is a viable and desirable option given the known limitations of Lynch syndrome pre-selection criteria based on age, history, and pathology, and recognizing the potential utility of dMMR for personalizing cancer therapy. Missed cases of Lynch syndrome resulting from a targeted dMMR testing strategy that is restricted to pre-selected high-risk individuals (e.g., selected based on the Revised Bethesda Guidelines) can be problematic and costly for the system, which would potentially support broader (universal) dMMR testing of all CRC tumours. Alternatively, universal testing carries with it additional costs associated with testing all CRC patients, most of whom will not have Lynch syndrome
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