Predictors of early recurrence after resection of colorectal liver metastases

In an era of modern chemotherapy, surgical resection of CLM can be justified and may yield long-term survival in selected patients [20-22]. However, disease recurrence after LR is common and negatively impacts on patient survival [13,18,22]. Disease recurrence presumably reflects the presence of viable tumour deposits that are undetected by conventional pre-operative CT [23]. MRI is increasingly being utilized to characterize benign and malignant liver lesions [14,24-26] and appears to be more sensitive than CT, particularly when used with liver-specific contrast agents [14]. The potential advantages of MRI over CT are particularly evident in patients with background hepatic steatosis after chemotherapy [27]. However, at present, there is insufficient evidence to justify the routine use of MRI prior to LR for CLM. Risk factors for early recurrence after LR have been suggested previously such as multiple (>8) CLM [13] with recurrence within the liver being the commonest cause of treatment failure [28]. However, no studies have identified factors that specifically predispose to early liver-only or systemic recurrence. Previous multivariate analysis has revealed node positive primary tumours, advanced T stage, presence of extrahepatic disease, CEA >200 ng/ml, multiple tumours, tumour size >5 cm and short disease-free interval as predictors for early recurrence and poor overall survival [5,18,29,30]. Using this data, a clinical risk score was created to help predict which patients will benefit most from surgical intervention [5]. The current study expands these known risk factors by clearly demonstrating that larger and multiple tumours increase the risk of early systemic recurrence and male gender and advanced CRC predispose to early liver-only recurrence after LR.

The first aim of our study was to determine if there are any preoperative risk factors that may predispose patients to tumour recurrence within the liver remnant specifically within the early post-operative period. On analysis, male sex and advanced primary tumours (Dukes C) increased the risk of early liver-only recurrence. Such patients may be candidates for pre-operative MRI, and they may also benefit from enhanced postoperative surveillance. Early post-operative imaging (CT or MRI) in high-risk patients may identify liver-only recurrence at an earlier, treatable stage, which may potentially influence long-term survival although there remains no conclusive data from the available literature. Other groups also investigating the risk factors for CLM recurrence after LR have failed to show any affect of gender unlike the reported study [31]. The precise reasons underlying this male preponderance remain unclear.

The second aim of our study was to identify any potential risk factors that predict systemic recurrence specifically in the early post-operative period. Our data has indicated that patients with multiple tumours (three or more) or tumours greater than 3.6 cm are at high risk of early systemic recurrence. This group of patients is unlikely to benefit from LR as an isolated strategy and should be considered for pre-operative CT-PET and systemic chemotherapy. Using this approach, some patients with detectable FDG avid extra-hepatic disease may be spared from futile liver surgery [32]. PET/CT produces a fusion image combining conventional cross-sectional, anatomical imaging of CT with the biological, functional imaging of PET [33]. It can be utilized successfully to identify and stage primary CRC [34] as well as metastases [33] and has also been used to great effect in the staging of pancreatic [35] and lung [36] cancers. PET/CT in CLM patients may be associated with alterations in patient management in 34% owing to disease upstaging [37]. Indeed, recent meta-analyses found FDG-PET was the most sensitive method for detection of liver metastases and extra-hepatic metastatic disease with sensitivities of 90% to 92% [15,17]. FDG-PET had a significantly higher pooled sensitivity and specificity for hepatic disease and EHD when compared to CT [38]. Moreover, PET/CT identifies more definitely normal and definitely abnormal lesions than with PET alone in CRC patients with improvements in staging and restaging [34]. Indeed, these changes in staging alter patient management in 25% of patients with the use of 18FDG-PET resulting in a reduction in unnecessary surgical interventions [39]. In a recent prospective study comparing 100 CLM patients staged by conventional techniques with 103 patients staged with an additional FDG-PET, the rate of non-therapeutic laparotomies was significantly reduced in patients having preoperative FDG-PET. [38]. The results of this study were mirrored by a randomized study of 150 CLM patients selected for surgical resection by CT imaging alone or CT plus FDG-PET, which similarly demonstrated a significantly reduced rate of futile laparotomies [40]. Taken together with previous studies, it appears that liver recurrence following resection for colorectal metastasis is associated with T3-T4 disease, synchronous CLM, limited resection margins, Dukes C stage and male sex. Systemic recurrence appears to correlate with tumour size and tumour number.