Gynaecological Oncology, Second Edition

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Gynaecological Oncology

Gynaecological Oncology Mahmood I. Shafi

Consultant Gynaecological Surgeon and Oncologist Department of Gynaecological Oncology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge

Helena M. Earl

Reader in Clinical Cancer Medicine and Honorary Consultant Medical Oncologist University of Cambridge Department of Oncology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge

Li Tee Tan

Consultant Clinical Oncologist Oncology Centre Addenbrooke’s Hospital Cambridge University Hospitals NHS Trust Cambridge

CAMBRIDGE UNIVERSITY PRESS

Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo, Delhi, Dubai, Tokyo Cambridge University Press The Edinburgh Building, Cambridge CB2 8RU, UK Published in the United States of America by Cambridge University Press, New York www.cambridge.org Information on this title: www.cambridge.org/9780521730242 © Cambridge University Press, 2010 This publication is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published in print format 2009 ISBN-13

978-0-511-69122-5

eBook (NetLibrary)

ISBN-13

978-0-521-73024-2

Paperback

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To our respective families for the support and love that we enjoy.

Contents List of contributors page viii Preface xi List of abbreviations xii

1

Epidemiology of gynaecological cancers 1 Anjum Memon

2

Screening and prevention of gynaecological cancers 15 Ranjit Manchanda and Ian J. Jacobs

3

Pathology of gynaecological cancers 33 Mark J. Arends

4

Imaging in gynaecological oncology 51 Nyree Griffin and Evis Sala

5 Surgery for gynaecological cancers 69 Alan Farthing 6

Radiotherapy for gynaecological cancers 79 Charlotte Coles

7

Systemic therapies for gynaecological cancers 91 Helena M. Earl

8

Palliative care in gynaecological oncology 103 Sara Booth

9

Ovarian cancer 119 Robin Crawford and Yin-Ling Woo

10

Endometrial cancer Catherine Holland

11

Cervical and vaginal cancer 147 Ahmed Ahmed, Li Tee Tan and Mahmood I. Shafi

12

Vulvar cancer Peter Baldwin

13

Gynaecological sarcomas 175 John Latimer and Helena M. Earl

14

Gestational trophoblastic disease and ovarian germ cell tumours 181 Neil J. Sebire and Michael J. Seckl

15

Decision making in oncology Li Tee Tan

133

163

199

Appendices Appendix 1:

Miscellaneous information Appendix 2: Incidence and mortality data Appendix 3: Staging: FIGO and TNM Appendix 4: Useful websites Index

207 209 213 223 225

Contributors Ahmed Ahmed Department of Obstetrics and Gynaecology and Department of Oncology University of Cambridge Cambridge Mark J. Arends Department of Histospathology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge Peter Baldwin Department of Gynaecological Oncology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge Sara Booth Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge Charlotte Coles Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge Robin Crawford Department of Gynaecological Oncology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge Helena M. Earl Department of Oncology Addenbrooke’s Hospital

Cambridge University Hospitals NHS Foundation Trust Cambridge Alan Farthing West London Gynaecological Cancer Centre Queen Charlotte’s Hospital London Nyree Griffin Department of Radiology Guy’s and St Thomas’ Hospitals London Catherine Holland Academic Unit of Obstetrics and Gynaecology University of Manchester School of Cancer and Imaging Science St Mary’s Hospital Manchester Ian J. Jacobs EGA Institute of Women’s Health University College London London John Latimer Department of Gynaecological Oncology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust and University of Cambridge Cambridge Ranjit Manchanda Department of Gynaecological Oncology Institute of Women’s Health University College London London

List of contributors

Anjum Memon Brighton and Sussex Medical School Falmer Sussex Evis Sala Department of Radiology University of Cambridge School of Clinical Medicine Cambridge Neil J. Sebire Department of Histopathology Great Ormond Street Hospital and Trophoblastic Disease Unit Charing Cross Hospital London Michael J. Seckl Trophoblastic Disease Unit Department of Medical Oncology Charing Cross Hospital London

Mahmood I. Shafi Department of Gynaecological Oncology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge Li Tee Tan Oncology Centre Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge Yin-Ling Woo Department of Gynaecological Oncology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge

ix

Preface The management of gynaecological cancers has seen considerable changes over recent years. We now have a greater understanding of cancer epidemiology and significant advances have been made in genetics/screening. The approach to women with cancer has become multidisciplinary, with many professionals contributing to the excellent care and outcome that we wish to see for those individuals we are privileged to look after. Women with gynaecological cancers have general as well as specific issues and these are addressed by the various experts who have contributed to this book. The overall desire for a holistic approach should be evident in trying to address these issues. This book is aimed at trainees in gynaecology and oncology as well as consultants with an interest in cancer care. Allied medical staff, palliative services and nurse specialists will also find it a useful adjunct to getting current information on the whole range of gynaecological oncology. Chapters 1–8 and 15 cover the broad issues in gynaecological oncology, while Chapters 9–14 discuss in some detail the issues in relation to site-specific gynaecological cancers. The further reading sections at the end of each chapter are intended to guide the interested reader wishing to seek detailed information relating to the issues covered in the chapters. Our task in editing this handbook has been made enjoyable by the contributors who have provided material relating to their area of expertise. It has been a pleasure working with colleagues and friends whom we respect and admire.

Abbreviations ACE α-AFP ASCCP ASCUS ASR ASTEC BCC BEP BMI BRCA BSCCP BSO BT CA125 CA19.9 CEA CGIN CHM CIN CNS CO CSF CT CXR D&C DES DNA DVT EBRT ECX EMA EOC EP ER EUA FBC FDG FIGO FNA(C) FOV

actinomycin D, cyclophosphamide, etoposide alpha fetoprotein – tumour marker for hepatic and germ cell tumours American Society of Colposcopy and Cervical Pathology atypical Squamous Cells of Undetermined Significance age-standardized incidence (or mortality) rate A Study in the Treatment of Endometrial Cancer basal cell carcinoma bleomycin, etoposide, cis-platinum body mass index breast cancer-associated antigen British Society for Colposcopy and Cervical Pathology bilateral salpingo-oophorectomy brachytherapy cancer-associated antigen 125 – tumour marker for ovarian cancer cancer-associated antigen 19.9 – tumour marker for pancreatic cancer carcinoembryonic antigen – tumour marker for colon cancer cervical glandular intraepithelial neoplasia complete hydatidiform mole cervical intraepithelial neoplasia central nervous system cyclophosphamide and vincristine cerebrospinal fluid computed tomography chest X-ray dilatation and curettage diethylstilbestrol deoxyribonucleic acid deep vein thrombosis external beam radiotherapy epirubicin, cisplatin, oral capecitabine etoposide, methotrexate and actinomycin D epithelial ovarian cancer etoposide and cisplatin estrogen receptor examination under anaesthesia full blood count fluorine-18-fluoro-2-deoxy-d-glucose International Federation of Gynecology and Obstetrics fine needle aspirate (cytology) field of view

List of abbreviations

GA GCT GFR GnRH GOG GTD GTN GTT β-hCG hCG HDR HIV HNPCC HPF HPL HPV HRT IACR IARC ICD ICON IU IVU LA LDH LLETZ MAS MDSCR MDT MMMT MOGCT MR(I) MRC MTD NHSCSP NOS NSAID ONS PE PET PHM PMP POMB PPV PSTT PVB

general anaesthesia granulosa cell tumour glomerular filtration rate gonadotrophin releasing hormone Gynecologic Oncology Group gestational trophoblastic disease gestational trophoblastic neoplasia gestational trophoblastic tumour beta human chorionic gonadotrophin human chorionic gonadotrophin high dose rate human immunodeficiency virus hereditary non-polyposis colorectal cancer high power field human placental lactogen human papillomavirus hormone replacement therapy International Association of Cancer Registries International Agency for Research on Cancer International Classification of Disease International Collaborative Ovarian Neoplasm international units intravenous urogram local anaesthesia lactate dehydrogenase large loop excision of the transformation zone minimal access surgery minimum data set for cancer registration multidisciplinary team malignant mixed Müllerian tumour malignant ovarian germ cell tumour magnetic resonance (imaging) Medical Research Council maximum tolerated dose National Health Service Cervical Screening Programme not otherwise specified non-steroidal anti-inflammatory drug Office for National Statistics pulmonary embolism positron emission tomography partial hydatidiform mole pseudomyxoma peritonei cisplatin, vincristine, methotrexate, bleomycin positive predictive value placental site trophoblastic tumour cisplatin, vinblastine, bleomycin

xiii

List of abbreviations

RMI RRS SCC SCCA SCJ SIL SLCT SLND STI TAH TNM TP-TE TVS TZ USS VAC VaIN VIA VIAM VILI VIN VTE WHO YST

xiv

risk of malignancy index risk reduction surgery squamous cell carcinoma squamous cell carcinoma antigen squamo-columnar junction squamous intraepithelial lesion Sertoli–Leydig cell tumour sentinel lymph node dissection sexually transmitted infection total abdominal hysterectomy Tumour, Node, Metastases (staging system) paclitaxel, cisplatin alternating with paclitaxel, etoposide transvaginal scan transformation zone ultrasound scan vincristine, doxorubicin (adriamycin), cyclophosphamide vaginal intraepithelial neoplasia visual inspection with acetic acid visual inspection with acetic acid and magnification visual inspection with Lugol’s iodine vulval intraepithelial neoplasia venous thromboembolism World Health Organization yolk sac tumour

1

Chapter

Epidemiology of gynaecological cancers Anjum Memon

Introduction Gynaecological cancers encompass a diverse group of tumours with different epidemiological and pathological features, clinical presentations and treatment strategies. This chapter aims to provide an overview of basic concepts in cancer epidemiology and to describe the global patterns and trends in incidence and mortality, aetiology and prevention of the five main types of gynaecological cancer.

What is epidemiology? Epidemiology is the basic science underpinning public health and clinical medicine. It describes the occurrence of health-related states or events (incidence, prevalence), quantifies the risk of disease (relative risk) and its outcome (prognosis, survival, mortality), and postulates causal mechanisms for disease in populations (aetiology, prevention). The main function of epidemiology is to provide evidence to guide public heath policy and clinical practice to protect, restore and promote health. The applications of epidemiology can be summarized as follows: *

*

*

*

*

*

To describe the spectrum and extent of disease in the population – e.g. what is the prevalence of human papillomavirus (HPV) infection among young girls? To identify factors that increase or decrease the risk of disease – e.g. what factors increase the risk of, or protect against, endometrial cancer? To study the natural history and prognosis of disease – e.g. does early diagnosis of cervical carcinoma in situ through cytological screening prevent future morbidity and improve survival? To monitor and predict disease trends in the population – e.g. what impact will the increasing prevalence of obesity in women have on future disease trends and healthcare needs? To provide evidence for developing public health policy and making regulatory decisions – e.g. will a smoking ban in public places promote smoking cessation and reduce the incidence of smoking-related disease? To evaluate the efficacy of preventive and therapeutic interventions – e.g. does postmenopausal hormone replacement therapy (HRT) do more harm than good?

Gynaecological Oncology, eds. Mahmood I. Shafi, Helena M. Earl and Li Tee Tan. Published by Cambridge University Press. © Cambridge University Press 2010.

Chapter 1: Epidemiology of gynaecological cancers

*

*

To evaluate public health programmes – e.g. will the mandatory vaccination of school girls against oncogenic HPV prevent vulvar/vaginal/cervical cancers and save lives? To evaluate the effectiveness of health services – e.g. are known contacts of people with sexually transmitted diseases (STDs) followed up and treated?

Classification of gynaecological cancers *

*

*

The International Classification of Diseases (ICD): this is the global standard diagnostic classification for epidemiological, clinical and health service data. It is used by hospital records departments, cancer registries and government agencies responsible for collection of health statistics (e.g. the Office for National Statistics in the UK) to classify diseases and other health problems recorded on many types of health and vital records. The ICD is essential for compilation of morbidity (e.g. cancer incidence) and mortality statistics (e.g. underlying cause of death) and allows comparison at an international level of health data collected in different countries at different times. In the Tenth Revision of the ICD (ICD-10), the malignant neoplasms of female genital organs are coded from C51 to C58. The category C57 includes neoplasms of the fallopian tube, broad and round ligaments, uterine adnexa and overlapping lesions (e.g. tubo-ovarian) (Table 1.1). The International Classification of Diseases for Oncology (ICD-O-3): this is used principally by cancer registries for coding the site (topography) and the histology (morphology) of neoplasms, usually obtained from a pathology report. The Tumour Node Metastasis Classification of Malignant Tumours (TNM-6): this is a cancer staging system used for describing the anatomical extent of cancer (see Appendix 3). It is based on the assessment of three components: T – describes the extent of the primary tumour; N – describes the absence/presence and extent of regional lymph node involvement/metastasis; and M – describes the absence/presence of distant metastasis. The classification is used to: (i) aid the clinician in the planning of treatment; (ii) assist in evaluation of the results of treatment; (iii) give some indication of prognosis; and (iv) facilitate the exchange of information between treatment centres. The TNM system is approved by the International Federation of Gynecology and Obstetrics (FIGO), and its categories have been defined to correspond to the FIGO classification.

Measuring the risk or burden of gynaecological cancers Incidence Incidence (or incident cases) is a count of new cases of cancer in the population during a specified time period. The incidence rate is the number of new cases of cancer in a defined population within a specified time period (usually a calendar year), divided by the total number of people in that population. Cancer incidence rates are typically expressed as per 100 000 population. Incidence rate measures the rapidity (or ‘speed’) at which new cases of cancer are occurring in the population within a specified time period. Increase in incidence of a cancer in the population can be due to: in-migration of susceptible people, a change in diagnostic criteria, improved case ascertainment, introduction of a new screening/diagnostic test, introduction of new, or changes in exposure to, existing aetiologic agent(s). Incidence rate is used to: predict

2

Chapter 1: Epidemiology of gynaecological cancers

Table 1.1 ICD-10 codes and morphological classification of malignant neoplasms of female genital organs

ICD-10 code

Organ

Morphological subtypes

C51

Vulva

Squamous cell carcinoma Extramammary Paget’s disease Malignant melanoma

C52

Vagina

Squamous cell carcinoma Adenocarcinoma, botryoid Rhabdomyosarcoma

C53

Cervix uteri

Squamous cell carcinoma Neuroendocrine carcinoma Adenocarcinoma

C54

Corpus uteri

Endometrial adenocarcinoma Malignant mixed Müllerian tumours Leiomyosarcoma

C55

Uterus (part unspecified)

C56

Ovary

Surface epithelial tumours Serous adenocarcinoma Endometrioid adenocarcinoma Mucinous adenocarcinoma Clear cell carcinoma Germ cell tumours Dysgerminoma Yolk sac tumour Choriocarcinoma Mature and immature teratoma Sex cord-stromal tumours Granulosa cell tumour Sertoli–Leydig cell tumour

C57

Other and unspecified female genital organs

C58

Placenta

Hydatidiform mole Placental site trophoblastic tumour Choriocarcinoma

the average risk of developing cancer; research causes and treatment of cancer; describe trends of cancer over time; and evaluate the effectiveness of prevention programmes.

Age-standardized incidence (or mortality) rate (ASR) As the risk of cancer increases exponentially with age, the crude incidence rate, which is influenced by the population age structure, cannot be used to evaluate whether the risk/

3

Chapter 1: Epidemiology of gynaecological cancers

burden of cancer differs between populations. It is therefore necessary to use ASRs when comparing rates of populations that have different age structures. The ASR is obtained by applying the (crude) age-specific rates in the observed population to the age-specific population counts (or weights) of a fixed reference (or standard) population. The most commonly used standard population is the world (and also European) standard population of Doll. Age-standardization controls for the confounding effect of age on cancer incidence and allows direct comparison of different populations.

Cumulative incidence (or cumulative risk) Cumulative incidence is the probability or risk of developing cancer during a specified period (e.g. lifetime). It measures the number or proportion of people (out of 100 or 1000) who would be expected to develop a particular cancer by the age of 64 (or 74) years if they had the rates of cancer currently observed. Like the ASR, cumulative incidence permits comparisons among populations of different age structures. For example, the cumulative risk of a woman in the UK developing ovarian cancer by age 74 is 14 per 1000, which can be interpreted as a 1.4% (1 in 71) probability or (lifetime) risk of developing ovarian cancer by the time she completes 74 years.

Prevalence Prevalence is the number of existing cases of cancer in a defined population at a notional point in time, divided by the total number of people in the population at that time. It is usually expressed as an absolute number of existing cases or as the proportion of a population that has the disease. For example, the prevalence of cervical cancer can be defined as the number of women in a defined population who have been diagnosed as having the cancer, and who are still alive at a given point in time. Mathematically, prevalence can be defined as follows: let a = the number of individuals in the population with the disease at a given time let b = the number of individuals in the population without the disease at a given time then prevalence ¼

a aþb

Thus prevalence is a measure of the burden of cancer in the population. The prevalence of a cancer in the population can increase due to: in-migration of cases, increase in incidence and/or improved prognosis/survival (e.g. due to better treatment). Prevalence data are used for planning health services, resource allocation and organization of prevention programmes.

4

*

Partial prevalence is the estimation of the number of cases of cancer diagnosed within one, three and five years to indicate the number of patients undergoing initial treatment (cases within one year of diagnosis), clinical follow-up (within three years) or not considered cured (before five years). Patients alive five years after diagnosis are usually considered cured because, for most cancers, the death rates among such patients are similar to those in the general population.

*

Complete prevalence represents the proportion of patients alive on a certain day who previously had a diagnosis of cancer, regardless of how long ago the diagnosis was, or if the patient is still under treatment or is considered cured.

Chapter 1: Epidemiology of gynaecological cancers

Survival Survival is the proportion (%) of people still alive one, three, five and 10 years after they have been diagnosed as having cancer. This observed survival probability is influenced by mortality both from the cancer itself and from other causes. For this reason, relative survival (%) is usually calculated (ratio of the observed survival in a particular group of patients to the survival expected in a group of people in the general population).

Quality-adjusted life-years (lost)/disability-adjusted life-years (lost) Quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) quantify the spectrum of morbidity (between the diagnosis and cure/death) due to cancer in terms of its duration and severity. The calculation of these indices requires three elements: the incidence of cancer, its mean duration (survival probability) and a measure of life ‘quality’ between the diagnosis and cure/death. These indices are used to estimate the impact of cancer on the individual and society, and for establishing priorities for healthcare programmes.

Mortality Mortality is the number of deaths occurring, and mortality rate is the number of deaths in a defined population within a specified time period (usually a calendar year), divided by the total number of persons in that population. Cancer mortality rates are expressed as per 100 000 persons per year. Mortality is the product of the incidence and the fatality of a given cancer, and measures the average risk to the population of dying from a specific cancer within a specified period. Fatality, the complement of per cent survival, is the probability (%) that a cancer patient will die from the disease.

Cancer screening Screening is the presumptive identification of an unrecognized disease or defect by the application of tests, examinations or other procedures that can be applied rapidly. Cancer screening is the testing of apparently healthy volunteers from the general population for the purpose of separating them into high and low probabilities of having a given cancer. The rationale behind cancer screening is that the disease has a natural history that includes a clearly defined preclinical phase with biological characteristics, which allows for detection of the disease in an early treatable stage that, in turn, will reduce the risk of future morbidity and improve survival (e.g. cytological screening for carcinoma in situ of uterine cervix → intervene with surgery → cure/reduced risk of invasive cervical cancer). Randomized controlled trials and both case–control and cohort observational study designs are used to evaluate cancer screening programmes. The performance of a screening test is based on its sensitivity, specificity and predictive value (Table 1.2). *

*

Sensitivity – this is the ability of the test to identify correctly those who have the disease (true positives). Specificity – this is the ability of the test to identify correctly those who do not have the disease (true negatives).

5

Chapter 1: Epidemiology of gynaecological cancers

Table 1.2 Calculation of sensitivity, specificity and predictive value of a screening test

Disease according to gold standard

Screening test result

Positive

Present

Absent

Total

A (True +)

B (False +)

A+B

Negative

C (False −)

D (True −)

C+D

Total

A+C

B+D

A+B+C+D

Sensitivity = A/(A + C) × 100 (%) Specificity = D/(B + D) × 100 (%) Positive predictive value = A/(A + B) × 100 (%) Negative predictive value = D/(C + D) × 100 (%) Prevalence of disease = A + C/(A + B + C + D) × 100 (%)

*

*

Positive predictive value (PPV) – this is the proportion of individuals who test positive and actually have the disease. PPV is a function of sensitivity, specificity and disease prevalence. A high PPV is essential for a successful screening programme, whereas a low PPV implies that resources are being wasted on diagnostic follow-ups of false-positive individuals. Negative predictive value – this is the proportion of individuals who test negative and actually do not have the disease.

Ovarian cancer Incidence and mortality Worldwide, ovarian cancer is the sixth most common cancer among women, with an estimated 204 000 new cases (4% of cancer in women) and 125 000 deaths (4.3% of cancer deaths in women) in the year 2002 and a five-year prevalence of 538 000 cases. The incidence rates of ovarian cancer vary from a low of about 2 per 100 000 women in Algeria to a high of 15 per 100 000 in Poland. In general, incidence rates are relatively higher in developed countries – the highest rates are observed in European populations – followed by the Philippines and Brazil (11–15/100 000 women), intermediate rates are observed in North America, Australia/New Zealand and some populations in Asia and South America, and the lowest rates (2–7/100 000 women) are observed in Africa, the Caribbean, the Middle East and parts of Asia. Evidence from the USA suggests that ovarian cancer is relatively more common in white than in black women (10.6 vs. 7.2/100 000 women). In the UK, ovarian cancer is the most common gynaecological cancer. It is the fourth most common cancer among women, with 6615 new cases in the year 2004 accounting for around 5% of all cancers in women, with a cumulative risk of 0.8% (1 in 125) by age 64 (Fig. 1.1). In most European populations, the incidence rates of ovarian cancer generally increase exponentially with age, with a sharp increase after about 40 years. It is predominantly a disease of older, postmenopausal women – almost 85% of cases occur in women aged over 50 (Fig. 1.2). In developed countries, the mortality/incidence ratio is 56% and ovarian cancer accounts for more deaths than all the other gynaecological cancers

6

Chapter 1: Epidemiology of gynaecological cancers

Breast

31

Colorectal

12

Lung

11

Ovary

5

Uterine corpus

5

Malignant melanoma

3

Non-Hodgkin’s

3

Type of cancer (%)

Pancreas

3

Stomach

2

Leukaemia

2

Bladder

2

Uterine cervix

2

Oesophagus

2

Kidney

2

Brain, CNS

1

Multiple myeloma

1

Oral

1

Thyroid

1

Liver

1

Vulva

1

0%

5%

10%

15%

20%

25%

30%

35%

Fig. 1.1 Frequency distribution (%) of the 20 most common cancers in women (UK, 2004).

put together. In 2005, 4447 women in the UK died from ovarian cancer, accounting for around 6% of all female deaths from cancer. Ovarian cancer has a relatively poor prognosis as most cases (about 75%) are diagnosed at an advanced stage – with overall survival rates of about 30–40%. When diagnosed at the localized stage, the five-year relative survival rate is about 75%.

Trends in incidence and mortality In most developed countries there has been little change in the incidence of ovarian cancer over the past 40 or so years. In the UK, the age-standardized (European standard) incidence rates of ovarian cancer increased by 16% during the period 1975–2004 (from 14.7/100 000 to 17.1/100 000 women). Most of this increase was observed in women aged over 65, in whom the rates increased by 48% during that period. The incidence in younger women has

7

Chapter 1: Epidemiology of gynaecological cancers

Uterine cervix

Uterine Corpus

Ovary

Vulva

Vagina

70

60

Rate per 100 000

50

40

30

20

10

0 0–

5– 10– 15– 20– 25– 30– 35– 40– 45– 50– 55– 60– 65– 70– 75– 80– 85+ Age at diagnosis (years)

Fig. 1.2 Age-specific incidence rates of gynaecological cancers (West Midlands, UK, 1998–2002). (Source: Curado MP, Edwards B, Shin HR, et al., 2007.

remained fairly stable or may be declining – which in part is owing to the protective effects of oral contraceptives widely used by younger women. In most populations, mortality rates have remained fairly stable or declined slightly over the past 40 years. In the UK, the agestandardized (European standard) mortality rates have remained stable over this period at between 10/100 000 and 12/100 000 women.

Aetiology Compared with other gynaecological cancers, little is known about the aetiology of ovarian cancer. In most studies, family history of ovarian cancer has been associated with an increased risk, whereas oral contraceptive use, increased parity, breastfeeding, tubal ligation and hysterectomy have been associated with decreased risk.

Prevention Apart from prophylactic oophorectomy, oral contraception and (possibly) tubal ligation, there are few readily modifiable risk factors for ovarian cancer. There is currently inconsistent evidence for a possible increase in risk with consumption of lactose/galactosecontaining foods, intake of saturated or animal fats and use of perineal talcum powder and postmenopausal HRT, and for a decrease in risk with consumption of vegetables. It is unclear whether obesity, body mass index (BMI) and physical activity influence ovarian cancer risk.

8

Chapter 1: Epidemiology of gynaecological cancers

Endometrial cancer Incidence and mortality Worldwide, endometrial cancer is the seventh most common cancer among women, with an estimated 199 000 new cases (3.9% of cancer in women) and 50 000 deaths (1.7% of cancer deaths in women) in the year 2002 and a five-year prevalence of 776 000 cases. In contrast with cervical cancer, endometrial cancer is relatively more common in developed countries. About 69% of the cases occur in developed countries where it accounts for 5.9% of all cancers in women, with a cumulative risk of 1.3% (1 in 77) by age 64. In developing countries, endometrial cancer accounts for only 2.3% of cancers in women, with a cumulative risk of 0.2% (1 in 500) by age 64. In the UK, endometrial cancer is the fifth most common cancer among women, with 6438 new cases in the year 2004 accounting for around 5% of all cancers in women, with a cumulative risk of 0.8% (1 in 125) by age 64 (Fig. 1.1). In most European populations, the incidence rates of endometrial cancer begin to rise steadily 5–10 years before the menopause and reach a peak usually around 65–70 years (Fig. 1.2). It is a cancer of postmenopausal women – over 90% of cases occur in women aged 50 or older, with very few cases diagnosed under the age of 35. The incidence rates of endometrial cancer vary from a low of 0.9 per 100 000 women in Oman to a high of 18.8 per 100 000 in white women in the USA . The highest rates are observed among women in North America, Europe, Australia/ New Zealand and Israel. Incidence rates are generally low in countries in Latin America, Asia (including China and Japan) and Africa. Evidence from the USA suggests that endometrial cancer is considerably more common in white than in black women (18.8 vs. 13.5/100 000 women). Mortality rates are substantially lower than the incidence. Worldwide, the mortality/incidence ratio is 25%. In Europe, the cumulative mortality rates are generally three to four times lower than the incidence; in North America, these rates are about eight times lower. Endometrial cancer has a relatively better prognosis than cervical cancer, with fiveyear survival rates of 86% in the USA and 78% in European cancer registries.

Trends in incidence and mortality The trends in incidence of endometrial cancer have varied among populations and by age groups over the past 40 or so years. In the UK, the overall incidence (i.e. all ages combined) remained stable between 1975 and 1992, and then increased by 24% between 1993 and 2004. Most of this increase has occurred in older women – since the mid 1980s, there has been a steady increase in incidence among women aged over 60. Generally, similar trends in incidence are observed in most other European countries. The mortality rates, however, have steadily declined in most developed countries over this time period. In the UK, the agestandardized (European standard) mortality rates decreased by 27% between 1971 and 2005 (from 4.8/100 000 to 3.5/100 000).

Aetiology In contrast with cervical cancer, which is a model of viral carcinogenesis, endometrial cancer is a model of hormonal carcinogenesis. The 10-fold variation in age-standardized incidence rates across populations point to the role of modifiable factors in the aetiology of endometrial cancer. Among these, oestrogens and progestins are considered to have an important role in malignant transformation. The most compelling evidence has come from studies of HRT

9

Chapter 1: Epidemiology of gynaecological cancers

following the menopause – unopposed oestrogen use for 10 or more years increases the risk about 10-fold. This excess risk can be counteracted substantially by combined use of oestrogens and progestins.

Prevention Obesity (which increases peripheral production of oestrogens) and diabetes mellitus are associated with an increased risk of developing endometrial cancer, whereas past oral contraceptive use, childbearing and physical activity (potentially mediated by hormones) are associated with risk reduction. It is therefore possible to substantially reduce the incidence of endometrial cancer through modification of lifestyle, maintenance of normal weight and optimal use of oral contraceptives and postmenopausal HRT.

Cervical cancer Incidence and mortality Worldwide, cervical cancer is the second most common cancer among women, with an estimated 493 000 new cases (or 9.7% of cancer in women) and 274 000 deaths (or 9.3% of cancer deaths in women) in the year 2002 and a five-year prevalence of 1.4 million cases. About 83% of the cases occur in developing countries, where cervical cancer accounts for 15% of all cancers in women, with a cumulative risk of 1.5% (1 in 67) by age 64. In developed countries, cervical cancer accounts for only 3.6% of cancers in women, with a cumulative risk of 0.8% (1 in 125) by age 64. In the UK, 2726 new cases of cervical cancer were diagnosed in the year 2004, accounting for around 2% of all cancers in women, with a cumulative risk of 0.6% (1 in 167) by age 64 (Fig. 1.1). In most European populations, the incidence of cervical cancer begins to increase at 20–24 years and the risk increases rapidly to reach a peak usually around 35–39 years (Fig. 1.2). The incidence rates of cervical cancer vary substantially between different regions, from a low of 2.8 per 100 000 women in China to a high of 47.3 per 100 000 in Zimbabwe. The highest rates are observed among the populations of sub-Saharan Africa, Melanesia, Latin America and the Caribbean, and south-central and south-east Asia. Incidence rates are generally low in developed countries in Europe, North America, Australia/New Zealand, the Middle East, China and Japan. Mortality rates are substantially lower than the incidence. Worldwide, the mortality/ incidence ratio is 55%. Five-year relative survival rates vary between regions and according to the extent of the disease (15–80%), with good prognosis in countries with a low incidence (63% in the European cancer registries).

Trends in incidence and mortality Overall, incidence and mortality have declined considerably during the past 40 years in Western Europe, North America, Australia/New Zealand, China and Japan. The decline has been attributed to a combination of factors, including improved genital hygiene, improved treatment modalities and the beneficial effects of organized population-based cytological screening programmes. In the UK, the age-standardized (European standard) incidence rates of cervical cancer declined by around 46% during the period 1975–2004 (from 14.9/100 000 to 8.0/100 000), whereas, in the same period, the mortality rates declined by around 63% (from 7.5/100 000 to 2.8/100 000).

10

Chapter 1: Epidemiology of gynaecological cancers

Aetiology A persistent infection with an oncogenic HPV type is now recognized as a causal factor for preceding precancerous changes and cervical cancer. However, infection with HPV is extremely common compared with the relatively rare development of cervical cancer. There is compelling evidence that HPV is necessary for cervical carcinogenesis, but infection alone is not sufficient for the cancer to develop. A number of co-factors have been identified as possible modifiers of HPV infection during the developmental stages of cervical cancer, including early sexual debut, increasing number of sexual partners, smoking, long-term oral contraceptive use, high parity, dietary factors, certain human leucocyte antigen (HLA) types and co-infection with other sexually transmitted agents such as Chlamydia trachomatis, herpesvirus type 2 and the human immunodeficiency virus (HIV).

Prevention Increased public awareness about sexually transmitted infections, early detection of precursor lesions by regular cytological screening, HPV testing and the recently developed vaccine against certain high-risk types of HPV makes cervical cancer one of the most preventable forms of cancer, on a global scale.

Vulvar and vaginal cancers Incidence and mortality Vulvar and vaginal cancers are rare throughout the world, and constitute less than 5% of all gynaecological cancers. The incidence rates of vulvar cancer vary from a low of 0.2 per 100 000 women in Japan to a high of 2.0 per 100 000 in Peru. In general, incidence rates are relatively higher in developed countries – the highest rates are observed in some European populations and in white women in the USA, followed by Peru and Brazil. The lowest rates (35 U/ml, with elevated levels found in 50% of women with stage I disease and over 90% of women with stage II–IV disease. CA125 levels are less frequently elevated in mucinous and borderline tumours compared with serous tumours. However, the levels can also be elevated in other malignancies, pregnancy, inflammatory disorders, non-gynaecological diseases (such as pancreatitis, hepatitis, cirrhosis, ascites and tuberculosis) and benign gynaecological conditions (such as endometriosis, fibroids, infections and pelvic inflammatory disease).

Improving CA125 sensitivity and specificity A specificity of 97% and positive predictive value (PPV) of 4.6% was achieved using CA125 (30 U/ml) in a prospective ovarian cancer screening study of 5550 volunteers aged over 50. Specificity of screening with CA125 was initially improved by the addition of pelvic ultrasound as a second-line test to assess ovarian volume and morphology. Transvaginal ultrasound is preferred to transabdominal ultrasound because of its better resolution, which

16

Chapter 2: Screening and prevention

allows more accurate assessment of ovarian morphology, and the lack of need for a full bladder. Persistence of abnormalities on repeat scanning four to six weeks following initial detection helps reduce false positive rates. A multimodal screening approach incorporating sequential CA125 measurements and pelvic ultrasound achieved a specificity of 99.9% and PPV of 26.8% (approximately four operations for each cancer) for detection of ovarian and fallopian tube cancer in 22 000 postmenopausal women. Further improvements in screening performance have been possible with the development of the statistical ‘risk of ovarian cancer’ algorithm (ROCA), which incorporates patient age and the rate of change of absolute CA125 values over time. The ROCA increases the sensitivity of CA125 compared with a single cut-off value because women with normal but rising levels are identified as being at increased risk. At the same time, specificity is improved, as women with static but elevated levels are now classified as low risk. For a target specificity of 98%, the ROCA calculation achieved a sensitivity of 86% for preclinical detection of ovarian cancer.

Improving discriminatory ability for benign and malignant adnexal masses Accurate ability to distinguish benign from malignant tumours is the key to avoiding unnecessary operations in women with benign lesions and planning appropriate surgery by gynae-oncologists in tertiary care centres for those with cancer. Using an upper limit of 35 U/ml for CA125, a sensitivity of 78%, specificity of 95% and PPV of 82% can be achieved for ovarian cancer. Using additional markers or artificial neural networks for interpretation can further increase sensitivity and specificity over CA125 alone. Various tumour marker panels have been reported to be better than CA125 alone: CA125, CA 72–4, CA 15–3 and lipid-associated sialic acid; leptin, prolactin, osteopontin, macrophage inhibitory factor, insulin growth factor (IGF)-II and CA125; CA125, SMRP, HE4, CA72–4, activin, inhibin, osteopontin, epidermal growth factor (EGFR) and ERBB2 (Her2). HE4 is emerging as a promising marker, with a combination of CA125 and HE4 having been shown to be a better predictor (sensitivity 76.4%, specificity 95%) than either marker alone. A recent report indicates it may hold promise for early-stage disease. The ‘risk of malignancy index’ (RMI), which combines serum CA125 values with ultrasound-based ovarian morphology and menopausal status, is a widely used discriminatory tool, which has been validated prospectively and retrospectively in gynaecological oncology and general gynaecological units. The risk score has a sensitivity of 85% and a specificity of 97%. It performs as well as most logistic regression or artificial neural network models. Women with an elevated RMI score have been shown to have, on average, a 42-fold increase in the background risk of ovarian cancer. The score’s sensitivity can be further increased by increasing the RMI cut-off and using artificial neural networks. Addition of specialist ultrasound, assessment for an ‘ovarian crescent sign’ and MRI further improves accuracy. The International Ovarian Tumour Analysis (IOTA) researchers recently reported an ultrasound-based pattern recognition model for discriminating benign from malignant ovarian masses, which they found to be superior to CA125 alone.

Screening trials An initial randomised trial in 21 935 women with ovarian cancer showed a markedly better median survival in women who underwent screening (72.9 months) compared with those who did not (41.8 months). Subsequently, a number of prospective trials have used CA125 alone or in combination with ultrasound to screen for ovarian cancer.

17

Chapter 2: Screening and prevention

Two large randomised controlled trials (RCTs) – the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) (www.ukctocs.org.uk) and the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) – in the USA are evaluating the impact of screening on ovarian cancer mortality in the postmenopausal population. In the UKCTOCS trial over 200 000 postmenopausal women are being randomised to annual screening with CA125 (multimodal) or transvaginal ultrasound (TVS) and control groups. The ROC algorithm is used to triage women into low-, intermediate- and elevated-risk categories based on their CA125 result. Intermediate-risk women have repeat CA125 screening in six to eight weeks, while those with elevated risk are referred for a TVS. An abnormal TVS leads to gynaecological assessment with a view to surgery. As the efficacy of the ROC algorithm in detecting early-stage disease is still a matter of research, the trial is also evaluating TVS alone as a firstline test for screening. In the PLCO trial, 78 000 postmenopausal women have been randomised to either screening with clinical examination, ultrasound and CA125 or to a control group. Any abnormal test leads to gynaecological assessment and further investigation. The recently published prevalence screen results of another study in 28 816 screened women included 29 cancers, of which 20 were invasive and 9 were borderline. The PPV for invasive cancer was 3.7%, 1% and 23.5% for abnormal CA125, TVS and both CA125 and TVS, respectively. A large Japanese RCT in which an annual ultrasound and absolute CA125based strategy was used in 82 487 low-risk postmenopausal women did not find a significant difference in the number of ovarian cancers detected in the screened arm (n = 27) and those occurring in the control arm (n = 32). Eight additional interval cancers occurred in the screened arm. The proportion of early-stage cancers was greater in the screened (63%) than the control group (38%). In the reproductive age group, screening for ovarian cancer is limited to research trials involving women at risk for familial ovarian cancer. These women belong to high-risk cancer families and many carry BRCA or mismatch repair gene (MMR) mutations. The sensitivity and effectiveness of screening in this younger population is still not established. Further, multifocal primary peritoneal cancer is considered to be a phenotypic variant of familial ovarian cancer and both CA125 and ultrasound are not reliable for detecting early-stage disease. Most studies have used a combination of absolute CA125 levels and ultrasound. Annual screening using this modality is not effective in detecting early-stage disease. A modified premenopausal version of the ROC algorithm is being piloted in phase II of the UK Familial Ovarian Cancer Screening Study (UKFOCSS) and in the Cancer Genetics Network (CGN) and Gynecologic Oncology Group (GOG) trials in the USA. These trials are evaluating more frequent three- to four-monthly screening. Preliminary results are available for the CGN trial, on 2343 high-risk women screened at three-monthly intervals. Thirty-eight women underwent surgery following 6284 screens. Five ovarian cancers were detected, two prevalent (one early, one late stage) and three incident (three early) cases, resulting in a PPV of 13%. The impact of ovarian cancer screening on mortality and the proportion of early cancers it will detect are not yet known. In addition, it is not known whether the screen-detected early-stage disease includes a significant number of high-grade serous carcinomas or just the cancers with better histological prognosis. The current recommendation following international consensus is that screening should only be carried out within the context of a clinical trial. The ongoing trials are expected to report after 2012 and should help address the above issues.

18

Chapter 2: Screening and prevention

Prevention A number of factors, such as early menarche, sub-fertility, obesity, hormone replacement therapy, smoking and nulliparity, have been linked to an increase risk of ovarian cancer. Pregnancy, breastfeeding (relative risk [RR] 0.5–0.7), taking the contraceptive pill (odds ratio [OR] 0.4–0.6), being sterilized/having a hysterectomy (OR 0.5–0.7) and a diet rich in carotenoids (found in carrots and tomatoes) can reduce the risk of ovarian cancer. The benefit gained by taking the contraceptive pill is cumulative and lasts well beyond the period of use. Although data on the benefit of physical exercise in preventing ovarian cancer are inconsistent, a number of studies suggest that it may have a modest protective effect.

Familial risk Most cancers are sporadic but up to 10% are associated with an inheritable genetic predisposition. Inherited mutations in the BRCA1, BRCA2 and MMR genes account for most of the known hereditary risk of breast, ovarian and endometrial cancer. MMR gene mutations are dealt with in a later section of this chapter. The prevalence of BRCA mutations in the general population is around 1 in 400 to 1 in 800. These mutations are found to occur more frequently in Ashkenazi Jews, and certain other population groups such as the Icelandic, Norwegian and Swedish communities. Three ‘founder’ mutations, two in BRCA1 (185delAG and 5382insC) and one in BRCA2 (6174delT), account for most of the BRCA-related risk in the Ashkenazi Jew population. These gene mutations are called ‘founder mutations’ because they are present in the population at an increased frequency (1 in 40) by virtue of having existed in a small isolated group of ‘founders’, who were the ancestors of most of the individuals in the present day population. BRCA mutation carriers have an increased risk for developing breast, ovarian, prostate and pancreatic cancer. Male breast cancer, prostate cancer and pancreatic cancer is linked more to BRCA2 than BRCA1 gene mutations. A recently published meta-analysis calculated the cumulative cancer risks for BRCA1 and BRCA2 mutations carriers at age 70 to be 57% and 49% for breast cancer and 40% and 18% for ovarian cancer, respectively. Much higher penetrance – over 80% for breast cancer and over 50% for ovarian cancer – has been documented in mutation carriers ascertained from high-risk families with multiple cancer cases. A number of risk models use family history-based criteria to predict carrier probability and identify these high-risk individuals. The criteria used by the UKFOCSS trial to identify women at high risk for ovarian cancer are given in Table 2.2. Individuals from high-risk families are managed in special carrier clinics by a multidisciplinary team consisting of clinical geneticists, gynae-oncologists, breast surgeons and psychologists with a special interest in familial cancer. They undergo extensive counselling regarding cancer risk, predictive gene testing and preventive options, which include screening/surgery and lifestyle issues. The decision-making process is complex and tailored to each patient.

Risk-reducing salpingo-oophorectomy Surgical removal of the fallopian tubes and ovaries can prevent cancer arising in the ovary or the tubes. However, a 2–4% residual risk of primary peritoneal cancer remains. Riskreducing salpingo-oophorectomy (RRSO) is an option offered to women at high risk (greater than 10% lifetime risk) for ovarian cancer and is usually performed laparoscopically. RRSO also decreases the risk of breast cancer by about 50% in premenopausal women. Preliminary

19

Chapter 2: Screening and prevention

Table 2.2 Criteria to identify high-risk families (used by UKFOCSS)

Volunteer/proband should either have been affected by cancer or be an FDR of an affected family member. Families with ovariana or ovariana and breast cancer Families with only breast cancer 1. ≥2 individuals with ovarian cancer who are FDRs

1. ≥4 breast cancers

2. One ovarian cancer and 1 breast cancer 1.0 mma, confined to the vulva or perineum, with negative nodes

Stage II

Tumour on any size with extension to adjacent perineal structures (⅓ lower urethra, ⅓ lower vagina, anus) with negative nodes

Stage III

Tumour of any size with or without extension to adjacent perineal structures (⅓ lower urethra, ⅓ lower vagina, anus) with positive inguinofemoral lymph nodes

Stage IIIA

(i)

With 1 lymph node metastasis (≥5 mm), or

(ii) 1–2 lymph node metastasis(es) (6 months from termination of antecedent pregnancy. The following factors should be considered and noted in reporting: Prior chemotherapy has been given for known gestational trophoblastic tumour. Placental site tumours should be reported separately. Histological verification of disease is not required.

222

Appendix 4: Useful websites ASCCP: www.asccp.org American Society for Colposcopy and Cervical Pathology BAAF: www.baaf.org.uk British Association of Adoption and Fostering BACKUP: www.cancerbackup.org.uk/Home Cancer Backup, MacMillan Cancer Support BASRT: www.basrt.org.uk British Association for Sexual and Relationship Therapy BGCS: www.bgcs.org.uk British Gynaecological Cancer Society BSCCP: www.bsccp.org.uk British Society for Colposcopy and Cervical Pathology Cancer Couselling: www.cctrust.org.uk Cancer Counselling Trust Carers UK: www.carers.org Advice and support for carers COTS: www.surrogacy.org.uk Childlessness Overcome Through Surrogacy CRUK: www.cancerresearchuk.org Cancer Research UK CRUSE: www.crusebereavementcare.org.uk CRUSE bereavement care Daisy Chain: www.daisynetwork.org.uk Information related to premature menopause Dial UK: www.dialuk.org.uk Network of disability information and advice services FIGO: www.figo.org International Federation of Gynecology and Obstetrics GOG: www.gog.org Gynecologic Oncology Group IGCS: www.igcs.org International Gynecologic Cancer Society Infertility Network UK: www.infertilitynetworkuk.com Infertility support Jo’s Trust: www.jotrust.co.uk National support group and patient information related to both cervical cancer and precancer Look Good … Feel Better: www.lookgoodfeelbetter.co.uk Cancer support charity that helps women manage the visible side effects of cancer treatments Lymphoedema: www.lymphoedema.org Lymphoedema support network Macmillan Cancer Support: www.macmillan.org.uk Macmillan cancer support

Appendix 4: Useful websites

Maggie’s cancer caring centres: www.maggiescentres.org Helping people live with cancer Marie Curie Cancer Care: www.mariecurie.org.uk National Cancer Institute (NCI): www.cancer.gov National Cancer Research Institute (NCRI): www.ncri.org.uk National Osteoporosis Society: www.nos.org.uk Ovacome: www.ovacome.org.uk Support group for anyone affected by ovarian cancer Ovarian Cancer Action: www.ovarian.org.uk Ovarian cancer research and patient information RCOG: www.rcog.org.uk Royal College of Obstetricians and Gynaecologists SGO: www.sgo.org Society of Gynaecologic Oncologists Vulva Awareness Campaign Organisation (VACO): www.vaco.co.uk Vulval awareness organization

224

Index 3DCRT, see Three-dimensional conformal radiotherapy abdominal hysterectomy, 139 abdominal incisions, 73 abortions, 183 actinomycin D, 187, 190, 196 acute side effects of radiotherapy, 86 addresses, 223 adenocarcinomas, 39–40, 46, 147, 150 adenofibroma tumours, 42 adenoma malignum, 46 adenosarcoma tumours, 42 adenosquamous carcinomas, 46 adjuvant treatments aims, 200 chemotherapy, 94–6, 128, 144, 179 decision making, 200, 201 progestogens, 145 radiotherapy, 79, 142–3, 178 adnexal masses, 17, 52 Adriamycin, see doxorubicin advanced-stage disease factors, 126, 128–9, 156–9 aetiology cervical cancer, 11 endometrial cancer, 9, 133–4 ovarian cancer, 8 vaginal cancer, 12 vulval cancer, 12, 163–4 age-standardized incidence rates (ASR), 3 aggressive surgery, 130 alpha-fetoproteins, 193 American Society of Colposcopy and Cervical Pathology (ASCCP), 29 Amsterdam criteria, 22 anaemia, 151 anaesthesia, 165 analgesics, 106 anthracyclines, 93 antibiotic prophylaxis, 72 anti-emetics, 110

anti-metabolite drugs, 94 anxiety, 116–17 appendiceal mucinous tumours, 36 appendices, 207 ASCCP, see American Society of Colposcopy and Cervical Pathology Ashkenazi Jewish ethnicity, 20 ASR, see age-standardized incidence rates assays β-human chorionic gonadotrophin, 182–3 ASTEC (A Study in the Treatment of Endometrial Cancer), 140 autosomal dominant syndrome, 21 Bartholin’s glands, 48, 163, 173 basal cell carcinomas, 48, 163, 173 beam arrangement, 88 benign tumours, 17, 33, 36 Bethesda criteria, 22 bilateral salpingo-oophorectomy (BSO), 24, 139 bisphosphonate, 113 bladder surgery, 75 bleomycin, 195, 196 blue round-cell tumours, 176 bone pain management, 108 borderline tumours, 34, 36 bowel constipation, 104, 111–12 injuries/damage, 74 irritable bowel syndrome, 204 obstruction, 130 palliative care, 104 preparation for surgery, 71 toxicity, 204 brachytherapy (BT), 52, 82, 143, 172 BRCA gene mutations, 19, 120 breathlessness, 114 Brenner tumours, 37

British Society of Colposcopy and Cervical Pathology (BSCCP), 27 BSO, see bilateral salpingooophorectomy BT, see brachytherapy burden measurements, 2 CA125 tumour marker, 16–17, 52, 122–3, 193 cachexia, 114 caesarean section, 160 Cancer Genetics Network (CGN), 18 capecitabine, 94 carboplatin, 91–2, 96–7, 98, 128 carcinofibroma tumours, 42 carcinoma in situ (CIN), 25 catheters, 75 CEA tumour marker, 122 cerebral metastases, 190 cervical cancer, 147–61 adenocarcinoma, 150 advanced-stage disease, 156–9 chemotherapy, 153, 156, 160 computed tomography, 57, 66, 149, 159 decision making, 203 early-stage disease, 153–6 epidemiology, 10–11, 147 FDG-PET, 66 FDG-PET/CT, 65, 66 FIGO staging, 149, 151, 219–20 follow-up treatments, 159–60 HPV, 11 hysterectomy, 154–6 imaging, 61, 65, 66, 149, 152, 159 lymph nodes, 156 magnetic resonance imaging, 61, 66, 149, 152, 159 management, 152–61 pathology, 44–7, 148, 149–51

Index

cervical cancer (cont.) positron emission tomography, 159 pregnancy, 160 prevention, 29–30 prognostic variables, 151–2 radical surgery, 153–6 radiotherapy, 80, 153, 156–9 rare variants, 46 risk factors, 147 screening, 25–9, 147 special clinical situations, 160 staging, 149 surgery, 153–6 trachelectomy, 160 ultrasound imaging, 53 X-rays, 149 cervical intraepithelial neoplasia (CIN), 12 CGN, see Cancer Genetics Network (CGN) Charing Cross scoring, 186 chemosensitivity, 37 chemotherapy, 91–101 anti-metabolite drugs, 94 cervical cancer, 153, 156, 160 dose intensity, 97 endometrial cancer, 91, 100–1, 144 epithelial ovarian cancer, 91, 94–7 gestational trophoblastic disease, 190 hydatidiform moles, 184, 185 malignant ovarian germ cell tumours, 194–7 metastatic sarcomas, 179 modes of action, 91–101 oral chemotherapy, 93, 99 ovarian cancer, 91, 127, 128–9 patients’ expectations, 99 platinum-free intervals, 98 quality of life, 99 sarcomas, 179 topo-isomerase inhibitors, 93 toxicity, 99 types, 91–101 see also individual drugs chest radiography, 138, 183, 184 Chlamydia trachomatis, 11

226

chlorambucil, 99 choriocarcinomas, 187, 188, 190, 192, 193 CIN, see cervical intraepithelial neoplasia cisplatin, 79, 91–2, 96, 98 gestational trophoblastic disease, 190 ovarian cancer, 128 ovarian germ cell tumours, 195, 196 classification systems, 2, 134 clear cell carcinomas, 36, 40, 46, 47 clinical examinations, 149 clinical presentation choriocarcinoma, 188 endometrial cancer, 137 hydatidiform moles, 183–7 malignant ovarian germ cell tumours, 193 ovarian cancer, 121 sarcomas, 177 vulval cancer, 164–6 clinical trial phases, 207 colour Doppler analysis, 52 colposcopy, 25, 27, 28 Common Toxicity Criteria (CTC), 99 co-morbidity, 166 complete prevalence, 4 complex wounds, 113–14 computed tomography (CT), 51, 54–7 cervical cancer, 57, 66, 149, 159 endometrial cancer, 56, 65, 138 hydatidiform moles, 184 malignant ovarian germ cell tumours, 195 ovarian cancer, 54–6, 65, 127 sarcomas, 178 technique, 54 vaginal cancer, 67 vulval cancer, 57, 63, 67 see also flourine-18-fluoro-2deoxy-d-glucose positron emission tomography concomitant chemotherapy, 79 conformal radiotherapy, 89 conisation, 153 consent to surgery, 73 consolidation therapy, 129–30

constipation, 104, 111–12 continuous subcutaneous infusion (CSCI), 109 contraception, 25 corpus uteri cancer (uterine corpus cancer), 216–17 counselling, 72, 116–17 criteria of response, 207 CSCI, see continuous subcutaneous infusion CT, see computed tomography CTC, see Common Toxicity Criteria cumulative incidence, 4 cumulative risk, 4 cyclophosphamide, 96, 128, 196 cytological sampling, 24 cytoreduction, 126 D&C, see dilatation and curettage DALYs, see disability-adjusted life-years (lost) decision making, 199–205 clinical examples, 203–5 patient factors, 202–5 treatment aims, 200–1 treatment selection, 201–5 deconditioning, 114 degree of differentiation, 216 deoxyribonucleic acid (DNA), 24, 83, 93 depression, 116–17 DES, see diethylstilbestrol diagnosis constipation, 112 diagnostic laparoscopy, 77 hypercalcaemia, 113 ovarian cancer, 121 see also pathology diethylstilbestrol (DES), 47 difficult pain management, 107 dilatation and curettage (D&C), 184 disability-adjusted life-years (lost) (DALYs), 5 disseminated peritoneal adenomucinosis, 36 distress management, 104 DNA, see deoxyribonucleic acid docetaxel, 179 Doppler analysis, 24, 52, 184, 195

Index

dose factors, 84, 97 doxorubicin, 96, 128, 179 drip and suck, 109 drug development phases, 207 drug resistance, 185, 190 duration of chemotherapy, 97 dysgerminomas, 192 early-stage disease, 126, 128, 153–6 EBRT, see external beam radiotherapy ectopic implantation, 181 embolism, 189 embryonal carcinoma, 192 embryonal rhabdomyosarcomas, 176 en bloc excision, 169 endocrines, 101, 145, 179 endodermal sinus, 192 endometrial cancer, 133–46 adjuvant radiotherapy, 142–3 aetiology, 133–4 chemotherapy, 91, 100–1, 144 classification, 134 clinical presentation, 137 computed tomography, 56, 138 decision making, 204 endometrial sampling, 23–4 epidemiology, 9–10 FDG-PET, 65, 139 FIGO staging, 140 hormonal treatments, 101, 145 hysterectomy, 139–42 hysteroscopy, 23–4 imaging, 53, 59–60, 65, 137, 138–9 laparoscopy, 141 magnetic resonance imaging, 59–60, 65, 138 minimal access surgery, 141 palliative radiotherapy, 144 pathology, 39–42, 134–6 positron-emission tomography, 139 prevention, 24–5 radiotherapy, 80, 142–4 risk factors, 133–4 sampling, 23–4 screening, 21–5

staging, 140 surgery, 139–42 tamoxifen, 101 transvaginal ultrasound, 23–4 treatment planning, 138–9 ultrasound imaging, 53, 65, 137 X-rays, 138 endometrial stromal sarcomas (ESS), 41, 42, 135, 176 endometrial thickness (ET), 23 endometrial volume, 24 endometrioid cancer, 36, 39–40, 41 endometriosis, 36 epidemiology, 1–12 cervical cancer, 10–11, 147 choriocarcinoma, 187 definition, 1–2 endometrial cancer, 9–10 hydatidiform moles, 181 ovarian cancer, 6–8 vaginal cancer, 11–12 vulval cancer, 11–12 epithelial ovarian cancer (EOC), 91, 119 adjuvant chemotherapy, 94–6 endocrine manipulation, 101 first-line chemotherapy, 96–7 neoadjuvant chemotherapy, 94–6 palliative chemotherapy, 97–100 epithelial tumour pathology, 33–5 ESS, see endometrial stromal sarcomas etoposide, 93, 98, 190, 195, 196 European standard population of Doll, 4 Ewing’s sarcoma, 176 examinations, 16, 71, 149 excision, 169 exfoliative cytology, 25 extended surgical staging, 140 external beam radiotherapy (EBRT), 79, 142, 156, 172 extrafascial hysterectomy, 155

fallopian tube cancer, 15–21, 215, 216 see also ovarian cancer familial endometrial cancer, 21–5 familial ovarian cancer, 18–21, 120–6 fatality, 5 FDG, see fluorine-18fluoro-2-deoxy-d-glucose imaging FDG-PET, see fluorine-18fluoro-2-deoxy-d-glucose positron-emission tomography FDG-PET/CT, see fluorine-18fluoro-2-deoxy-d-glucose positron-emission tomography computed tomography Federation of Gynecology and Obstetrics (FIGO) ovarian cancer, 54 Federation of Gynecology and Obstetrics (FIGO) staging cervical cancer, 149, 151, 219–20 corpus uteri cancer, 216–17 endometrial cancer, 140 fallopian tube cancer, 215, 216 gestational trophoblastic tumours, 186, 221–2 hydatidiform moles, 185 ovarian cancer, 214 rules, 213–22 uteri cancer, 216–17 vaginal cancer, 161, 220 vulval cancer, 166, 220–1 fertility factors, 128, 203 fine needle aspiration (FNA), 166 first-line chemotherapy, 96–7 fluorine-18-fluoro-2-deoxy-dglucose (FDG) imaging, 51, 63–5 fluorine-18-fluoro-2-deoxy-dglucose positron-emission tomography (FDG-PET), 63–5, 66, 139 fluorine-18-fluoro-2-deoxy-dglucose positron-emission tomography computed tomography (FDG-PET/ CT), 64, 65, 66

227

Index

fluorouracil, 94 FNA, see fine needle aspiration follow-up factors, 159–60, 191 fractionation, 84 frequency of screening fungating wounds, 113–14 gastrointestinal obstruction, 109 gemcitabine, 94, 179, 196 gene mutations, 19, 120 germ cell tumours, 37, 38, 176, 191–7 gestational choriocarcinoma, 181 gestational trophoblastic disease (GTD), 181–91 gestational trophoblastic tumours (GTT), 181–91, 221–2 GnRH, see gonadotrophinreleasing hormone GOG, see Gynecologic Oncology Group gonadotrophin-releasing hormone (GnRH), 145 granulosa cell tumours, 37 gray unit, 84 GTD, see gestational trophoblastic disease GTT, see gestational trophoblastic tumours Gynecologic Oncology Group (GOG), 18, 96 haematogenous spread, 56 haemorrhage, 76, 105, 189 Hasson insertion, 77 hCG, see human chorionic gonadotrophin HDR, see high dose rate hereditary non-polyposis colon cancer (HNPCC), 21, 25, 39, 121, 133 herpes virus type 2, 11 high dose rate (HDR) brachytherapy, 83 high-grade sarcoma tumours, 175 high-risk population screening, 22 histology, 202 histopathology, 152, 216 history factors, 71 HIV, see human immunodeficiency virus

228

HNPCC, see hereditary non-polyposis colon cancer hormonal treatments, 100, 101, 129, 145 hormone replacement therapy (HRT), 24, 133 HPV, see human papilloma virus HRT, see hormone replacement therapy human chorionic gonadotrophin (hCG), 182–7, 194 human immunodeficiency virus (HIV), 11 human papillomavirus (HPV) cervical cancer, 11, 45, 147 DNA testing, 26 vaccines, 29 vaginal cancer, 12 vulval cancer, 12, 47, 163 hydatidiform moles, 181–91 chemotherapy, 184, 185 clinical presentation, 183–7 computed tomography, 184 Doppler analysis, 184 epidemiology, 181 follow-up, 191 imaging, 183, 184 magnetic resonance imaging, 184 management, 183–7 origins, 181 pathology, 181 prognosis, 191 radiotherapy, 183 registration, 183–7 staging, 185 ultrasound, 183 hypercalcaemia, 37, 112–13 hyperplasia, 24 hypofractionation, 84 hysterectomy cervical cancer, 154–6 decision making, 203 endometrial cancer, 24, 139–42 minimal access surgery, 77 sarcomas, 178 hysteroscopy, 23–4

ICD-10, see International Classification of Diseases ICD-O-3, see International Classification of Diseases for Oncology ICON, see International Collaborative Ovarian Neoplasm ifosfamide, 179, 196 imaging, 51–68 cervical cancer, 66, 149, 152, 159 endometrial cancer, 53, 59–60, 65, 137, 138–9 hydatidiform moles, 183, 184 ovarian cancer, 65 ovarian germ cell tumours, 194 recommended algorithms, 65–7 sarcomas, 178 vulval cancer, 51, 67 see also individual modalities immunohistochemistry, 22, 175 immunosuppression, 163, 164 IMRT, see intensity-modulated radiotherapy incidence data, 209 endometrial cancer, 9 ovarian cancer, 6 rates, 2 vulvar and vaginal cancers, 11 incident cases, 2 incident pain management, 107 indications for radiotherapy, 79–80 infantile choriocarcinoma, 190 infertility, 194 inheritable genetic predisposition, 19 intensity-modulated radiotherapy (IMRT), 89 Intergroup Study OV10, 96 International Classification of Diseases (ICD-10), 2 International Classification of Diseases for Oncology (ICD-O-3), 2 International Collaborative Ovarian Neoplasm (ICON), 96, 128

Index

International Ovarian Tumour Analysis (IOTA), 17 international trials for rare diseases, 179 intracavitary brachytherapy, 143, 156 intraoperative complications, 74 intraperitoneal bleeding, 183 intraperitoneal chemotherapy, 129 intravenous fluids, 109 invasion depth, 45, 167 invasive carcinoma of the vulva, 47 invasive moles, 181 invasive squamous cell carcinomas, 45 investigation factors, 71, 164–6, 193 IOTA, see International Ovarian Tumour Analysis iridium-192, 83 irritable bowel syndrome, 204 Keyes punch, 165 lactate dehydrogenase, 193 laparoscopy, 77–8, 141, 194 large bowel surgery, 75 large loop excision of the transformation zone (LLETZ), 153 late side effects of radiography, 86 LBC, see liquid-based cytology leiomyosarcomas, 41, 175, 178, 180 Leydig cell tumours, 38 lichen sclerosus, 163, 164 linear accelerators, 79 lipid cell tumours, 38 liquid-based cytology (LBC), 25 LLETZ, see large loop excision of the transformation zone local anaesthesia, 165 local treatments decision making, 201 vulval cancer, 167 locoregional lymph nodes, 165, 168–9 low-grade sarcoma tumours, 175 low-risk population screening, 23

Lugol’s iodine, 26 LVSI, see lymph-vascular space invasion lymph nodes cervical cancer, 45, 152, 156 dissection, 171 magnetic resonance lymphography, 67 vulval cancer, 168–9, 171 lymphadenectomy, 156 lymphatic spread, 202 lymphoscintigraphy, 171 lymph-vascular space invasion (LVSI), 45, 152, 153 Lynch syndrome, 21, 39, 121, 133 magnetic resonance imaging (MRI), 51, 57–63 cervical cancer, 61, 66, 149, 152, 159 endometrial cancer, 59–60, 65, 138 hydatidiform moles, 184 magnetic lymphography, 67 malignant ovarian germ cell tumours, 195 ovarian cancer, 58–9, 65 sarcomas, 178 technique, 57–8 vulval cancer, 62, 67, 166 magnetic resonance lymphography, 67 maintenance therapies, 129–30 malignant adnexal masses, 17 malignant melanomas, 48 malignant mesenchymal tumours, 41–4 malignant mixed germ cell tumours, 193 malignant mixed Müllerian tumours (MMMT), 42, 176 malignant mucinous tumours, 35, 36 malignant neoplasm classification, 2 malignant ovarian germ cell tumours (MOGCT), 191–7 chemotherapy, 194–7 computed tomography, 195 investigations, 193 long-term outlook, 197

magnetic resonance imaging, 195 management, 194–7 pathology, 191–3 presentation, 193 relapse, 194–7 surgery, 193 ultrasound, 195 malodorous wounds, 113–14 management cervical cancer, 152–61 choriocarcinoma, 188 hydatidiform moles, 183–7 malignant ovarian germ cell tumours, 194–7 MAS, see minimal access surgery measuring risk or burden, 2 medroxyprogesterone acetate, 145 melanomas, 163, 173 mesonephric carcinomas, 46 metastasis cervical cancer, 44, 45, 46 microinvasive squamous cells, 44 vulval cancer, 47 metastatic sarcomas, 178, 179 methotrexate, 185, 187, 196 metoclopramide, 109 microinvasive carcinoma, 44, 47 microinvasive squamous cells, 44 microsatellite instability (MSI), 22 minimal access surgery (MAS), 76–8 advantages, 76 complications, 76 endometrial cancer, 141 laparoscopy, 77–8 minimal deviation adenocarcinoma, 46 Mirena-IUS insertion, 25 mismatch repair (MMR) genes, 19, 21 mixed germ cell tumours, 193 mixed Müllerian tumours of the uterus, 42 MMMT, see malignant mixed Müllerian tumours MMR, see mismatch repair

229

Index

modes of action chemotherapy, 91–101 radiotherapy, 83 MOGCT, see malignant ovarian germ cell tumours moles, 181–91 morbidity, 166 morphological classification, 3 mortality, 5 cervical cancer, 10 data, 209 endometrial cancer, 9 ovarian cancer, 6 rates, 3, 5 vulvar and vaginal cancers, 11 MRI, see magnetic resonance imaging MSI, see microsatellite instability mucinous adenocarcinomas, 36, 41 mucinous ascites, 36 mucinous tumours, 35 Müllerian tumours, 42, 176 myometrial invasion, 40 nasogastric tubes, 109 nausea, 108–11 neoadjuvant chemotherapy, 94–6 neoplasm classification, 2 neuroendocrine tumours, 151 neuropathic pain management, 108 NHS cervical screening programme (NHSCSP), 25 nodal metastasis, 44, 45, 151, 152 non-dysgerminomatous tissue, 192 non-gestational choriocarcinoma, 193 normal tissue tolerance, 85 normal tissue volume, 88 oestrogenic tumours, 37 open Hasson insertion, 77 oral chemotherapy, 93, 99 oral constipation treatments, 112 organizing mucinous fluid, 36 origins of choriocarcinoma, 187 origins of hydatidiform moles, 181 orthovoltage X-ray machines, 81

230

outpatient endometrial assessment, 138 OV10, see Intergroup Study ovarian cancer, 119–31 adjuvant chemotherapy, 94–6 advanced-stage disease, 126, 128–9 chemotherapy, 91, 97–100, 127, 128–9 clinical presentation, 121 computed tomography, 54–6, 65 consolidation, 129–30 cytoreduction, 126 diagnosis, 121 early-stage disease, 126, 128 endocrine manipulation, 101 epidemiology, 6–8 examinations, 16 FDG-PET, 64 FDG-PET/CT, 64, 65 fertility-sparing procedures, 128 FIGO staging, 214 first-line chemotherapy, 96–7 hormonal therapies, 129 imaging, 54–6, 64, 65 intraperitoneal chemotherapy, 129 magnetic resonance imaging, 58–9, 65 maintenance therapies, 129–30 neoadjuvant chemotherapy, 94–6 new therapeutic strategies, 130 palliative care, 97–100, 130 pathology, 33–9, 119–20 radiotherapy, 80 recurrent disease chemotherapy, 129 risk factors, 120 screening, 15–21, 121 staging, 123, 126–9 surgery, 123–6, 130 treatment, 123–6 tumour markers, 16–18, 122–3 ultrasound imaging, 52 ovarian germ cell tumours, 191–7 ovarian masses, 52, 55, 58

paclitaxel, 96–7, 128, 190, 196 Paget’s disease, 48, 163 pain management, 104, 106–8 palliative care, 103–17, 201 analgesics, 106 anxiety, 116–17 bowel habit, 104 breathlessness, 114, 115 chemotherapy, 97–100 complex wounds, 113–14 constipation, 104, 111–12 counselling, 116–17 decision making, 201 depression, 116–17 difficult pains, 107 distress, 104 entering the palliative phase, 115 fungating wounds, 113–14 haemorrhage, 105 hypercalcaemia, 112–13 malodorous wounds, 113–14 nausea, 108–11 ovarian cancer, 97–100, 130 pain management, 104, 106–8 radiotherapy, 79, 144 symptom management, 103–17 vomiting, 108–11 vulval cancer, 172 wounds, 104, 113–14 papillary squamous cell carcinomas, 45 pap smears, 25 partial obstruction, 108 partial prevalence, 4 pathology, 33–48 cervical cancer, 44–7, 148, 149–51 choriocarcinoma, 187 endometrial cancer, 39–42, 134–6 epithelial tumours, 33–5 grading, 217 hydatidiform moles, 181 malignant mesenchymal tumours, 41–4 malignant ovarian germ cell tumours, 191–3 neuroendocrine tumours, 151

Index

ovarian cancer, 33–9, 119–20 serous tumours, 33–5 squamous cell carcinoma, 149 uterus malignant mesenchymal tumours, 41–4 vaginal cancer, 47 vulval cancer, 47–8, 163 patient factors chemotherapy expectations, 99 treatment selection, 202–5 pelvic lymph nodes, 169 pelvic lymphadenectomy, 169 PEPI trial, 24 performance scales, 207 peritoneal deposits, 55 PET, see positron-emission tomography pipelle sampling, 24 Piver–Rutledge classification, 155 placental site trophoblastic tumours (PSTT), 181, 189 platinum compounds, 91–2, 96–7, 99, 128 platinum-free intervals, 98 platinum sensitivity, 98 PLCO, see Prostate Lung Colorectal and Ovarian Cancer Screening Trial pleural effusions, 72, 114 PMP, see pseudomyxoma peritonei positron-emission tomography (PET), 51, 63–5, 139, 159 postmenopausal bleeding, 23, 137–8, 148 power Doppler analysis, 24 predictive values of screening tests, 5 pregnancy cervical cancer, 160 decision making, 203 gestational trophoblastic tumours, 181–91 ovarian germ cell tumours, 191–7 preoperative assessments, 70, 171, 177 presentation, see clinical presentation prevalence, 4

prevention, 15–30 cervical cancer, 11, 29–30 endometrial cancer, 10, 24–5 ovarian cancer, 8 vulvar and vaginal cancers, 12 primary curative radiotherapy, 79 primary tumours, 164 primitive neuroectodermal tumours, 176 principles of radiotherapy, 83–5 progestogens, 25, 145 prognosis cervical cancer, 151–2 endometrial carcinomas, 40 hydatidiform moles, 191 sarcomas, 178 vulval cancer, 167 prophylactic hysterectomy, 24 Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO), 18 protocols for screening, 27 pseudomyxoma peritonei (PMP), 36 PSTT, see placental site trophoblastic tumours pulmonary embolus, 114 quality-adjusted life-years (lost) (QALYs), 5 quality of life, 99 Querleu–Morrow classification, 155 radical treatments aims, 200 cervical cancer, 153–6 decision making, 200, 201 hysterectomy, 77 minimal access surgery, 77, 78 primary radiotherapy, 143 radiotherapy, 79, 143 surgery, 77, 78, 153–6, 168, 169 trachelectomy, 78 vulval cancer, 168, 169 radiobiological differences, 87 radiotherapy, 79–80 acute side effects, 86 cervical cancer, 80, 153, 156–9

decision making, 204 dose, 84 endometrial cancer, 80, 142–4 fractionation, 84 hydatidiform moles, 183 indications, 79–80 late side effects, 86 modes of action, 83 normal tissue tolerance, 85 normal tissue volume, 88 ovarian cancer, 80 principles, 83–5 radiobiological differences, 87 sarcomas, 178, 179 side effects, 85–7, 144, 158 therapeutic ratio/index, 87 tolerance, 85 vaginal cancer, 161 vulval cancer, 80, 169, 172 recurrent disease cervical cancer, 61, 159–60 chemotherapy, 129 endometrial cancer, 145–6 ovarian cancer, 59, 64, 129 vulval cancer, 172 registration factors, 183–7 relapse ovarian cancer, 97–100, 129 ovarian germ cell tumours, 194–7 relative survival, 5 repetitive exfoliative cytology, 25 resectability, 54, 59 respiratory failure, 189 response criteria, 207 risk factors cervical cancer, 147 endometrial cancer, 133–4 measuring risk, 2 ovarian cancer, 17, 18, 120 risk of malignancy index (RMI), 17, 122 risk-reducing salpingooophorectomy (RRSO), 19–21 RMI, see risk of malignancy index routine investigations, 149 RRSO, see risk-reducing salpingo-oophorectomy rules for FIGO staging, 213–22

231

Index

saline infusion sonohysterography, 24, 52 sarcomas, 175–80 blue round-cell tumours, 176 carcinosarcomas, 41, 42, 176 chemotherapy, 179 clinical presentation, 177 computed tomography, 178 endometrial stromal sarcomas, 176 germ cell tumours, 176 imaging, 178 leiomyosarcomas of the uterus, 175 magnetic resonance imaging, 178 malignant mixed Müllerian tumours, 176 Müllerian tumours, 176 preoperative assessments, 177 prognosis, 178 radiotherapy, 178, 179 staging, 177 surgery, 178 tamoxifen, 180 screening, 15–30 cervical cancer, 25–9, 147 colposcopy, 27, 28 definition, 5–6 endometrial cancer, 21–5 fallopian tube cancer, 15–21 familial endometrial cancer, 21–5 familial ovarian cancer, 18–21 frequency, 27 ovarian cancer, 15–21, 121 tests, 5, 15 trials, 17 tubal cancer, 15–21 World Health Organization Criteria, 16 second-line chemotherapy, 98 second-look laparoscopy, 77 selecting treatments, 201–2 decision making, 202–5 patient factors, 202–5 sensitivity CA125, 16 ovarian cancer, 16 platinum, 98 screening tests, 5 sentinel lymph node dissection (SLND), 171

232

serous carcinomas, 40, 46 serous tumours, 33–5, 36 Sertoli–Leydig cell tumours (SLCT), 37, 38 sex-cord stromal tumours, 37 shaving, 73 shielding, 88 side effects radiotherapy, 85–7, 144, 158 surgery, 141 single photon emission computed tomography (SPECT), 67 skeletal scintigraphy, 51, 67 skin preparation, 73 SLCT, see Sertoli–Leydig cell tumours slide-reading techniques, 27 SLND, see sentinel lymph node dissection small bowel surgery, 74 small cell carcinoma, 37 smoking, 163, 164 soft tissue sarcomas, 175–80 sonography, 24 specificity CA125, 16 ovarian cancer, 16 screening tests, 5 SPECT, see single photon emission computed tomography squamous cell carcinomas cervical cancer, 44–5, 147 endometrial cancer, 41 ovarian cancer, 37 ovarian germ cell tumours, 193 pathology, 149 vaginal cancer, 47 vulval cancer, 47, 163–73 squamous epithelial tumours, 153 staging cervical cancer, 61, 149 decision making, 202 endometrial cancer, 59, 140 hydatidiform moles, 185 ovarian cancer, 54, 59, 64, 123, 126–9 sarcomas, 177

vaginal cancer, 161 vulval cancer, 54, 166 see also Federation of Gynecology and Obstetrics staging, Tumour, Node, Metastases (staging system) steroid cell tumours, 38 stromal luteoma, 38 stromal sarcomas, 41, 42 superficial/orthovoltage X-ray machines, 81 superficially invasive carcinoma of the vulva, 47, 169 surgery, 69–78 abdominal incisions, 73 antibiotic prophylaxis, 72 bladder, 75 bowel injuries/damage, 74 bowel preparation, 71 cervical cancer, 153–6 complications, 141, 169 consent, 73 counselling, 72 endometrial cancer, 139–42 examinations, 71 haemorrhage, 76 history factors, 71 intraoperative complications, 74 malignant ovarian germ cell tumours (MOGCT), 193 minimal access surgery, 76–8 ovarian cancer, 123–6, 130 pleural effusion drainage, 72 preoperative assessments, 70, 171, 177 sarcomas, 178 skin preparation, 73 special investigations, 71 thromboprophylaxis, 72 urinary tract, 75 vaginal cancer, 161 vulval cancer, 167–71 survival, 5, 151 symptom management, 103–17 symptoms of vulval cancer, 164 systemic therapies, 91–101, 145, 201 tamoxifen, 101, 133, 180 taxanes, 92

Index

teletherapy, see external-beam radiotherapy teratomas, 38, 176, 192, 193 term delivery, 181, 187 therapeutic laparoscopy, 77 therapeutic ratio/index, 87, 200, 201, 203 three-dimensional conformal radiotherapy (3DCRT), 89 three-dimensional ultrasonography, 24 thromboprophylaxis, 72 tissue tolerance, 85 tissue volume minimisation, 88 TNM, see Tumour, Node, Metastases (staging system) tolerance factors, 85 topo-isomerase inhibitors, 93 total abdominal hysterectomy, 139 total pain management, 108 toxicity, 99, 201, 204 trachelectomy, 78, 160, 203 transabdominal ultrasound imaging, 51 transitional cell carcinomas, 37 transrectal ultrasound imaging, 52 transvaginal ultrasound (TVS), 18, 23–4, 51 treatment aims of, 200–1 constipation, 112 follow-up, 61 hormonal, 100, 101, 129, 145 hypercalcaemia, 113 ovarian cancer, 123–6 patient factors, 202–5 planning, 59, 138–9 recurrent cancers, 145–6, 159–60 response, 64 selection, 201–5 triple incision, 168, 169 trophoblastic tumour, see gestational trophoblastic tumours tubal cancer, 15–21, 215, 216 tumour factors and decision making, 202 tumour markers CA125, 16–17, 52, 122–3, 193

human chorionic gonadotrophin, 183 malignant ovarian germ cell tumours, 195 ovarian cancer, 16–18, 122–3 ovarian germ cell tumours, 193, 194 tumour response, 64 tumour volumetry, 61 Tumour, Node, Metastases TNM (staging system), 2, 54, 167, 201, 213 TVS, see transvaginal ultrasound twin pregnancies, 190 UKCTOCS, see United Kingdom Collaborative Trial of Ovarian Cancer Screening UKFOCSS, see United Kingdom Familial Ovarian Cancer Screening Study UKTOCS, see United Kingdom Trial of Ovarian Cancer Screening ultrasonography, 24 ultrasound imaging, 51–4 cervical cancer, 53 endometrial cancer, 53, 65, 137 hydatidiform moles, 183 ovarian cancer, 52 ovarian germ cell tumours, 195 technique, 51–2 vulval cancer, 53, 67, 165 United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 18 United Kingdom Familial Ovarian Cancer Screening Study (UKFOCSS), 18 United Kingdom Trial of Ovarian Cancer Screening (UKTOCS), 52, 121 ureters, 75 urinary tract surgery, 75 uterus corpus uteri cancer, 216–17 FIGO staging, 216–17

leiomyosarcomas of the uterus, 175 malignant mesenchymal tumours, 41–4 sarcoma surgery, 178 uterine sarcomas, 179 vaginal bleeding, 148 vaginal cancer, 161 decision making, 204 epidemiology, 11–12 FIGO staging, 161, 220 pathology, 47 radiotherapy, 161 staging, 161 surgery, 161 vaginal hysterectomy, 141 vaginal intraepithelial neoplasia (VaIN), 47 Verres needle insertion, 77 verrucous carcinomas, 45, 149, 163, 173 villoglandular adenocarcinoma, 46 villoglandular endometrioid carcinomas, 39 VIN, see vulval intraepithelial neoplasia vincristine, 196 visual inspections, 26 vomiting, 108–11 vulval cancer, 163–73 aetiology, 163–4 clinical presentation, 164–6 computed tomography, 57 epidemiology, 11–12 FDG-PET, 65 FIGO staging, 166, 220–1 imaging, 53, 57, 62, 65, 67, 165, 166 investigations, 164–6 local treatments, 167 magnetic resonance imaging, 62, 67, 166 palliative care, 172 pathology, 47–8, 163 prognosis, 167 radiotherapy, 80, 169, 172 recurrent disease, 172 sentinel lymph node dissection, 171

233

Index

vulval cancer (cont.) signs, 164 staging, 166 superficially invasive carcinoma, 169 surgery, 167–71 symptoms, 164 ultrasound imaging, 53, 67, 165

234

vulval intraepithelial neoplasia (VIN), 12, 47, 163 warty carcinomas, 45 weight loss, 114 World Health Organization (WHO) criteria of response, 207 performance scale, 207

screening criteria, 16 world standard population of Doll, 4 wounds palliative care, 104, 113–14 X-rays, 79, 138, 149 yolk sac tumours, 39, 192