Mismatch repair status and synchronous metastases in colorectal cancer: A nationwide cohort study

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 -