P116: Influence of preoperative Lynch syndrome diagnosis on surgery in patients with colorectal cancer

Introduction: Lynch Syndrome (LS) can guide surgery for colorectal cancer (CRC), particularly for MLH1/MSH2 heterozygotes, who may benefit from extended procedures: total colectomy (TC) or total proctocolectomy (TP).We investigated timing of germline genetic testing (GGT) and surgical approach in patients with LS and CRC.Methods: Integrated GGT (Labcorp, formerly Invitae Corp.) and insurance claims (Komodo Healthcare Map) data for adult patients with non-metastatic colon (CC) or rectal (RC) cancer and CRC surgery from 2015-23, 6 months of claims pre-CRC diagnosis, and GGT for EPCAM, MLH1, MSH2, MSH6, and PMS2.2 and t-tests and multivariable logistic regression compared GGT results and surgical approach.Results: Of 1616 CRC patients (1553 CC, 63 RC), 15% were LS positive (15% CC, 11% RC).Compared to patients with negative GGT, patients with LS were more likely male (43% vs 56%, p=0.001),Black (7% vs 13%, p<0.026), younger at diagnosis (mean 55 vs 52, p<0.001) and younger at time of GGT (mean 55 vs 52, p<0.001), to have family history of GI cancer (47% vs 70%, p<0.001) to have family history of any cancer (67% vs 80%, p<0.001) and to have GGT pre-CRC surgery (19% vs 28%, p=0.006).Of 129 LS patients with CC and MLH1/MSH2/EPCAM, 41 (32%) had GGT pre-surgery and 20/41 (49%) had TC/ TP. 5/6 (83%) of the corresponding RC patients had GGT pre-surgery and 3/5 (60%) had TP.88 CC MLH1/MSH2/EPCAM patients had GGT post-surgery and 17/88 (19%) had TC/TP. 1 MLH1/MSH2/EPCAM RC patient had GGT post-surgery and 0 had TP.More CC patients had TC/TP than RC patients (p<0.001).Compared to patients with negative GGT, patients with LS and CRC were more likely to have TC/TP (21% vs 6%, p<0.001), particularly with GGT presurgery (43% vs 13%, p<0.001).Reassuringly, CRC patients with LS variant(s) of uncertain significance results did not have higher odds of undergoing TC/TP compared to patients with negative results (0/63 (0%) vs 81/1317 (6%), p=0.048).RC LS patients with GGT pre-surgery had shorter mean months from GGT to surgery than patients with negative GGT (6 vs 14, p=0.026).CC patients with MLH1 or MSH2/EPCAM and GGT pre-surgery had higher odds of undergoing TC/TP (odds ratio (OR): 6, confidence interval (CI): 3-10; OR: 7, CI: 4-14; OR: 4, CI: 2-6) than patients with negative or post-surgery GGT.Neither MSH6 or PMS2 were significantly associated with increased odds of TC/TP compared to patients with negative results.Conclusion: GGT performed pre-surgery for a new diagnosis of CRC was more likely to result in extended procedures, especially in MLH1/MSH2/EPCAM carriers, which is concordant with guidelines.More data in RC is needed to better understand the influence of GGT on surgical approach.