A Systematic Review of Conversion to Resectability in Unresectable Metastatic Colorectal Cancer Chemotherapy Trials

Objectives: Metastasectomy in patients with metastatic colorectal cancer (mCRC) confers a significant survival benefit. We hypothesized that conversion to resectability (C2R) correlates with superior overall survival (OS) in patients with unresectable mCRC. Methods: A prospectively registered systematic review (PROSPERO CRD42015024104) of randomized clinical trials published after 2003 was conducted. Exposure of interest was C2R with a primary outcome of OS. Clinical trials were classified based on difference in C2R between study arms (<2%, 2% to 2.9%, >= 3%). Generalized estimating equations were used to measure associations while adjusting for multiple observations from the same trial. Results: Of 2902 studies reviewed, 30 satisfied selection criteria (n=13,618 patients). Median C2R was 7.3% (interquartile range [IQR]: 5% to 12.9%), with maximum C2R in the FOLFOX/FOLFIRI+cetuximab arm (28.6%). The median difference in C2R between 2 arms of the same study was 2.3% (IQR: 1.3% to 3.4%) with a maximum difference of 15.4% seen in FOLFOX/FOLFIRI+cetuximab versus FOLFOX/FOLFIRI. Median OS for the entire patient cohort was 20.7 months (IQR: 18.9 to 22.7 mo), with a between group difference of 1.3 months (IQR: -1.2 to 3.6 mo). The median survival difference between the 2 study arms with <2% C2R difference was 0.8 months versus 1.6 months with >= 3% C2R rates . Increasing C2R had an incremental dose-effect response on OS (P=0.021), and higher response rates correlated with C2R rates (P=0.003). Conclusions: C2R occurs infrequently and variably in clinical trials enrolling patients with unresectable mCRC. Prioritization of chemotherapeutic agents that enhance C2R might improve OS of patients.