On 22 November, an update was presented of the ‘BCLC System', a global reference point for staging, prediction, prognosis and decision-making in the treatment of patients with liver cancer. What does this update mean?

The update of the Barcelona Clinic Liver Cancer (BCLC) staging system reflects all the scientific advances in hepatocellular carcinoma that can be applied in clinical practice, as they are based on scientific evidence. On this occasion, the update not only includes new factors for classifying patients and new treatments, but also a new section called, 'Clinical Decisions'. This aspect is of key importance in adding value to the process of personalizing the best treatment for each patient. The BCLC staging system is the one most recommended by clinical practice guidelines for hepatocellular carcinoma worldwide, and is also used when classifying patients in clinical trials. This update maintains the leadership the Hospital Clínic has exercised in this field over the years.

How have liver cancer patients experienced COVID-19?

Patients with liver cancer, just like the rest of the population, experienced the first wave with great uncertainty and fear because they were cancer patients. As a Hepatic Oncology Unit, we reorganized ourselves: we started telephone a 24-hour telephone service to care for patients and we worked with radiologists to structure the prioritization of the patients who had to be treated without fail. Nursing played a key role in this process and the patients felt that the health system, and the Hospital Clínic in particular, was with them. We organized ourselves to ensure that all the patients were able to stay in contact with us, even if it was only by telephone. In terms of human resources, we also restructured ourselves, given that the fellows
helped on the frontline of COVID-19. For that reason, we consultants divided our time between treating COVID-19 patients and monitoring patients remotely. Uncertainty, reorganization and prioritization of treatment were the three pillars that defined the start of the pandemic in our unit.

Those that suffered most were the patients at 'risk of cancer', because the scheduled liver cancer screening tests had to be cancelled.

Did COVID-19 also affect screening in order to make new diagnoses?

Yes, it did. Those that suffered most were the patients at 'risk of cancer', because the scheduled liver cancer screening tests had to be cancelled. In a project with over 73 hospitals worldwide to see how COVID-19 had affected liver cancer diagnosis, we found that 80% of the hospitals cancelled their screening programmes – which involve something as simple as carrying out an ultrasound scan. The drop in the new diagnoses affected patients with liver cancer and other diseases, as shown in different studies.

Have you noticed that there are more initial consultations now?

We had a drop in initial consultations during the first phase of the pandemic. Now we have more referrals with more advanced cancer, although it is not possible to attribute this unequivocally to delayed detection. The screening was interrupted and patients were slow to lose their fear of going to hospitals. This fear has been lost and now patients can safely come to the hospital for all types of visit. So, patients at risk of liver cancer have recovered screening by abdominal ultrasound scan every 6 months and only one check-up was missed. In some cases, this loss may have delayed detection and led to a diagnosis at a later stage.

Early diagnosis is crucial.

The aim of early cancer diagnosis is to be able to offer curative treatment with long-term survival without a recurrence of the disease. Today, liver cancer can be diagnosed when there is only a single nodule smaller than 2 cm. This is the objective of the screening, to be able to offer the patient conventional surgery, transplantation and ablative treatment with curative intent.

The incorporation of immunotherapy is another of the major milestones in the treatment of liver cancer in which the Unit has been actively involved.

What has changed in recent years?

The criteria for considering a patient with liver cancer for liver transplantation were extended recently. Thus, more patients diagnosed in the early and intermediate stages can benefit from this option, although there is still a great shortage of donors to cover the demand for organs.

Major advances have been made in the field of advanced-stage treatment. Various systemic treatments (oral and intravenous) have been shown to benefit survival. These options reduce the extension of the tumour and slow the tumour growth. They avoid or delay complications due to tumour progression. This radical change was shown in a study led by Dr Bruix from the Hospital Clínic in which the efficacy of this type of systemic treatment in liver cancer was demonstrated. In 2016, another study, also led by Dr Bruix, allowed the first ‘second-line’ treatment to be incorporated. This means that, if a treatment loses its efficacy, several options are available depending on the characteristics of the patient and the cancer. At present, more than one type of systemic treatment is available and this is of great benefit to patients.

The incorporation of immunotherapy is another of the major milestones in the treatment of liver cancer in which the Unit has been actively involved. This year, the combination of immunotherapy and anti-angiogenesis was incorporated, which surpasses the survival benefit of previous options and thus constitutes paradigmatic progress.

So, is the key to choose the right treatment?

The best treatment option for a patient depends on their profile in terms of the extent of the disease, the degree to which the liver function is affected, and any possible coexisting diseases. We doctors must take all this information into consideration and then recommend the best option. This is where the BCLC staging system is so important, given that it takes all the aspects into account. In any case, we doctors have the responsibility to recommend the best treatment for the patient and the patient needs to have all the information. Therefore, the recommendation is established in a joint and coordinated manner by the hepatologists, surgeons, pathologists, oncologists, radiologists and the nursing team dealing with the side effects, and the patients decide whether they want to go ahead with the treatment or not depending on the recommendation.

The Hospital Clínic Hepatic Oncology Unit is a global reference point. What would be a summary of your activity?

We see between 250 and 300 new patients with different types of primary liver cancer. The two most frequent types are hepatocellular carcinoma and cholangiocarcinoma. However, we also see patients with ultra-rare malignant tumours and with benign tumours. This year, due to the pandemic, we are been having more initial consultations than we had last year. Around 20% of the patients are candidates for surgery or transplantation. Around 50% of the patients we see, come to the Hospital with advanced-stage cancer. In the past, this situation was perceived as having a very poor short-term prognosis and no chance of treatment. Now, different treatment options are available for patients with advanced cancer with preserved hepatic function, and their life expectancy is the same as for patients with other better-known tumours such as breast or bowel cancer.

In 2007, life expectancy for patients with advanced cancer was 6-8 months. Now we can be speaking about 2-4 and even up to 6 years. Over the last 15 years, there has been a revolution in the treatments for advanced liver cancer, and also for the other stages, as I mentioned earlier.

In what aspects have you set trends worldwide?

The Hospital Clínic de Barcelona is a pioneer in the treatment of and the approach to liver cancer, and we are proud of that. At the start, before it was a Unit but simply a team devoted to liver cancer, the way of classifying and treating these patients in accordance with scientific evidence was defined and organized. I think that was of key importance in influencing (in the good sense of the word) the rest of the world. Liver cancer is associated with the Hospital Clínic de Barcelona. The Unit’s philosophy is transversal, multidisciplinary, patient-centred work, so as to offer the patient the best care and the best treatment. One of the keys to this successful model is that the care is very well organized and protocolized. This means we have valuable clinical information, which allows us to carry out translational research and, at the same time, clinical research. This work philosophy has been exported to other centres and countries around the world.

What challenges will liver cancer research and treatment face in the next 10-15 years?

When we see and treat patients in outpatient or inpatient consultations, many clinical questions arise that generate clinical or laboratory studies in which we have to find the answers. Connecting experts in each area is essential in order to make progress. This is why we need the clinical or surgical expert, the laboratory expert, the radiology expert, etc. to work in the most transversal and coordinated manner possible in order to get the answers. In liver cancer there is a lot of basic and translational research, but there are very few studies that allow us to obtain palpable results in the patient. This is why we have redesigned the way of carrying out translational research, and we hope to obtain results in the next few years. My challenge is to be able to incorporate solid translational results into the next BCLC updates, and to achieve what is known as Precision Oncology based on molecular profiling.

Another aspect is artificial intelligence. There is still a long way to go here. We must find synergies with specialists with different profiles to those in the healthcare field, who can help us with our work: engineers, physicists, etc. This is research too, and we have a long road ahead of us.

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