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Recurrence-Free Survival as Surrogate for Overall Survival in Patients Undergoing Resection of Colorectal Liver Metastases


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In a single-center retrospective study and a separate meta-analysis reported in The Lancet Oncology, Ecker et al found low correlations between recurrence-free survival and overall survival among patients undergoing resection of colorectal cancer liver metastases.

As stated by the investigators, “Recurrence-free survival has been used as a surrogate endpoint for overall survival in trials involving patients with resected colorectal liver metastases. We aimed to assess the correlation between recurrence-free survival and overall survival after resection of colorectal liver metastases to determine the adequacy of this surrogate endpoint.”

Study Details

The retrospective study included data on 2,983 eligible consecutive patients who underwent complete resection of colorectal liver metastases (hepatectomy with or without operative ablation) between January 1991 and April 2019 from the Memorial Sloan Kettering Cancer Center prospective database. The meta-analysis included six trials of adjuvant chemotherapy in this setting identified in a literature search through January 2022 including a total of 1,185 patients.

Key Findings

Median follow-up in the institutional cohort of 2,983 patients was 8.4 years (95% confidence interval [CI] = 7.9–9.1 years). During this period, 1,995 patients (67%) had recurrence and 1,684 patients (56%) died. Median recurrence-free survival was 1.3 years (95% CI = 1.3–1.4 years) and median overall survival was 5.2 years (95% CI = 5.0–5.5 years). Among the 1,684 deaths, 1,428 (85%) were preceded by recurrence; median time from recurrence to death was 2.0 years (interquartile range = 1.0–3.4 years). Pairwise correlations between recurrence-free survival and overall survival were low to moderate, with a Spearman’s rank correlation estimate ranging from 0.30 (standard deviation [SD] = 0.17) to 0.56 (SD = 0.13).

In the meta-analysis of adjuvant clinical trials, the Spearman’s correlation coefficient between the recurrence-free survival hazard ratio and overall survival hazard ratio was r =0.20 (standard error = 0.58, P = .71).

The investigators concluded, “We found a minimal correlation between recurrence-free survival and overall survival after resection of colorectal liver metastases. Recurrence-free survival is an inadequate surrogate endpoint for overall survival in this disease setting.”

Michael I. D’Angelica, MD, of the Department of Surgery, Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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