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Diagnosis of Ovarian Cancer

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Surgical treatment
Chemotherapy
Relapse Treatment
New therapies
Treatment complications

The treatment of ovarian cancer combines surgery and chemotherapy, to which new options have recently been added, such as targeted or biological therapies. Sometimes surgery is not possible while, in other cases, such as when the disease is limited to the ovary and there is a good prognosis in young patients, surgery (with no subsequent chemotherapy) that preserves the uterus and the other ovary may be both sufficient and safe. The type of tumour diagnosed may also condition the treatment.

Depending on the type of tumour and the extent of the disease, the strategy may be to start treatment by surgery or, conversely, to start treatment with chemotherapy and postpone surgery until several cycles of chemotherapy have been completed. This is known as neoadjuvant chemotherapy followed by interval surgery. The medical team will propose the best strategy after a personalised assessment of the diagnostic tests.

A very important factor in the disease prognosis is that the surgery manages to eradicate all visible disease in the pelvis and abdomen. This means that the residual disease after surgery is zero, which is known as complete surgery. The less disease removed in the surgery (residual post-surgical disease), the worse the outcome for the patient.

Therefore, in cases where it is unlikely that the tumour can be removed, or where multiple total or partial resections of different organs (intestine, spleen, liver, etc.) must be performed to achieve this, chemotherapy treatment is chosen initially with the aim of reducing the tumour mass. This, in turn, facilitates a subsequent operation and helps to achieve complete surgery.

The decision to apply one or another treatment is taken by a coordinated multidisciplinary team of professionals who are experts in this disease.

Degree and extent

The degree and extent of the disease is assigned a stage, following classification rules that are based on the tissue structures and organs affected by the tumour. There are four stages, with as many substages, ranked from less to more severe. The different stages correspond to different outcomes.

Stage I. Tumour growth is limited to the ovaries or fallopian tubes.

Stage II. The tumour growth affects one or both ovaries or fallopian tubes, but has also spread to neighbouring tissues located in the pelvis (such as the uterus, bladder, sigmoid colon, or rectum).

Stage III. The tumour involves one or both ovaries or fallopian tubes with peritoneal implants outside the pelvis and/or with the involvement of the pelvic or aortic lymph nodes or the inguinal lymph nodes. Superficial liver metastases are equivalent to stage III. The tumour is limited to the lesser or true pelvis (the space enclosed by the pelvic girdle and below the edge of the pelvis: between the entrance of the pelvis and the pelvic floor), but with histologically proven malignant extension into the small intestine or omentum (fold of the peritoneum).

Stage IV. The growth affects one or both ovaries with distant metastases. If there is pleural effusion (fluid build-up between the layers of tissue covering the lungs) and positive cytology (cancer cells), the cancer is assigned to stage IV. Parenchymal liver metastases (inside the liver) are also equivalent to stage IV.

Surgical treatment

Surgical treatment of ovarian cancer depends on how far the disease has spread, which may be:

contiguously to neighbouring pelvic organs and the abdomen (peritoneum, omentum, intestine, etc.)
via the lymphatic pathway (retroperitoneal pelvic and para-aortic lymph nodes)
at a distance (haematogenous route). This is rare and, in general, only occurs in advanced stages.

The goals of surgery are, firstly, to remove as much malignant tissue as possible, including all the cancerous nodules that are visible due to their size; and secondly, to assess areas that appear apparently normal when inspected surgically, because these may present disease when analysed under the microscope.

If no surgery is performed because the ovarian tumour appears to be benign, the extent of the disease cannot adequately be assessed, which may worsen the patient's prognosis.

Detecting disease that is not apparent in the clinical setting is critical to staging, assigning a prognosis, and, occasionally, modulating the post-surgical chemotherapy treatment.

If the medical team considers that the surgery will not achieve the complete resection of all the lesions, surgery will be delayed until a few cycles of neoadjuvant chemotherapy have been completed.

Chemotherapy

Chemotherapy is usually administered in combination with surgery. However, for tumours that are in very early and not very aggressive stages (well-differentiated epithelial ovarian cancers and some non-epithelial varieties), a single operation is feasible, with no added chemotherapy. In addition, if the patient wishes to become pregnant, preserving the uterus and the other ovary can be considered.

Exclusive chemotherapy (with no surgery) may also be applied in cases of metastatic disease (outside the abdomen).

There are various ways of administering chemotherapy, as well as several different drugs:

Neoadjuvant chemotherapy and interval surgery

When surgery cannot completely resect the lesions (patients with advanced disease, voluminous or unresectable disease, contraindication for extensive surgery requiring large resections), the strategy is changed: chemotherapy (neoadjuvant) is applied first, and then the response to this is monitored. If the response is satisfactory, and the volume of the tumour reduces, then cytoreductive surgery is indicated. This is not aimed at complete removal of the tumour, but rather at palliation, to prolong the life of the patient, or to make it easier for the chemotherapy to work.

This often occurs after about three cycles of chemotherapy. After surgery, the chemotherapy is completed, until all the planned cycles have been administered.

Adjuvant chemotherapy

In most cases, where surgery is the first line of treatment, complementary chemotherapy is also indicated.

Drugs used and guidelines

Standard chemotherapy treatment consists of two drugs, paclitaxel and carboplatin, both given intravenously once every three weeks and over six treatment cycles. For women who develop an allergy to paclitaxel or who cannot tolerate it, docetaxel or pegylated liposomal doxorubicin can be substituted and administered with carboplatin.

Intraperitoneal chemotherapy

Intraperitoneal chemotherapy is applied through a catheter that is inserted directly into the abdomen. Intraperitoneal chemotherapy is usually given in combination with intravenous chemotherapy. This treatment has proven effective in patients with advanced disease at the intra-abdominal level, where surgery has achieved either optimal cytoreduction (complete surgery) or near-optimal. Due to its side effects, it should only be performed on selected patients.

Hyperthermic intraperitoneal chemotherapy

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a recently introduced therapeutic option. It consists of cytoreductive surgery (aggressive surgery that removes all visible tumour masses), which often involves the removal of the entire peritoneum (a peritonectomy) and, if required, the removal of other organs such as parts of the colon or small intestine, spleen, and so on, followed, in the same operation, by the administration of intra-abdominal chemotherapy.

This is usually indicated in cases of advanced, extensive abdominal disease, in situations where there is no response to standard chemotherapy. There are still no long-term results for this treatment applied to ovarian cancer. In general, it is administered as part of a clinical trial.

Relapse Treatment

Despite the initial treatment of the disease, there is a possibility that the cancer may recur. In fact, this happens fairly often.

The treatment options for a relapse of the disease may include a second operation, chemotherapy and targeted therapies. The decision to administer a specific treatment will depend on the time elapsed since the initial treatment, the volume of the disease, the associated symptoms, previous treatments, any toxicity from a prior treatment and the histological and molecular characteristics of the tumour, as well as the individual circumstances of each patient.

Support measures and palliative care also play a very important role in managing the symptoms associated with disease relapse.

New therapies

As ovarian cancer develops and grows, just like with other types of cancer, new blood vessels are formed and directed towards the tumour. In this way, the tumour ensures that it receives the supply of nutrients it needs to continue its growth. Bevacizumab, a drug that targets vascular endothelial growth factor (VEGF), a protein that helps form these new vessels, is used to block the formation of new blood vessels.

Bevacizumab is administered together with intravenous chemotherapy every three weeks in patients with advanced epithelial ovarian cancer. The side effects are different from the adverse effects associated with chemotherapy. The most frequent are arterial hypertension (high blood pressure) and proteinuria (appearance of proteins in the urine). For this reason, during treatment the blood pressure is monitored and urine tests are performed.

PARP inhibitors, on the other hand, are drugs that work by inhibiting a protein called PARP. This protein is necessary for the tumour cells to repair their DNA and continue to grow, so inhibiting this causes the tumour cells to die.

PARP inhibitors are indicated as maintenance treatment in patients who have relapsed, have been treated with carboplatin-based chemotherapy, and who present decreased disease volume. They are given orally on a daily basis and continuously while the disease is under control and there are no major side effects. The most frequent side effects are nausea, vomiting, tiredness, anaemia, neutropaenia;(lowered defences)and thrombocytopaenia (lowered platelet count).

Clinical research is also underway (not available at the care level) for other therapies that act on the immune system.

Treatment complications

Treatment complications may be secondary to both surgical and chemotherapy treatment.

Surgical complications

In premenopausal patients, surgery to remove the ovaries triggers surgically induced menopause, as sufficient oestrogen is no longer produced. Depleted oestrogen levels can cause a loss of bone density as well as cardiovascular disease, in addition to the common symptoms of menopause, like hot flashes and vaginal dryness.

Complications from the surgery itself are rare. One of the most common is the formation of intra-abdominal scars or adhesions, which can cause problems including abdominal pain and difficulties passing stools. Also, extensive abdominal surgery can lead to the development of a hernia, where part of the intestine pushes through an abnormal opening in the abdominal wall. Some patients may need surgical procedures to correct one or both of these complications.

Chemotherapy complications

Chemotherapy is a treatment that destroys the cells that are growing too fast. It attacks the cells when they divide and reproduce. The faster they divide, the more effective the chemotherapy treatment is. Our bodies have normal cells that are constantly multiplying and which are susceptible to the effects of chemotherapy, leading to the appearance of side effects. There are different side effects to treatment depending on the specific type of chemotherapy administered.

Substantiated information by:

Lydia Gaba Medical oncologist

Published: 3 July 2020
Updated: 3 July 2020

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