Tumor-size responses to first-line is a predictor of overall survival in metastatic colorectal cancer.

Abstract

Early tumor shrinkage (ETS) has been reported to be associated with survival of metastatic colorectal cancer (mCRC) patients. Our aim was to analyze long-term tumor-size evolution, according to early mCRC best responses during the first-line therapy, to evaluate first best response-survival links. Sixty-five patients with unresectable mCRCs, treated between 2010 and 2015, were included retrospectively in this descriptive monocenter study and grouped according to their RECIST 1.1 first-line best responses: progressive disease (PD_fl), stable disease with tumor-size evolution between 0 and + 19% (SD_fl+) or 0 and - 29% (SD_fl-), and partial responders (PRs), who were classed PR with ETS (ETS_fl) or without (PR_fl). Tumor-size evolution and best tumor responses to each chemotherapy line were analyzed. Tumor loads of ETS_fl or PR_fl mCRCs tended to remain inferior to their initial values: 60% of patients died with target lesion sums below baseline. For first-line SD_fl+ or PD_fl mCRCs, rapid tumor load increases continued during successive lines: > 80% died with target lesion sums above baseline. ETS_fl mCRCs responded better to subsequent lines (37.5% second-line PR), whereas PD_fl mCRCs remained refractory to other therapies (0% second- and third-line PR). Overall survival rates were significantly (p = 0.03) longer for the ETS_fl group (29.9 [95% CI: 12.6-47.1] months) and shorter for the PD_fl group (17.1 [95% CI: 1.5-37.5] months). Tumors responding to first-line chemotherapy also responded better to subsequent lines, whereas PD_fl mCRCs remained refractory, which may explain the better survival associated with ETS_fl. • Early shrinking tumors under first-line chemotherapy responded better to subsequent lines, maintaining low tumor loads, potentially explaining the link between early tumor shrinkage and overall survival of metastatic colorectal cancer (mCRC) patients. • mCRCs progressing under first-line chemotherapy remained refractory to other therapies and their tumor loads increased rapidly. • Even outside a clinical trial, an early first CT scan reevaluation with RECIST criteria 8 weeks after starting first-line therapy is crucial to determine long-term mCRC evolution.