Q:Please describe for us what is the current state of the epidemiology, diagnosis, and treatment of liver cancer in the Asia Pacific region?
Dr Chow: We carried out a real-world data study as a registry that we conducted over a number of years in nine countries in the Asia Pacific. The patients are diagnosed, they receive treatment and follow-up according to local practices. By doing this, we understood much better what real-world practices are, as opposed to, for example, data from clinical trials, which are, in a way, artificial because they choose only a very specific group of patients. This real-world data is very important because to do effective healthcare policies, we really need to know what is happening on the ground.
Also, for the pharmaceutical companies, they need to know why certain drugs are used and why other drugs are not used in order to come up with a strategy to develop treatments for patients. In our findings, we found that the Asia Pacific is very heterogenous in terms of the treatment of patients with liver cancer. What we have found in the presentation is actually quite different, because in some countries, patients are much older than in other countries. This impacts on the ways that the patients are treated. For example, patients in Japan have the highest average age at the time of diagnosis of 71.1 years, but in China, the age at diagnosis on average is 53.4 years, which is about a twenty-year difference. This affects the ways the doctors treat their patients too, because where the positive population is younger, more treatment will be done. What we have found is that, stage for stage, in the different countries, the therapies used are quite different. For example, in stage A, it is more uniform, because most countries would use surgery. But once we go to stage B and stage C, then we see a lot of differences. The differences are due to, firstly, of course, the patient profile - if the patient is younger, then surgery is used more often.
Secondly, because of access to therapy. Some of these new therapies are not available in many countries, and not even available in all countries. That is an important thing to understand. If we look at the treatment outcomes for every single stage, forexample, if I were to use stage A patients as an example, most of these patients are treated with surgery across the Asia Pacific region, but the overall survival is significantly different. For example, we see very good overall survival in Singapore and Hong Kong, less so in Korea and in China. When we look at the reason why, we find that in many places, patients have more than one line of treatment. This means that after they have surgery, there will be a second line treatment, then a third line treatment and a fourth line treatment. The more lines of treatment they have, thelonger the survival. Patients with stage A, for example, in Singapore, after surgery, 71.4% of them will receive additional lines of therapy and more than two lines of therapy. Whereas the number of patients who receive more than two lines of therapy after surgical resection is only 21.8% in Japan. In the real-world, patients who receive multiple lines tend to live much longer. If it’s a recurrence, then they can go for radiofrequency ablation, and if there is further recurrence, then they can use other modalities like Y90 or maybe also immunotherapy. So many lines of treatment is actually associated with much longer survival in a very significant manner.
Q:Please share for us what important initiatives Singapore has in the early screening and prevention of HCC that contribute to the improvement of patient's efficacy and prognostic survival?
Dr Chow: In fact, the country with the most developed screening program is Japan. Japan is by far the country with the most developed screening program. It is not Singapore. In Japan, a large proportion of patients are diagnosed early. But I think the thing that is different about Singapore is that we tend to have multidisciplinary care, which means patients are looked after by different specialties so that there are multiple lines of treatment. That is where it is different in Singapore. The multiple lines of treatment really translate - our data are very clear. The more lines of treatment a patient receives, the longer the survival. For example, in the natural history of a patient with early liver cancer, the first line of treatment may be surgery. Maybe two years later there is a recurrence, and receives a second line now - either surgery or RFA - and they live longer. If in another years time it recurs and there are multiple recurrences, they would use Y90. So on and so forth. The multiple lines of treatment are actually very important on top of a screening program. The screening program picks them up early, but after they are picked up, how long they live is also dependenton how many lines of treatment are used for these patients.
Q:How can the risk of liver cancer recurrence be reduced and the long-term survival benefit of patients further improved? Where are the future directions?
When asking what are the ways we can improve survival of patients treated with liver resection or liver transplantation, I think the most important thing that can prolong survival is the use of adjuvant therapy. So, for example, in most other cancers (breast or colorectal, for example, or even lung), after surgery, there is systemic therapy in order to prevent recurrence. Unfortunately, in HCC, today there is no proven systemic therapy that can prevent recurrence. In other words, HCC is one of the few unfortunate cancers (yet a very common cancer) that has no proven adjuvant therapy. Currently, a number of companies are running clinical trials trying to use systemic therapy, especially immunotherapy, as adjuvant therapy in such patients. I think these trials are going to mature very soon, and in the next few years, we would expect that some of these trials will be positive, and patients after surgical resection oreven liver transplantation can receive adjuvant therapy so that their survival becomes significantly longer.
Q:For early-stage liver cancer, systemic therapy is not currently recommended by any of the major guidelines. So, what do you think there are major aspects to doing systemic therapy for patients with early-stage liver cancer?
Dr Chow: Increasingly, I think we are going to see systemic treatment moving from advanced HCC to intermediate HCC, and then maybe to early HCC. I will consider the three groups of HCC differently. For early HCC, the standard of care will still remain liver resection and transplantation, because this gives huge survival advantages. But I foresee that in the near future, after surgical resection or liver transplantation, we will be able to use adjuvant systemic therapy to improve the survival of these patients even more. For patients in the intermediate group, today, the standard of care treatment is locoregional therapy, for example TACE, Y90, and so on.
Here we are seeing a number of clinical trials running where systemic therapy is added on top of locoregional therapy. I think these trials will be positive, and this may well become standard of care in the future - first treat with locoregional therapy followed by systemic therapy. Eventually, the systemic therapy may be good enough to be stand alone, so we can treat patients with systemic therapy upfront, but I think that is many years down the road. For advanced HCC, the efficacy of systemictherapy will progressively increase and get even better as we understand the biology of HCC better. I think in many instances moving forward we will see combination therapies rather than monotherapies. We expect to see immunotherapy combined with non-immunotherapy in improving outcomes of patients with advanced HCC. So this is how I see systemic therapy coming into play in the treatment of HCC.
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