Joaquín Mosquera, oncologist: ‘The big obstacle in lung cancer is not having screening to get ahead of the disease’

Throughout this year, around 31,200 cases of lung cancer will be diagnosed in Spain, according to estimates by the Spanish Society of Medical Oncology (SEOM). It is one of the most common tumors and also one of the most devastating: in many cases, its ability to remain silent, without showing symptoms until the disease is already advanced, hinders the therapeutic approach. The five-year overall survival barely reaches 13%, although each patient’s prognosis depends greatly on the precise nature of that tumor.

Under the umbrella of lung cancer there are, in fact, “many different diseases,” explains Joaquín Mosquera, oncologist at the University Hospital of A Coruña complex (CHUAC). “Each patient is different,” he says, and the course that the disease follows can be radically different depending on the subtype of tumor that they have. Mosquera claims that, despite the complexity of this cancer, there have been scientific advances that have taken small steps to improve survival. One of the latest studies in which he himself has participated was NADIM II, which has confirmed the effectiveness of a combination of immunotherapy and chemotherapy before undergoing surgery for a subgroup of patients with stage III-A of the disease. The research, coordinated by the Spanish Lung Cancer Group and published in the New England Journal of Medicine, showed that patients who were administered the combination of drugs had a longer survival than those who received chemotherapy alone: 85% of patients were still alive after two years compared to 63% with the traditional approach.

Question. Lung cancer is still a disease with the one of the worst prognoses. Why hasn’t there been much progress?

Answer. I think there is progress, but, in the end, lung cancer is many different diseases: small cell or microcytic tumor has nothing to do with non-small cell (non-microcytic) cancer, where there have been many advances indeed. And then, it is very important to determine if there is a molecular alteration to be able to apply a treatment directed against it. Each one is a different disease that has different survival rates and different responses to treatments. But there is progress: the biggest advance of the last 10 or 15 years has been identifying different molecular alterations and developing therapies directed against them and then, incorporating immunotherapy into the different stages of the disease.

Q. Now lung tumors have indeed begun to be given specific names, but what are the main obstacles that the biology of the tumor itself poses to combat it?

A. The problem is that by the time lung cancer shows symptoms, it is already advanced. That is why it is very important to try to do screening, as in breast cancer, to try to detect it in earlier stages and so that it can be treated with surgery or radiotherapy. The more advanced the tumor is, the more aggressive it is, the more symptoms the patient suffers and the more difficult it is to attempt treatment. Small cell lung cancer is the most aggressive type and, generally, when it is diagnosed, it is already advanced. But, non-small cell lung tumor can be detected earlier, in some cases. The big obstacle in lung cancer is not having screening that allows you to get ahead of the disease.

Q. Regarding screening, at a meeting of the Spanish Lung Cancer Group there was a debate on the topic, with arguments for and against. Do you think it should be implemented?

A. Yes. It has to be done by risk groups: in patients who are heavy smokers, a low-density CT scan should be attempted to detect incipient nodules before they grow or spread throughout the body.

Q. Is there enough evidence right now to support this strategy?

A. Yes, there is. Like all screening, it has a significant economic impact, but anything that involves anticipating the appearance of the disease will benefit both people and national health systems. The main cause of lung cancer is tobacco, so heavy smokers would probably be the first to present tutors at the usual ages of onset of this, which would be between 50 and 70 years.

Q. The population knows that smoking is bad, but there are still 20% of daily smokers. What's wrong?

A. It is a complex issue because it is not that smoking automatically causes a disease. There is a latency time for that. Right now we are seeing a big boom in female smokers in consultations because they are the ones who started smoking in the sixties or seventies and are now developing a tumor. To see the effect of non-smoking campaigns on young people, we will have to wait years. But I do believe that there is a paradigm shift: people continue to smoke, but less and less in percentage terms. Smoking bans in more public places and awareness at the level of audiovisual media (series, movies, etc.) are having a greater impact. People are more aware of all that. Unfortunately, there will always be smokers, because there is a very significant social component of tobacco, especially at parties and meetings. So, until there truly is awareness about tobacco at the government level, it will continue to be a snake that bites its own tail: no matter how many campaigns they run, if tobacco continues to be accessible, the problem will persist.

Q. What do patients tell you in the consultation when they arrive with a diagnosis of lung cancer due to tobacco?

A. Each patient is unique. There are people who take it as if they have been playing with Russian roulette and they have lost; there is also a lot of guilt. Others are surprised because they are people who stopped smoking 15 years ago and after all those years, lung cancer has appeared because the damage was already done. There are also people who continue smoking because they say: ‘Well, it’s too late to stop smoking now...’ But here we must clarify that the response to treatments is worse among people who continue smoking compared to those who have quit.

Q. A study estimated that quitting smoking before age 35 equals the risk of death with non-smokers. What is the real impact of quitting? How is it related to the risk of having a tumor?

A. I couldn’t say anything about what age it equals. Unfortunately, the body has memory and the risk is there and remains. But the important thing is not so much the time as the consumption. Sporadic smoking of a single cigarette is not the same compared to a continuous habit. And when these heavy smokers light their first cigarette is also important for us to know: there are people who light their first cigarette in bed when they get up, and that is a marker of the severity of their consumption.

Q. Science advances through research and the NADIM II study is an example of personalized precision medicine. What will the repercussions be?

A. Unfortunately, in most cases of lung cancer today, diagnosis comes after metastasis or in an advanced stage — that is, there are affected nodes. So, everything we can anticipate for that to appear is a great advance. NADIM II seeks to combine chemotherapy and immunotherapy before surgery to try to find the most complete response possible to facilitate surgery and, in some way, the patient’s cure. In this study, we managed to operate on 93% of patients compared to 69% treated with chemotherapy alone.

Q. Immunotherapy has also reached small cells in a modest way, but what happens with that tumor? Is it detected late or do they have particularities that make it especially complex?

A. It is a very different tumor. Microcytic cell cancer has nothing to do with non-small cell, they are two completely different diseases. Small cell cancer is a cancer in which molecular alterations do not usually appear, on which we can perform targeted treatment and practically all of it is associated with tobacco consumption. Furthermore, it is more in the lineage of neuroendocrine tumors and is a cancer in which, in the last 30 years, there has been very little progress. Incorporating immunotherapy into chemotherapy for the treatment of advanced microcytric cell cancer has been revolutionary because it has brought light to a field in which there was not much.

Q. Is research now focusing on exploiting the combination of drugs?

A. Indeed, drug combinations are a very good weapon, but they are also a double-edged sword. They are not harmless, they cause side effects and, although we are increasingly trained to see them, we cannot let our guard down because they also add effects. For example, there are immune-related toxicities: what we do with immunotherapy is to modulate the body’s own immune response, making our own defense cells, the T lymphocytes, attack the cancer cells. But, sometimes these lymphocytes rebel against the body itself and cause damage. Fortunately, it doesn’t happen often, but we do not currently have the tools to be able to differentiate which patients are going to be good responders, which are not going to respond, or which patients will develop toxicity before starting a treatment.

Q. When we talk about lung cancer, we immediately think about tobacco. What happens to non-smokers who develop these types of tumors? How is it explained?

A. Tobacco is the main cause without any doubt. But there are other established causes: asbestos or radon, for example. But there are people who, unfortunately, do not have a risk factor identified and in these patients, the first thing to do is look for an underlying molecular alteration and try to treat it in the most targeted way possible.

Q. A study published in Nature also pointed to the role of pollution in thousands of deaths from lung cancer. What do you know about the role of pollution in this phenomenon?

A. It is very difficult to quantify the damage caused by just one factor because, when evaluating these population studies, many factors come into play. Environmental pollution, especially in large cities, plays a very important role, not only in terms of developing a tumor, but also in other respiratory diseases. But quantifying the real impact is difficult. Obviously, there is a clear trend of increasing diseases with greater environmental pollution.

Q. Now more cases of cancer are appearing in smokers who are women. Do lung tumors behave the same in men and women?

A. They behave differently. The presence of different tumors is slightly different and the response profile for the treatments is different, especially with immunotherapy. It seems that there is a certain tendency towards a worse response, but I don’t want to cause alarm by saying that. Not because a woman who smokes will always respond worse, but these are small factors that must be taken into account, above all, when evaluating the response. The symptoms, apparently, are the same, but medicine has been very androcentric, and now we see that how we perceive illness and pain is different between men and women.

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