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Annals of Surgical Oncology

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The Disease-Free Interval Between Resection of Primary Colorectal Malignancy and the Detection of Hepatic Metastases Predicts Disease Recurrence But Not Overall Survival

Diederik J. Höppener MD, Pieter M. H. Nierop MD, Martinus J. van Amerongen MD, PhD, Pim B. Olthof MD, PhD, Boris Galjart BSc, Thomas M. van Gulik MD, PhD, Johannes H. W. de Wilt MD, PhD, Dirk J. Grünhagen MD, PhD, Nuh N. Rahbari MD, Cornelis Verhoef MD, PhD
Colorectal Cancer
Volume 26, Issue 9 / September , 2019



The disease-free interval (DFI) between resection of primary colorectal cancer (CRC) and diagnosis of liver metastases is considered an important prognostic indicator; however, recent analyses in metastatic CRC found limited evidence to support this notion.


The current study aims to determine the prognostic value of the DFI in patients with resectable colorectal liver metastases (CRLM).


Patients undergoing first surgical treatment of CRLM at three academic centers in The Netherlands were eligible for inclusion. The DFI was defined as the time between resection of CRC and detection of CRLM. Baseline characteristics and Kaplan–Meier survival estimates were stratified by DFI. Cox regression analyses were performed for overall (OS) and disease-free survival (DFS), with the DFI entered as a continuous measure using a restricted cubic spline function with three knots.


In total, 1374 patients were included. Patients with a shorter DFI more often had lymph node involvement of the primary, more frequently received neoadjuvant chemotherapy for CRLM, and had higher number of CRLM at diagnosis. The DFI significantly contributed to DFS prediction (p =0.002), but not for predicting OS (p =0.169). Point estimates of the hazard ratio (95% confidence interval) for a DFI of 0 versus 12 months and 0 versus 24 months were 1.284 (1.114–1.480) and 1.444 (1.180–1.766), respectively, for DFS, and 1.111 (0.928–1.330) and 1.202 (0.933–1.550), respectively, for OS.


The DFI is of prognostic value for predicting disease recurrence following surgical treatment of CRLM, but not for predicting OS outcomes.

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