|Which Patients Should Be
Treated by Radiofrequency Ablation, and Which Patients Should Not Be
Treated by Radiofrequency Ablation? Cancer 2004;100:641
Steven A. Curley, M.D.
Patients with bilobar,
otherwise unresectable colorectal carcinoma liver metastases.
Patients who have disease scattered in their liver in a pattern that
precludes complete surgical resection may be candidates for resection of
the dominant or larger tumors with radiofrequency ablation of remaining,
smaller lesions. This combined procedure can be performed with no increase
in morbidity or mortality rates. Preliminary results from the University
of Texas M. D. Anderson Cancer Center suggest that a subset of these
patients who are treated with a combination of resection and
radiofrequency ablation may achieve long-term disease-free and overall
unresectable colorectal carcinoma liver metastases who are treated on
protocol with adjuvant hepatic artery infusion chemotherapy.
Complete thermal ablation of measurable disease followed by regional
and systemic chemotherapy is a concept that is being studied on protocol
at a number of centers. To date, it is has not been determined whether
there is a survival advantage to this combined-modality approach, but the
concept is sound and should be studied further.
Selected patients with
otherwise unresectable, nonneuroendocrine liver metastases with disease
confined to the liver.
Occasionally, patients with primary carcinoma arising at sites other
than the colon or rectum may present with metastases only in the liver.
This includes patients with breast, kidney, ovarian, skin (melanoma), or
ocular (melanoma) malignancies. If patients have stable or responsive
disease on appropriate systemic chemotherapy regimens and have reached
maximum response to therapy, then it may be appropriate to consider
thermal ablation of the remaining malignant disease. These patients may be
treated percutaneously, laparoscopically, or during an open surgical
approach, depending on the size and location of the hepatic metastases.
Like in patients with colorectal carcinoma liver metastases, I do not
perform radiofrequency ablation of liver metastases if extrahepatic
disease is present. There is no demonstrable benefit to thermal ablation
or other cytodestructive techniques to treat hepatic metastases in
patients with extrahepatic disease.
Gerald D. Dodd III,
The answer to this question is evolving and is somewhat complex. The
current dogma is that radiofrequency ablation should be used only in
patients who are not candidates for surgical resection, who have limited
hepatic tumor burden, and who have no evidence of extrahepatic tumor.
Candidacy for hepatic resection is determined by many factors, including
the size, number, and location of tumors; the general health of the
patient; and their willingness to undergo surgery. The definition of
tumors that are surgically resectable varies with the training, skill, and
confidence of each surgeon; it is not defined universally. Therefore, the
decision to use radiofrequency ablation instead of resection varies from
physician to physician and from medical center to medical center.
Generally, radiofrequency ablation should be limited to patients
with fewer than five hepatic tumors. However, in patients with
slow-growing tumors, such as neuroendocrine or gastrointestinal stromal
tumors, or in patients with symptomatic hepatic carcinoid tumors, the
number of tumors that might be treated may be increased. The size of a
tumor that can be treated effectively by radiofrequency ablation is
limited by the size of the ablation zone created by existing
radiofrequency ablation devices. Although larger ablation zones
occasionally are produced, the average diameter of radiofrequency
ablation-induced thermal injuries rarely exceeds 3.5 cm irrespective of
the brand of device used. Thus, the best outcome is achieved with
tumors that measure < 3.5 cm. Although larger tumors can be treated by
overlapping ablations, the chance of missing tumor and, thus, increasing
the local recurrence rate is increased markedly. In all instances, the
size of the ablation should be larger than the tumor so that an adequate
nontumoral margin is created.
The location of a tumor is a significant factor in patient selection
for radiofrequency ablation. The best tumors are those that are imbedded
deeply in the hepatic parenchyma and remote from large blood vessels.
Tumors adjacent to large blood vessels are harder to treat, because the
blood flow in the vessel cools the heating process, thus potentially
leading to residual viable tumor against the vessel wall. Tumors adjacent
to major branches of the portal vein are particularly problematic, because
the ablation is likely to cause obstruction of the associated bile duct.
This may not be significant if only a small biliary radical is involved;
however, obstruction of the central bile ducts can lead to atrophy of the
affected liver and jaundice. Finally, tumors adjacent to bowel or the
diaphragm require specific approaches. Ablation of tumors touching bowel
can produce a significant thermal injury of the bowel wall with the
subsequent risk of perforation. Thus, the bowel must be insulated from the
thermal process. Ablation of tumors adjacent to the diaphragm can result
in injury to the diaphragm if performed improperly. The risk of thermal
injury is greatest when the multitine retractable probes are used
In patients with a few small liver tumors, surgery usually is the
procedure of choice; however, it is exactly these patients who may be the
best candidates for radiofrequency ablation. In the future, radiofrequency
ablation may replace surgery in the treatment of these patients.
Allan E. Siperstein,
The selection criteria for radiofrequency ablation differ by tumor
type. It also must be emphasized that these criteria continue to evolve
over time given the rapid advancements in ablation technology, as well as
our evolving understanding of which patients benefit best from ablative
The largest group of patients treated are those with colorectal
metastases to the liver. Current treatment criteria are patients who are
not candidates for resectional therapy and who have failed chemotherapy. A
minority of patients have been treated at the time of their colon
resection. In terms of the extent of hepatic disease, in general, we
treat patients with 8 hepatic tumors seen on
a preoperative computed tomography (CT) scan with < 20% total liver volume
replacement. My belief is that patients with many lesions have a
different biology of their disease and often harbor multiple
micrometastases that are unrecognized at the time of ablation. These
patients tend to have multifocal development of new lesions within the
liver, so that survival may not be impacted significantly by a local
ablative therapy. We have been in the practice of treating patients with
limited amounts of extrahepatic disease. We presented a study at the 2003
American Society for Clinical Oncology meeting looked at the preoperative
factors that determine survival after radiofrequency thermal ablation. It
is noteworthy that those patients with a limited amount of extrahepatic
disease did not have poorer survival compared with patients who had
hepatic tumors only.
Patients with breast carcinoma metastatic to the liver frequently are
referred for evaluation. Although metastatic breast carcinoma,
unfortunately, is quite common, these patients more commonly succumb to
extrahepatic disease rather than hepatic disease. We have been very
selective in treating patients who have been followed for many months on
chemotherapy and whose preoperative imaging studies, including head and
bone scans, failed to show extrahepatic disease. The treatment of such
patients often requires complex multimodality therapy. I feel that the
treatment strategy at a given institution is arrived at best through
presentation of these patients at a multidisciplinary conference.
Therefore, a consensus may be formed at each institution regarding not
only the indications for radiofrequency ablation but also the best
technique to be used.
S. Nahum Goldberg, M.D.
Regardless of radiofrequency's potential for ablating focal liver
tumors, it should be remembered that the largest and longest experience
treating both metastases and hepatocellular carcinoma belongs to surgical
resection (notwithstanding the fact that there have been no randomized
clinical trials for surgery). Thus, the newness of radiofrequency ablation
and the limited data must be overcome with clinical trials if
radiofrequency ablation is to be embraced by a wider proportion of the
When dealing with the question of which patients should undergo
radiofrequency ablation, a distinction needs to be drawn between primary
liver tumors, such as hepatocellular carcinoma, and metastatic disease.
For hepatocellular carcinoma, there is greater rationale for performing
ablation over resection, including the higher surgical risk of many of
these patients due to comorbidity from underlying liver disease and
coagulopathy. Furthermore, because these tumors most often are seen in the
setting of cirrhosis, there is also a high risk for new foci of disease,
requiring the identification of further treatment over time. In addition,
there is now a large body of data from Europe and Asia demonstrating that,
for patients with small hepatocellular carcinomas (< 3 cm in greatest
dimension), survival results are similar to surgery, percutaneous ethanol
instillation (PEI), and other ablative techniques. Given limited
therapeutic options, radiofrequency ablation also often affords the best
chance for eradication of larger hepatocellular carcinomas (up to 5-7 cm
in greatest dimension). However, currently, there are very little data to
support using radiofrequency ablation to treat infiltrating hepatocellular
carcinomas or hepatocellular carcinomas > than 7 cm.
Currently, there are insufficient data to warrant performing
radiofrequency ablation over surgical resection for optimal surgical
candidates for colorectal and neuroendocrine metastases. Nevertheless,
many patients are not optimal surgical candidates and should be considered
for radiofrequency ablation either alone or in combination with
chemotherapy. For these patients, tumor size often is a primary
determinant of anticipated outcome, with good local tumor control expected
only for patients with tumors no greater than 3-5 cm in greatest
Given the likelihood of additional undetected tumors, there is
considerable debate regarding the appropriateness of early resection of
synchronous intrahepatic metastases at the time of initial colectomy.
Nonetheless, conservative management (watchful waiting for 4-6 months
before formal liver resection) allows for the possibility of interval
tumor growth of known metastases. Thus, one approach being touted is
radiofrequency ablation, which can destroy the index tumors with reduced
morbidity while waiting for the true tumor burden to be declared.
For both hepatocellular carcinoma and metastases, patients whose life
expectancy and quality of life are not expected to improve from
radiofrequency ablation should not be treated. Thus, there currently is
little evidence to support using radiofrequency ablation in patients with
Child C disease or the ablation of large tumors for palliative debulking.
By the same token, treatment of hematogenously spread tumors, such as lung
tumors, pancreatic tumors, and melanoma, likely is unwarranted, because
the ablation of these lesions is unlikely to change the patients' clinical
outcomes. A notable exception is the treatment of patients with limited,
focal breast metastases, for which improved outcomes have been suggested.
Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases.
Abdalla EK, Vauthey JN, Ellis LM, Ellis V, Pollock R, Broglio KR, Hess K, Curley SA.Ann Surg.
Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
OBJECTIVE: To examine recurrence and survival rates for patients treated with hepatic resection only, radiofrequency ablation (RFA) plus resection or RFA only for colorectal liver metastases. SUMMARY BACKGROUND DATA: Thermal destruction techniques, particularly RFA, have been rapidly accepted into surgical practice in the last 5 years. Long-term survival data following treatment of colorectal liver metastasis using RFA with or without hepatic resection are lacking. METHODS: Data from 358 consecutive patients with colorectal liver metastases treated for cure with hepatic resection +/- RFA and 70 patients found at laparotomy to have liver-only disease but not to be candidates for potentially curative treatment were compared (1992-2002). RESULTS: Of 418 patients treated, 190 (45%) underwent resection only, 101 RFA + resection (24%), 57 RFA only (14%), and 70 laparotomy with biopsy only or arterial infusion pump placement ("chemotherapy only," 17%). RFA was used in operative candidates who could not undergo complete resection of disease.
Overall recurrence was most common after RFA (84% vs. 64% RFA + resection vs. 52% resection only, P < 0.001). Liver-only recurrence after RFA was fourfold the rate after resection (44% vs. 11% of patients, P < 0.001), and true local recurrence was most common after RFA (9% of patients vs. 5% RFA + resection vs. 2% resection only, P = 0.02).
Overall survival rate was highest after resection (58% at 5 years); 4-year survival after resection, RFA + resection and RFA only were 65%, 36%, and 22%, respectively
(P < 0.0001). Survival for "unresectable" patients treated with RFA + resection or RFA only was greater than chemotherapy only (P = 0.0017). CONCLUSIONS: Hepatic resection is the treatment of choice for colorectal liver metastases. RFA alone or in combination with resection for unresectable patients does not provide survival comparable to resection, and provides survival only slightly superior to nonsurgical treatment.
Thermic ablation with RF of liver metastases from colorectal cancer.
Azzarello G, Hepatogastroenterology. 2003 Dec;50 Suppl 2:ccv-ccvii.
Department of Surgical Sciences, Organ Transplantations and Advanced Technologies, General Surgery, University of Catania, Italy.
Aim of this study was to evaluate the role of radiofrequency ablation in the treatment of the hepatic metastasis of colorectal cancer. From November 1997 to July 2002 49 radiofrequency ablations have been performed in 19 patients (11 male and 8 female; mean age 65 years: range 50-78 years). The disease-free period was between 5 and 32 months. Nodules had a diameter <3 cm in 4 cases while in 3 cases a single lesion was present. One patient had a single lesion after 2 courses of intravenous systemic chemotherapy which had a reduced greater lesion (from 6 to 3 cm) while a 2 cm lesion had disappeared. In the remaining 12 patients the mean number of lesions is 3 (range 1-13) with a diameter between 3 and 12 cm. The radiofrequency ablation has been performed during laparotomy and vascular exclusion through clampage of the liver hilum in 4 cases and percutaneously under ultrasound guide in the remaining 15 cases. All patients underwent follow up by computed tomography, CEA level and ultrasound every 3 months. One patient only has completed a 4 year follow up and is alive without local recurrence but with a cerebral metastasis.
The other 18 patients have a 32 months follow up with a survival of 50% (9 on 18). In conclusion in our experience the radiofrequency ablation is a valid alternative method in the treatment of the hepatic metastasis of colorectal cancer.
Early and late complications after radiofrequency ablation of malignant liver tumors in 608 patients.
Curley SA .Ann Surg. 2004 Apr;239(4):450-8.
Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4095, USA. email@example.com
BACKGROUND: Radiofrequency ablation (RFA) has become a common treatment of patients with unresectable primary and secondary hepatic malignancies. We performed this prospective analysis to determine early (within 30 days) and late (more than 30 days after) complication rates associated with hepatic tumor RFA. METHODS: All patients treated between January 1, 1996 and June 30, 2002 with RFA for hepatic malignancies were entered into a prospective database. Patients were evaluated during RFA treatment, throughout the immediate post RFA course, and then every 3 months after RFA to assess for the development of treatment-related complications. RESULTS: A total of 608 patients, 345 men (56.7%) and 263 women (43.3%), with a median age of 58 years (range 18-85 years) underwent RFA of 1225 malignant liver tumors. Open intraoperative RFA was performed in 382 patients (62.8%), while percutaneous RFA was performed in 226 (37.2%). The treatment-related mortality rate was 0.5%.
Early complications developed in 43 patients (7.1%). Early complications were more likely to occur in patients treated with open RFA (33 [8.6%] of 382 patients) compared with percutaneous RFA (10 [4.4%] 226 patients, P < 0.01), and in patients with cirrhosis (25 [12.9%] complications in 194 patients) compared with noncirrhotic patients (31 [7.5%] complications in 414 patients, P < 0.05). Late complications arose in 15 patients (2.4%) with no difference in incidence between open and percutaneous RFA treatment. The combined overall early and late complication rate was 9.5%. CONCLUSIONS: Hepatic tumor RFA can be performed with low mortality and morbidity rates. Though relatively rare, late complications can develop and physicians performing hepatic RFA must be cognizant of these delayed treatment-related problems.
Radiofrequency ablation of primary and metastatic hepatic malignancies.
Curley SA, Izzo F. Int J Clin Oncol. 2002 Apr;7(2):72-81.
Department of Surgical Oncology, Box 444, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Boulevard, Houston, TX 777030, USA. firstname.lastname@example.org
The majority of patients with primary of metastatic hepatic tumors are not candidates for resection, because of tumor size, location near major intrahepatic blood vessels precluding a margin-negative resection, multifocality, or inadequate hepatic function related to coexistent cirrhosis. Radiofrequency ablation (RFA) is an evolving technology being used to treat patients with unresectable primary and metastatic hepatic cancers. RFA produces coagulative necrosis of the tumor through local tissue heating. Liver tumors are treated percutaneously, laparoscopically, or during laparotomy, using ultrasonography to identify tumors and to guide placement of the RFA needle electrode. For tumors smaller than 2.0 cm in diameter, one or two deployments of the monopolar multiple-array needle electrode are sufficient to produce complete coagulative necrosis of the tumor. However, with increasing size of the tumor, there is a concomitant increase in the number of deployments of the needle electrode and the overall time necessary to produce complete coagulative necrosis of the tumor.
In general, RFA is a safe, well-tolerated, effective treatment for unresectable hepatic malignancies less than 6.0 cm in diameter. Effective treatment of larger tumors awaits the development of more powerful, larger array monopolar and bipolar RFA technologies.
Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year.
de Baere T, AJR Am J Roentgenol. 2000 Dec;175(6):1619-25.
Departement d'Imagerie Medicale, Institut Gustave Roussy, Villejuif, France.
OBJECTIVE: The objective of our study was to evaluate the efficacy and safety of radiofrequency ablation of hepatic metastases performed either percutaneously for treatment of hepatic metastases in patients deemed ineligible for surgery or intraoperatively during partial hepatectomy to destroy unresectable metastases. SUBJECTS AND METHODS: Sixty-eight patients with 121 hepatic metastases (<5 metastases per patient) that were mainly colorectal in origin underwent 76 sessions of radiofrequency ablation with cooled-needle electrodes under sonographic guidance. Twenty-one patients with 33 metastases of 5-20 mm in diameter (mean +/- SD,13 +/- 7 mm) underwent intraoperative radiofrequency ablation. Forty-seven patients with 88 metastases of 10 to 42 mm in diameter (mean +/- SD, 26 +/- 9 mm) were treated with percutaneous radiofrequency ablation. Procedure efficacy was evaluated with dynamic enhanced CT and MR imaging performed 2, 4, and 6 months after treatment and then every 3 months. RESULTS: Radiofrequency ablation allowed
eradication of 91% of the 100 treated metastases that were followed up for 4-23 months (mean, 13.7 months). Tumor control was equivalent for percutaneous radiofrequency ablation (90%) and for intraoperative radiofrequency ablation (94%). Failure to achieve tumor control occurred mostly with the largest tumor nodules. One bilioperitoneum and two abscesses were the major complications encountered after treatment of 121 metastases with a follow-up of more than 2 months. CONCLUSION: Radiofrequency ablation appears to be a promising therapeutic modality capable of extending the possibilities of partial hepatectomy and of efficiently treating small metastases percutaneously.
Non-resection approaches for colorectal liver metastases.
Khatri VP, McGahan J. Surg Clin North Am. 2004 Apr;84(2):587-606.
Division of Surgical Oncology, UC Davis Cancer Center, University of California-Davis, 4501 X Street, Sacramento, CA 95817, USA. email@example.com
The field of in situ destruction of liver tumors has expanded rapidly with various institutions' results suggesting that these methods represent viable palliative options, primarily because of the low associated morbidity and mortality. Despite this enthusiasm, clinical trials are needed to determine the true nature and degree of palliation. Treating a systemic disease such as colorectal liver metastases with local therapy strategies alone is of dubious value. In fact, it has been shown by most reports that the limiting factor inpatient outcome is disease progression rather than technical failure. For optimal results, physicians performing in situ ablation of liver lesions should be familiar with tumor biology and the natural history of the malignancy, and possess expertise in proper integration of other therapeutic modalities (eg, systemic chemotherapy and hepatic artery chemotherapy). Patients with liver metastases from colorectal carcinoma should therefore be evaluated for curability by a surgical oncologist within the context of a multidisciplinary team, as surgical resection remains the best treatment to achieve long-term survival. Such an assessment offers the patient the opportunity of a tailored therapy that may consist of hepatic resection, intravenous or regional chemotherapy, and local ablative therapy. Furthermore, results of RF ablation should be reported in terms of well-established oncological outcomes (eg, overall survival, disease-free survival, progression-free survival) that are more meaningful to the patient, rather than lesion-oriented outcomes. Because most of the ablative techniques have not yet been validated, it is imperative that well-designed clinical trials are conducted under the auspices of national cooperative groups. To consider them standard independent therapies otherwise would be premature.
Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases.
Oshowo A, Br J Surg. 2003 Oct;90(10):1240-3.
Department of Surgery, Royal Free and University College Medical School, University College London, London, UK.
BACKGROUND: Liver resection is the treatment of choice for patients with solitary colorectal liver metastases. In recent years, however, radiofrequency ablation has been used increasingly in the treatment of colorectal liver metastases. In the absence of randomized clinical trials, this study aimed to compare outcome in patients with solitary colorectal liver metastases treated by surgery or by radiofrequency ablation. METHODS: Solitary colorectal liver metastases were treated by radiofrequency destruction in 25 patients. The indications were extrahepatic disease in seven, vessel contiguity in nine and co-morbidity in nine patients. Outcome was compared with that of 20 patients who were treated by liver resection for solitary metastases and had no evidence of extrahepatic disease. Most patients in both groups also received systemic chemotherapy. RESULTS:
Median survival after liver resection was 41 (range 0-97) months with a 3-year survival rate of 55.4 per cent. There was one postoperative death and morbidity was minimal. Median survival after radiofrequency ablation was 37 (range 9-67) months with a 3-year survival rate of 52.6 per cent. CONCLUSION: Survival after resection and radiofrequency
ablation of solitary colorectal liver metastases was comparable. The
latter is less invasive and requires either an overnight stay or day-case
Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients.
Solbiati L, Radiology. 2001 Oct;221(1):159-66.
Department of Radiology, Ospedale Generale, Busto Arsizio, Italy.
PURPOSE: To describe the results of an ongoing radio-frequency (RF) ablation study in patients with hepatic metastases from colorectal carcinoma. MATERIALS AND METHODS: In 117 patients, 179 metachronous colorectal carcinoma hepatic metastases (0.9-9.6 cm in diameter) were treated with RF ablation by using 17-gauge internally cooled electrodes. Computed tomographic follow-up was performed every 4-6 months. Recurrent tumors were retreated when feasible. Time to new metastases and death for each patient and time to local recurrence for individual lesions were modeled with Kaplan-Meier analysis. Modeling determined the effect of number of metastases on the time to new metastases and death and effect of tumor size on local recurrence. RESULTS:
Estimated median survival was 36 months (95% CI; 28, 52 months). Estimated 1, 2, and 3-year survival rates were 93%, 69%, and 46%, respectively. Survival was not significantly related to number of metastases treated. In 77 (66%) of 117 patients, new metastases were observed at follow-up. Estimated median time until new metastases was 12 months (95% CI; 10, 18 months). Percentages of patients with no new metastases after initial treatment at 1 and 2 years were 49% and 35%, respectively. Time to new metastases was not significantly related to number of metastases.
Seventy (39%) of 179 lesions developed local recurrence after treatment. Of these, 54 were observed by 6 months and 67 by 1 year. No local recurrence was observed after 18 months. Frequency and time to local recurrence were related to lesion size (P < or =.001). CONCLUSION: RF ablation is an effective method to treat hepatic metastases from colorectal carcinoma.