Abstract
BackgroundLynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. Comparison of prognosis between LS and sporadic CRC (SCRC) were rare, with conflicting results. This study aimed to compare the long-term outcomes between patients with LS and SCRC.MethodsBetween June 2008 and September 2018, a total of 47 patients were diagnosed with LS by genetic testing at Fudan University Shanghai Cancer Center. A 1:2 propensity score matching was performed to obtain homogeneous cohorts from SCRC group. Thereafter, 94 SCRC patients were enrolled as control group. All of enrolled patients received curative surgeries and standardized postoperative monitoring. The long-term survival rates between the two groups were compared, and the prognostic factors were also analyzed.ResultsThe 5-year overall survival rate of LS group was 97.6%, which was significantly higher than of 82.6% for SCRC group (χ2 = 4.745, p = 0.029). The 5-year recurrence free survival rate showed no significant differences between the two groups (78.0% for LS group vs. 70.6% for SCRC patients; χ2 = 1.260, p = 0.262). The 5-year tumor free survival rates in LS group was 62.1% for LS patients, which were significantly lower than of 70.6% for SCRC group (χ2 = 4.258, p = 0.039). Subgroup analysis of recurrent patients show that the LS group had longer overall survival than the SCRC group after combined chemotherapy. By multivariate analysis, we found that tumor recurrence of primary CRC [Risk ratio (95% (confidence interval): 48.917(9.866–242.539); p < 0.001] and late TNM staging [Risk ratio (95% (confidence interval): 2.968(1.478–5.964); p = 0.002] were independent risk factors for OS.ConclusionLS patients have better long-term survival prognosis than SCRC patients, even though the two groups have statistically comparable recurrence free survival. Combined chemotherapy is an effective treatment for LS patients who developed primary CRC recurrence. Standardized postoperative monitoring for LS patients may enable detection of metachronous tumors at earlier stages, which was a guarantee of a favorable prognosis despite lower tumor free survival.
Highlights
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome
We found that overall survival (OS) period in LS patients was significantly longer than in sporadic CRC (SCRC) patients, which may indicate that long-term prognosis for LS patients is better than that of SCRC patients
We used tumor recurrence of primary CRC to calculate recurrence free survival (RFS) and included metachronous tumor occurrence into the calculations for tumor free survival (TFS), because LS patients have higher metachronous tumor occurrence rates, the occurrence of such second primary tumors is different from primary tumor recurrence in clinical significance
Summary
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. Comparison of prognosis between LS and sporadic CRC (SCRC) were rare, with conflicting results. CRC has been recognized as a heterogeneous disease based on different molecular mechanisms, presenting heterogeneous outcomes and drug responses [2,3,4]. Lynch syndrome (LS) is the most common hereditary CRC syndrome. It results from heterozygous pathogenic germline variants in the mismatch repair (MMR) genes (path_MLH1, path_MSH2, path_MSH6, and path_ PMS2), accounting for approximately 3–5% of all cases of CRC [5, 6]. In addition to higher risk for CRC, LS presents significantly higher risks for cancers in organs including the endometrium, ovaries, stomach, small bowel, bile duct, pancreas and upper urinary tract [5, 6]. The consequent tumors present the phenotypes of MMR protein deficiency (dMMR) under immunohistochemistry (IHC) and microsatellite instability (MSI)
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