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WHAT YOU DON'T KNOW CAN HURT YOU: PREOPERATIVE MISMATCH REPAIR DEFICIENCY TESTING AFFECTS SURGICAL DECISION MAKING
Jared Hendren
*, Leonardo Duraes, Joshua Sommovilla, Carol A. Burke, Carole Macaron, Michael Cruise, Sarah McGee, David Liska
Cleveland Clinic, Cleveland, OH
Guidelines recommend all colorectal cancers (CRCs) undergo testing with MSI PCR or MMR IHC for evidence of MMR deficiency (dMMR). However, there is lack of standardization regarding if this testing should be done on preoperative biopsy specimen or resected surgical specimen. Screening for dMMR has implications for diagnosing Lynch Syndrome (LS) and use of immunotherapy (IT) which has led to updated guidelines recommending dMMR testing be performed at time of CRC diagnosis instead of waiting to test a resection specimen. This study aims to assess potential implications of dMMR testing done at time of diagnosis on surgical decision making.
Natural language processing was used to query pathology reports at our institution between 2010-2021 to identify unselected CRCs. Patient demographics, specimen type, frequency of dMMR results, and CRC stage were recorded. The number of CRCs undergoing dMMR testing on biopsy or resection was assessed. Testing for BRAF pathogenic variant (PV) or MLH1 promoter hypermethylation was recorded to assess how many dMMR tumors indicated a sporadic tumor. For dMMR tumors indicative of LS, medical records were reviewed to obtain genetic counseling (GC) and testing (GT) results. Surgery type was recorded for patients with a LS PV to assess how many underwent extended vs segmental resection. Finally, the number of locally advanced dMMR CRCs was determined to assess how many patients may benefit from IT.
5157 CRCs were identified of which 2231(43.2%) tumors underwent MSI PCR and 4644 (90.0%) underwent MMR IHC. 804 (15.6%) tumors had evidence of dMMR; 111 (13.8%) tested on biopsy and 693 (86.2%) on resection specimen. 581 (72.3%) dMMR tumors had a BRAF PV or MLH1 promoter hypermethylation. Of patients with dMMR suspicious for LS, 150 (67.3%, 150/223) were referred for GC. 105 (70%, 105/150) completed GC, 95 (90%, 95/105) completed GT, and 48 (45.7%, 48/105) were germline carriers of a LS PV. There were 14 (29.2%) LS patients who had dMMR screening on biopsy specimen vs 34 (70.8%) on resection specimen. 7 (50.0%) LS patients had an extended colonic resection (ER) after dMMR testing on biopsy specimen vs only 5 (14.7%) on resection specimen (p=0.02). 554 (68.9%, 554/804) dMMR CRCs were locally advanced which could be potential candidates for neoadjuvant IT with or without organ preservation and 504 (91.0%, 504/554) were diagnosed after resection. Overall, 568 (70.6%, 568/804) patients would have special considerations (potential ER or IT) before surgery had their MMR status been known.
In this CRC patient population, dMMR results available preoperatively could guide potential decisions for neoadjuvant IT and discussion regarding ER for LS. Thus, surgeons should pay close attention to obtaining and reviewing dMMR results preoperatively as these results may affect decision making in a small but significant subset of patients.
Figure 1: Special Considerations for dMMR Colorectal CancersThis figure displays the number of locally advanced colorectal cancers who, with current knowledge, may benefit from neoadjuvant immunotherapy with or without organ preservation and also shows the number of patients diagnosed with Lynch Syndrome who may benefit from preoperative discussion regarding extended colonic resection.
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