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Cancer and Reproductive Health
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Book description

While cancer affects primarily the elderly, it also occurs in younger age groups, with different implications specifically relating to reproduction. Cancer can also occur during pregnancy itself. This brings together two diverse areas of medicine, encompassing the complexity of cancer and its varied biology and the equally challenging areas of fertility, conception and pregnancy. The 55th RCOG Study Group brought together a range of experts to examine these issues. This book presents the findings of the Study Group, with sections covering:• epidemiology, genetics and basic principles of chemotherapy and radiotherapy• fertility issues and paediatric cancers• gynaecological cancers and precancer• diagnostic dilemmas• the placenta• non-gynaecological cancers• multidisciplinary care and service provision.

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Contents


Page 1 of 2


  • 1 - Epidemiology of cancer in women during reproductive life
    pp 3-12
  • View abstract

    Summary

    While malignancies in women of reproductive age are relatively uncommon, they are, after accidents, the most common cause of death in women aged 20-39 in the USA. Malignant melanoma was the most frequently diagnosed cancer occurring in pregnancy, followed by cervical cancer and breast cancer, reflecting the high melanoma risk in the fair-skinned Swedish population. The incidence of melanoma increases steadily from the age of 20 years and thus is a relatively common cancer in women during their reproductive years and is more common than breast cancer in the under-30s. Thyroid cancer is 2.5 times more common in women than men and the incidence varies between different populations owing to genetic and environmental factors. Gestation trophoblastic neoplasia is a malignancy intimately related to pregnancy. Improved data could be obtained by the central population-based registries formally collecting data on cancer during pregnancy.
  • 2 - Cancer genetics and reproduction
    pp 13-22
  • View abstract

    Summary

    A small proportion of malignancies have a clear genetic aetiology resulting from mutations in genes inherited usually as an autosomal dominant trait. Risk assessment and genetic counselling around genetic testing and reproductive decision-making should be undertaken in a regional genetic service. If a mutation is identified within an individual, it should be confirmed in another affected member of the family, if possible. A predictive genetic test is then available for unaffected adult members of the family. Adoption or conception using donor gametes may be alternatives for families with genetic conditions who wish to avoid prenatal diagnosis. The issue of the appropriateness of prenatal diagnosis and of preimplantation genetic diagnosis (PGD) for inherited conditions with an onset in adulthood is controversial. PGD may be more acceptable than prenatal diagnosis as it obviates the need for termination of an affected pregnancy.
  • 3 - Chemotherapy in the treatment of pregnant women with cancer
    pp 23-54
  • View abstract

    Summary

    A number of key issues must be considered regarding the treatment of a malignancy in pregnancy. The optimal dosing of chemotherapy during pregnancy is an important issue that requires consideration as the blood volume is 50% higher in pregnant women. The main adverse effect from dose-dense chemotherapy is neutropenia, which in nonpregnant patients is frequently managed by the use of granulocyte colony stimulating factor (G-CSF). Antimetabolites are small, weakly acidic molecules used to treat leukaemia, lymphoma and breast cancer. The concentrations in milk are variable and related to the dose and timing of chemotherapy and all standard advice is that breastfeeding is contraindicated while undergoing chemotherapy. The maternal benefits of receiving chemotherapy before delivery must outweigh the fetal risks of exposure and the maternal risk of delaying treatment until after delivery at a gestational age optimal for both fetal survival and wellbeing.
  • 4 - Radiotherapy and cancer
    pp 55-60
  • View abstract

    Summary

    The principles of treating cancer in a pregnant woman should be the same as for a nonpregnant woman but the timing of the treatment may be influenced by the natural history of the cancer and its prognosis, and the stage of the pregnancy. The radiation dose to the fetus depends on a number of factors, including the type of machine, prescribed dose, and anatomical area to be treated and the gestational age of the fetus. The management of early-stage Hodgkin's disease involves chemotherapy and involved-field radiotherapy rather than the larger 'mantle' radiotherapy fields, and hence the risk to the fetus from modern treatment should be considerably less. Current studies are investigating the role of dose-dense neoadjuvant chemotherapy before definitive chemoradiation in nonpregnant women with locally advanced cervical cancer. Brain tumours, and head and neck cancers are much less frequently encountered in pregnancy but in general would require radiotherapy without delay.
  • 5 - Assisted reproductive technology for preserving fertility in women with cancer
    pp 63-72
  • View abstract

    Summary

    Assisted reproductive techniques (ART) that can help women under the age of 40 years are: in vitro fertilisation (IVF) with embryo cryopreservation; ovarian stimulation with mature oocyte cryopreservation; and ovarian tissue banking. Cryopreservation of embryos, oocytes or ovarian tissue is indicated where treatment for cancer is likely to lead to significant damage to the ovaries and reduction in subsequent fertility. Ovarian tissue cryopreservation, which shows great promise for female fertility preservation, is not an established technique and should be considered to be investigational. Embryo, sperm and oocyte storage is licensed by the Human Fertilisation and Embryology Authority (HFEA), which requires infection screening of the gamete and embryo providers. This chapter discusses the cryopreservation methods for each method of fertility preservation. Orthotopic transplantation can be performed laparoscopically or as an open procedure. Consent for all these procedures should be fully informed and the women should have access to specialist counseling.
  • 6 - Fertility after cancer therapy
    pp 73-86
  • View abstract

    Summary

    Fertility is an important issue for cancer survivors. In women, fertility may be directly affected by cancers involving the cervix, uterus and ovaries or by other pelvic tumours. Fertility-sparing surgery holds great hope for certain diseases, for example radical trachelectomy for early-stage cancer of the cervix in young women. The patients at highest risk of infertility are those who have received total body irradiation with chemotherapy, bone marrow transplant conditioning chemotherapy, and pelvic radiotherapy. In women, there are also implications of fertility treatment and pregnancy itself for cancer recurrence. The evidence on unassisted pregnancy after cancer is informed by several large follow-up series. In children and adolescents, no specific test is available to predict future fertility. For men with reduced semen quality after therapy, modern laboratory techniques give a good chance of fatherhood. Services are likely to develop in tertiary centres with reproductive medicine units incorporating the necessary laboratory facilities.
  • 7 - Fertility-preserving surgery in women with cancer of the cervix
    pp 87-100
  • View abstract

    Summary

    While cervical cancer remains the second most common female tumour with over 500,000 cases per year, the incidence has fallen dramatically in countries that have introduced successful screening programmes, predominantly in the western world. Traditionally, staging assessments have been carried out under anaesthesia and have used standard and widely available radiological techniques such as a chest X-ray and an intravenous urogram. Radical vaginal trachelectomy comprises the first part or distal resection of the cervix, paracervical tissue and upper vagina, as in a Schauta vaginal hysterectomy. All women are carefully counselled with regard to treatment options, as well as the risks of the procedure and the relative lack of experience compared with conventional radical hysterectomy or chemo/radiotherapy. As this is a new procedure, a strict follow-up protocol is undertaken, with a review of the pathology and discussion of early postoperative care and management at 2 weeks.
  • 8 - Gonadal function and fertility issues in children and young people treated for cancer
    pp 101-108
  • View abstract

    Summary

    This chapter discusses the impaired fertility in both males and females and adverse pregnancy outcomes following successful treatment of cancer in childhood. The ovaries may be damaged following total body, abdominal or pelvic irradiation and the extent of the damage is related to the radiation dose, fractionation schedule and age at time of treatment. Gonadotrophin deficiency following high-dose cranial irradiation will be manifest as delayed puberty or absent menses, and can be treated by hormone replacement therapy. The uterus is at significant risk of damage following abdominal, pelvic or total body irradiation, in a dose- and age-dependent manner. Within the paediatric and adolescent age group, testicular damage occurs with direct irradiation of the testis. Semen cryopreservation is an established and successful technique for the adult male but is more challenging to carry out in children and teenagers. Following cryopreservation, stored spermatozoa may be used for in vitro fertilisation (IVF).
  • 9 - Management of cervical intraepithelial neoplasia during pregnancy
    pp 111-114
  • View abstract

    Summary

    Cervical intraepithelial neoplasia (CIN) has a high incidence in the reproductive age groups. Colposcopy is safe in pregnancy and, as a result of the extension of the squamous-columnar junction (SCJ) to the ectocervix, it is also satisfactory in the majority of the cases. Generally, the rate of CIN progression during pregnancy is known to be small, and no evidence reveals an increase in the risk of invasive cervical cancer in pregnancy. Infants can acquire human papillomavirus (HPV) from their mothers during labour as they descend through an infected genital tract. A caesarean section should not be recommended for a pregnant woman with CIN solely for the purpose of prevention of HPV transmission to the infant. Modifications of the management principles are required mainly because treatment of CIN during pregnancy can cause serious morbidity and should only be reserved for special circumstances.
  • 10 - Impact of LLETZ on subsequent pregnancies
    pp 115-124
  • View abstract

    Summary

    Large loop excision of the transformation zone (LLETZ) was introduced in the late 1980s and has now become the most popular method of treatment for cervical intraepithelial neoplasia (CIN). It is well known that women with CIN have demographic, behavioural, and sexual characteristics that put them at increased risk of pregnancy-related morbidity. Outcomes related to fertility are reported in two studies after LLETZ, one after laser conisation and after laser ablation, and one after cold knife conisation (CKC). The differences in the seriousness of adverse effects noted between CKC and LLETZ might be related to variations in the amount of tissue removed. Clinicians should counsel women appropriately before excisional treatment regarding the increased risk of preterm birth in a future pregnancy. Women requiring treatment with either CKC, laser conisation or a relatively large loop excision should be warned that they may warrant closer antenatal care in a subsequent pregnancy.
  • 11 - Ovarian masses and malignancies
    pp 125-132
  • View abstract

    Summary

    The widespread use of ultrasound in the first trimester for dating and for viability and nuchal fold assessment has increased the detection of ovarian masses. The use of high-frequency transvaginal probes has allowed the detailed imaging of cystic pelvic masses. Cervical and ovarian cancers are the gynaecological malignancies most frequently diagnosed in pregnancy. Most non-benign ovarian cysts found in pregnancy are borderline tumours or germ cell tumours. Ultrasound imaging of ovarian cysts or masses is helpful in identifying lesions that are of a suspicious nature. A significant proportion of germ cell tumours in pregnancy are dysgerminomas. Presentation and diagnosis at an early stage of pregnancy does not always warrant termination of pregnancy as there are several reports of uneventful term pregnancies despite administration of chemotherapy. If malignancy is suspected, a full staging laparotomy is needed either immediately or after delivery.
  • 12 - Cervical and endometrial cancer in relation to pregnancy
    pp 133-144
  • View abstract

    Summary

    This chapter considers cervical and endometrial cancer in relation to pregnancy, dealing with both the situation where the diagnosis is made at a time when future pregnancy is desired and the situation where the diagnosis is made during pregnancy. In general, surgical treatment for cervical cancer is reserved for early-stage disease or, rarely, for women with recurrent disease. The number of women who develop endometrial cancer during the reproductive phase of their lives is small, and the number who is diagnosed in pregnancy is very small indeed. However, there are a number of epidemiological factors that may be relevant in this group and these are discussed in this chapter. The standard management for women with endometrial cancer is a staging laparotomy according to Federation of Gynecology and Obstetrics (FIGO) guidelines, at which a total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy are performed.
  • 13 - Imaging techniques
    pp 147-154
  • View abstract

    Summary

    Ionising radiation in medicine is used in two broad areas, namely diagnostic imaging and radiotherapy, and these are distinguished from each other only in the magnitude of the radiation. If computed tomography (CT) is indispensable to the management of the patient, there are several techniques that can be employed to reduce the dose to the fetus. Wherever possible, non-ionising alternatives such as ultrasound or magnetic resonance imaging (MRI) should be used instead of CT. This chapter describes imaging requirements for staging of the following cancers: ovarian cancer, endometrial cancer, cervical cancer, and vaginal/vulval tumours. The staging of any cancer requires an assessment of local tumour extent, involvement of regional or distant lymph nodes and the detection of distant metastases. This is clearly encapsulated in the tumour, node, metastasis (TNM) staging system proposed by the International Union Against Cancer (UICC).
  • 14 - Serum markers for gynaecological cancer in the reproductive years
    pp 155-178
  • View abstract

    Summary

    This chapter focuses on the various tumour markers relevant to gynaecological malignancies in premenopausal women and their role in management. No serological markers have been found to be sufficiently sensitive for early-stage disease or specific for screening purposes. Squamous cell carcinoma antigen (SCC) is probably a marker of cellular differentiation of squamous cells. Beta human chorionic gonadotrophin (ßhCG) has been described as an 'ideal tumour marker' in gestational trophoblastic tumours (GTN) and plays a primary role in its management. Alpha-fetoprotein (AFP) has been used as a reliable marker for monitoring treatment and detecting early relapse in nonpregnant women. None of the serum markers has a well-established role in the clinical management of endometrial cancer. The role of serum CA125 in screening women in the reproductive age group with increased risk of familial ovarian cancer is being investigated.
  • 15 - Diagnostic dilemmas in cellular pathology
    pp 179-184
  • View abstract

    Summary

    There are many diagnostic dilemmas in gynaecological cellular pathology, spanning across all age groups. This chapter considers the six most challenging pathological entities in the reproductive age group. The dilemmas in ovarian cysts arises when the cyst is deemed to be complex as there may be a reluctance to aspirate in case of spillage of malignant cells. The most significant diagnostic dilemma with regard to cervical neoplasia is in the staging of microinvasive carcinoma. All the diagnostic difficulties in cervical neoplasia are compounded by the need to excise as small a piece of the cervix as possible to preserve fertility and prevent miscarriage. The problem with the diagnosis of atypical hyperplasia is in the vague criteria used for cytological atypia, rounding up of nuclei with clearing of chromatin and prominent nucleoli, which results in considerable variation of opinion among pathologists.
  • 16 - Placental and fetal malignancies
    pp 187-204
  • View abstract

    Summary

    This chapter reviews the unusual entities and focuses on the role of noninvasive investigation in placental and fetal malignancies antenatal diagnosis, antenatal follow-up and management of affected pregnancies. The group of placental malignant tumours includes mainly gestational trophoblastic neoplasia (GTN) involving the proliferation of one or more trophoblast cell types. Complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) can also be found in association with a normal fetus in a dizygotic twin pregnancy. Placental metastases from fetal malignancies such as neuroblastomas, leukaemia and congenital hepatoblastoma, can also spread to the placenta and could theoretically pass over to the mother. Acute congenital leukaemia is the second most common fetal malignancy, with an incidence of around 5 per million live births per year. A wide range of malignancies affecting the fetus or infant have been reported, involving almost every organ system, including most of the recognised paediatric malignant tumours.
  • 17 - Gestational trophoblastic neoplasia
    pp 205-226
  • View abstract

    Summary

    Gestational trophoblastic neoplasia (GTN) comprises a spectrum of related conditions, all of which are characterised by low incidence and high cure rates. Placental site trophoblastic tumours (PSTT) are the rarest form of GTN and can complicate any form of conception but most frequently follow a normal pregnancy. Choriocarcinoma can present with extremely varied symptoms and signs associated with the differing sites of metastatic disease and occur at a wide range of time after the causative pregnancy. For most women with GTN following a recent molar pregnancy, the investigations performed before chemotherapy treatment are limited to a Doppler ultrasound of the pelvis and a chest X-ray. The use of routine first-trimester ultrasound combined with effective follow-up programmes has produced near 100% cure rates for women following molar pregnancies. Optimising molar pregnancy follow-up services and education of clinicians to GTN in women with cancer are most important to produce effective patient care.
  • 18 - Pregnancy and breast cancer
    pp 229-242
  • View abstract

    Summary

    This chapter attempts to identify how pregnancy and lactation modify breast cancer risk, and highlights what can be regarded as state of the art in the diagnosis and treatment of pregnancy-associated breast cancer (PABC). It also considers the issue of preserving fertility during the treatment of breast cancer. The factor known to consistently decrease lifetime breast cancer risk regardless of ethnicity is early childbirth. An independent study found that breastfeeding decreased the risk of both hormone receptor-positive and hormone receptor-negative breast cancer. External beam radiation is an integral part of breast-conserving therapy and is, depending on the stage, also used after mastectomy. Women who want to conceive after breast cancer should receive individual counseling on prognosis with special attention to medical and psychosocial support. There may be a simple way of managing patients at risk of chemotherapy-induced infertility by deliberately producing a state of temporary, reversible medical castration during chemotherapy.
  • 19 - The haematological malignancies
    pp 243-256
  • View abstract

    Summary

    The haematological malignancies comprise the acute and chronic leukaemias, myelodysplastic syndromes (MDS), chronic myeloproliferative disorders, Hodgkin's disease and non-Hodgkin's lymphomas and multiple myeloma. This chapter is devoted to the rare but problematic situation in which pregnancy occurs during therapy or, more commonly, the haematological disease is diagnosed as a result of simple blood investigations during an established pregnancy. The acute leukaemias reflect a situation of maturation arrest in blood cell development resulting in proliferation and accumulation of immature precursors of the myeloid or lymphoid lineages. Chronic myeloid leukaemia (CML) typically presents in the chronic phase but terminates in blast crisis, a condition very similar to, but more resistant to therapy than acute leukaemia. Appropriate management will depend on due consideration of the underlying disease, the disease status, its treatment, and the immediacy of the requirement for that treatment.
  • 20 - Melanoma and reproductive health
    pp 257-264
  • View abstract

    Summary

    Cutaneous melanoma has increased in incidence progressively in white-skinned populations since the beginning of the 20th century. Genetic factors play a significant role in determining melanoma risk. A recent meta-analysis explored whether pregnancy is a risk factor for melanoma. The majority of melanomas in all age ranges and both sexes are of the sub-type known as a superficial spreading melanoma. As most melanomas are superficial spreading melanomas, the lesions are usually irregular in shape and colour, often with three or more colours. Women with many atypical naevi, particularly those who have a family or personal history of melanoma, should probably receive enhanced supervision during pregnancy. The prognosis for people with vertical growth phase melanoma is determined by the nature of the primary tumour. The management of primary melanoma in pregnancy is normally the same as in those who are not pregnant, namely excision of the tumour under local anaesthesia.

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