1. In patients with colorectal cancer liver metastases (CLMs), targeted treatment of extrahepatic disease (EHD) using radiofrequency showed significantly improved long-term survival, particularly in those with lung-only extrahepatic disease.
2. Median overall survival (OS) was longest in patients who experienced no additional hepatic metastatic activity following radiofrequency ablation (RFA). Tumors less than 3 cm and ablation margins greater than 5 mm were the best candidates for treatment, with the greatest local tumor response to RFA.
Evidence Rating Level: 2 (Good)
Study Rundown: The majority of colorectal cancer–related deaths are attributed to metastatic disease. As such, patients often require multiple surgeries to resect metachronous metastases and still suffer from a high recurrence rate. While the most successful treatment for tumors has been surgical resection, a substantial proportion of patients present with metastases not suitable for surgical intervention or may be high-risk surgical candidates due to other comorbidities. Less invasive therapies are being explored to improve the long-term survival and quality of life in patients who are poor surgical candidates. RFA is a percutaneous technique which applies focal radiowaves to generate a high-temperature cytotoxic reaction at targeted tumor sites, and has been incorporated into the treatment regimen for a range of tumors, including unresectable liver metastases from colorectal cancer. Although radiofrequency ablation is increasingly used in patients with unresectable CLMs, data supporting its role in a defined therapeutic setting has been scarce, and is therefore the investigative focus of the present study. A 10-year review of the therapeutic outcomes following percutaneous RFA of CLMs was performed to evaluate the procedure using a clinical risk score (CRS) in order to stratify tumor response to treatment. This study found that RFA prolonged overall survival in patients with less EHD and limited tumor progression following ablation. Additionally, tumors that were smaller (<3 cm) with broader resection margins (>5 mm) responded most optimally to RFA in select patients as demonstrated by significantly longer progression-free survival. Median overall survival in patients with lung-only EHD was 35 months as compared 14 months in those with multiple sites of EHD, versus 36 months an aggregate of all patients. The primary limitation of the study was its retrospective methodology and reliance on inconsistent and incomplete records provided by one study site. Future prospective, controlled trials are necessary to validate these findings in a larger patient cohort.
In-Depth [retrospective cohort]: A total of 162 consecutive patients underwent 188 percutaneous RFA treatments between 2002 and 2012; 233 CLMs (mean tumor diameter: 1.8 cm; range: 0.5–5.7 cm) were included in this study. The procedure was effectively implemented in 94% (218 of 233) of the subjects as confirmed using contrast material–enhanced CT at 4-8 weeks following the procedure. Contrast-enhanced CT evaluation was repeated at 2-4 month intervals to determine OS (median OS: 36 months, 31%) and local tumor progression-free survival (median: 26 months), which were calculated using the Kaplan-Meier method. Overall, shorter local tumor progression-free survival was associated with tumor size >3 cm (p < 0.001), ablation margin ≤5 mm (p < 0.001), high modified CRS (p = 0.009), male sex (p = 0.03), and a lack of hepatectomy history (p = 0.04) or hepatic arterial infusion chemotherapy (p = 0.01) . However, only tumor size >3 cm (p = 0.01) and margins ≤5 mm (p < 0.001) were independent predictors of shorter LTPFS on multivariate analysis. Univariate analysis using log-rank tests and Cox-regression models determined negative predictors of OS to be tumor size >3 cm (p = 0.005), carcinoembryonic antigen level > 30 ng/mL (p = 0.003), high modified CRS (p = 0.02), and EHD (p < 0.001). Tumor size >3 cm (p = 0.006) and more EHD sites (p < 0.001) were determined to be independent predictors of shorter OS outcomes on multivariate analysis.
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