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A scientific revolution underpins the foundations of the fight against cancer: it is now known that no two tumors are the same, even if they are housed in the same organ, and oncological research, immersed in knowing the fine print of tumors that molecular biology reveals , is moving towards more and more personalized drugs, thought and designed, even tailored to each patient. “Targeted drugs have been discovered that will allow us to select which treatments will be most effective and appropriate for patients based on their molecular alterations,” explains oncologist Martín Lázaro (A Coruña, 59 years old), doctor at the University Hospital Complex. from Vigo and architect, together with his colleagues Sergio Vázquez and Joaquín Casal, of the National Symposium on Precision Oncology, which was held a couple of weeks ago in Vigo.
Lázaro, president of the Oncological Society of Galicia and specialist in lung and genitourinary tumors, dissects the different spheres of this new personalized precision medicine: it implies a therapeutic arsenal with increasingly targeted treatments, but also a greater role for the patient in the decision making. “Fortunately, we have passed the stage of paternalistic medicine. Now we take into account patient preferences and they also decide what is best for them.” And he gives an example: “If a patient has an advanced disease of a tumor with a poor prognosis, in which a survival of one year can be expected, and we are going to offer him a treatment that can prolong his survival on average by two months, he You may decide that, perhaps, it is not worth it to go back and forth to the hospital having side effects that may limit you and you prefer to invest that time in another way, because you have to take into account what we call time toxicity [el tiempo dedicado a recibir atención médica relacionada con el cáncer, incluidos los viajes y los tiempos de espera]”, explains the oncologist.
Ask. How much does that toxicity of time weigh?
Answer. There are patients who spend a lot of time between tests, trips to the hospital, treatments… In pancreatic cancer, this can involve almost 20% of a patient’s remaining survival time. And that is something that we have to take into account as well.
P. Does that mean that not all of the therapeutic arsenal is worth it?
R. I always tell patients that we have treatments that may be more or less effective. We know that a drug can prolong survival, that this prolongation in survival is significant at a statistical level, but that perhaps it is more or less significant at a clinical level. That is to say, I see the statistics and the influence of this treatment on survival is real, but perhaps the time in which we increase survival is more or less important, and the real significance of what it is must be assessed in the consultation with each patient.
P. A few days ago, the announcement of a saliva test for early detection of cancer went viral and the Spanish Society of Medical Oncology had to come out to warn that this experiment had no medical value. Are the findings magnified?
R. This saliva detection study is something very early to say that it can help us find patients early. It is true that, sometimes, we magnify what is published. We are so eager to see good news in that sense that we see the part that catches our attention, but we have a hard time seeing the connotations it has afterwards and whether that really implies something or not. We have to be very cautious because that sometimes leads people to have false hopes.
P. Has precision personalized oncology reached a stage of maturity?
R. We are in a stage of maturity in some parts: there is more and more knowledge of molecular biology and more drugs are being implemented in some tumors. I use lung cancer as an example: when I studied the specialty, a median survival of 10 or 11 months could be expected. Fortunately, this cancer has been segmented into small parts, which are like slightly different tumors, and if a person comes to me with ALK positive lung cancer [con una alteración en este gen, que supone el 4% de los tumores de pulmón], I am going to start therapy knowing that when the treatment stops working for that patient, new drugs will surely have already been released that will allow me to select a better treatment for that person. The problem is that this is not the case in all tumors, in some cancers we still have a way to go: there is a significant percentage of patients for whom we cannot correctly select the treatment.
P. You specialize in lung cancer, a type of tumor where immunotherapy has worked and changed the course of the disease in some cases, but the overall prognosis remains unfavorable. How is that interpreted?
R. There are still many subgroups of people who do not do well with treatment, but there are patients who respond to immunotherapy and the response is of higher quality and, sometimes, very long-lasting. So much so that we are already beginning to have patients who, after having received two years of treatment and having stopped it, have been living a normal life for two or three or even four years, without any progression of the disease and without needing to receive more treatments. There are tumors, however, that grow in a colder immunological environment, with less enhanced immunity, and there we have to explore strategies that allow us to convert that cold tumor into a hot tumor and for immunotherapy to also work better. But there are many things we don’t know about immunity against cancer.
“Lung cancer screening will have to be implemented because it improves survival”
P. In lung cancer, a change in profile is being seen: it decreases in men and increases in women. Does the tumor change?
R. It is beginning to be seen that women have a greater incidence because they have adopted the smoking habit later. But it is true that in women it seems to be a slightly different tumor. In men, the habit of tobacco is present in more than 90% of patients and in women, in 50% or 80%. There are other factors that are influencing them: the hormonal environment has been discussed, which could be one of the favorable ones; It has also been seen that there are procarcinogens in tobacco that need to be activated so that they later become carcinogens, and this can be done through cytochromes. [unas proteínas] and some are more expressed in women. It is also true that it seems that women have a better prognosis compared to men.
P. They are different tumors, but is their way of treating them also different?
R. We should take that into account because, until now, the way of treating is very similar. Women, in general, with chemotherapy and some drugs, have somewhat more toxicity and it is not well known why. We know that the disease looks a little different and we must learn to stratify in studies based on gender as well.
P. Lung cancer screening is controversial among scientists, but European authorities recommend it. How do you see it?
R. In my opinion, screening will have to be implemented because it has been shown in studies to improve survival or reduce mortality from lung cancer. What’s happening? Which has many connotations because of what it entails. It is a population in which we are going to detect few tumors and we are also going to provoke examinations as a result of findings that we are going to see in the CT scans and who do not know what they are, which will require making a diagnosis and which will often be benign lesions, which can lead to sometimes important complications. And we also have to see how this significant amount of diagnostic tests are going to be implemented.
P. The survival of some tumors has gone from being counted in months to being counted in years, but oncologists always find it difficult to talk about curing or making it chronic. Is the ultimate goal to save time?
R. There are situations in which we help to cure and, when the disease is advanced, what we do is try to prolong the disease for as long as possible. With immunotherapy we are already achieving that, in some tumors where it was unthinkable before, there are long survivors that we did not have before. And that is an irrefutable fact. But, to begin with, in advanced disease, the approach in most tumors will be to delay their evolution.