Influence of preoperative Lynch syndrome diagnosis on surgery in patients with colorectal cancer.
Authors: Mohammad Ali Abbass, Sarah M. Nielsen Young, Emily M. Russell, Ed Esplin, Daniel Pineda-Alvarez, Brandie Heald
Journal: Journal of Clinical Oncology (2025)

94 Background: Lynch Syndrome (LS) can guide surgery for colorectal cancer (CRC), particularly for MLH1/MSH2 carriers, 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 (pts) with LS and CRC. Methods: Integrated GGT (Labcorp, formerly Invitae Corp.) and insurance claims (Komodo Healthcare Map) data for adult pts 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 . Χ 2 and t tests and multivariable logistic regression compared GGT results and surgical approach. Results: Of 1616 CRC pts (1553 CC, 63 RC), 15% were LS positive (15% CC, 11% RC). Compared to pts with negative GGT, pts with LS were more likely male, Black, younger at diagnosis and GGT, to have family history of GI/any cancer and to have GGT pre-CRC surgery. Of 129 LS pts with CC and MLH1/MSH2/EPCAM, 41 (32%) had GGT pre-surgery and 20/41 (49%) had TC/TP (Table). 5/6 (83%) of the corresponding RC pts had GGT pre-surgery and 3/5 (60%) had TP. 88 CC MLH1 / MSH2 / EPCAM pts 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 pts had TC/TP than RC pts (p&lt;0.001). Compared to pts with negative GGT, pts with LS and CRC were more likely to have TC/TP (21% vs. 6%, p&lt;0.001), particularly with GGT pre-surgery (43% vs. 13%, p&lt;0.001). RC LS pts with GGT pre-surgery had shorter mean months from GGT to surgery than pts with negative GGT (6 vs 14, p=0.026). CC pts 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 pts with negative or post-surgery GGT. Conclusions: GGT performed pre-surgery for a new diagnosis of CRC was more likely to result in extended procedures, especially in MLH1/MSH2/EPCAM carriers. More data in RC is needed to better understand the influence of GGT on surgical approach. CC surgery type and timing in relation to GGT. Pts w/ CC surgery GGT pre-surgery (N=295) GGT post-surgery (N=1258) Total Partial Colectomy (N=245)N (% total) TC/TP (N=50) N (% total) P-value: partial vs TC/TP^ Total Partial Colectomy (N=1203)N (% total) TC/TP (N=55)N (% total) P-value: partial vs TC/TP^ MLH1 (N=75) 24 (32) 13 (54) 11 (46) 0.001 51 (68) 42 (82) 9 (18) &lt;0.001 MSH2/ EPCAM (N=54) 17 (32) 8 (47) 9 (53) 0.006 37 (69) 29 (78) 8 (22) &lt;0.001 MSH6 (N=49) 13 (27) 11 (85) 2 (15) 1 36 (74) 35 (97) 1 (3) 1 PMS2 (N=51) 6 (12) 3 (50) 3 (50) 0.252 45 (88) 43 (96) 2 (4) 1 LS positive (N=229) 60 (26) 35 (58) 25 (42) &lt;0.001 169 (74) 149 (88) 20 (12) &lt;0.001 LS VUS (N=61) 6 (10) 6 (100) 0 (0) 1 55 (90) 55 (100) 0 (0) 0.526 LS Negative (N=1263) 229 (18) 204 (89) 25 (11) &lt;0.001 1034 (82) 995 (96) 39 (4) 0.006 Note: Excludes pts with RC due to small N. ^Adjusted for multiple testing.