Ovarian Cancer

An overview of disease, diagnosis and treatment

Ovarian Cancer

Ovarian cancer includes cancer in the ovaries, fallopian tubes and primary peritoneal cancer.

Most tumors arise from the surface (epithelial lining) of these structures and present with few or no symptoms in the lower stages (stage 1-2). The majority of patients have stage 3 or 4 disease (advanced disease) upon diagnosis.  

Since the disease has very few or no symptoms initially, many patients have presented with vague or diffuse symptoms to their primary physician, thereby unintentially extending the diagnostic phase.

Symptoms and Diagnosis

Ovarian cancer is predominantly diagnosed in stage 3 and 4. Symptoms are often unspecific and may include pelvic/abdominal symptoms like discomfort, pain, obstipation, bloating (due to fluid (ascites)), urinary tract irritation/infection, dyspnea, and deep venous thrombosis.

Patients presenting to their primary physician with symptoms indicating ovarian tumor, should be referred for specialized gynaecological evaluation with gynaecological examination, vaginal ultrasound and blood tests incl. the tumor marker Ca-125, which is used for ovarian cancer.

Verification of the diagnosis and histological subtype is required. The gynaecologist will retrieve tumor tissue sample(s) (biopsies) either by ultrasound-guided biopsy, or laparoscopy.

For final staging of ovarian cancer, an imaging examination must be performed to determine the extent of disease. The modality of choice varies between locations between PET/CT, CT, and MRI.

If larger quantities of fluids has accumulated in the abdomen (ascites) or chest (pleural effusion), patients can experience marked abdominal swelling, gastrointestinal irregularities or shortness of breath.

It can be indicated to drain the fluid from the abdomen or chest with a needle (paracentesis or thoracentesis) to alleviate severe symptoms. The extracted fluid may contain cancerous cells, and  can be send for histological examination to document the diagnosis, if indicated.

Multi Disciplinary Team (MDT) Conference: When results from abovementioned examinations are available, best advised treatment strategy is discussed between doctors in the Multi Disciplinary Team. If initial surgery (Primary debulking Surgery (PDS)) is deemed technically and medically feasible, this will be recommended initially.         

Patients with stage 4 ovarian cancer can start their cancer treatment with chemotherapy. The aim is to decrease the tumor bulk, before undergoing interval surgery later (Interval Debulking Surgery (IDS)).

Epidemiology

Women diagnosed with ovarian cancer are a median age of 63 years, and most are post-menopausal.

The ethiology of the disease is multifactoriel, and approximately 10 % are hereditary (mainly BRCA 1/2 mutation). 

As the prognosis is dependent upon stage at diagnosis, and most patients are diagnosed with metastatic disease (stage 3-4), ovarian cancer has a rather poor diagnosis. The 5 year survival rate is  above 80 % in stage 1, but 20% in stage 4.

Tumor stage, and whether complete resection of cancerous tissue can be attained at surgery, are the most important factors in terms of long-term prognosis and survival. 

Examination Methods

Transvaginal Ultrasound

An ultrasound examination of the internal genital organs is carried out with an ultrasound probe inserted into the vagina (transvaginal sonography). It demonstrates pelvic structures well, but is insufficient to visualize cancerous lesions on e.g. bowel surfaces.

It is painless and can be repeated any number of times. It does not expose the patient to any radiation.

Blood Tests

Blood tests provide information about the general health condition of the patient.

The test results are important with regard to any upcoming treatment, and usually evaluates both haematological status, kidney- and liverfunction, coagulation status and the tumor marker Ca-125.

Tumor markers are of particular use for monitoring the course of the disease during chemotherapy, and in the event of a relapse. In the post-treatment phase, a rise in level of tumor marker can be an indicator of relapse. 

Abdominal Ultrasound

Ultrasound examination of the abdomen provides view of the internal organs such as the liver, kidneys, spleen, and to some degree the intestines. It may visualize, possible tumorspread (metastases) to nearby organs or structures.

The presence of abnormal fluid effusions accumulated in the abdominal cavity (ascites) or in the chest (pleural effusion) can cause debilitating symptoms for the patient.

The size/amount, and exact location of effusions/fluid pools can be determined with ultrasound, and a needle and tube be inserted for drainage and fast symptom relieve. The risk of unintentionally damaging nearby structures is diminshed by ultrasound-guidance during the procedure.

Treatment Options

Chemotherapy

For patients who undergo primary debulking surgery: Based on the stage, histological type, surgical findings and outcome, the recommendation/option of receiving post-surgical treatment with “adjuvant” chemotherapy will be discussed with you. Only for certain malignant ovarian tumors in stage 1, surgical treatment is deemed sufficient, and omitting “adjuvant” chemotherapy is advised.

For patients who undergo interval debulking surgery: To reduce the tumor bulk before surgical removal of the remaining tumor, patients will be treated with “neoadjuvant” chemotherapy.  Here 3 series (rounds) of combination chemotherapy is given, followed by new imaging and blood sample evaluation of the tumor response. If deemed surgically and medically feasible, patients will undergo surgical resection af remaining tumor.

Chemotherapy are powerful pharmaceutical drugs used to destroy/kill cancer cells throughout the body. The drugs work by inhibiting cell growth, thereby aiming to induce tumor regression.

The standard option for ovarian cancer is a combination chemotherapy with two drugs (carboplatin and paclitaxel/docetaxel), which are given 6 times with 3 weeks apart.

In advanced stages (stage 3 & 4) the antibody bevacizumab or a parp inhibitor can be administered during/following the chemotherapy according to guidelines. The intention is to extend the time until relapse.

What are the side effects of chemotherapy?

Treatment with chemotherapy also affects normal tissue, which can cause side effects. Especially tissues which renew themselves quickly, are likely to be affected. These include the mucous membranes of the mouth, stomach and intestines, the hematopoietic system in the bone marrow, and the hair roots. Several side effects can be alleviated well with medication, and usually disappear/diminishes significantly, when chemotherapy is no longer administered.

Surgery

Patients are operated for ovarian cancer under general anesthesia. It is a complex and large procedure performed by specialized oncological surgeons in gynaecologic surgical departments. A longitudinal abdominal incision is made during the operation.

The aim of the operation is to completely remove all tumor tissue, which involves removing both ovaries, fallopian tubes, the uterus, the abdominal fatty network, appendix, and parts of the peritoneum and lymph nodes. The size of the operation depends on the extent of invasion and type of the tumor. Sometimes parts of the intestine are removed also, and a stoma can be necessary to accomplish surgical radicality.

In selected cases, where only one ovary is affected (stage 1) in fertile women, fertility-preserving surgery may be considered.

Antibody Therapy and PARP-inhibitors

Research demonstrated, that adding the anti-angiogenesis antibody bevacizumab to the chemotherapy regimen, can considerably extend the time to relapse of cancer. Bevacizumab treatment is referred to as “targeted therapy”. Via binding to the VEGF-receptor in patients, bevacizumab inhibits the formation of new blood vessels, thereby reducing the blood supply to the tumor. (OCEANS, GOG-213 studies)

Important clinical studies demonstrated significant effect of PARP-inhibitor maintenance treatment on progression free survival following platinum-based chemotherapy in ovarian cancer patients. Patients with BRCA 1/2 mutation and/or HRD have the highest degree of effect of PARP-inhibitor maintenance. (NEJM, 2019, PRIMA, PAOLA studies)

In Case of a relapse

Despite initial surgery and chemotherapy success, many patients experience relapse of the cancer. The treatment approach will in each case be evaluated thorougly, to determine best possible options.

In most cases relapsed disease is not curable. The treatment focuses on preventing tumor growth and further spread of metastases for as long as possible, thereby relieving symptoms and hopefully prolonging duration of good quality of life.

Depending on how fast, and in which form, the tumor relapse occurs, an  additional surgical procedure may be advised, followed by a subsequent new round of chemotherapy. 

If relapse occurs within half a year after initial surgery and completion of the first line of chemotherapy, the choice of next chemotherapy will typically be pegylated liposomal doxorubicin. For further future relapses or progressions paclitaxel or other drugs may be administered. 

Inclusion in ongoing clinical trials in your oncological department may also be possible. Participation in a clinical trial can in some cases have a direct impact on your quality of life and/or your prognosis. However, in other cases the study will mainly benefit future patients. Ask you treating dorctor(s) about your possibilities and options.

Making Decisions About Your Care

The choice of therapy for your cancer is an individual decision, and many factors are taken in to consideration, when your doctor(s) discuss the best option(s) with you. These include the type, size and location/spread of the tumor, as well as your age and general health status. 

We recommend, that you have a thorough discussion with your doctor(s) about the results upon your diagnosis, the treatment-plan and your chances of recovery (e.g. prognosis).

You are encouraged to include family and/or friends for participation in doctors appointments etc. for improving your/their understanding and remembrance of relevant information, as well as for emotional and physical support during appointments and treatments. 

Your doctor can give a detailed explanation of the various therapy options, and has knowledge of the possibility to participate in a clinical trial. Each patient is different and so is their wish upon information needed/wanted prior to making important decisions. 

Well designed and conducted clinical trials are essential to determine the effectiveness of a promising new drug or intervention. Many gynaecologic oncology departments have studies open for inclusion during the course of your cancer treatment. Talk to your doctor(s) about your thoughts regarding possible inclusion in a clinical trial now or in the future.

                                                                                                               (References; www.DGCG.DK, Kræft Klinik og sygepleje, FADL’s forlag 2019) 

Author: Kristine Madsen, MD, Deputy Medical Director NSGO-CTU

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Privacy Policy for NSGO

NSGO treats personal information and complies with the laws and principles of good data processing practices. Therefore, we have adopted this Privacy Policy, which briefly describes how we treat personal information, so legal and transparent processing is ensured.

We are responsible for processing your personal information:

NSGO is the data controller and you can always contact the organization’s data protection officer:

Mansoor Raza Mirza

Nordic Society of Gynecologic Oncology – Clinical Trial Unit
Copenhagen University Hospital
Department of Oncology, 9431
Blegdamsvej 60
DK-2100 Copenhagen
Office phone: +45 35 45 33 78
fax: +45 3545 2898
Mansoor.Raza.Mirza@regionh.dk.

We treat the following personal information about members:

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Storing and deleting your personal information:

For historical reasons and as your details might be saved in old attendance lists, email correspondence and minutes from meetings, we cannot promise that all personal information about you will be deleted, if you terminate your membership.

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You have a number of rights via the General Data Protection Regulation (GDPR):

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You may make use of your rights by contacting us. If you submit a request to have your personal information corrected or deleted, we will investigate whether the conditions are met and, in that case, make changes or deletions as soon as possible and, if applicable, also notify our data processors to do so.

You can file a complaint with the supervisory authorities – The Danish ‘Datatilsynet’ – About processing your personal information (www.datatilsynet.dk).

Revision of Privacy Policy:

We reserve the right to change the organization’s privacy policy. When we change privacy policy, we also change the date and version number at the bottom of this document. In case of significant changes, you will receive a notification.

The current privacy policy is always available on our website.

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Privacy Policy for NSGO-CTU

NSGO-CTU treats personal information and complies with the laws and principles of good data
processing practices. Therefore, we have adopted this Privacy Policy, which briefly describes how we treat personal information, so legal and transparent processing is ensured.

We are responsible for processing your personal information:

NSGO-CTU is the data controller and you can contact the organization’s data protection officer:

Mansoor Raza Mirza

Nordic Society of Gynecologic Oncology – Clinical Trial Unit
Copenhagen University Hospital
Department of Oncology, 9431
Blegdamsvej 60
DK-2100 Copenhagen
Office phone: +45 35 45 33 78
fax: +45 3545 2898
Mansoor.Raza.Mirza@regionh.dk.

We treat the following personal information about personnel participating in NSGO-CTU trials:
• General personal information: For example; contact information such as name, work
address, work phone number, date of birth, email address, country, work title, date of start
of participation and termination in a trial and, if applicable, CV, GCP certificates, records of
training and other qualification data.
• If applicable, financial disclosure forms and/or Bank account number for reimbursement
purposes.

We collect personal information from:
• We will ask you to provide us the information yourself, when you in decide to take part
in NSGO-CTU trials.
The organization’s legal basis to process personal information:
• That we as an organization have a (legitimate) interest in processing your information, for
example to secure your qualifications in handling the care of the participants in a trial.
• That it is necessary for us to fulfill an agreement with your employer
• You have agreed that we can process your information via signing the delegation log.
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• The participation of an investigator or of other individuals in a clinical trial which is being
conducted according to the principals governing clinical research as set out in the
Declaration of Helsinki and with the acceptance of all involved Regulatory Health
Authorities and involved Ethical Committees, requires collection, recording, storage,
transfer and/or other use of personal data (personal data processing).
• Communicate regarding studies.
• To handle payments and reimbursements.
• To comply with legislation.
• To deliver services, in the form of the possibility to participate in the Annual Meeting,
Investigator Meeting.
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of each individual trial.

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your employer where terms and conditions are described, or if you put your name on the
Delegation Log of a trial, you agree to the information described in this Privacy Policy.
However, it may happen that we judge it necessary to obtain your written consent for other
purposes. In that case you will have the opportunity to voluntarily agree, and you may withdraw it
at any time by notifying us.
Be aware that there are legal bases for certain forms of processing of your data for the abovementioned purposes and that your consent is the only legal basis for other forms of processing.

Dispatch of your personal information:
Depending on your role in a trial, your personal information might be shared with personnel at
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CRO staff, Ethics Committees and Competent Authorities, both in Europe, but also in countries
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also if a less severe data protection law should exist.
We do not disclose information about you to anyone outside the organization without the above
consent, however, it should be noted, that if you e.g. accept an invitation to a meeting, your
personal information might be forwarded to the meeting location or the meeting organizer. Only
personal information relevant for the 3rd party will be disclosed in these circumstances.
Furthermore, your data can be transmitted to public databases for registration, as well as
publication of a trial and your data can be stored and published in those databases.
Storing and deleting your personal information:
For historical reasons and as your details might be saved in old attendance lists, email
correspondence and minutes from meetings, we cannot promise that all personal information
about you will be deleted, when you end your participation in a study. In general, all information
about a trial is deleted at least 20 years after end of study.

Your rights:
You have a number of rights via the General Data Protection Regulation (GDPR):
• The Right to Information (to be informed what information we process about you)
• The Right of Access (to get a print of the information we process about you)
• The Right to Rectification (to have false information about you corrected)
• The Right to Erasure (to delete information we process about you, however, information
already received cannot be deleted)
• The Right to Restriction of processing (under certain conditions, to have the processing of
your data restricted)
• The Right to Object (to object to your information being used for wrong purposes)

You may make use of your rights by contacting us, however, the legality of the processing carried out
prior to e.g., a withdrawal will not be affected. If you submit a request to have your personal
information corrected or deleted, we will investigate whether the conditions are met and, in that
case, make changes or deletions as soon as possible and, if applicable, also notify our data
processors to do so.

If you do not believe that NSGO-CTU handles your data correctly, you can file a complaint with the
supervisory authorities – The Danish ‘Datatilsynet’ – About processing your personal information
(www.datatilsynet.dk).

Revision of Privacy Policy:
We reserve the right to change the organization’s privacy policy. When we change privacy policy,
we also change the date and version number at the bottom of this document. In case of significant
changes, you will receive a notification.

The current privacy policy for NSGO-CTU is always available on our website.

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