Sarah White (Medical College of Wisconsin, Milwaukee, USA) opened the liver interventional oncology (IO) session at the Pan Arab Interventional Radiology Society (PAIRS) annual meeting (11–14 February, Dubai, UAE) with a presentation that set out what she believes to be the salient points of the latest Barcelona Clinic Liver Cancer (BCLC) guidelines. Last updated in early 2022, White emphasised the fact that “many key aspects of hepatocellular carcinoma [HCC] treatment are still missing”, including combination therapy with transarterial chemoembolization (TACE) and ablation and transarterial radioembolization (TARE).
White began by outlining a “historical overview” of the BCLC guidelines. “Initially published as a prognostic system in 1999,” it was not “designed” to stage liver cancers, the presenter shared with attendees. Neither was it formulated using “guideline methodology,” White added. “Many recommendations are not supported by high-quality data.” Other limitations include metastatic and non-metastatic patients being combined into one category and treatment modalities “not [being] unique to disease stage,” White furthered, before stating that BCLC oncologic outcomes “are worse than other staging systems”. Providing a counterexample, White stated that the National Comprehensive Cancer Network (NCCN) guidelines, which have a “strict policy of who sits on the committee” and a “strict conflict of interest policy”, as well as a “methodological way to review all of the data [it deals with]”.
Nevertheless, the most recent update to the BCLC guidelines is “much more” in-depth compared to the first set, “largely because now we have nine drugs that we did not have in the past,” White attested.
What is new in the guidelines?
A first example of the 2022 additions is the focus on the “potential candidacy for liver transplantation” for patients with early-stage malignancies, which, White said, before had “never really been put in the guidelines”. Within the scope of this addition is recommendations on eligibility for transplant and alternatives for those who are not suitable, for reasons such as heart disease, for example, the presenter relayed. “Ablation is really frontline for a patient who is not a transplant candidate, whereas before, it was resection that was frontline,” White said, expanding on the latest change to advice. Now, the consensus is that ablation and resection are “really on a par”, according to the speaker, with some concerns surrounding recurrence after resection, which was not the case two decades ago.
Next, White addressed what the guidelines now recommend for patients unable to have any of the aforementioned treatments. “You will see that the algorithm recommends TACE and TARE. What this really is talking about is when you cannot do ablation because of the location of the tumour.”
For stage B liver cancers, White proceeded to convey to delegates, “instead of having one category there are now three. There are now multiple treatment approaches, whereas it used to be straight to chemoembolization.” The speaker also noted that for patients in this category, overall survival used to be 20 months with the old guidelines, but this is now “up to five years”. In summary, “no matter what [treatment you receive] the outcome is much better than it used to be,” White celebrated.
There is now also a “vast difference” when it comes to treatment guidelines for advanced-stage liver cancer, White said, elaborating by saying that “before, with portal vein invasion and metastatic implants, sorafenib was our only choice”. Overall survival was 11 months, whereas it is now greater than two years for these patients, the speaker underlined.
And what is missing?
“So, what did they fail to include?” White moved on to answer her own question, emphasising that one “really important” omission is the use of prospective data to compare ablation directly to resection. Moreover, she added, “the difference between ablation modalities—maybe that does not matter as long as you are in good hands, but there is no differentiation” between using a particular modality in a patient, versus choosing another.
“They [also] did not talk about liver-directed therapy [LDT] as a bridge to liver transplant,” White lamented. “At my centre, it is an 18-month waiting period,” she explained, going on to say that waiting for a patient with 3cm HCC for that duration may take them outside of the transplant criteria—LDT can ensure they remain eligible, on the other hand. LDT is also an option for those who are not on the transplant waiting list, White went on, as it can confer an increase in overall survival, yet this too is not referenced in the 2022 update. Likewise, LDT in the setting of advanced or extrahepatic disease—the guidelines recommend “systemic therapy only”, the prudence of which in the context of an isolated lesion White invited the audience to question.
Adding to her list of important omissions in the most recent iteration of guidelines, White stated that radiation segmentectomy “either by itself or in addition to ablation” would have merited inclusion as “we have some pretty good data surrounding that”. Similarly, TACE and ablation for lesions over 3cm—”I do not think that anyone in this room would use a [single modality alone]” on a lesion greater than 3cm, White averred.
“They do not even talk about stereotactic body radiation therapy [SBRT], or the different TACE modalities. Drug-eluting beads are not the same as conventional TACE. And there is no stratification of when we should be using which one,” White continued. “[Neither do they] talk about radioembolization in the setting of intermediate disease [although] there are really good data,” the presenter said, rounding off the section of her presentation addressing the 2022 edition omissions.
On a final note, White acknowledged that “[failure] to mention any kind of combination therapy is likely because there are still data coming out—with many trials in the pipeline”. The speaker anticipated that the release of new data will continue to ”drastically change the BCLC guidelines,” which, while evolving in line with research findings, “has many limitations as a staging system”.
