Treatments

Cancer treatment goals and strategies vary according to the clinical circumstances. A woman diagnosed with a gynaecological cancer that is still confined to the organ of origin, e.g. the ovary or vagina, may be advised that it can probably be cured by surgery or radiation therapy alone. On the other hand, if the cancer has already spread to other parts of the body when first diagnosed (i.e., it is at an advanced stage), cure may not be possible and she is likely to be offered more than one modality of treatment. A more realistic goal in this situation may be to control the growth of the cancer and put it into remission, so that she may continue to live a good life for many years. In either case, the treatment will include one or more of the following:

All treatment choices are guided by expert advice, given by specialists who work together in a multidisciplinary team. The specific treatment recommendations will be discussed with the patient and her close supporters in extended counselling sessions by the relevant medical and nursing experts.

Surgery

Surgery for early stage cancers

If a woman’s cancer is apparently limited to the primary site, eg the cervix or ovary, surgery will usually be the treatment of choice. Most operations are performed through an abdominal incision (open operation or laparotomy), but in some women, particularly those with endometrial cancer, the surgery may be via a keyhole approach (laparoscopy, or occasionally robotic surgery). The objective of surgery for stage 1 cancer is to obtain wide clearance of the cancer. The surgical specimen is sent to the pathologist for examination under the microscope. Particular attention must be paid by the pathologist to the surgical margins ie, the extent of normal tissue between the edge of cancer and the edge of the surgical specimen. If the surgical margins are too close to the cancer, it may be necessary to remove more tissue or give some postoperative radiation to be confident that the cancer has been adequately treated.

Proper surgical treatment for an early stage cancer, eg, cervical or endometrial cancer, may require removal of normal or enlarged lymph nodes (lymphadenectomy), small nodules of tissue that filter the lymph fluid that drains away from the reproductive organs and eventually re-enters the blood stream. If the lymph nodes are found to contain cancer cells when examined by the pathologist, the outlook for the cancer will usually be worse and other modalities of therapy will usually be needed, such as radiation or chemotherapy.

Surgery for advanced stage cancers

If imaging shows a woman’s cancer has spread beyond the primary site, it may be considered inoperable and treated with radiation and/or chemotherapy. Ovarian cancer is commonly widely spread at the time of diagnosis, but surgery still plays a vital part in its management. The objective of surgery in patients with advanced ovarian cancer is not to remove the cancer with good surgical margins, but rather to try to remove as much cancer as possible, knowing that some cancer cells will inevitably be left behind. This type of surgery is called debulking or cytoreductive surgery and its aim is to improve the effectiveness of the subsequent chemotherapy.

Planning and preparation for an operation

After discussion of the nature of the operation, its likely benefits and possible complications, the surgeon will ask the woman to sign an informed consent document. Before the operation, the woman will need a thorough assessment of her current health status. This will typically involve her general practitioner, anaesthetist and surgeon, but if she has active health problems, she may need assessment and advice from a consultant physician. The Australian Government’s personally controlled electronic health record system, (eHealth record), makes the process of collecting and recording important health facts faster, safer and easier. A woman diagnosed with cancer should register for an eHealth record – a secure, electronic summary of her important health information. Her GP can usually arrange this. http://www.yourhealth.gov.au/internet/yourhealth/publishing.nsf/Content/pcehr has more details.

Blood tests and imaging studies will be organised to identify any problems. If a woman is anaemic from heavy bleeding, she may need iron therapy to help restore her blood count. If she is taking any medication that would increase her risk of bleeding, such as aspirin or warfarin to thin her blood, this will need to be stopped or replaced with safer medication well before the surgery.

A consultation about cancer is always a stressful time and it is important to have a support person at the consultation. The woman should not be afraid to come with a list of questions and should not be afraid to ask further questions. It is often very helpful for a woman to discuss the medical advice with an oncology nurse who specialises in gynaecological cancer. If the woman is still not happy with the advice, she should not be afraid to ask for a second opinion.

Surgery complications

Common surgical complications include:

  • anaesthetic problems, such as heart irregularities
  • bleeding from surgical cuts
  • wound infections
  • bladder infection, (cystitis) because a catheter is used to drain urine,
  • chest infection, (pneumonia), particularly in heavy smokers or after a long anaesthetic
  • clots in a vein, (venous thrombosis), that can break off and travel to the lung (pulmonary embolus)
  • temporary cessation of movement of bowels (ileus) or urine flow (urinary retention)

The more extensive the surgery, the greater the risk of unintentional injury to important structure such as nerves, the bowel, the bladder, or a ureter, (the tube taking urine from kidney to bladder). These injuries are usually recognized and repaired during the operation

All complications tend to be more common and more severe in women who are

  • overweight and/or
  • smokers and/or
  • medically unfit

Post surgery care

After major surgery, most women will be in hospital between 4 to 6 days after an open operation (laparotomy) and 1 to 2 days after keyhole surgery (laparoscopy or robotic surgery). Suitable pain relieving medication will be given and she will be encouraged to take deep breaths every hour, sit out of bed on the first post-operative day and move about as soon as reasonably possible. This early mobilisation helps to decrease the risk of chest infection and clots in the leg veins. It is likely there will be a urinary catheter in her bladder and an intravenous line in her arm. Both will usually be taken out on the first or second postoperative day. She will be allowed to start drinking and eating as desired, unless she has had a bowel resection.

Her surgeon will talk to her about the operation and tell her what was found at surgery. The final pathology results will not be available for several days.

On leaving hospital, she may have wound closure devices such as clips still in place, which will usually be taken out by a nurse or by her general practitioner. She may be able go home to the care of her family, or she may need to be visited regularly by community nurses. If she is particularly frail, she may need to go to a convalescent facility

Chemotherapy

Chemotherapeutic agents are selected on the basis of previous experience with a particular drug for a given tumor. The drugs are usually given intravenously, so that they can circulate around the body and treat the tumor regardless of its anatomic location. To increase the local concentration, certain drugs may occasionally be administered by local instillation (e.g. intraperitoneal therapy for ovarian cancer).

Chemotherapy is generally not administered if the blood count is too low. The lowest counts occur 7 to 14 days after treatment and subsequent doses may need to be reduced if the counts are particularly low. Dose reduction may also be necessary because of toxicity to other organs, such as the liver or kidneys.

Chemotherapeutic drugs

There are numerous chemotherapeutic drugs available for the treatment of gynaecological cancers and a description of all of them is beyond the scope of this website. Three commonly used agents are:

Carboplatin
This is the most widely used drug and is used particularly for patients with ovarian cancer. Its main side effect is bone marrow suppression causing a low blood count. It does not cause hair loss and any nausea is usually mild and easily controlled.

Paclitaxel (Taxol)
This drug, which is derived from the bark of the Pacific yew tree, is commonly combined with carboplatin in the combination which is usually called “carbo/taxol”. This combination is considered to be first-line therapy for ovarian cancer. It causes hair loss and bone marrow suppression and some patients develop an allergic reaction to it.

Cisplatin
This drug was used for patients with ovarian cancer before the development of carboplatin. It is toxic to the kidneys, so patients have to be hydrated with intravenous fluids before it is administered. It also is toxic to nerves and hearing loss may be a problem. It may cause severe nausea and vomiting, particularly with repeated cycles of treatment. Low dose cisplatin is usually given concurrently with radiation therapy once a week in patients being treated for cervical cancer, to make the cancer cells more sensitive to the radiation. This is called chemoradiation.

Why chemotherapy and radiotherapy are recommended

A woman is most likely to be advised to have chemotherapy, radiotherapy, or both if the cancer is considered to be inoperable, or if there are likely to be cancer cells remaining after the surgery.

Chemotherapy usually follows surgery, but may sometimes be given first – it is then called neoadjuvant chemotherapy. An example would be a woman with extensive fluid in the abdomen (ascites) or around the lungs (pleural effusion) from advanced ovarian cancer. The chemotherapy is usually given first to dry up the fluid, which then makes the surgery safer.

Cancer cells are very abnormal. They divide rapidly and without control, because the genetic material that controls cell division, the DNA inside the cell nucleus, is abnormal. Cancer cells have an ability to burrow into (invade) the primary organ, but they can also burrow into blood and lymphatic vessels and travel around the body (metastasise).
Another characteristic feature of a malignant tumour is its ability to encourage the formation of new blood channels (angiogenesis) that are necessary to feed the cancer. The blood vessels are very abnormal compared with those in healthy body organs and this may explain why cancer cells can enter the bloodstream fairly readily.

All these special features of malignant tumours can be targets for anti-cancer treatment. The rapid rate of cell division compared to normal tissues is the prime target. Chemotherapeutic agents and radiation are most effective against actively dividing cells, because cells that are not dividing are better able to repair any damage that does not kill them outright. Unfortunately, both chemotherapy and radiation also suppress rapidly dividing normal cells, such as those in the gut, bone marrow and hair follicles, so mouth ulcers, low blood counts and hair loss are common side effects of both treatment modalities. Low blood cell counts are caused by bone marrow suppression. Low red cell counts make a woman feel weak from anaemia, while low white cell counts can create a high risk of infection and low platelet counts create a high risk of bleeding.

Chemotherapy and radiotherapy are sometimes combined (chemoradiation) because they work better together than either would alone in some situations.

How chemotherapy and radiotherapy work

Cancer cells are very abnormal. They divide rapidly and without control, because the genetic material that controls cell division, the DNA inside the cell nucleus, is abnormal. Cancer cells have an ability to burrow into (invade) the primary organ, but they can also burrow into blood and lymphatic vessels and travel around the body (metastasise).
Another characteristic feature of a malignant tumour is its ability to encourage the formation of new blood channels (angiogenesis) that are necessary to feed the cancer. The blood vessels are very abnormal compared with those in healthy body organs and this may explain why cancer cells can enter the bloodstream fairly readily.

All these special features of malignant tumours can be targets for anti-cancer treatment. The rapid rate of cell division compared to normal tissues is the prime target. Chemotherapeutic agents and radiation are most effective against actively dividing cells, because cells that are not dividing are better able to repair any damage that does not kill them outright. Unfortunately, both chemotherapy and radiation also suppress rapidly dividing normal cells, such as those in the gut, bone marrow and hair follicles, so mouth ulcers, low blood counts and hair loss are common side effects of both treatment modalities. Low blood cell counts are caused by bone marrow suppression. Low red cell counts make a woman feel weak from anaemia, while low white cell counts can create a high risk of infection and low platelet counts create a high risk of bleeding.

Chemotherapy and radiotherapy are sometimes combined (chemoradiation) because they work better together than either would alone in some situations.

Radiation therapy

There are many forms of radiation including visible, infrared and ultraviolet light. The powerful light of a laser may be used to treat pre-cancer of the surface layers of a woman’s cervix. If she has an internal cancer, the radiation must be able to penetrate the skin, fat, muscles and bone in order to get to the organ, e.g. the cervix, and to damage the DNA. Therefore, the radiation must have much higher energy and X-rays and gamma rays are required. Radiation may be given as external beam radiation, using machines called linear accelerators, or as brachytherapy, where sources of radioactive material are placed in contact with the cancer.

Successful radiation therapy requires a delicate balance between the dosage to the tumour and that to the surrounding normal tissues. A dose of radiation that is too high kills the tumour, but results in an unacceptably high complication rate because of the damage to the normal tissues.

Most normal tissues, such as bowel and bone marrow, have a remarkable capacity to recover from radiation damage by the division of stem cells, as well as by repair of sub-lethal radiation damage. Tumours have less ability to repair damage. This difference is exploited by administering the radiation in multiple fractions, thereby allowing some recovery of normal cells between fractions. For example, with pelvic radiation, treatments are given daily Monday to Friday for 5 to 6 weeks. The major factors influencing the outcome of radiation therapy are:

  • the tolerance of normal tissues to toxic effects. Is her body robust or frail?
  • the malignant cell type and rate of cell division. These factors help to determine the sensitivity or resistance to treatment
  • the oxygen concentration in the cancer
  • the total volume of cancer needing to be treated. A large volume of resistant cancer is harder to treat successfully than a small volume of sensitive cancer.
  • the total dose of radiation delivered
  • the number of treatment cycles or fractions
  • the total duration of therapy.

Chemoradiation

A variety of drugs are capable of enhancing the lethal effects of radiation. Clinical trials have demonstrated a significant survival advantage when cisplatin-containing chemotherapy is given concurrently with radiation for advanced cervical cancer. This pharmacologic modification of the effects of radiation is called chemoradiation.

External beam therapy

In external beam radiation, a machine called a linear accelerator is used to deliver the radiation. External radiation allows a uniform dose to be delivered to a given field, eg the pelvis. The tolerance of the normal tissues (e.g., bowel, bladder, liver, kidneys) limits the total dosage that can be delivered. External radiation is usually used to shrink a large tumor mass before brachytherapy is used. When used alone, it is generally useful only when there is very small or microscopic residual disease following surgery. With highly radiosensitive tumors (e.g. ovarian dysgerminoma), external radiation alone may sterilize even bulky disease.

Brachytherapy

Brachytherapy involves the use of radioactive implants – the radioactive material is placed either within or close to the cancer. For example, applicators containing the radioactive substance may be placed in the cervix and upper vagina under general anesthesia. It is used particularly in the treatment of cancers of the cervix and vagina and to prevent recurrence at the top of the vagina after hysterectomy for endometrial cancer in selected patients.

Radiotherapy complications

The success of radiation therapy depends on exploiting the increased likelihood of killing cancer cells compared to killing normal tissue cells. Unfortunately, most malignant tumors are only marginally more sensitive to radiation than are normal tissues, so the total dose that can be delivered is limited by the associated complications.

Acute Complications

Acute reactions to radiation usually occur in the first 2 or 3 weeks. In the management of gynecologic tumors, acute complication may include effects on:

  • the urinary bladder, (acute cystitis), manifested by blood in the urine, urgency and frequency
  • the lower large bowel, (proctosigmoiditis), manifested by diarrhea and passage of blood and mucus in the stool
  • the small bowel (enteritis), manifested by nausea, vomiting, diarrhea and spasmodic abdominal pain and
  • the bone marrow (bone marrow suppression), manifested by low blood counts. Bone marrow problems are uncommon with pelvic radiation, but common with extended-field radiation, (radiation of the pelvis and alongside the abdominal aorta) which is sometimes given for cancers of the cervix or endometrium if the patient has positive lymph nodes. Bone marrow suppression is also more common with chemoradiation
  • tiredness
  • Acute complications are like sunburn. Any woman lying in the sun without skin protection will get sunburnt, but when she gets out of the sun, the burn will get better over time. Similarly, any woman undergoing radiation treatment will get some of these problems, but they are usually well tolerated, and when the radiation treatment stops, they will progressively disappear over the next 3 to 4 months.

Chronic Complications

Chronic complications occur 6 months or more after completion of radiation and are caused by damage to small blood vessels (endarteritis). When the blood supply to an organ is decreased, there is progressive scarring (fibrosis) and permanent shrinkage of that organ.

About 5% to 10% of women receiving external beam and brachytherapy may develop significant chronic complications, which may be slowly progressive over several years.

Common chronic complications of radiation include:

  • Radiation Enteritis, which is caused by damage to the small bowel. It usually presents with cramping abdominal pain and vomiting, or with alternating diarrhea and constipation. Previous surgery, with resultant small bowel adhesions in the pelvis, may predispose a woman to radiation enteritis
  • Radiation Proctitis, which is caused by damage to the rectum. Symptoms include diarrhoea and rectal bleeding. If there is progressive fibrosis, narrowing of the rectum may occur (“stenosis”), leading to increasing constipation. There may be progressive ulceration of the rectum, ultimately leading to the development of a hole between the rectum and vagina, called a rectovaginal fistula, which is manifested by passage of stool through the vagina. Radiation proctitis is best diagnosed by sigmoidoscopy or colonoscopy
  • Vaginal stenosis, which is caused by damage to the walls of the vagina. The lining of the vagina may become thin and there may be progressive scarring (fibrosis), leading to narrowing and occasionally complete closure of the vagina. Diligent use of vaginal dilators will help to prevent this.
  • Radiation cystitis, which is caused by damage to the urinary bladder. The most common problem is the passage of blood in the urine and blood transfusions may be necessary. The most serious complication is the development of a hole between the bladder and the vagina, called a vesicovaginal fistula, which is manifested by the constant leakage of urine through the vagina. Radiation cystitis is best diagnosed by cystoscopy.

All of these chronic complications may be significantly improved by a course of hyperbaric oxygen therapy.

Hormonal therapies

Growth of a woman’s cancer, particularly an endometrial cancer, may be stimulated by oestrogen and inhibited by progesterone, the female sex hormones, because the cancer cells contain “receptors” for these hormones on their surface. After a cancer has been surgically removed, it may be tested for oestrogen receptors (ER, being the acronym derived from the US spelling, estrogen) and progesterone receptors (PR). Tumour growth in a woman whose tumour contains ER and PR is likely to be stimulated by oestrogen exposure, while tumour regression should occur if oestrogen production is abolished, or if she is treated with an anti-oestrogen or a progestin. A progestin (or progestagen) is a synthetic drug that has hormonal effects similar to the natural hormone progesterone.

Tamoxifen binds with the ER and acts as an anti-oestrogen. It is commonly used in treating breast cancer and is effective in about 30-40% of women with recurrent ovarian cancer. The progestin Provera is often helpful in patients with endometrial and other cancers.

Generally, hormonal therapy is well tolerated, particularly if a woman is already post-menopausal. A premenopausal woman will experience menopausal symptoms, such as hot flushes. A woman treated with tamoxifen for ovarian cancer is likely to have had her uterus removed but, in other circumstances the potential for tamoxifen to induce endometrial cancer may justify close observation for early detection of that effect.

Targeted therapies

Hormonal therapies target the oestrogen and progesterone receptors (ER and PR) in cancer cells and are a form of targeted therapy. These treatments have been used for many years, but newer targeted therapies, sometimes known as gene therapies, have been used increasingly in recent years. They are therapies that target a particular molecular pathway or an abnormal gene that is present in the cancer. These drugs can often be taken by mouth and are generally much better tolerated than chemotherapy. Commonly used drugs are:

  • Bevacizumab (Avastin). The formation of new blood vessels is important for cancer growth. Bevacizumab is a monoclonal antibody that suppresses tumour growth by interfering with the blood vessels of the cancer. This effect is termed anti-angiogenesis. Bevacizumab is sometimes used in patients with ovarian cancer
  • PARP inhibitors. PARP is an acronym for Poly Adenosine diphosphate Ribose Polymerase. These drugs are designed to target the repair of DNA, leading to death of cancer cells. They are particularly effective in patients with one of the BRCA mutations, which are responsible for hereditary breast and ovarian cancer.

Use of targeted therapy is increasing and it is an exciting and challenging field of research.