Early tumour shrinkage as a prognostic factor and surrogate end-point in colorectal cancer: A systematic review and pooled-analysis

Purpose Early tumour shrinkage (ETS), defined as a reduction of at least 20% in tumour size at first reassessment, has been recently investigated retrospectively in first-line trials of metastatic colorectal cancer (CRC), and appears to be associated with better outcomes. We have performed a systematic review and meta-analysis of published trials to evaluate the prognostic value of ETS in CRC in terms of overall survival (OS) and progression-free survival (PFS). Material and methods An electronic search of the PubMed, SCOPUS, EMBASE, the Web of Science, and the Cochrane Central Register of Controlled Trial databases identified trials that compared outcomes of patients with or without ETS during first-line chemotherapy for metastatic CRC. The OS, reported as a hazard ratio (HR) with a 95% confidence interval (CI), was the primary outcome measure; the correlation coefficient (R) between ETS with median OS was also estimated. Results Twenty-one trials from 10 publications were analysed. Overall, patients with ETS were associated with a better OS (HR, 0.58; 95% CI, 0.53 to 0.64; P < 0.00001) and PFS (HR, 0.57; 95% CI, 0.47-0.69; P < 0.00001) compared with patients who were early non-responders. However, ETS was poorly correlated with OS in terms of surrogacy (R = 0.37; 95% CI - 0.31-0.78; P = 0.28). Conclusions ETS is a good prognostic factor but an inappropriate surrogate for predicting outcome in CRC patients. These findings support ETS as prognostic tool in ascertaining earlier non-responders; however, its role as a surrogate end-point deserves further evaluation.