Throughout this year, some 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 giving symptoms until the disease is advanced, hinders the therapeutic approach. The five-year overall survival barely reaches 13%, although the prognosis of each patient depends greatly on the last name of that tumor.
Within the bag of lung cancer, in fact, “many different diseases” coexist, explains Joaquín Mosquera, oncologist at the University Hospital Complex of A Coruña (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 manifests. Mosquera (A Coruña, 37 years old) 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, for example, NADIM II, has confirmed the effectiveness of a combination of immunotherapy and chemotherapy before undergoing surgery for a subgroup of patients with advanced disease – in stage III. TO-. The research, coordinated by the Spanish Lung Cancer Group and published in the prestigious New England Journal of Medicine, showed that patients who were administered the combination of drugs had greater survival than those who received chemotherapy alone: a 85% of patients were alive at two years compared to 63% with the traditional approach.
Ask. Lung cancer continues to be one of the tumors with the worst prognosis. Why isn’t there so much progress?
Answer. I think there is progress, but, in the end, lung cancer is many different diseases: small cell or small cell tumor has nothing to do with non-small cell (non-small cell) cancer, where there is a lot of progress . And then, it is very important to determine if there is a molecular alteration to be able to do a treatment directed against it. Each one is a different disease that has different survival rates and responses to treatments. But there is progress: the great advance of the last 10 or 15 years is identifying different molecular alterations and developing therapies directed against them and then, the incorporation of immunotherapy to the different stages of the disease.
Q. Now lung tumors have indeed begun to be given surnames, but what are the main obstacles that the biology of the tumor itself poses to combating it?
A. The problem is that lung cancer generally, when it shows symptoms, 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 addressed with surgery or radiotherapy. The more advanced the tumor is, the more aggressive it is, the more symptoms it gives the patient 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, in some cases, earlier. 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.
“Lung cancer is many different diseases that have different survival rates and responses to treatments.”
Q. Is there enough evidence right now to support this strategy?
A. Yes there is. Like all screening, it entails a significant economic impact, but anything that involves anticipating the appearance of the disease will be a benefit to both people and national health systems. The main cause of lung cancer is tobacco, so heavy smokers would probably be the first to be indicated 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. Prohibition campaigns in more public places and awareness at the level of audiovisual media (series, movies…) are having more impact. People are more aware of all that. Smokers, unfortunately, will always be seen, because there is a very important social component of tobacco, especially at parties and meetings, and then, until there is truly awareness at the government level about tobacco, and in the end it will to be a whiting that bites its tail: no matter how many campaigns they run, if tobacco continues to be accessible, the problem is there.
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 a world. There are people who take it as if he has been playing with Russian roulette and has won; There is also a lot of guilt; Others are surprised because there are people who stopped smoking 15 years ago and after those years lung cancer appears because the damage is there. There are also people who continue smoking because they say: ‘Total, for what I have left…’. But here we must clarify that the response to treatments is worse among people who continue smoking compared to those who have quit.
Q. One study estimated that quitting smoking before age 35 equals the risk of death with non-smokers. What is the impact of quitting really? How is it related to the risk of having a tumor?
A. I couldn’t say anything about what age it is equal to. 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 that was made. Sporadic consumption of a single cigarette is not the same as that of people who have a continuous habit. And it is also highly valued in these heavy smokers when they light the first cigarette: there are people who, in bed, when they get up, already light the first cigarette and that is a marker of severity of consumption.
Joaquín Mosquera, oncologist at the Hospital of A Coruña, in one of the corridors of the health complex.VANESSA CASTELEIRO
Q. Science is advancing in research and the NADIM II study is an example of personalized precision medicine. What repercussions will it have?
A. Unfortunately, lung cancer today, in most cases, is diagnosed with metastasis or in an advanced stage—that is, at least lymph nodes are affected. So, everything we can anticipate for that to appear is a great advance. NADIM II seeks to combine chemotherapy and immunotherapy before surgery—that is neoadjuvant—to try to find the most complete response possible to facilitate surgery and, in some way, the patient’s cure. In this study, 93% of patients managed to operate compared to 69% treated with chemotherapy alone who achieved it.
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 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 it is practically all 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. The incorporation of immunotherapy with chemotherapy for the treatment of microcitrus with advanced disease has been a revolution because it has brought light to a field in which there was not much.
Q. Are you now focusing on exploiting the combination of drugs in research?
A. Indeed, drug combinations are a very good weapon, but they also have a double edge. 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 add effects. For example, there are immune-related toxicities: what we do with immunotherapy is to modulate the body’s own immune response, making it our own defense cells, the T lymphocytes, that attack the cancer cells; But, sometimes, it happens that these lymphocytes rebel against the body itself and cause damage. Fortunately, they are not frequent, but we do not currently have the tools to, before starting a treatment, be able to differentiate which patients are going to be good responders, which are not going to respond or which patients will develop toxicity.
There are people who, in their own bed, when they get up, already light their first cigarette and that is a marker of seriousness of consumption.”
Q. When we talk about lung cancer, we think directly of 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, for example asbestos or radon. 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?
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. More cases of cancer are now appearing in female smokers. 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 from immunotherapy: it seems that there is a certain tendency towards a worse response, but I do not like to raise alarm with this. Not because she is 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 it is seen that the perception of illness and pain is different between men and women.
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