Background: Patients (pts) with L sided primary tumors and mCRC have a significantly longer overall survival (mOS) than R sided tumors. Reasons for this remain unclear. The objective of this study was to compare systemic and surgical therapy received by tumor side and correlate this with mOS. Methods: Sequential pts with mCRC referred to the British Columbia Cancer Agency in 4 treatment eras were included. Pts with unresected primary tumors were excluded to ensure accurate ascertainment of tumor location. Receipt of systemic therapy includes Òall 3 drugsÓ (irinotecan, oxaliplatin, fluouracil), bevacizumab and epidermal growth factor receptor inhibitors (EGFRi). Cox-regression survival analysis for sidedness was performed controlling for age, sex, tumor grade, lymphovascular/perineural invasion, nodes removed and metastatectomy. Results: Among 3242 pts, a progressive improvement in mOS is documented in both L and R sided tumors since 1995. L and R tumors received Òall 3 drugsÓ, bevacizumab and EGFRi therapy with similar frequency which plateaued after the introduction of EGFRiÕs in 2009. Patients with L sided tumors were significantly more likely to have a hepatic or pulmonary resection. In Cox regression analysis, the mOS difference between L and R sided tumors was more pronounced in more recent eras. Conclusions: Patients with R sided tumors receive similar systemic therapy compared to L sided tumors, but are significantly less likely to undergo resection of distant disease. Resection of distant metastases may be an important consideration to understand the survival differences between R vs L mCRC.

* P-value is significant at 0.05 level