Better do not do RFA for resectable CRC liver mets. Our group investigates RFA more than 12 years, and the results still cannot reach those obtained with resection. The literature shows the same. You can take a look at one brief editorial paper here:

https://www.researchgate.net/profile/Alexander_Julianov/publication/236582156_Radiofrequency_ablation_or_resection_for_small_colorectal_liver_metastases_-_a_plea_for_caution/file/72e7e5184d7d985fa0.pdf?origin=publication_detail

Article Radiofrequency ablation or resection for small colorectal li...

I could prefer RF for presented case

Dr. Saglam,

Could you share please the indications for RFA of colorectal liver mets in your center?

Dear all!

It depends on the location and on the quality of the RFA. If you can achieve an ablation margin of 1cm in this anatomical location and with your equipment and you are able to check with image fusion in three dimensions I definitely would go for RFA! I recommend to use a navigation system to achieve overlapping ablation zones. For further information check the featured publications about stereotactic radiofrequency ablation on my personal research gate page.

Dear Dr. Bale,

I agree with you if we talk about HCC. However in CRC liver mets the situation looks different. We use LeVeen electrodes, 2cm margin and vascular control during RFA. Even the recurrence at the ablation site is very low (below 7%) in our experience, the incidence of new mets is about 5 times higher in RFA vs. resection. The MD Anderson group published similar results years ago - 50% disease-free survival at 5 years in the resection group of small solitary mets vs. 0% disease-free in RFA group. The local control can easily be achieved with RFA but the long-term consequences of ablation compares unfavourably to resection. It is not a problem of local control but of change of natural course of disease. The survival achieved with RFA is lower than those of resection even in completely ablated solitary CRC metastasis. And this is not related to quality of ablation.

Dear Dr. Julianov,

thank you very much for your comment.

1. I agree with you if you talk about extended anatomical resection. The likelihood of recurrence is 0 in the segments that were completely removed. However, the morbidity is of course much higher. In addition, you remove not only potential new mets but also healthy liver parenchyma. There is no guarantee that new mets develop only in the removed segments. The small liver remnant volume may limit treatment of recurrent new lesions.

2. The likelihood for the development of new lesions in the remaining liver may be equal after R0 resection as compared to A0 ablation. Why do atypical resection if you can achieve the same local result with minimal invasive RFA?

3. If a more aggressive approach is necessary you may also perform percutaneous functional anatomical resection by (S)RFA (see attachment).

4. In conclusion, I would definitely go for (S)RFA followed by MRI FU within 3 months intervals for the first year. If new metastases develop there would be still options for SRFA (or resection).

..this is just an example for functional anatomical resection by SRFA.

Dear Dr. Bale,

The answer to your question "Why do resection...?" is simple - the equivalence of RFA to resection in local control of CRCLM and more importantly in long- term results had never been proven. Moreover all of the comparative studies showed better survival outcomes after resection. This is why there is still no RCT comparing LR and RFA in CRC mets. I just follow the current evidence. In our early experience (2001-2004) with RFA we do very large volumes of ablation (SRFA in your terminology) but we are dissatisfied from long-term results. And never did RFA for resectable colorectal metastasis. No scientific evidence to do that.

Percutaneous stereotactic radiofrequency ablation of colorectal liver metastases.

Reto Bale, Gerlig Widmann, Peter Schullian, Marion Haidu, Georg Pall, Alexander Klaus, Helmut Weiss, Matthias Biebl, Raimund Margreiter

Department of Microinvasive Therapy (SIP), Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

European Radiology (Impact Factor: 3.55). 11/2011; 22(4):930-7. DOI:10.1007/s00330-011-2314-0

Source: PubMed

Edit

ABSTRACT To evaluate the outcome of patients with colorectal liver metastasis (CRLM) treated with stereotactic radiofrequency ablation (SRFA).

Following IRB approval, a retrospective evaluation of 98 SRFA treatment sessions of 189 CRLMs in 63 consecutive patients was performed. Local recurrence rate (LR), overall survival (OS) and disease-free survival (DFS) were analysed.

LR was identified in 16% of the tumours (31/189), with no significant differences (P = 0.635) when comparing tumour sizes 5 cm (17.4%). The median OS from SRFA treatment was 33.2 months after a mean follow-up of 25 months (range 2-66); the corresponding 1-, 3- and 5- year survival rates were 87%, 44% and 27%. The median OS was significantly different when comparing unresectable and resectable patients (27 vs. 58 months, P = 0.002) with OS rates of 92%, 66% and 48% at 1, 3 and 5 years in resectable patients. Tumour size did not affect OS and DFS.

Due to the favourable outcome, SRFA challenges resection as first-line local treatment of patients with CRLM. As long as randomised studies are pending, we recommend entering an individual decision-making process with every patient.

Large colorectal liver metastases can be effectively treated by stereotactic radiofrequency ablation (SRFA). Using SRFA the overall survival is not affected by tumour size. SRFA achieves similar overall and disease-free survival rates as surgical resection. SRFA challenges surgical resection as the first-line treatment for colorectal liver metastases.

Dear Dr. Julianov,

thanks for your reply. Yes, the answer is simple but it is also logical. There are two main simple and logical ,-)) reasons for the worse long-term results of RFA in the literature:

First, the local recuurrence rate after RFA using conventional guidance is still higher as compared to resection.

Therefore:

Second, conventional RFA is applied in patients that are no candidates for surgery. These patients have per se a worse prognosis as compared to the surgery group.

The reason that the survival after RFA of small HCC is similar to resection is the fact that the local control of RFA in small HCC is comparable to surgery.

There is time for a randomized study comparing long term survival after R0 resection vs. A0 ablation of colorectal liver metastases. I bet that there will be no diference between R0 atypical resection and A0 ablation.

Thank you Dr. Bale,

Unfortunately I strongly disagree with you. You can read my point of view on the Editorial paper below. However I hope that you are right, not me, but still no high quality evidence to support your statements.

https://www.researchgate.net/publication/236582156_Radiofrequency_ablation_or_resection_for_small_colorectal_liver_metastases_-_a_plea_for_caution

Article Radiofrequency ablation or resection for small colorectal li...

Dear Dr. Julianov,

I agree with you that the evidence for my statement is low since no direct comparison of resection vs. rfa is available in the literature - as you also state in your review paper. However, the evidence for the statement " A0 resection is superior to A0 ablation in terms of survival" is equally low for the same reason.

Nevertheless it would be interesting for me to know if you really think that even atypical non-anatomical resection is superior to complete histology proven ablation in terms of survival. at least in my opinion and in our data it does not make any difference if you completely remove or ablate all tumor cells.

To overcome this lack of knowledge we should perform a randomized multicenter study comparing A0 with R0. It would be great if we could set up such a study via researchgate!

Dear Dr. Bale,

Regarding your comment - there is no need to prove that resection is better, RFA should demonstrate at least non inferiority compared to liver resection and this was not done yet.

To answer your question - I am just very, very cautious with RFA. Not because of doubt related to local control. I see over the years that it is not so difficult to obtain complete ablation with large security margin even in most challenging cases (take a look for example the link to one paper below). However what we see (and many other liver surgeons) is that in a subset of patients RFA triggers very uncontrollable progression of metastatic disease at sites different from ablated zone. Some data demonstrated that thermal injury to the liver lead to over expression of MMP 7&9, as well as HSP70. It is well known that they make cells resistant to proapoptosic stimuli including radiation and chemotherapy. Macroscopically we also see during resection of incompletely ablated CRCLM that those lesions acquired growth pattern never seen before for this type of metastasis. So I would like to know how to exclude pts for which RFA will open Pandora's box. Before this data is available I will remain very cautious, despite the fact that some of our first patients are 10-years disease-free now after RFA. This is not a position to think or believe as you see. I need strong evidence to do this or that when dealing with someone's health and life.

https://www.researchgate.net/publication/233991056_A_five-year_disease-free_survival_after_combined_hepatectomy_and_radiofrequency_ablation_of_large_hepatocellular_carcinoma_adjacent_to_vena_cava

Article A five-year disease-free survival after combined hepatectomy...

Dear Dr. Julianov,

yes you are right. Resection was the first "kid on the block" and was established due to the lack of other minimal invasive alternative local treatments. Resection is still the first choice in resectable colorectal liver metastasis in most centers.

Unfortunately randomized studies comparing resection and ablation are still missing.

The reasons therefore are:

First, the local recurrence rate after conventional RFA is still higher as compared to resection in many centers.

Second, the disease free survival and the overall survival after RFA is shorter as compared to resection in most centers.

As I have already stated in a previous posting RFA is only used in patients with non-resectable CRLM in most centers. It is obvious that many of these patients have initially a higher likelihood for the development of new mets at other sites in the liver due to their worse initial prognosis. I think that your explanation of experimental data about overexpression of MMPs or HSP is far from any clinical evidence. Contrary data is available discussing positive immunological effects after RFA - this is of course also far from clinical evidence.

In contrast to your experience my personal experience as an abdominal radiologist is that there are also subsets of patients where very uncontrollable progression of metastatic disease at sites different from the resection zone is diagnosed. In contrast to your statement I do not like the BOX of PANDORA theory. If I would stress the BOX of PANDORA theory - as you try to do with RFA - I would argue that the application of novel technical equipment like ultrasonic dissection is responsible.

I do not think that surgery has triggered these unfavourable progression, i think that the reasons therefore are micrometastases that were not diagnosed initally developed....

I am sorry that you could not convince me - if I was a patient I would still prefer (S)RFA as first choice if I can achieve complete ablation (if the safety margin of 1 cm can be achieved). This preference is not only based on my experience with > 700 patients and > 1100 tumors over the last 15 years but also on the studies that we published.

Again: We should perform a randomized multicenter study comparing A0 (complete ablation) with R0 (complete resection). It would be great if we could set up such a study via researchgate!

Great comment Dr. Bale!

You make me to start to think seriously about the scientifically sound design of such a trial.

Dear prof julianov and prof bale

Great discussion.

Exactly the kind of discussion we have in our joint clinic every week. I still believe surgery is superior in terms of local recurrence and 5 year survival rates. Even for lesions less than 3 cm surgery seems to be superior, with 5 yr survival after liver resection of 70% aloia t md Anderson. While some studies like bieber have shown comparable results of Rfa and surgery, 5 yr survival after liver resection was quite low.

While all these studies are old 2006 and Rfa techniques are superior now, however unless trials show Rfa equivalent or superior, standard of care remains resection.

I agree with dr rete, it is time for a trial. We also have to admit, the most important factor in all studies related to colorectal liver mets is a good liver surgeon, as respectability is surgeon dependent.

Dr saklani

dear dr julianov

thank you very much for yourpositive feedback. i would propose a randomized controlled study comparing resection and (s)rfa. the interventional radiologist should only include lesions that can be ablated completely with the respective safety margin using his specific technique/equipment., e.g. if only equipment / technique is available to achieve a 3 cm lesion he should only treat lesion up to 1cm. if srfa is available he may also include large lesions. the same should be applied to the surgical arm. if local progression is noted in the followup mri scans (every three months) these patients may be retreated by the opposite technique and excluded from the study. all the others may be observed for further outcome.

who would be interested to participate in such a study?

maybe this would be the first researchgate triggered multicenter study!!

dear dr saklani

thank you very much for your comment. you are right. the result after resection is depending on the surgical technique and the surgeon. the same is of course true for rfa. if you want to compete with surgery you should achieve the same local result vice versa! however, if the local result is the same the patients will definitely go for the minimal invasive technique. it is the responsibilty of the surgeon to achieve r0 resection and the responsibility of the interventionalist to perform a0 ablation. if he fails it is his responsibility! it is very important to use rfa only if you are confident that you can treat the tumor completely - as for surgery!

we have developed the stereotactic rfa which allows you to completely ablate tumors larger than 10 cm completely. it is just a question of 3d planning, precise placement of needles and burning at multiple locations. in addition image fusion during the ablation procedure using contrast media is necessary to verify a sufficient safety margin.

why should i not use this technique for resectable tumors? the only argument would be the BOX of PANDORA i do not like...

Dear sirs.

With high precision in needle guidance (as with guded CT, for exampel with CAScinations system) we frequently get the microwave needle (acculis) within 3mm of any point we are aiming for in the liver. With a predictable ablation (I'm not sure we are completely there yet) of a lesion

There is also the immune response to consider, for example a recent study entitled "PD-1 Blockade Boosts Radiofrequency Ablation-Elicited Adaptive Immune Responses Against Tumor" (http://news.medlive.cn/uploadfile/20160302/14568978913330.pdf) where CRC liver mets were ablated, it was shown that localized RFA induced t-cell mediated immune responses in a distant tumor site in human carcinoma. They're coupling it with PD-1 blockade to allow the t-cells to do their thing once they're successfully deployed to the site/s. Will be interesting to see where this goes, and again it's just another angle to consider.