TY - JOUR
T1 - Mismatch repair status and synchronous metastases in colorectal cancer
T2 - A nationwide cohort study
AU - Nordholm-Carstensen, Andreas
AU - Krarup, Peter-Martin
AU - Morton, Dion
AU - Harling, Henrik
AU - Danish Colorectal Cancer Group
N1 - © 2015 UICC.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis. A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial logistic- and Cox-regression and proportional excess hazards analyses were used for confounder adjustment and to adjust for the general population mortality. In total, 983 of 6,692 patients (14.7%) had dMMR and 935 (14.0%) had SCCM. dMMR was associated with a decreased risk of SCCM, adjusted Odds Ratio (aOR)=0.54 (95% confidence interval (CI):0.40-0.70, p<0.001). The association only applied to confined hepatic metastases (aOR=0.30, 95%CI: 0.18-0.49, p<0.001), whereas the presence of confined pulmonary metastases (aOR=0.71, 95% CI: 0.39-1.29, p=0.258) or synchronous hepatic and pulmonary metastases (aOR=0.69, 95% CI:0.26-1.29, p=0.436) were unaffected by MMR. MMR in patients with SCCM had no impact on survival (Cox: adjusted Hazard Ratio (aHR)=0.76, 95% CI: 0.54-1.06, p=0.101; Proportional excess hazards: aHR=0.73, 95% CI: 0.50-1.07, p=0.111) when adjusting for other prognostic factors. The metastatic pattern varied according to MMR status. MMR had no impact on survival in patients with UICC Stage IV CRC. These findings may be important for the understanding of the metastatic processes and thus for optimizing staging and treatment in CRC patients. What's new? At the time of diagnosis, more than one-fifth of colorectal cancer (CRC) patients present with stage IV disease, involving synchronous metastases, which are notoriously difficult to manage. This study suggests that the metastatic pattern in stage IV CRC depends at least in part on the status of the mismatch repair (MMR) system. In particular, deficient MMR was associated with a reduced risk of synchronous metastases confined to the liver. No such association was detected for metastases to the lungs. MMR status also had no impact on survival among stage IV patients.
AB - The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis. A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial logistic- and Cox-regression and proportional excess hazards analyses were used for confounder adjustment and to adjust for the general population mortality. In total, 983 of 6,692 patients (14.7%) had dMMR and 935 (14.0%) had SCCM. dMMR was associated with a decreased risk of SCCM, adjusted Odds Ratio (aOR)=0.54 (95% confidence interval (CI):0.40-0.70, p<0.001). The association only applied to confined hepatic metastases (aOR=0.30, 95%CI: 0.18-0.49, p<0.001), whereas the presence of confined pulmonary metastases (aOR=0.71, 95% CI: 0.39-1.29, p=0.258) or synchronous hepatic and pulmonary metastases (aOR=0.69, 95% CI:0.26-1.29, p=0.436) were unaffected by MMR. MMR in patients with SCCM had no impact on survival (Cox: adjusted Hazard Ratio (aHR)=0.76, 95% CI: 0.54-1.06, p=0.101; Proportional excess hazards: aHR=0.73, 95% CI: 0.50-1.07, p=0.111) when adjusting for other prognostic factors. The metastatic pattern varied according to MMR status. MMR had no impact on survival in patients with UICC Stage IV CRC. These findings may be important for the understanding of the metastatic processes and thus for optimizing staging and treatment in CRC patients. What's new? At the time of diagnosis, more than one-fifth of colorectal cancer (CRC) patients present with stage IV disease, involving synchronous metastases, which are notoriously difficult to manage. This study suggests that the metastatic pattern in stage IV CRC depends at least in part on the status of the mismatch repair (MMR) system. In particular, deficient MMR was associated with a reduced risk of synchronous metastases confined to the liver. No such association was detected for metastases to the lungs. MMR status also had no impact on survival among stage IV patients.
KW - Adenocarcinoma
KW - Aged
KW - Aged, 80 and over
KW - Cohort Studies
KW - Colorectal Neoplasms
KW - DNA Mismatch Repair
KW - Denmark
KW - Female
KW - Humans
KW - Lymphatic Metastasis
KW - Male
KW - Middle Aged
KW - Proportional Hazards Models
U2 - 10.1002/ijc.29585
DO - 10.1002/ijc.29585
M3 - Journal article
C2 - 25921209
SN - 0020-7136
VL - 137
SP - 2139
EP - 2148
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 9
ER -
