Ovarian cancer – screening, diagnosis and treatment including chemotherapy

Introduction

Cancer is characterised by an abnormal, uncontrolled growth that may destroy and invade adjacent healthy body tissues or elsewhere in the body (secondary spread – secondary deposits secondaries – metastases).

Living organisms (all animals and plants) are made of cells. The simplest organisms consist of just a single cell. Each cell has a central control, the nucleus surrounded by cytoplasm. The nucleus contains the genes, which are the biological blueprints that control the structure and function of the organism. The genes are the chromosomes each human cell has twenty-three pairs. Each chromosome is composed of DNA (Deoxyribose nucleic acid) and the DNA is a string of nucleotides. There are four nucleotides (A, C, G and T). The genetic code is a long string of these nucleotides grouped in threes e.g. ACG, TTT, CAG etc. The analysis of the human genetic coding has reached completion. It has been suggested that the full code would require 40 large volumes using a standard print size.

The human body has billions of cells (Q 2.1). Most cells have a limited life-span and need to be replaced. Cells are capable of duplicating themselves. Before birth and through childhood our bodies grow mainly through increase in cell numbers. The body’s cells are dividing throughout life. The red blood cells, for example, only survive for 120 days about one per cent of the circulating red cells are therefore replaced each day. Little is currently known about how the cells are replaced in such an orderly and precise fashion. Fundamental to the process is the doubling of the chromosomes (mitosis) during cell replication so that each new cell has an exact copy of the chromosomes laid down in the original egg at the time of fertilisation. There are natural mechanisms that speed up the process if there has been an excessive amount of cell loss: for example, following blood loss the process of red blood cell replacement is temporarily increased.

Millions of cell divisions and replications occur daily in the body and it is astounding that the process occurs so perfectly most of the time every cell division requires replication of the 40 volumes of genetic coding. On rare occasions there is some defect in a division and a rogue (mutant), potentially malignant cell arises. The immune system seems to recognise such occurrences and is generally capable of removing the abnormal cells before they have an opportunity to proliferate. Rarely, there is a failure of the mechanism and a potentially malignant cell survives, replicates and cancer is the result.

The four more common female cancers have their origins in the ovaries, body of the uterus, cervix of the uterus and breast, and they strike at the heart of femininity and sexuality.

Cancer Staging

Cancer staging is an agreed and defined classification of the spread of the disease determined around the time of the initial diagnosis. Stage I disease usually indicates that the tumour is confined to the organ of origin when surgical removal of the tumour or organ is likely to be associated with a good prognosis. Stage IV disease usually indicates that the tumour has spread widely and the prognosis is less favourable.

Cancer Prevalence

Internationally, it has been estimated that one in four people will develop cancer during their life and one in five will die as a result. One in three British people will develop cancer. Whilst children can develop some malignancies such as leukaemia, cancer becomes increasingly common as we age. Table shows the increase in the incidence of cancer associated deaths in relation to women’s cancers. More than 70% of cancers first appear after the age of 65 years. In the USA, there are 2.3 million deaths annually. The commonest cause of death is heart disease (732,000 deaths 32%) and cancer is the second most common cause (534,000 23.4%).Figure 32.1 shows the incidence of new cancer cases according to site of origin and the number of deaths in the USA for 1997 estimated by the National Cancer Institute. The cost for all healthcare in the USA in 1990 was $585 billion and 6% of this was for cancer. Figure 3 showing the major causes of mortality in the USA in 2002. (The American Cancer Society)

 In the United States the combined incidence rates of the three main s (uterine cervix, body of the uterus and ovary) is 43.6 per 100,000 women whereas the incidence of breast cancer is 109.5 per 100,000 women.

Table 32. 1 Incidence and survival of female cancers in the UK (1984)

 % of cancer registrations New Cases/yr  5 year survival UK deaths /year  % of cancer deaths
Breast 19 24,471 62% 15,245 20
Cervix 4 4,567 58% 2,234 3
Ovary 4 5,160 28% 4345 6
Endometrial 3 3,741 70% 1,050 1.6

Ovarian Cancer – Symptons, Signs & Diagnosis

The ovaries are to be found deep inside the pelvis on either side of the uterus. Cancer of the ovary is usually silent until it becomes advanced. At the time of diagnosis, 75% of ovarian cancers have advanced to Stage III or IV (Q32.2). The commonest presentation is enlargement of the abdomen either due to the tumour or the large amount of fluid associated with it (ascites). The two more common reasons for the abdomen to become distended, however, is laxity of the abdominal wall muscles or the bowel becoming too full. Ovarian Cancer

 

Prevalence

Ovarian cancer is the fifth commonest cancer in women. In 2003 there were 6,906 new cases reported in the United Kingdom.

The majority of ovarian cancer is found in women aged more than 45 years. Women who have had children or taken the combined oral contraceptive pill are afforded a degree of protection.

Tumour Markers

A tumour marker is a chemical that is produced by tumour cells and can be measured in the blood or other body fluids. It may be used to detect the presence of a tumour and subsequently to monitor the progress of the disease and response to treatment. An ideal tumour marker (which remains to be discovered) would have a cut-off point where there would be no false positives or negatives (screening tests).

Recent technological advances have allowed the evaluation of a large number of chemicals as potential tumour markers. In gynaecology there are three tumour markers of proven value Ca125, HCG and alpha-fetoprotein.

Ca125 is a tumour marker that is associated with ovarian cancer. Some ovarian cancers may not result in an increase in Ca125 levels. There are several reasons that limit the value of currently available tumour markers. Most tumour-associated markers are also produced by healthy tissues so that there is an overlap of levels between those with a tumour and healthy people. Ca125, the ovarian cancer marker, increases in 20% of healthy women during their periods and in 50% of women during pregnancy. It is non-specific and may be increased in some endometrial or bowel cancers. Raised levels may also be found in association with benign conditions of the ovary, pelvic inflammation and endometriosis.

The pre-placental tissue of pregnancy (trophoblast) produces human chorionic gonadotrophic hormone (HCG) and its presence is the first evidence of pregnancy. Occasionally (about one pregnancy in a thousand) in the UK, the trophoblast becomes an innocent tumour (hydatidiform mole). Rarely, this may become malignant choriocarcinoma; HCG levels are useful to monitor patients who have had a hydatidiform mole. Disgerminomas, (rare ovarian tumours in young women) may result in high levels of HCG. Alpha-fetoprotein (AFP) is produced by foetal tissues. When there is an open spina bifida the levels of AFP in the amniotic fluid and mother’s blood rise. This was the first useful test for detecting spina bifida during pregnancy but has become superseded by ultrasound examination of the fetus. AFP levels may be increased in association with some rare germ cell tumours of the ovaries.

Ovarian Cancer Screening

As ovarian cancer usually first makes itself apparent at a relatively late stage, the concept of screening to detect ovarian cancer at a relatively early stage is particularly attractive. There are two screening tests currently available for ovarian cancer ultrasound and a blood test for Ca125. Some ovarian cancers, but not all, are associated with an increase of a chemical in the blood called Ca-125. If a blood test shows a raised level of Ca125 there is an increased risk that there are cancer cells in the ovaries. The Ca125 level is raised (<35ku/l) in 80% of all ovarian cancers but in only 50% of patients with cancer confined to one ovary (Stage I0). False positive results of Ca125 can occur with endometriosis, benign ovarian cysts, pelvic inflammation and cancers from other sites. Other tumour markers are being evaluated. One new tumour marker, OVX1, has shown elevated levels when the Ca125 was giving a false negative result.

A fifty-three year old lady was known to have a fibroid uterus the size of a four month pregnancy. She arranged an ovarian screening Ca125 test at another hospital and the result was elevated. They recommended surgery but as we had previously known about the fibroid we managed to avoid an operation for her. Six years later on she remains well and the fibroid has become smaller as she has gone through her menopause.

An ultrasound scan (pelvic ultrasound) may show a picture suggestive of cancer. The vaginal probe allows the picture to be seen from very close to the ovaries. Neither ultrasound nor the Ca125 tests can absolutely confirm or refute the possibility of cancer. It has been suggested that for every 10 women with a positive result, only one will actually have cancer. The limit of resolution for ultrasound is about 1 cm. For one malignant cell to multiply to reach the size of 1 cm requires 10 billion cell divisions. There is only another 1000 fold increase required to reach a weight of 1 Kg.

Ovarian cancer screening is at an early stage of development so that there are as yet no large studies to confirm the potential benefits. In 1989, a committee in the UK assessed the situation and concluded that it was of unproven benefit and could not be recommended as a routine. An American committee came to a similar conclusion in 1994. Screening, therefore, remains an area for research.

Some women have a family history of ovarian cancer. For women with no family history of ovarian cancer the cumulative risk of ovarian cancer by the age of 70 is about 1% and if there is one close relative with the disease the risk is about 3%. With two close relatives the cumulative risk may lie between 15 and 30%. For women in the UK in this high risk group screening is available in the National Ovarian Cancer Registry Screening Programme, which is organised from Addenbrooke’s Hospital in Cambridge. There is a relationship between ovarian cancer and Breast Cancer

Women with two affected close relatives with breast cancer before the age of 40 or one with ovarian cancer and one with breast cancer diagnosed before the age of 50 are also eligible. A genetic screen on a blood sample can identify women at increased risk. (Q32.40)

Several hospitals have research interests evaluating screening the ovaries. If you feel that you may be at high risk they may be happy to screen you regularly. Screening is usually conducted annually.

Sadly, screening by CA125 and transvaginal ultrasound for ovarian cancer in high risk and low risk women has so far proven to be ineffective

Infertility And Ovarian Cancer

Women who have a history of infertility seem to have a slightly higher risk of developing ovarian cancer.

A study of nearly 4,000 women investigated for infertility in Seattle, USA between 1974 and 1985 was reported in 1994. Eleven women had developed ovarian cancer or borderline malignancy, whereas statistically four would have been expected. Nine of the affected women had taken clomiphene (a fertility drug 7). Five of these had taken the clomiphene for at least 12 months. Treatment with clomiphene for less than 12 months was not associated with increased risk of ovarian cancer. Following this report The Committee on Safety of Medicines in the UK, whilst accepting that further studies were required, recommended that clomiphene should not normally be prescribed for more than six cycles. Women could take it for longer provided that they were made aware of the risks and gave their informed consent. There is evidence that the majority of women would accept a modest increase in their lifetime risk of ovarian cancer that might be associated with their fertility treatment. Several groups have reported their data on this issue. Some provide reassurance that there is no strong association between fertility drugs and subsequent of ovarian cancer. Others support the contention that there may be an increased risk. The latest research is leaning towards reassurance.

The Combined Oral Contraceptive Pill And Cancer

The relationship between the combined oral contraceptive pill and cancer is discussed in Q15.19 -21 andQ32.43 .

Preventing Ovarian Cancer

Removing the ovaries (prophylactic oophorectomy) can prevent ovarian cancer. There are two clinical situations currently where the gynaecologist may need to address the question of removing the ovaries. The first is at the time of elective pelvic surgery, hysterectomy (Q 24.19) being the obvious example. The second is when there is a strong family history of ovarian malignancy. At one time removing ovaries was frequently performed as part of the management of Breast Cancer.

These days, oestrogen antagonists such as tamoxifen appear to be as effective (Q32.42).

Talc And Ovarian Cancer

A number of studies have suggested that the use of talcum powder applied to the genital area may increase the risk of ovarian cancer but the credibility of this association has been questioned. The debate continues with one recent report concluding that there is a significant association and that formal public health warnings are warranted.

Ovarian Cancer Treatment

Whenever possible, surgical removal of the ovaries and uterus is performed. Chemotherapy has an important part to play.

New delivery systems for delivering chemotherapy are under development.

Thank you for choosing to visit us.

This is the personal website of David A Viniker MD FRCOG, Consultant Obstetrician and Gynaecologist – Specialist Interests – Reproductive Medicine including Infertility, PCOS, PMS, Menopause and HRT.

I do hope that you find the answers to your women’s health questions in the patient information and medical advice provided.

The aim of this web site is to provide a general guide and it is not intended as a substitute for a consultation with an appropriate specialist in respect of individual care and treatment.

David Viniker retired from active clinical practice in 2012.

Website Design And SEO For SMEs

In 1999, he setup this website – www.2womenshealth.com – to provide detailed Employment Tribunals
information many of his patients requested. The website attracts thousands of visitors every day from around the world.
Website design and search engine optimization became hobbies that he plans to pursue in his retirement. If you would like advice on your website, please visit his website www.firstwebsitedesign.com or email him on david@firstwebsitedesign.com. In his retirement, he has continued to work on his websites and also for clients for their Internet marketing. Top positioning on Google depends on incoming links. Article writing for SMEsThe best way to produce those links it to write articles on authority websites. David has written articles on numerous subjects to this end including stars such as Kate Winslet, the Queen’s House Greenwich, andMargaret Thatcher. Other articles include employment tribunals and doctors and wedding magicians.

Ovarian Cancer Support Groups

http://www.gaovariancancer.org/support.htm Ovarian cancer support group in Georgia
http://www. Mnovarian.org/support_groups.htm Minnesota Ovarian Cancer Support Group
http://www.cancersa.org. Au/aspx/ovarian_cancer. Aspx Ovarian Cancer Support Group in Australia