Cancer develops because it can trick our immune system. However, thanks to immunotherapy, our body is more difficult to cheat. – Then our immune system more efficiently finds these cancer cells, goes to fight and eliminates them – says prof. dr hab. n. med. Paweł Blecharz, head of the Gynecological Oncology Clinic at the National Oncology Institute M. Skłodowskiej-Curie – National Research Institute, Krakow Branch.
- The main causes of endometrial cancer include diabetes, hypertension and obesity.
- Surgical treatment is mainly used for patients, although immunotherapy is more and more often referred to, which seems to be a more precise form of therapy.
- Immunological therapies usually concern advanced cancers, we cannot think of them as an alternative to early detection, prevention or typical treatment of early stages – emphasizes Prof. Paweł Blecharz
- More current information can be found on the Onet homepage
The pandemic situation which has been going on for two years has been compounded by another crisis: refugees from Ukraine who are fleeing the war and want to protect their lives. Among them there are people who need medical help, including oncology. How do you assess this situation?
Prof. Paweł Blecharz: It is too early for general health care assessments, including oncology. We do not have central data yet, but from the point of view of large oncology centers, we do not observe an organizational catastrophe related to the number of refugees. It is hard to say what it will look like in the future. For now, we know that this higher oncological burden occurs in facilities located closer to the border with Ukraine. The further away from it, this situation is less noticeable. At our place, at the National Institute of Oncology in Krakow, we have patients from Ukraine in virtually every ward. After a month of war, there were about 90 people.
Let’s move on, professor, to the main topic of the conversation, which is endometrial cancer, also known as endometrial cancer. What are the main causes of this disease?
Well-identified causes of endometrial cancer that make up the picture of a patient at risk include diabetes, hypertension, and obesity. Endometrial cancer is a hormone-dependent cancer, which means that female estrogens unbalanced by gestagens have a large impact on its development. Overweight patients are patients with an overproduction of oestrogens, because oestrogens, in addition to the ovaries, are also produced in adipose tissue. The impact of diabetes is somewhat more complex, as is hypertension, which appears to be rather secondary to the other two causes. Endometrial cancer affects postmenopausal women with these three major risk factors, although, of course, patients without these factors also experience it. We can historically divide endometrial cancer into two types. The first concerns women aged 50-60, and the second, in which this triad of risk factors is not observed, concerns the elderly.
What are the symptoms of this disease? How do we diagnose it?
The symptoms are characteristic: it is mainly vaginal bleeding in women who no longer have periods. Women who care about their health never ignore such a signal and report to a gynecologist. In this situation, the diagnostic path is unequivocal: the woman should have a verified endometrium, i.e. the lining of the uterine cavity. This is done with uterine curettage, a simple procedure available in any gynecology department. Other cancers, especially ovarian cancer, often have non-specific symptoms. It could be a feeling of fullness, belching, or back pain. Postmenopausal bleeding, on the other hand, is quite unambiguous, therefore these patients are diagnosed quickly and endometrial cancer is most often detected in the early, first or second stage of advancement.
How fast does this disease progress?
The rate of endometrial cancer development is difficult to assess, because we would have to monitor the patient from normal endometrium to pathological changes. Usually, however, it is believed that the neogenesis of this neoplasm is a period not exceeding a few years. Of course, it sometimes happens that tumors develop rapidly, within a few months, but typically it takes two to four years.
How is endometrial cancer treated and what treatment options are available for Polish patients?
Fortunately, endometrial cancer is most often diagnosed at an early stage, so it is usually operable. The standard gynecological procedure and the key method of treating this disease is the excision of the uterus inside which the tumor is hidden. In some patients, lymph node diagnostics is also recommended. We do so because endometrial cancer in certain histological subtypes, with certain degrees of differentiation, more often metastasizes to the lymph nodes. Then, apart from the hysterectomy, we also remove pelvic lymph nodes. More and more often, instead of the systematic removal of lymph nodes, we use the so-called sentinel node technique – we only remove some representative lymph nodes selected by modern diagnostic methods. This allows us to limit the procedure and at the same time gives us information whether the patient has lymph node metastases or not.
How is the surgical treatment performed?
At some disease level, this procedure is relatively uncomplicated. However, we must remember that comorbidities are a problem in surgical treatment. If the patient is obese, the relatively simple procedure becomes a surgical challenge. Especially that we want to introduce more and more methods of minimally invasive surgery in surgical treatment, with laparoscopy at the forefront. Laparoscopy is the optimal method of treating patients, including the obese. It is associated with a shorter operation time, a lower risk of complications, blood loss, wound infection, wound dehiscence, and faster activation of the wound. We would like to use this surgical procedure for all patients, but it depends on the general condition of the patient.
Operation and what next?
If we are dealing with a well-diagnosed and well-operated patient, histopathological information is crucial, whether it is a tumor with a low recurrence or metastasis potential, or the opposite is true. In the latter case, although the disease may be quite early, the patient requires additional adjuvant treatment, usually radiotherapy. In the case of higher stages and higher aggressiveness of cancer, it is recommended to combine radiotherapy with chemotherapy.
We must also remember about rarer but also common cases of diseases that are diagnosed at an advanced stage – the chances of curing them are completely different. This disease has two clinical faces: early clinical cancers with good and very good prognosis, and advanced patients at the time of diagnosis, which unfortunately have a poor prognosis. The aim of adjuvant treatment, such as radiotherapy or radiochemotherapy, is to avoid relapse and prolong life. This is very important because endometrial cancer recurrence after primary treatment is a serious disease and we have very limited treatment options.
When talking about so-called female cancers, the term genetic mutation is often used. What does it look like in endometrial cancer, is its aggressiveness dependent on mutation?
Cancer is a disease of mutations. A cancer cell is nothing else than a cell in our body that has mutated, that is, changed in various ways at the level of the genetic code. It began to divide in an uncontrolled way and acquired the ability to destroy neighboring tissues, the so-called “Metastasis”. Thanks to molecular tests that can “read” the genetic code of a cell, including a cancer cell, we are able to create a profile of it, get to know the image of its character.
In endometrial cancer, we have identified four groups depending on their genetic profile, the presence of certain single or few molecular changes that make the disease completely different from what we previously thought. There are patients who initially have a very good prognosis and whose genetic profile is negative, yet these patients have a recurrence of the disease within a year. It is also the opposite: there are patients who, despite the presence of classic, unfavorable risk factors, for example lymph node metastases, have such a genetic profile that we do not need to undergo any additional treatment. It is difficult to explain, but the sick ones will still be healthy after the primary surgery.
We are on the eve of a new molecular classification of endometrial cancer, which will allow us to treat patients more precisely, e.g. with immunotherapy.
What is the mechanism of immune therapy?
All cancers develop because they have ‘tricked’ the immune system. The immune system of our body can destroy any foreign antigenic cell and theoretically should destroy all neoplasms in their nucleus. When a cell mutates and begins to divide uncontrollably, these divisions obviously take hours, days or weeks. Only then will we be able to talk about a lump that is visible in any research. This is the time when we would count on our immune system to recognize this cell and simply destroy it. This does not happen, however, because cancer cells have the ability to deceive the immune system, they can “blind” T lymphocytes. Figuratively speaking, they put a blindfold on their eyes, which prevents T lymphocytes from being able to see foreign cancer cells in their environment. Certain receptors are responsible for this and become “clogged” by the cancer cell.
This is where immunotherapy comes in?
Yes, the response of modern oncology is immunological treatment, using the potential of the immune system, giving it strength or “removing the blindfolds” of lymphocytes. Then the T cells can see again that the tumor in the body is its enemy. This is where the so-called checkpoint inhibitors, or Dostarlimab, come in for endometrial cancer.
How it’s working? Some cancers, including some endometrial cancers, are perfectly visible in the body after such treatment. You can say that they “shine” for the immune system. We say in professional terms that they are very immunogenic: after “unblinding” the immune system finds these cancer cells more efficiently. To sum up: as an immunological drug, delivery of the drug delivery “takes the blindfold” off the T lymphocytes and makes the cells of the immune system go to fight the cancer, see it as if from scratch and – using natural methods of destroying the cancer cell – cause its elimination.
Is Dostarlimab immune therapy available to Polish patients?
Endometrial cancer concerns patients who have already received one classic line of treatment, i.e. chemotherapy based on platinum derivatives, and this form of treatment has not worked. This is the group of patients with the worst prognosis in endometrial cancer. In this case, the Dostarlimab registered in Poland is also precisely targeted at a specific group of patients. We also need to find out if they have so-called microsatellite instability. It is about answering the question of whether the cancer we want to treat with parlimab is really the one that the immune system will recognize very clearly – and hence – successfully healed. This diagnosis is not particularly complicated, an immunohistochemical test (DMMR) is performed.
I got limab at the moment, unfortunately, it is not reimbursed even in this narrow group of patients. I know that efforts are underway to make it available under so-called drug programs, carefully monitored and available at specific centers.
Who are immune therapies for?
We must remember that immunological therapies usually apply to advanced cancers, we cannot think of them as an alternative to early detection, prevention or typical treatment of early stages. We talk about immunological therapies in the context of recurrent disease, which is where the greatest therapeutic needs exist.
In order to take better care of our own health, we should increase our oncological vigilance. We should also pay attention to the health of Ukrainian women who are among us …
The most important thing is to constantly disseminate knowledge about the possibilities of early cancer detection. You have to remember about pap smears, mammograms, and regular visits to the doctor. You should pay attention to any non-specific symptoms that have not occurred before.
I also appeal to doctors to support patients and guide them on the appropriate diagnostic and treatment paths.
I am asking women from Ukraine not to be afraid of the Polish health service. Cancer centers in Poland are prepared both linguistically and organizationally to provide them with the best care. Financing is also provided, so there is no problem with either starting or continuing treatment.
We are with Ukraine at heart.
Authorized press interview prepared by the Journalists for Health Association in connection with the debate «Gynecological cancer – TIME TO ACT! How do we treat? », Organized as part of the Quo Vadis Salus Feminae series? 2022