Evaluation of prognostic factors in liver-limited metastatic colorectal cancer: a preplanned analysis of the FIRE-1 trial

Abstract

Background:Liver-limited disease (LLD) denotes a specific subgroup of metastatic colorectal cancer (mCRC) patients.Patients and Methods:A total of 479 patients with unresectable mCRC from an irinotecan-based randomised phase III trial were evaluated. Patients with LLD and non-LLD and hepatic resection were differentiated. Based on baseline patient characteristic, prognostic factors for hepatic resection were evaluated. Furthermore, prognostic factors for median overall survival (OS) were estimated via Cox regression in LLD patients.Results:Secondary liver resection was performed in 38 out of 479 patients (resection rate: 7.9%). Prognostic factors for hepatic resection were LLD, lactate dehydrogenase (LDH), node-negative primary, alkaline phosphatase (AP) and Karnofsky performance status (PS). Median OS was significantly increased after hepatic resection (48 months), whereas OS in LLD (17 months) and non-LLD (19 months) was comparable in non-resected patients. With the inapplicability of Koehne's risk classification in LLD patients, a new score based on only the independent prognostic factors LDH and white blood cell (WBC) provided markedly improved information on the outcome.Conclusion:Patients undergoing hepatic resection showed favourable long-term survival, whereas non-resected LLD patients and non-LLD patients did not differ with regard to progression-free survival and OS. The LDH levels and WBC count were confirmed as prognostic factors and provide a useful and simple score for OS-related risk stratification also in LLD.

Relevance of CEA and LDH in relation to KRAS status in patients with unresectable colorectal liver metastases.

“…Other investigators have also shown LDH is a strong factor [11]. While serum CEA is the most commonly performed serum tumor marker in this patient population, our study validates the additional importance of serum LDH.…”

“…LDH is a metabolic enzyme that catalyzes the conversion of pyruvate to lactate under anaerobic conditions and is overproduced in cancer cells [8]. Several studies have demonstrated a negative association between elevated LDH and OS [9][10][11]. CEA is a glycoprotein involved in cell adhesion, immunity and apoptosis [12].…”

Relevance of liver‐limited disease in metastatic colorectal cancer: Subgroup findings of the FIRE‐3/AIO KRK0306 trial

“…In clear contrast, LLD status was associated with secondary hepatic resection leading to an excellent median OS of 56.2 months. This compares well to previous findings from unselected patients who had been treated with chemotherapy only . In the FIRE‐1 trial comparing FUFIRI to mIROX, median OS was 48 months in LLD patients who became resectable during treatment.…”

Relevance of CEA and LDH in relation to KRAS status in patients with unresectable colorectal liver metastases

“…LDH is a metabolic enzyme that catalyzes the conversion of pyruvate to lactate under anaerobic conditions and is over‐produced in cancer cells . Several studies have demonstrated a negative association between elevated LDH and OS . CEA is a glycoprotein involved in cell adhesion, immunity, and apoptosis .…”