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

Objectives: 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.

Methods: 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), stable disease with tumor-size evolution between 0 and + 19% (SD+) or 0 and - 29% (SD-), and partial responders (PRs), who were classed PR with ETS (ETS) or without (PR). Tumor-size evolution and best tumor responses to each chemotherapy line were analyzed.

Results: Tumor loads of ETS or PR mCRCs tended to remain inferior to their initial values: 60% of patients died with target lesion sums below baseline. For first-line SD+ or PD mCRCs, rapid tumor load increases continued during successive lines: > 80% died with target lesion sums above baseline. ETS mCRCs responded better to subsequent lines (37.5% second-line PR), whereas PD mCRCs remained refractory to other therapies (0% second- and third-line PR). Overall survival rates were significantly (p = 0.03) longer for the ETS group (29.9 [95% CI: 12.6-47.1] months) and shorter for the PD group (17.1 [95% CI: 1.5-37.5] months).

Conclusion: Tumors responding to first-line chemotherapy also responded better to subsequent lines, whereas PD mCRCs remained refractory, which may explain the better survival associated with ETS.

Key Points: • 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.