From the Guidelines
The key prognostic factors in colorectal cancer liver metastasis include tumor burden, surgical margin status, response to preoperative chemotherapy, presence of extrahepatic disease, primary tumor characteristics, and patient-specific factors, as highlighted in the most recent guidelines from the National Comprehensive Cancer Network (NCCN) in 2021 1.
Prognostic Factors
The following factors significantly impact outcomes in patients with colorectal cancer liver metastasis:
- Tumor burden: number, size, and distribution of metastases, with fewer, smaller, and unilobar metastases associated with better survival rates
- Surgical margin status: achieving negative surgical margins (R0 resection) is crucial for long-term survival
- Response to preoperative chemotherapy: serves as an important biological marker, with good responders showing improved outcomes
- Presence of extrahepatic disease: typically indicates more advanced disease and poorer prognosis
- Primary tumor characteristics: lymph node status, T-stage, and molecular features (KRAS/BRAF mutations, microsatellite instability) provide additional prognostic information
- Patient-specific factors: age, performance status, and comorbidities affect treatment tolerance and survival
Clinical Implications
Understanding these prognostic factors helps clinicians develop personalized treatment strategies, determine optimal surgical approaches, guide chemotherapy decisions, and provide more accurate prognostic information to patients with colorectal cancer liver metastases. The NCCN guidelines emphasize the importance of a multidisciplinary approach in managing patients with colorectal cancer liver metastasis, taking into account the latest evidence and expert consensus 1.
Treatment Considerations
Perioperative combination chemotherapy with the FOLFOX regimen has been shown to improve progression-free survival in patients with resectable liver metastases, as reported in the ESMO clinical practice guidelines for treatment of advanced colorectal cancer in 2010 1. Additionally, the use of targeted agents, such as bevacizumab or cetuximab, may be considered in selected cases, although concerns about toxicity limit their use to highly selected patients 1.
Patient Management
In patients with initially unresectable liver metastases, downsizing with chemotherapy may convert unresectable metastases to resectable metastases, and resection should be considered after multidisciplinary discussions 1. The strategy when treating patients with initially unresectable disease is to try to achieve high response rates in order to convert unresectable metastases to resectable metastases, with pathological response serving as a surrogate for predicting the outcome 1.
From the FDA Drug Label
The efficacy of ERBITUX with irinotecan or ERBITUX single-agent, based on durable objective responses, was evaluated in all randomized patients and in two pre-specified subpopulations: irinotecan refractory and irinotecan and oxaliplatin failures. Of the 329 patients, the median age was 59 years, 63% were male, 98% were White, and 88% had baseline Karnofsky performance status ≥80 Approximately two-thirds had previously failed oxaliplatin treatment. In patients receiving ERBITUX with irinotecan, the ORR was 23% (95% CI 18%, 29%), median DoR was 5.7 months, and median time to progression was 4.1 months. In patients receiving ERBITUX as a single-agent, the ORR was 11% (95% CI 6%, 18%), median DoR was 4.2 months, and median time to progression was 1. 5 months. Eligible patients were required to have BRAF V600E mutation-positive metastatic CRC, as detected using the Qiagen therascreen BRAF V600E RGQ polymerase chain reaction (PCR) Kit, with disease progression after 1 or 2 prior regimens Other key eligibility criteria included absence of prior treatment with a RAF, MEK, or EGFR inhibitor, eligibility to receive cetuximab per local labeling with respect to tumor RAS status, and ECOG performance status (PS) 0–1. Randomization was stratified by ECOG performance status (0 versus 1), prior use of irinotecan (yes versus no), and cetuximab product used (US-licensed versus EU-approved) The major efficacy outcome measure was OS. Additional efficacy outcome measures included PFS, ORR, and DoR as assessed by blinded independent central review (BICR). OS and PFS were assessed in all randomized patients ORR and DoR were assessed in the subset of the first 220 patients included in the randomized portion of the ERBITUX/encorafenib and control arm of the study. A total of 220 patients were randomized to the ERBITUX/encorafenib arm and 221 to the control arm. Of these 441 patients, the median age was 61 years; 53% were female; 80% were White and 15% were Asian Fifty percent (50%) had baseline ECOG performance status of 0; 66% received 1 prior therapy and 34% received 2; 93% received prior oxaliplatin and 52% received prior irinotecan. ERBITUX in combination with encorafenib demonstrated a statistically significant improvement in OS, ORR, and PFS compared to the active comparator.
The prognostic factors in Colorectal Cancer (CRC) with Liver Metastasis mentioned in the label are:
- ECOG performance status: Patients with ECOG performance status of 0 had better outcomes compared to those with ECOG performance status of 1.
- Prior use of irinotecan: Prior use of irinotecan was a stratification factor for randomization.
- Prior oxaliplatin treatment: Approximately two-thirds of patients had previously failed oxaliplatin treatment.
- BRAF V600E mutation status: Patients with BRAF V600E mutation-positive metastatic CRC had improved outcomes with ERBITUX in combination with encorafenib.
- Tumor RAS status: Eligibility to receive cetuximab per local labeling with respect to tumor RAS status was an inclusion criterion.
- Age: The median age of patients was 59 years in one study and 61 years in another.
- Karnofsky performance status: 88% of patients had a baseline Karnofsky performance status ≥80. 2
From the Research
Prognostic Factors in Colorectal Cancer with Liver Metastasis
The following are some of the key prognostic factors in Colorectal Cancer (CRC) with Liver Metastasis:
- Number of liver metastases: This factor was consistently reported as a prognostic factor in multiple studies 3, 4, 5, 6
- Regional lymph node metastization of primary tumor: This factor was identified as a prognostic factor in several studies 3, 6
- Preoperative CEA level: Elevated preoperative CEA levels were associated with poor prognosis in several studies 3, 4, 5, 6
- Maximum size of metastases: The size of the metastases was identified as a prognostic factor in some studies 3, 4
- Degree of primary tumor differentiation: Poor differentiation of the primary tumor was associated with poor prognosis in some studies 4, 5
- Resection margin: Positive resection margins were associated with poor prognosis in some studies 4
- Adjuvant chemotherapy: The use of adjuvant chemotherapy was associated with improved survival in some studies 7, 5
- Radical resection: Radical resection of the primary tumor and liver metastases was associated with improved survival in some studies 4, 5
Prognostic Scoring Systems
Several prognostic scoring systems have been proposed to predict survival in patients with CRC and liver metastasis 3, 6. These systems often incorporate multiple prognostic factors, including those listed above. However, there is no consensus on a single, ideal scoring system.
Survival Rates
The survival rates for patients with CRC and liver metastasis vary widely depending on the study and the prognostic factors present. Overall survival rates at 1,3, and 5 years have been reported as follows: