Journal of Visceral Surgery (2014) 151, S33—S44

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REVIEW

Radiofrequency ablation for colorectal liver metastases A. Stoltz , J. Gagnière , A. Dupré , M. Rivoire ∗ Département d’Oncologie Chirurgicale, Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France Available online 28 February 2014

KEYWORDS Liver metastases; Colorectal cancer; Radiofrequency ablation; Focused destruction; Hepatectomy

Summary The management of hepatic metastases from colorectal cancer (HMCRC) is multimodal including chemotherapy, surgical resection, radiation therapy, and focused destruction technologies. Radiofrequency ablation (RFA) is the most commonly used focused destruction technology. It represents a therapeutic option that may be potentially curative in cases where surgical excision is contra-indicated. It also increases the number of candidates for surgical resection among patients whose liver metastases were initially deemed unresectable. This article explains the techniques, indications, and results of radiofrequency ablation in the treatment of hepatic colorectal metastases. © 2014 Elsevier Masson SAS. All rights reserved.

Introduction Colorectal cancer is the most common digestive cancer in France with more than 40,000 new cases per year [1] and a fairly gloomy prognosis with 17,000 deaths per year [2]. Between 30% and 50% of patients with colorectal cancer will develop liver metastases, either synchronously (10—25%) or metachronously (20—25%) [3]. When surgical excision can achieve an R0 resection, it remains the only potentially curative treatment of hepatic metastasis from colorectal cancer (HMCRC) [4], with a 5-year survival between 25% and 50% depending on the series [5,6]. Only 10—20% of patients with HMCRC can benefit from such an approach [7]. In the absence of surgical excision, the median survival of patients with HMCRC ranges from 6 months (with no chemotherapy) to 2 years (with 5-FU-based chemotherapy [CT] regimens combining 5-FU with oxaliplatin or irinotecan ± targeted therapy) [8].

∗

Corresponding author. E-mail address: [email protected] (M. Rivoire).

1878-7886/$ — see front matter © 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.jviscsurg.2013.12.005

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Figure 1. Decision tree for management of hepatic metastases from colorectal cancer.

Focal ablation technologies (of which RFA is the main representative) can be used either as an alternative to surgical treatment or in combination with it [9]; the principal goal is to achieve tumor destruction while maximally sparing the non-tumorous liver parenchyma. Most published series have shown RFA to be less effective than resection, with a local recurrence rate of 6—40%. Some indications are straightforward: RFA is a good alternative for patients who are inoperable (refusal, co-morbidities). Similarly, for patients with unresectable HMCRC anything that can help to make surgical resection possible is worthy of consideration; here RFA has an ideal role when used in combination with surgery. Other indications are more debatable such as for treatment of a single deep-seated HMCRC located well away from large vessels or for palliative debulking of an unresectable tumor (Fig. 1).

Mechanism of action and technical aspects RFA causes tissue destruction through focused hyperthermia. It allows in situ delivery of a high-frequency sinusoidal electromagnetic current (375 to 500 kHz) through one or several electrode(s) positioned within or around the tumor(s), supplied by a 60—250 W generator. This RFA current causes tissue heating and when the tissue temperature reaches 55—60 ◦ C, it results in irreversible tissue damage through DNA denaturation [10,11]. Tissue temperatures between 60 and 100 ◦ C result in coagulation necrosis. Tissue heating above 100 ◦ C is not desirable because it causes tissue vaporization and carbonization, which decrease the efficiency of further RFA energy delivery. There are two principal modes of RFA application: monopolar and bipolar. The monopolar mode is by far the most widespread and commonly used technique at present. The bipolar mode is used less often because of its cost and technical requirements. In the monopolar mode, the electrical circuit is closed through a grounding plate applied to

A. Stoltz et al. the skin. Intratumoral electrodes are inserted centered on the area to be destroyed. In the bipolar mode, the grounding plate is replaced by a second inserted electrode, to create a relatively uniform high-density electrical field between the two electrodes. This allows better control of the orientation and extent of the induced electric field. For metastases smaller than 3.0 cm, the monopolar mode reliably provides reproducible spherical zones of necrosis. For larger lesions, multifocal or multiple overlapping applications of RFA may be necessary [12]. Application of RFA energy is discontinued when current is no longer conducted through the lesion due to cellular coagulation and dessication. Total duration of treatment averages 15 minutes (10—30 minutes depending on the devices used and the tumor volume treated) [13]. Single-use disposable electrodes (diameter: 14 to 17 Gauge) are generally used. Three main types may be distinguished: • linear internally-cooled electrodes: these are cooled by water circulating in a double internal channel, preventing premature tissue charring and thereby increasing the volume of tissue that can be destroyed; • linear electrodes perfused by isotonic or hypertonic saline: this approach allows a local increase in tissue conductivity by cooling of the electrode-tissue interface with constant irrigation of water and electrolytes; • deployable electrodes (Fig. 2): these systems increase the surface area of the active electrode by the deployment of an array of multiple secondary electrodes inserted through a cannula after initial puncture of the lesion.

Modalities and approaches Surgical resection remains the standard curative treatment of HMCRC. At present, RFA cannot be considered to be equivalent to surgery in terms of oncologic outcomes [13]. RFA can be performed either percutaneously or at the time of laparoscopic or open surgery [14]. When the procedure was first developed, the small size of RFA electrodes favored a direct percutaneous approach, typically performed by a radiologist. The surgical community then began to use RFA in an effort to increase the number of patients eligible for liver resection. Percutaneous RFA is generally used to treat patients with HMCRC who are at high risk for surgery (complex medical history, previous liver surgery). Ultrasound-guided percutaneous RFA allows for rapid, inexpensive outpatient treatment with relative ease of access. The main disadvantages are inability to accurately assess the adequacy of the zone of thermal injury and unreliability when used in certain locations: i.e., lesions that are subcapsular or close to large vessels or other organs (gallbladder, gastrointestinal tract, diaphragm). The deliberate creation of effusions overcomes certain difficulties: ascites helps to protect adjacent abdominal organs and hydrothorax protects the lung during ablation of hepatic dome lesions [15,16]. Within 3—5 days of RFA, a third of patients will develop pain at the site of the probe tip and a flu-like syndrome (fever, myalgias, weakness). The symptoms correspond to the volume of tissue destroyed [17,18]. The benefits of a surgical approach for RFA are: optimal intra-abdominal staging (detection of unsuspected carcinomatosis and increased diagnostic sensitivity of intraoperative ultrasound), the ability to perform simultaneous resection (hepatic and/or primary tumor), to interrupt hepatic inflow (Pringle maneuver), and to better protect

Radiofrequency ablation for colorectal liver metastases

Figure 2.

Deployable radiofrequency electrode.

adjacent organs. Its disadvantages are the need for general anesthesia, increased invasiveness, longer duration of hospital stay, and increased costs compared to the percutaneous route, especially in cases of recurrence with adhesions. The minimally invasive laparoscopic approach can be performed on an outpatient basis. It has most of the advantages of an open approach, albeit with some limitations due to the technical difficulties of laparoscopic liver mobilization and performance of ultrasound. By whatever approach, the crucial element of the technique is the precise positioning of the RFA electrode, which requires a learning curve of 50 patients [19].

Complications A large number of published studies (involving several thousand patients) offers sufficient follow-up to evaluate the morbidity of RFA [20—26]. Technical morbidity does not exceed 10.6% and mortality is 0.5%. The approach used, whether percutaneous or surgical, does not seem to influence morbidity, with reported rates of 0.9—7.2% and 2.4—10.6% respectively. The most commonly reported complications are bleeding (1.6%), abscess (1.1%), biliary ductal injury (1%), malignant

S35 seeding of the puncture tract (0.9%), gastrointestinal perforation (0.3%), pneumothorax and/or pleural effusion, acute cholecystitis, vascular thrombosis, or arteriovenous fistula. Skin burns were frequently reported in the early series, but have become rare since the introduction of modern systems using grounding plates with a much larger surface. Some complications occur more frequently with percutaneous RFA than with the open surgical route (gastrointestinal perforation, cholecystitis, pleural effusions, skin burns). Identified risk factors for complications include: bilirubin > 2.0 mmol/dL, cirrhosis, subcapsular or deep central tumor location, multiple tumors requiring multiple RFA applications, presence of a biliary-enteric anastomosis, and operator experience of < 50 procedures [19,20,25]. Indirect punctures through an area of healthy liver and coagulation of the tract are recommended to reduce the risk of bleeding and tumor implantation, especially for subcapsular lesions. However, the actual risk of seeding the puncture tract is low. In a retrospective study of 1314 patients (215 with subcapsular tumor), Livraghi et al. [27] reported a seeding rate of 0.9%. The proximity of HMCRC to the right or left hepatic ducts, sectoral bile ducts or common bile duct increases the risk of biliary stricture or biliary fistula due to heat-induced necrosis and/or direct ductal puncture. In such complex cases, when RFA is the only therapeutic option, the biliary tree should be cooled by infusion of chilled saline [28], either percutaneously or by direct surgical route. The bipolar RFA mode may be preferred in such cases because it allows better control of the orientation and extent of induced electric fields. For liver metastases located near the hepatic dome, the diaphragm is particularly exposed to the risk of thermal injury; the consequences are generally limited to a reactive pleural effusion and to a more intense and prolonged pain syndrome, amenable to simple treatment by analgesics. The risk of pulmonary splinting resulting in atelectasis must be a concern, particularly in patients with pre-existing respiratory insufficiency. Cholecystitis due to thermal injury is exceptional and is asymptomatic in most cases [29]. The risk of gallbladder perforation is present only when large tumors lie adjacent to the gallbladder requiring prolonged RFA time and high levels of energy. Lesions that lie adjacent to digestive structures are rare and the intestine can be protected by interposition of induced ascites [30]. Hyperthermia-related vascular thrombosis is only observed in vessels smaller than 3 mm [31] and has no symptomatic consequences. Larger caliber vessels are protected by the continuous cooling effect of blood flow. Finally, RFA may result in increased technical difficulty and morbidity of subsequent hepatic surgery in patients with hepatic recurrence after RFA. Previous RFA results in a frequent need to extend resection to adjacent organs and in increased intraoperative bleeding, leading to a higher postoperative complication rate [32].

Assessment of therapeutic effect — Risk factors for recurrence Intraoperative guidance and therapeutic evaluation The objective of RFA is to destroy the tumor as well as a margin of healthy peritumoral parenchyma in order to

S36 obtain ‘‘tumor-free margins’’. Ideally, the zone of RFA should extend 10 mm beyond the tumor, analogous to surgical resection margins of HMCRC [33—40]. Recent advances in chemotherapy seem to allow reduction of this margin of safety while still achieving the equivalent of an ‘‘R1 resection’’ [41]. Although the requirement of a 10 mm margin for RFA is exaggerated, this notion of lesser (although still R1) margins applies mainly to HMCRC that was initially deemed unresectable. The success of RFA depends on several parameters: the ability to detect and target all lesions needing treatment and to monitor in real time the extent and effectiveness of treatment (imaging by ultrasound, CT or MRI). Different techniques can be used to guide the puncture. There are no randomized controlled trials comparing the efficacy of guidance techniques. Beyond technical capabilities, the choice of imaging modality for guidance also depends on cost, accessibility and operator experience. While ultrasound is the only available intraoperative guidance technique, CT and MRI can be used to guide percutaneous RFA. Ultrasound guidance is still the most commonly used modality, combining availability, safety, low cost and speed of use. The main disadvantage of ultrasound is difficulty in real-time visualization of the effects of RFA. During thermal destruction, a hyperechoic area gradually appears around the end of the electrode, corresponding to vaporization of the treated tissues with formation of gaseous microbubbles [42] (Fig. 3). This hyperechoic appearance persists for 30 minutes to 6 hours after the procedure [43]. In addition, the hyperechoic area does not correspond precisely to the zone of thermocoagulation and therefore gives only a rough overview of the area of thermally-induced necrosis [42,44]. Thus, the final evaluation of the zone of thermal ablation should be evaluated by another technique (CT, MRI) [42] or by the use of enhanced ultrasound techniques to assess the vascularization of tissues. Color Doppler ultrasound is rarely useful for this purpose [44]. Echographic contrast products seem to improve ultrasound assessment to differentiate the area of tumor necrosis (with no contrast uptake) from residual hypervascularized tumor, with a sensitivity of 90% and a specificity close to 100% [44—46]. CT guidance is most often used for lesions that are not visible on ultrasound (isoechoic) (Fig. 4). CT has several disadvantages: lower availability, higher cost, radiation exposure, the need for potentially nephrotoxic contrast agents, inability to use in conjunction with surgery, and the lack of real-time visualization of the puncture and the effects of RFA application. Since HMCRC are usually hypovascular, the lesion itself and the area of thermal ablation both appear hypodense, and offer little contrast to distinguish between the pre- and post-treatment images. In addition, the CT images at the end of the procedure show poor correlation between the scanographic zone of thermal ablation and the actual zone of heat-induced necrosis [47]. RFA can be performed using guidance provided by open MRI scanners. The advantages of MRI are: high sensitivity and specificity for the diagnosis and characterization of HMCRC [48], the possibility of multiplanar guidance, safety, and the avoidance of contrast nephrotoxicity [49,50]. Its disadvantages are: cost, lengthy procedures, lack of availability of MRI machines, electromagnetic interference with the RFA equipment, inability to combine RFA with surgery, and the lack of real-time visualization during puncture and current application. However, MRI appears to be the most reliable technique for early assessment of the area of thermo-induced necrosis [51]: necrosis appears hypointense

A. Stoltz et al. on T1 and T2 images without contrast enhancement. MRI also allows temperature monitoring (MRI thermometry) and adjustment of RFA power intensity during treatment, allowing achievement of a more uniform temperature in the target area [52].

Post-therapeutic assessment and surveillance As mentioned above, it is difficult to assess the degree of tumor destruction during the procedure; this explains, in part, the high rate of local recurrence (Fig. 5). It is therefore important to use reliable and accurate imaging techniques to assess the long-term effectiveness of the RFA procedure and to set up a program of ongoing surveillance. Early and accurate diagnosis of tumor persistence or recurrence is also essential to avoid unnecessary biopsies and treatment of false positives. Early diagnosis also allows repeat RFA to be performed as early as possible for cases of residual tumor or early recurrence. The initial scar resulting from RFA is larger or at least equivalent to the tumor size, and only decreases in size after a period of time. It is therefore impossible to use the usual morphometric criteria to assess RFA response, based solely on variation in size of the tumor, as is typical using RECIST criteria. The scar does not decrease in size until the third month post-procedure and usually persists for years after RFA. CT and MRI are the two most commonly used imaging techniques for surveillance [49,53,54]. Their sensitivity and specificity to detect recurrence after RFA are respectively 65% and 60% for CT, and 65% and 85% for MRI [55]. Recurrent tumor enhances with IV contrast on CT scan (especially at the periphery of the thermal ablation area). On MRI, areas of necrosis remain hypointense in T1 and T2 images, and do not enhance with contrast. Several recent studies have suggested that Positron Emission Tomography (PET) is superior to CT or MRI for detection of residual tumor and recurrence after RFA [55—61]; PET has a sensitivity approaching 95%, a specificity exceeding 80%, and positive and negative predictive values of 85% and 93%. Within several days of RFA, hyperemia in the periphery of the thermal ablation area results in peripheral contrast enhancement on CT or MRI, but there is no increased uptake on PET scan [62,63]. PET therefore seems particularly useful for diagnosing residual tumor or early recurrence [56,58,62,64].

Indications and oncological results HMCRC can be classified into two broad categories: resectable metastases and metastases deemed irresectable. We will define the role of RFA for each category.

Resectable hepatic metastases Surgical resection combined with perioperative chemotherapy is presently the standard treatment for HMCRC. According to a recent Cochrane Library review, the level of evidence for the use of RFA as a therapeutic equivalent of surgery was (and remains) inadequate [13]. The variability of results in published literature on the theme ‘‘hepatectomy versus RFA’’ is explained by selection bias due to non-randomization. Patients in the two treatment arms had different characteristics. For example, in the RFA group, all patients had a contraindication for surgery

Results of the principal published series concerning resection versus radiofrequency ablation in the treatment of hepatic metastases from colorectal cancer.

Author (year)

Treatment

Patients (n)

Mean tumor size (cm)

Criteria of non-resectability

Median follow-up (months)

3-year overall survival (%)

Oshowo 2003 [65]

RFA (p) HR

25

3 [1—10] 4 [2—7]

Single HMCRC with EHM or in proximity to vessels, or co-morbidities

18

53% 55%

3 [1—7]

Single HMCRC with insufficient size of residual liver, or co-morbidities

31.3 (4—138)

57% 79%

27% 71%

—

0 50%

2.4 [1—5] 2.7 [1—5]

Single HMCRC with previous major HR, or co-morbidities

17 68

26% 82%

0 57%

31 80

0 32%

2 [0.6—4] 3.1 [0.5—8]

Single HMCRC with insufficient size of future residual liver, or co-morbidities

49 (10—149)

—

19% 48%

36 56

—

2.5 3.5

Insufficient size of future residual liver or proximity to vessels or co-morbidities

—

72.7% 74.1%

—

—

—

2.25 (0.8—5) 3.29 (0.5—18)

Refusal of surgery, poor indocyanine green test, co-morbidities

53 88

43% 83%

48.5% 65.7%

38.2 (0.1—132.8) 25.7% 48.2 (0.9—133.9) 30.1%

20 Aloia 2006 [66]

RFA (o) RFA (p) HR

27

3 160 White 2007 [73]

RFA (p) HR

22

5-year overall survival (%) —

Median overall survival (months) 37 41

5-year disease-free survival (%) —

Radiofrequency ablation for colorectal liver metastases

Table 1

30 Park 2008 [67]

RFA (p) HR

30

59 Gleisner 2008 [68]

RFA (o) HR

11

192 Lee 2008 [69]

RFA (o) or (p) HR

37

116

S37

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Table 1 (Continued) Author (year)

Treatment

Patients (n)

Mean tumor size (cm)

Criteria of non-resectability

Median follow-up (months)

3-year overall survival (%)

5-year overall survival (%)

Berber 2008 [74]

RFA laparoscopy HR

68

3.7 3.8

Technical reasons, patient choice, EHM, co-morbidities

27 (2—86) 41 (2—132)

35% 70%

30% 40%

2.5 (0.8—3.6) Insufficient size 2.8 (0.6—8) of future residual liver or proximity to vessels, or patient choice

42 (13—120)

60% 70%

—

Not defined

—

Median overall survival (months) —

5-year disease-free survival (%) —

26% 50%

41 60

—

—

26% 58%

—

—

90 Hur 2009 [70]

RFA (o) RFA (p) HR

13

12 42 31 136

RFA (o) or (p) RH

McKay 2009 [71]

RFA (o) HR

43 58

4.1 [1—7.5] 3 [1.2—7]

Not defined

42 (15—85) 25 (4—106)

—

23% 43%

—

Otto 2010 [76]

RFA (o) or (p) HR

28

3 (1—5) 5 (1—14)

RFA favored treatment if HMCRC developed within 1 year following excision of primary cancer

814 (49—1642) 644 (76—2452)

67% 60%

48% 51%

—

15% 17% —

3.9 5.6

Single HMCRC with insufficient size of future residual liver, or co-morbidities or patient choice

25.9

—

—

112.7 50.2

42.6 months 55.2 months

2.1 (±1) 2.6 (±1)

Severe co-morbidities, insufficient size of future residual liver, > 4 HMCRC

—

50.3% 62%

31.2% 45.3%

—

23.1% 36.6%

82 Schiffman 2010 [72]

RF HR

46

94 Kim 2011 [77]

RFA (o) or (p) HR

99

127

EHM: extrahepatic metastases; HR: hepatic resection; RFA (o), (p): radiofrequency: (open), (percutaneous).

A. Stoltz et al.

Vyslouzil 2009 [75]

Radiofrequency ablation for colorectal liver metastases

S39

Figure 3. Echography-guided radiofrequency ablation: a: targeting with electrode in place; b: immediate image after radiofrequency ablation (a hyper-echogenic zone prevents evaluation of the treated area zone).

Figure 4.

Radiofrequency ablation using CT scan guidance (left: lesion 2 - needle in place; right: lesion 2 - before treatment).

(co-morbidities, extrahepatic metastases) and received no chemotherapy, unlike the patients in the surgical group [65]. We have analyzed seven observational studies [66—72] and six controlled studies [65,73—77]; these are summarized in Table 1. For RFA, the overall 5-year survival rate was 27—50% and recurrence-free survival rate varied from 0 to 34%. The

local recurrence rate was 11—37%. In most published series, patients who underwent RFA were unresectable and had a poor prognosis based on clinicopathological characteristics compared to patients who underwent hepatic resection [68]. Analysis of the published data is difficult and is akin to ‘‘comparing apples and oranges’’ [78].

Figure 5. Follow-up CT scan one month after radiofrequency ablation. White arrows: deformation of the thermal ablation zone adjacent to the Glissonian pedicles.

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A. Stoltz et al.

Figure 6. Example of a patient included in the ARF 2003 study: a and b: preoperative CT scan; white arrows: hepatic metastases (×4); c: follow-up CT scan 1 month after extended left hepatectomy including Segments I, V, VIII and metastasectomy of Segment VII: radiofrequency ablation in Segment VII — white star: zone of thermal ablation; d: follow-up CT scan 4 months later (spontaneous resolution of biloma).

Isolated intrahepatic recurrence is a special case, in that it may sometimes be resectable and therefore amenable to surgical salvage [79]. Iterative liver surgery can be a technically difficult procedure depending on the initial surgery and any postoperative complications (e.g., an obese patient with an incisional hernia); in such cases, RFA can then be considered as an alternative [80]. Available data from the literature are not sufficient to demonstrate that RFA is equivalent to surgery for resectable HMCRC. However, RFA does provide favorable overall survival and disease-free survival rates in patients with metastatic disease; it is therefore a therapeutic option when surgical treatment is contra-indicated.

Unresectable metastases After induction chemotherapy, 10 to 30% of patients with HMCRC who were initially deemed unresectable are subsequently considered potentially resectable. In these cases, RFA can be used alone or in combination with surgical resection. The combination of RFA with resection of HMCRC is of particularly interest when the metastases are bilobar; treatment can be performed in one [81] or two stages. In the course of a 2-stage hepatectomy, RFA was performed to clear the future residual liver during the first stage in 3—35% of cases and during the second stage in 2—18% of cases [82]. Percutaneous RFA in conjunction with portal vein embolization can also be used to ablate metastases in the future remnant liver [83]. If the size of the future remnant liver is considered insufficient with a metastasis located in the transection plane, the metastasis can first be ablated with RFA

followed by hepatectomy carried across the area of thermal ablation [84]. Evidence-based evaluation of RFA in the treatment of unresectable HMCRC is difficult. The need for a randomized controlled trial seems essential, yet the implementation of such a test is difficult as evidenced by the premature termination of the FFCD 2002-02 trial due to a lack of patient enrollment. In 2003, the CLOCC trial of Ruers et al. (chemotherapy alone versus chemotherapy + RFA) started in 2002 [85] was discontinued for the same reason. More precisely, this was initially a Phase III study, but was ‘‘demoted’’ to a Phase II trial; the lack of patient enrollment was attributed to strong preferences on the part of investigators in favor of a particular treatment arm. This change in methodology and the lack of power of the study prevented detection of a difference in overall survival between the two arms. To overcome this lack of power, Evrard et al. proposed a new Phase II study (ARF 2003) where the primary endpoint was complete hepatic response at three months [86]; the main interest of this study is to provide a prospective study of RFA for unresectable HMCRC (Fig. 6). The characteristics and results of these two studies are summarized in Table 2. The ARF2003 and CLOCC trials found a 3-year progression-free survival of 10% and 27.6% respectively in the RFA arm versus 10.6% in the chemotherapy-alone arm. In the CLOCC trial, overall survival at 30 months increased slightly from 57.6% in the chemotherapy-alone arm to 61.7% in the RFA arm. In the ARF2003 trial, overall survival at 5 years was 43%. It should be remembered that Nordlinger’s EORTC study (surgery ± perioperative FOLFOX for resectable HMCRC) showed a progression-free 3-year survival of 28.1—35.4% with a median follow-up of 3.9 years [87]

Results of radiofrequency ablation for non-resectable hepatic metastases from colorectal cancer.

Study

Inclusion criteria

Principal endpoint

Study duration

Patients included

Median follow-up (years)

Local recurrence

Overall survival (months)

Disease-free survival (months)

CLOCC [85] (RF + CT versus CT alone)

< 10 HMCRC Diameter < 4 cm (if RF) Synchronous and metachronous HMCRC Remaining at least stable under CT Percutaneous or open RF

Overall survival at 30 months > 38%

April 2002—June 2007

119 RFA arm: (60 patients): 30 RF, 20 RF + hepatic resection CT arm: 8.5% of patients became resectable after CT

4.4

16.1% of all patients 6.5% of RFA patients

Median: 45.3 vs 40.5 months At 30 months: 6.7% vs 57.6%

Median: 16.8 vs 9.9 months At 3 years: 27.6% vs 10.6%

ARF 2003 [86] (RF ± Surgery)

Synchronous and metachronous HMCRC At least stable with RFA open approach

Complete hepatic response at 3 months > 60%

June 2003—Oct 2008

52 (intention to treat) RFA + surgery: 42 patients 242 HMCRC treated 118 HMCRC treated by RF, median size 10 mm (2—40)

2.9

4% of patients

5 years: 43%

1 year: 27% 3 years: 10% Without hepatic progression: 3 months: 75% 1 year: 46% 3 years: 19%

Radiofrequency ablation for colorectal liver metastases

Table 2

HMCRC: hepatic metastases of colorectal cancer; RFA: radiofrequency ablation; CT: chemotherapy.

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S42 and an overall 5-year survival of 47.8—51.2% with a median follow-up of 8.5 years [88]. RFA can therefore be used effectively in combination with chemotherapy and surgery to treat unresectable HMCRC, with the aim of improving progression-free survival. It remains difficult to demonstrate an impact on overall survival (and is likely to remain so) because of a lack of power and patient heterogeneity; for example, in the CLOCC study, treatment of recurrence was different between the two arms (more surgery and RFA in the RF + chemotherapy arm). This difference may explain why the overall survival results were not identical to the progression-free survival.

Conclusion Surgery remains the only curative treatment for hepatic metastases from colorectal cancer. Radiofrequency ablation has been shown to be safe in practice, but hepatic resection should be preferred to RFA whenever possible. RFA is an alternative therapeutic option for patients with inoperable HMCRC or in the context of hepatic parenchymal sparing approaches. For unresectable metastases, radiofrequency ablation can be used as a complementary technique to surgery. The combination of these two technologies can increase the number of patients who are candidates for surgical resection, resulting in improvement in progression-free survival and overall survival.

Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.

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