Influence of Preoperative Lynch Syndrome Diagnosis on Surgery in Patients with Colorectal Cancer
Cancer Genetics and Therapeutics
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Primary Categories:
- Cancer
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Secondary Categories:
- Cancer
Introduction:
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 with LS and CRC.
Methods:
Integrated GGT (Labcorp, formerly Invitae Corp.) and insurance claims (Komodo Healthcare MapTM) 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. Χ2 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 pre-surgery (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.
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 with LS and CRC.
Methods:
Integrated GGT (Labcorp, formerly Invitae Corp.) and insurance claims (Komodo Healthcare MapTM) 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. Χ2 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 pre-surgery (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.
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