Tumor size is an independent risk predictor for metachronous colorectal cancer

Non-hereditary colorectal cancer (CRC) patients are at higher risk of developing independent metachronous CRC than cancer-naïve individuals, but the reason is unknown. We studied metachronous CRC risk factors among one thousand five Japanese CRC patients who underwent surgery for CRC. Relative hazard risk of clinical and pathological features was assessed by univariate and multivariate Cox's proportional hazard regression analysis. Observed metachronous CRC incidence was also compared with the expected cancer incidence of the general population in Japan. Twenty-seven metachronous CRCs developed in 24 patients (2.4%) during a follow-up period of 3,676 person-years. Multivariate analysis revealed two factors associated with a high metachronous CRC risk: synchronous CRC (HR = 6.13; p = 1.3x10(-4)) and tumor size ≥ 6.5 cm (HR = 4.34; p = 1x10(-3)). Patients with either synchronous or large solitary tumors exhibited a higher risk for metachronous CRC than patients with solitary small tumors (HR = 7.3; p = 4.3x10(-6)) and that the general Japanese population (SIR = 7.01; p = 3.5x10(-9)), while patients with solitary small tumors did not (SIR = 1.07; p = 0.8). If patients younger than 60 years were excluded, the observations remained unchanged, with tumor size becoming stronger predictor (HR = 5.67; p = 1.7x10(-4)) than the presence of synchronous CRC (HR = 5.34; p = 9.6x10(-4)). Our novel finding that primary tumor size is a strong independent risk factor for metachronous CRC increases the sensitivity of prediction more than twice the presence of synchronous CRC. Our data provides new insights to assess the risk for metachronous lesions that should improve the surveillance regimen for CRC.