Conversion to resectability in unresectable metastatic colorectal cancer chemotherapy (mCRC) trials.

641 Background: Patients with mCRC undergoing surgical metastasectomy have been shown to derive significant survival benefit with a potential for cure. We hypothesized that conversion to resectability (c2r) is correlated with increased overall survival in patients with unresectable mCRC. Methods: Prospectively registered systematic review (PROSPERO CRD42015024104) was utilized to identify randomized clinical trials published after 2003. Exposure of interest was c2r from unresectable disease, while the outcome was overall survival (OS). Clinical trials were classified into three groups based on difference in c2r between the two study groups ( < 2, 2-2.9, ≥ 3 %). Generalized estimating equations(GEE) were used to measure associations while adjusting for multiple observations from the same trial. The Cochrane risk of bias tool was used to evaluate the methodological quality. Results: Out of 2,902 studies reviewed, 30 satisfied selection criteria (n = 13,618 patients). All studies had two arms only (100%). Median c2r was 7.3% (Interquartile Range 5%-12.9%), with maximum c2r in FOLFOX/FOLFIRI+ cetuximab arm (28.6%). The median difference in c2r between two arms of the same study was 2.3% (IQR 1.3 – 3.4%) and the maximum difference was 15.4% seen in FOLFOX/FOLFIRI+ cetuximab vs. FOLFOX/FOLFIRI (Ye, 2013). Median OS for the entire cohort of patients was 20.7 months (IQR 18.9 – 22.7 months), with a between group difference of 1.3 (IQR -1.2 – 3.6 months). The maximum survival benefit between two study arms was 9.9 months. Median survival difference between the two study arms with a minimal c2r difference ( < 2%) was 0.8 months, as compared to 1.6 months with higher c2r ( ≥ 3%). Incremental dose effect response was noted with an increasing c2r leading to improved overall survival in regression models (p = 0.021, r2= 0.16). Higher response rates also correlated with higher c2r rates (p = 0.003, r2= 0.25). Conclusions: Conversion to resectability is positively correlated with an improvement in survival in trials examining therapies for unresectable mCRC. Patient level data examining the contribution of metastasectomy to the overall survival benefit of systemic chemotherapy needs to be further examined.