Keywords: cancer, epidemiology, statistics, propensity score, hazard ratio, mortality, colon cancer, metastatic
Importance:Biologic therapy(BT;bevacizumab or cetuximab) is increasingly used to treat metastatic colorectal cancer(mCRC). Recent investigations have suggested that right- or left-sided primary tumor origin impacts survival and BT.Objective:To evaluate impact of tumor origin on mortality in a diverse population-based dataset.Methods:Using the California Cancer Registry data(2004-2014) to identify patients aged 40-85 years diagnosed with mCRC and treated with systemic chemotherapy(SC) only or plus BT. Mortality hazards by tumor origin(right vs left) were assessed for patients receiving SC alone or SC plus bevacizumab or cetuximab. Subgroup analysis for KRAS wild-type patients was also performed.Results:Between 2004-2014, 11,905 mCRC patients were eligible for study. Among these, 4,632 patients received SC and BT. Compared to SC alone, SC plus bevacizumab reduced mortality in both right- and left-sided mCRC, while SC plus cetuximab reduced mortality only in the left and was associated with significantly higher mortality in the right(HR=1.31;95%CI=1.14-1.51). Among patients treated with SC plus BT, right-sided tumor origin was associated with higher mortality regardless of BT type [bevacizumab(HR=1.31;95%CI=1.25-1.36) and cetuximab(HR=1.88;95%CI=1.68-2.12)], compared to left. In KRAS wild-type patients(n=668), cetuximab was associated with reduced mortality only in left-sided mCRC compared to bevacizumab(HR=0.75;95%CI=0.63-0.90), while right-sided cancers had more than double the mortality compared to left (HR=2.44;95%CI=1.83-3.25).Conclusions:Primary tumor site is predictive of response to BT in mCRC. Right-sided is associated with higher mortality regardless of BT type. In KRAS wild-type patients, treatment with cetuximab benefited only left-sided mCRC patients and was associated with significantly poorer survival in right-sided patients. Our results underscore the importance of stratification by tumor site for current treatment guidelines and future clinical trials.