Key messages
– Transarterial chemoembolisation (abbreviated as TACE) is a method of destroying cancer cells by giving anticancer medicines and tiny beads that block the blood supply to the tumour directly or giving beads that are coated with anticancer medication. TACE may reduce deaths compared with an anticancer medicine that is given by injection into a blood vessel travelling to cells all over the body (called systemic chemotherapy), but the evidence is very uncertain. TACE may have little to no effect on time to death, unwanted effects, quality of life, the length of time people survived without the cancer getting worse, and changes in the size of tumours, but the evidence is very uncertain.
– We found no studies assessing another method of destroying cancer cells called transarterial embolisation (which is similar to TACE in that tiny beads are injected but differs in that no anticancer medicines are given; abbreviated as TAE) versus systemic chemotherapy.
– Further research is needed as we found only three small studies and confidence in these results is limited. New studies might bring additional evidence and change the results and our confidence in them.
What are metastases?
Metastases are new cancer growths that spread to different parts of the body from the original cancer site (sometimes called secondaries). One of the most common sites for colorectal (bowel) cancer metastases is the liver.
How are metastases treated?
There are several different ways to treat liver metastases. We were interested in comparing three methods; transarterial chemoembolisation (abbreviated as TACE), transarterial embolisation (abbreviated as TAE), and systemic chemotherapy.
TACE involves injection of an anticancer medicine and an injection of tiny beads directly into the blood vessel (the hepatic artery) that feeds the tumour or the use of beads that are coated in anticancer medication. The anticancer medicine is toxic and the beads block the blood supply to the tumour, so some of the tumour cells die. Other parts of the liver are kept alive as they receive their blood supply mainly from a different blood vessel (the portal vein).
TAE is similar to TACE in that an injection of tiny beads is given to block the blood vessel but differs in that no anticancer medicines are given.
Systemic chemotherapy is where anticancer medicines are given through a blood vessel on the back of the hand or forearm (usually) so they travel to, and affect, all cells in the body.
What did we want to find out?
We wanted to find out if TACE or TAE was better than systemic chemotherapy by looking at deaths, how long people survived, how often cancer returned and progressed (got worse), how the treatments affected how well the people felt, and if there were any unwanted effects.
What did we do?
We searched for studies comparing TACE or TAE versus systemic chemotherapy in people with bowel cancer that had spread to the liver.
What did we find?
We found three small studies with 238 people with metastases only or mainly in the liver that compared TACE versus systemic chemotherapy. It was not possible to remove the cancers with surgery. The studies reported no details on funding. We found no studies comparing TAE versus systemic chemotherapy in people with colorectal cancer liver metastases.
TACE compared with systemic chemotherapy may reduce death, but the evidence is very uncertain (3 studies, 234 people). About 79 out of 100 people died with TACE compared with 92 out of 100 people with systemic chemotherapy.
One small study (70 people) reported time to death, but we were very uncertain about the results. People who received TACE survived about 22 months, while those who received systemic chemotherapy survived about 15 months.
In one small study (70 people), people who had TACE had a longer time before their cancer got worse in the liver (seven months) compared with those who received systemic chemotherapy (four months), but we were very uncertain about the results.
We were very uncertain about the effects of TACE compared with systemic chemotherapy when looking at how metastases changed in size and unwanted effects.
There was no information on the likelihood of death specifically due to cancer, the proportion of people dying or surviving with worsening of the disease, and recurrence (return) of liver metastases.
What are the limitations of the evidence?
Our confidence in the results is limited because none of the studies clearly reported their methods. It was unclear whether investigators, healthcare staff, and people taking part in the studies knew what treatment they had received. Not all the studies provided data about everything that we were interested in. All of this could have influenced the results.
Further research is needed, which may change the results.
How up to date is this evidence?
The evidence is up to date to 4 April 2024.
The evidence regarding effectiveness of TACE versus systemic chemotherapy in people with colorectal cancer liver metastases is of very low certainty and is based on three trials. Our confidence in the results is limited due to the risk of bias, inconsistency, indirectness, and imprecision.
It is very uncertain whether TACE confers benefits with regard to reduction in mortality, overall survival (time to mortality), reduction in adverse events or complications, improvement in health-related quality of life, improvement in progression-free survival, and tumour response measures (presented as the overall response rate). Data on cancer mortality, proportion of participants dying or surviving with progression of the disease, and recurrence of liver metastases are lacking.
We found no trials assessing TAE versus systemic chemotherapy.
More randomised clinical trials are needed to strengthen the body of evidence and provide insight into the benefits and harms of TACE or TAE in comparison with systemic chemotherapy in people with liver metastases from colorectal cancer.
The liver is affected by two groups of malignant tumours: primary liver cancers and liver metastases. Liver metastases are significantly more common than primary liver cancer, and five-year survival after radical surgical treatment of liver metastases ranges from 28% to 50%, depending on primary cancer site. However, R0 resection (resection for cure) is not feasible in most people; therefore, other treatments have to be considered in the case of non-resectability. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the peripheral branches of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents and can lead to selective necrosis of the cancer tissue while leaving normal liver parenchyma virtually unaffected. The entire procedure can be performed without infusion of chemotherapy and is then called bland transarterial embolisation (TAE). These procedures are usually applied over a few sessions. Another possible treatment option is systemic chemotherapy which, in the case of colorectal cancer metastases, is most commonly performed using FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) and FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) regimens applied in multiple sessions over a long period of time. These therapies disrupt the cell cycle, leading to death of rapidly dividing malignant cells. Current guidelines determine the role of TAE and TACE as non-curative treatment options applicable in people with liver-only or liver-dominant metastatic disease that is unresectable or non-ablatable, and in people who have failed systemic chemotherapy. Regarding the treatment modalities in people with colorectal cancer liver metastases, we found no systematic reviews comparing the efficacy of TAE or TACE versus systemic chemotherapy.
To evaluate the beneficial and harmful effects of transarterial embolisation (TAE) or transarterial chemoembolisation (TACE) compared with systemic chemotherapy in people with liver-dominant unresectable colorectal cancer liver metastases.
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and three additional databases up to 4 April 2024. We also searched two trials registers and the European Medicines Agency database and checked reference lists of retrieved publications.
We included randomised clinical trials assessing beneficial and harmful effects of TAE or TACE versus systemic chemotherapy in adults (aged 18 years or older) with colorectal cancer liver metastases.
We used standard Cochrane methods. Our primary outcomes were all-cause mortality; overall survival (time to mortality); and any adverse events or complications. Our secondary outcomes were cancer mortality; health-related quality of life; progression-free survival; proportion of participants dying or surviving with progression of the disease; time to progression of liver metastases; recurrence of liver metastases; and tumour response measures (complete response, partial response, stable disease, and progressive disease). For the purpose of the review and to perform necessary analyses, whenever possible, we converted survival rates to mortality rates, as this was our primary outcome. For the analysis of dichotomous outcomes, we used the risk ratio (RR); for continuous outcomes, we used the mean difference; and for time to event outcomes, we calculated hazard ratios (HRs), all with 95% confidence intervals (CI). We used the standardised mean difference with 95% CIs when the trials used different instruments. We used GRADE to assess the certainty of evidence for each outcome. We based our conclusions on outcomes analysed at the longest follow-up.
We included three trials with 118 participants randomised to TACE versus 120 participants to systemic chemotherapy. Four participants were excluded; one due to disease progression prior to treatment and three due to decline in health. The trials reported data on one or more outcomes. Two trials were performed in China and one in Italy. The trials differed in terms of embolisation techniques and chemotherapeutic agents. Follow-up ranged from 12 months to 50 months.
TACE may reduce mortality at longest follow-up (RR 0.86, 95% CI 0.79 to 0.94; 3 trials, 234 participants; very low-certainty evidence), but the evidence is very uncertain. TACE may have little to no effect on overall survival (time to mortality) (HR 0.61, 95% CI 0.37 to 1.01; 1 trial, 70 participants; very low-certainty evidence), any adverse events or complications (3 trials, 234 participants; very low-certainty evidence), health-related quality of life (2 trials, 154 participants; very low-certainty evidence), progression-free survival (1 trial, 70 participants; very low-certainty evidence), and tumour response measures (presented as the overall response rate) (RR 1.81, 95% CI 1.11 to 2.96; 3 trials, 234 participants; very low-certainty evidence), but the evidence is very uncertain. No trials reported cancer mortality, proportion of participants dying or surviving with progression of the disease, and recurrence of liver metastases.
We found no trials comparing the effects of TAE versus systemic chemotherapy in people with colorectal cancer liver metastases.