08 May 2023
Today, 80% of women with ovarian cancer are diagnosed when already in advanced stages of the disease. But things could change in a not so distant future, largely thanks to research taking place at the Champalimaud Foundation.
Ovarian cancer is the eighth most frequent cancer and the seventh most prevalent cause of death by cancer in women. In Portugal, in 2020, 560 new cases were diagnosed, and 408 deaths occurred, proving that this relatively rare cancer is highly lethal. On World Ovarian Cancer Day, which is celebrated on May 8th, gynaecologist and Unit Director, Henrique Nabais (H.N.) and medical oncologist Filipa Ferreira da Silva (F.S.), from the Champalimaud Foundation’s Multidisciplinary Unit of Oncologic Gynaecology, talk about this daunting disease and in particular about the need to develop an efficient screening method, as well as a referencing and treatment programme in order to save more lives.
F.S.: This is because, compared to other gynaecological cancers, most women are diagnosed in advanced stages of the disease. This is due to the fact that there is no validated screening method for early diagnosis of ovarian cancer. Also, in the initial stages, symptoms and signs are very unspecific and similar to those of many other totally benign pathologies. For this reason, nearly 80% of cases are diagnosed when they are already in advanced stages.
H.N.: It has nothing to do with bad medical practice, but with the fact, as Filipa just said, that we do not have a good screening method. For cervical cancer, for instance, we have cytology and HPV screening, for breast cancer we have mammograms. There are several research projects in the field of ovarian cancer, including here at the Champalimaud Foundation, but until now none of them has been validated. It is also a fact that symptoms such as the increase of abdominal volume, abdominal discomfort or pain, or feeling stuffed after a meal are not at all specific. Women frequently have these kinds of complaints, but they are often associated with chronic constipation. The truth is that such symptoms are not considered important, neither by women nor by their doctors.
H.N.: Not necessarily. The gynaecologist can only palpate voluminous ovarian tumours, and in that case, there may already be a very extensive ovarian cancer, sometimes inoperable. This explains why some patients may have had a recent exam that did not reveal anything abnormal – and three months later, there is an inoperable cancer. That is why we don’t use ultrasounds as a screening method.
F.S.: The most common ones – so-called epithelial ovarian cancers – have four main types. Of these, the most frequent is high-grade serous ovarian cancer (aggressive and rapidly growing), followed by endometrioid ovarian cancer, clear cell ovarian cancer and mucinous ovarian cancer. The latter two are less frequent, and when they are diagnosed in advanced stages they are more resistant to chemotherapy.
F.S.: We know today that nearly 20% of ovarian cancers, and in particular high-grade serous cancers, are associated with mutations, namely in the BRAC1 and BRAC2 genes, which are also strongly associated with breast cancer. Nowadays, the majority of women diagnosed with ovarian cancer have an indication for a study of those mutations. Their presence has important therapeutic implications with prognostic repercussions.
H.N.: I would like to add that family members of women with ovarian cancer and with an identified mutation should also do a genetic study. If a mutation is identified, doctors have to propose to those family members a different surveillance plan from that of the general population, as well as the possibility of a risk-reducing surgery.
H.N.: No screening would be recommended in the general population; just paying attention to new complaints that arise or whose pattern changes, and clinically assessing them in due manner and time. In women with BRAC1 or BRAC2 mutations, gynaecological ultrasound and removal of the ovaries and the Falopian tubes after age 35 are recommended. This surgery reduces the risk of having ovarian cancer by around 70%. However, the surgery should only be performed once the patient has come to the terms with the fact that they will no longer be able to conceive and when it is perceived as medically beneficial. For women who do not intend to remove the ovaries and Falopian tubes, we propose the surveillance protocol described above.
H.N.: No. In general, it is a simple laparoscopic procedure that entails a 12 to 24-hour hospitalisation and a rapid recovery. One of the problems associated with this risk-reducing surgery – I think the most relevant one – is that the woman will enter menopause. In these cases, hormonal menopause therapeutics can be used for at least five years. We also observed that women with a close family history of ovarian cancer (for example, their mother or a sister), more readily accept the surgery and have less complaints than others. This has to do with how each one feels about the risk of having or not having cancer.
F.S.: Overall, the initial treatment is multimodal, and includes surgery and systemic therapy (chemotherapy). The first line treatment we offer a woman who has been diagnosed with ovarian cancer is surgery. This means that the first decision-making step – always in a multidisciplinary context – has to involve a gynaecological oncologist to evaluate whether the patient is a candidate for surgery. When the disease cannot be completely removed surgically, we need to initiate a treatment plan with chemotherapy. After chemotherapy, some patients are candidates for maintenance therapy.
H.N.: In the initial stages of the disease, we perform a so-called staging surgery, which means we remove the uterus, the ovaries, the Falopian tubes, the pelvic and para-aortic lymph nodes, and the greater omentum [https://en.wikipedia.org/wiki/Greater_omentum]. The main goal here is to assess the extent of the disease, the possibility of its complete removal and to determine the need of an adjuvant therapy and the associated prognostic.
However, in more than 80% of cases, we have an advanced disease. In this case, we do not perform a staging surgery, but rather a cytoreductive surgery, which only has therapeutic value if we succeed in removing all the visible disease.
When this is not possible, we start chemotherapy and periodically reassess the feasibility of cytoreductive surgery, which we now designate as an “interval surgery”. In cytoreductive interval surgery, most of the time the option is to do chemotherapy during the surgery, a procedure called HIPEC (Hyperthermic IntrapPEritoneal Chemotherapy). This means that, after complete removal of the disease, chemotherapy is directly applied inside the abdominal cavity in order to eliminate residual, microscopic, cancer cells. Only a few centres in Portugal perform HIPEC, the Champalimaud Foundation being one of them.
It may still be necessary to do chemotherapy after surgery. Our goal is always the complete removal of the disease.
F.S.: In terms of overall five-year survival, the latest studies show some improvement, with 40 to 45% of women surviving five years. In the initial stages of the disease, I and II, the five-year survival rate is close to 80 or even 85%. In advanced stages, nearly 70% of the patients will have a recurrence of the disease within the first five years.
F.S.: Yes. In the last few years, the big therapeutic revolution for women with ovarian cancer has been the introduction of so-called PARP inhibitors (olaparib®, niraparib®) into therapeutic algorithms. It’s an oral treatment used for maintenance, either as first-line treatment or in case of recurrence. Available data about the use of these drugs show that they significantly increase progression-free survival.
There are also multiple ongoing clinical trials of promising treatments, which may be able to extend survival and improve quality of life.
F.S.: Yes. As ovarian cancer is the most lethal gynaecological cancer, we are very keen to participate and develop projects in this area. We participate in multiple clinical trials and we have our own projects.
H.N.: As Filipa already indicated, that is one of the areas of interest of our Unit. We have an ongoing project in collaboration with Dr. Pedro Vaz, a researcher at the Champalimaud Foundation [in the Lung Unit – see here], whose goal is to identify compounds that are specific of ovarian cancer in the air exhaled from the lungs. The results, until now, look very promising, not only for ovarian cancer, but also for endometrial cancer and cervical cancer screening.
We are also involved in a research project about a potential ovarian cancer screening method based on compounds in the urine, in collaboration with Dr. João Lagarto, coordinator of the Biophotonics Platform at the Champalimaud Foundation [here].
