Precise diagnostics and immunotherapy: new opportunities for women with endometrial cancer

Endometrial cancer (uterine body) is the most common gynecological cancer: approximately 6,000 cases occur in Poland every year. women hear such a diagnosis. For many years it was considered relatively promising, primarily because even 90 percent cases were diagnosed at an early stage. Unlike other cancers, it usually causes symptoms at an early stage (e.g. unusual, prolonged bleeding and bleeding after menopause). They usually prompt a woman to visit a gynecologist.

– We have been experiencing a very disturbing phenomenon for over 10 years: after a period of decline, the mortality rate has begun to increase again. In Poland, mortality rates for other cancers are decreasing; endometrial cancer is unique in this respect. We are very concerned about this situation, says Prof. Joanna Didkowska, head of the National Cancer Registry of the National Institute of Oncology. Currently, approximately 1,800 women die from endometrial cancer in Poland every year.

There is a chance that this disturbing trend will reverse in the near future. It is already known that the prognosis of patients is largely determined by the molecular subtype of endometrial cancer. Therefore, the treatment undertaken should depend not only on the stage of cancer advancement, but also on the molecular subtype.

The results of clinical trials also showed that immunotherapy, optimally used in the first line of advanced ovarian cancer, is a chance for some patients with advanced endometrial cancer. The first drug for this indication has already been registered by the European Medicines Agency.

Precise diagnostics before starting treatment

In the case of breast cancer or lung cancer, treatment is not started until the exact diagnosis of the subtype of cancer is made. Until recently, endometrial cancer was treated as one cancer, but now it is known that there are four subtypes with different prognosis, which means that their treatment should be different. Therefore, accurate molecular diagnostics should be performed immediately after cancer is confirmed.

– Endometrial cancer is usually diagnosed early when a woman sees a gynecologist because of abnormal bleeding. We obtain material for histopathological and molecular tests quite easily: usually thanks to hysteroscopy.

If cancer is confirmed, molecular tests should be performed immediately and one of the four tumor subtypes should be determined. Imaging tests are also necessary. The results influence both the scope of the surgery performed and the method of treatment after surgery, says Prof. Radosław Mądry, head of the Gynecological Oncology Clinic of the Medical University of Poznań.

– Approx. 8-10 percent cases of endometrial cancer are the so-called subtype FIELD; most promising. In this case, postoperative treatment may not be necessary because the risk of recurrence is minimal. The dMMR subtype (with so-called microsatellite instability, i.e. base pair mismatch repair disorders) also has a good prognosis. This is the so-called hot cancers, associated with a large infiltration of T lymphocytes; they are more visible to the immune system. The prognosis is better than in the case of “cold” cancers, invisible to the immune system: these are two less prognostic endometrial cancers associated with a mutation in the P53 gene – notes Prof. Paweł Blecharz, head of the Gynecological Oncology Clinic at the National Institute of Oncology, Branch in Krakow.

If molecular tests indicate a high risk of recurrence, postoperative treatment is necessary – radiotherapy and sometimes chemotherapy to reduce the risk of recurrence.

New indications for immunotherapy

In some women, endometrial cancer is already in an advanced stage at the time of diagnosis; some recurrence occurs despite treatment. Until recently, only chemotherapy could be used in such cases. However, research results have shown that – especially in the case of endometrial cancer with diagnosed mismatch repair disorders (dMMR) or microsatellite instability (MSI) – a more effective treatment will be a combination of immunotherapy and chemotherapy. From September 2023, in Poland, in the second-line (and subsequent) drug program, after chemotherapy failure, dostarlimab can be used as another line of treatment for endometrial cancer.

This subtype of endometrial cancer has an incidence of up to 30%. women. – Its feature is high immunogenicity, i.e. the ability to generate an immune response. Patients may clearly benefit from immunological treatment. Immunotherapy in endometrial cancer is the future and will apply to an increasingly wider group of patients – emphasizes Prof. Blecharz.

In 2023, the European Medicines Agency registered a new indication for dostarlimab, based on the results of the RUBY clinical trial. They demonstrated the benefits of administering dostarlimab, in combination with chemotherapy, in patients with mismatch repair disorders or microsatellite instability already in the first line of treatment for advanced cancer: when the cancer is detected at an advanced stage or when the disease recurs.

– Administration of dostarlimab in combination with chemotherapy at this early stage reduces by as much as 70%. risk of disease progression. This is a very significant statistical difference, also important from a purely human point of view: in these patients, thanks to treatment, we can control the disease for a long time and significantly reduce the risk of recurrence – adds Prof. Lubomir Bodnar, head of the Department of Clinical Oncology and Radiotherapy at the Siedlce Oncology Center.

Patients are also waiting for the possibility of using such treatment in the first line. – Registration of dostarlimab in the first line is a great joy for us. In oncology, many new therapies have already been moved to the front line. A patient who is well treated already in the first stage is a patient who heals much better, generates fewer indirect costs, and requires less care. We would be very happy if such treatment was available in Poland as soon as possible, says Anna Kupiecka, president of the OncoCafe Razem Better Foundation.

Compliance with recommendations plus new effective treatment

The risk of endometrial cancer is much higher in people who are obese, so it is very important to maintain a healthy weight and be physically active. You cannot forget about regular visits to the gynecologist (also after menopause) and do not delay the visit if you experience unusual bleeding or bleeding after menopause. If endometrial cancer is diagnosed, the molecular profile of the tumor should be checked before surgery (and if this has not been done, it must be done from surgical material).

– It is also important to be able to use new, effective drugs when they become available. Today, immunotherapy is already the first line of treatment for some patients. Diagnostics and appropriate treatment can change the “rules of the game” in this cancer, which too often lulls our vigilance because it is diagnosed early, says Prof. Jacek Sznurkowski from the Medical University of Gdańsk, under whose leadership new recommendations of the Polish Society of Gynecological Oncology for the treatment of endometrial cancer were created.