Influence of preoperative Lynch syndrome diagnosis on surgery in patients with colorectal cancer.
Authors: Abbass Mohammad Ali , Nielsen Young Sarah M. , Russell Emily M. , Esplin Ed , Pineda-Alvarez Daniel , Heald Brandie 
Published: January 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<0.001). Compared to pts with negative GGT, pts 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). 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)

<0.001

MSH2/
EPCAM
(N=54)

17 (32)
8 (47)
9 (53)

0.006

37 (69)
29 (78)
8 (22)

<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)

<0.001

169 (74)
149 (88)
20 (12)

<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)

<0.001

1034 (82)
995 (96)
39 (4)

0.006

Note: Excludes pts with RC due to small N.

^Adjusted for multiple testing.