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99 Management of cervical cancer


A national clinical guideline

1 Introduction 1
2 Multidisciplinary team working 3
3 Presentation and referral 4
4 Diagnosis and staging 6
5 Surgery 12
6 Non-surgical treatment 16
7 Treatment during pregnancy 21
8 Sexual morbidity 22
9 Lymphoedema 24
10 Follow up 27
11 Management of recurrent disease 30
12 Management of complications in
advanced disease 34
13 Psychosocial care and support for
patients and carers 40
14 Implementation and recommendations
for research 48
15 Resource implications 50
16 Development of the guideline 52
Abbreviations 55
Annexes 57
References 67

January 2008

COPIES OF ALL SIGN GUIDELINES ARE AVAILABLE ONLINE AT WWW.SIGN.AC.UK


KEY TO EVIDENCE STATEMENTS AND GRADES OF RECOMMENDATIONS

LEVELS OF EVIDENCE

1++ High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
1+ Well conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias
1 - Meta-analyses, systematic reviews, or RCTs with a high risk of bias
2++ High quality systematic reviews of case control or cohort studies
High quality case control or cohort studies with a very low risk of confounding or bias and a
high probability that the relationship is causal
2+ Well conducted case control or cohort studies with a low risk of confounding or bias and a
moderate probability that the relationship is causal
2 - Case control or cohort studies with a high risk of confounding or bias and a significant risk that
the relationship is not causal
3 Non-analytic studies, eg case reports, case series
4 Expert opinion

GRADES OF RECOMMENDATION

Note: The grade of recommendation relates to the strength of the evidence on which the
recommendation is based. It does not reflect the clinical importance of the recommendation.

A At least one meta-analysis, systematic review, or RCT rated as 1++,


and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+,
directly applicable to the target population, and demonstrating overall consistency of results
B A body of evidence including studies rated as 2++,
directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C A body of evidence including studies rated as 2+,
directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+

GOOD PRACTICE POINTS


Recommended best practice based on the clinical experience of the guideline development
group.

NHS Quality Improvement Scotland (NHS QIS) is committed to equality and diversity. This
guideline has been assessed for its likely impact on the six equality groups defined by age, disability,
gender, race, religion/belief, and sexual orientation.
For the full equality and diversity impact assessment report please see the published guidelines
section of the SIGN website at www.sign.ac.uk/guidelines/published/numlist.html. The full report
in paper form and/or alternative format is available on request from the NHS QIS Equality and
Diversity Officer.

This document is produced from elemental chlorine-free material and is sourced from sustainable forests
Scottish Intercollegiate Guidelines Network

Management of cervical cancer


A national clinical guideline

January 2008
Scottish Intercollegiate Guidelines Network
ISBN 978 1 905813 24 7
First published 2008

SIGN consents to the photocopying of this guideline for the


purpose of implementation in NHSScotland
Scottish Intercollegiate Guidelines Network
28 Thistle Street, Edinburgh EH2 1EN
www.sign.ac.uk
1 INTRODUCTION

1 Introduction
1.1 the need for a guideline
Despite the presence of a well established UK screening programme for detecting cervical
pre-invasive disease there are approximately 2,800 cases of cervical cancer per annum and
1,000 women still die from cervical cancer each year.1 In Scotland there were 282 new cases
diagnosed in 20042 and 127 deaths from the disease in 2005.3 The five-year relative survival
rate in Scotland between 1997 and 2001 was 70.6%.4
Only 30% of cervical cancers are screen detected,2 and the majority of cases occur in women who
have never had a smear, or have not been regular participants in the screening programme.
The optimal management of cervical cancer involves a multidisciplinary team. The challenge
for the team is to individualise treatment. As cervical cancer commonly occurs between the
ages of 30 and 45, this includes offering women with early disease the option of having fertility
conserving surgery, where appropriate. For those with intermediate or advanced disease the
aim is to minimise treatment side effects without compromising the outcome.

1.1.1 cervical screening programmes


Cervical cytology detects precancerous changes of the cervix, known as cervical intraepithelial
neoplasia (CIN). Abnormal cytology is a possible presentation for cervical cancer.
Population screening has been shown to reduce the incidence of cervical cancer and reduce
the proportion of women with advanced disease.5 It has been estimated that the screening
programme in the UK saves approximately 5,000 lives per year.6
The Scottish Cervical Screening Programme was established in 1987. More than 90% of tests in
the programme are reported as negative.7 Treatment of women who have CIN has been shown
to reduce the incidence of, and mortality from, cervical cancer. To date, both have fallen by
more than 40%.8

1.1.2 Vaccination
Any woman who is sexually active is at risk of infection from human papillomavirus (HPV).
Over 100 subtypes of HPV have been identified.9 A significant proportion of HPV disease is
attributed to four subtypes; 6,11,16 and 18. HPV subtypes 16 and 18 cause approximately
70% of cervical cancer cases worldwide. HPV subtypes 6 and 11 infections are responsible
for genital warts.10 One or more co-factors that increase the likelihood of persistence of HPV
infection are also needed for cervical cancer to develop.
Two HPV vaccines have been developed: Cervarix, a bivalent HPV (types 16,18) vaccine and
Gardasil, a quadrivalent HPV (types 6,11,16,18) vaccine. Both are prophylactic vaccines that
have been shown to be effective in young women prior to HPV exposure.
Following the advice of the Joint Committee on Vaccination and Immunisation (JCVI) the Scottish
Government and the Department of Health are to introduce HPV vaccines for girls aged around
12 to 13 years of age, starting from September 2008.11,12


management of cervical cancer

1.2 remit of the guideline


This guideline will cover presentation, referral, diagnosis, staging and treatment of cervical
cancer. The management of small cell and large cell neuroendocrine carcinomas is not
covered.
The aim of this guideline is to ensure that optimal management by a multidisciplinary team
minimises the huge social, economic and emotional burden experienced by women with the
disease and their families.

1.3 Statement of intent


This guideline is not intended to be construed or to serve as a standard of care. Standards
of care are determined on the basis of all clinical data available for an individual case and
are subject to change as scientific knowledge and technology advance and patterns of care
evolve. Adherence to guideline recommendations will not ensure a successful outcome in
every case, nor should they be construed as including all proper methods of care or excluding
other acceptable methods of care aimed at the same results. The ultimate judgement must be
made by the appropriate healthcare professional(s) responsible for clinical decisions regarding
a particular clinical procedure or treatment plan. This judgement should only be arrived at
following discussion of the options with the patient, covering the diagnostic and treatment
choices available. It is advised, however, that significant departures from the national guideline
or any local guidelines derived from it should be fully documented in the patients case notes
at the time the relevant decision is taken.

1.3.1 additional advice to nhsscotland from NHS quality improvement


scotland and the scottish medicines consortium
NHS QIS processes multiple technology appraisals (MTAs) for NHSScotland that have been
produced by the National Institute for Health and Clinical Excellence (NICE) in England and
Wales.
The Scottish Medicines Consortium (SMC) provides advice to NHS Boards and their Area Drug
and Therapeutics Committees about the status of all newly licensed medicines and any major
new indications for established products.
SMC advice and NHS QIS validated NICE MTAs relevant to this guideline are summarised in
the section on implementation.

1.4 review and updating


This guideline was issued in 2008 and will be considered for review in three years. Any updates
to the guideline in the interim period will be noted on the SIGN website: www.sign.ac.uk.


2 MULTIDISCIPLINARY TEAM WORKING

2 Multidisciplinary team working


Patients with cancer often have complex needs that cannot be addressed by a single specialty
or discipline. Multidisciplinary team working should ensure a consistent and equitable
approach to planning and managing care. No evidence was identified to determine the effect of
multidisciplinary working or managed clinical networks (MCN) on the management of patients
with cervical cancer.
Cervical cancer is a relatively uncommon tumour and there may be lack of expertise in
managing the complex diagnostic, surgical, oncological and palliative issues of patients in a
district general hospital setting.
There is some evidence to suggest that diagnostic imaging accuracies in secondary care/district
2++
general hospitals may be poorer than from tertiary care/specialist referral centres.13

All patients with invasive cervical cancer should be referred to a multidisciplinary team
to determine optimal management. This should include specialist radiological review of
any imaging.

2.1 the role of the clinical nurse specialist


The clinical nurse specialist (CNS) is an integral part of an MCN. Key components of the CNS
role are to coordinate care between settings and to provide support, advice and information
for patients and their carers throughout their illness.

All patients newly diagnosed with cervical cancer should have access at diagnosis to a
clinical nurse specialist for support, advice and information.

2.2 case volume


With the incidence of cervical cancer declining due to well organised screening programmes,
a new set of problems has emerged for the specialist teams involved in delivering care. For
pathologists, radiologists and surgeons in particular, the critical issue of what constitutes an
adequate volume of cases to maintain specialist skills is pertinent.
In the UK it is now accepted that only gynaecologists who have been appropriately trained
should undertake radical hysterectomy and pelvic lymph node dissection. With the fall in the
incidence of cervical cancer there will be regions in the UK where recognised gynaecological
oncological surgeons will have a very small number of cases.14 To ensure that women get the
best outcome from their surgery, in terms of cure, lowest risk of side effects, and the possibility
of appropriate, newer, less radical procedures, particularly where fertility conservation is an
issue, it may be necessary to concentrate surgical services for cervical cancer in supraregional
centres.


management of cervical cancer

3 Presentation and referral


3.1 signs and symptoms
Prior to the introduction of a national cervical cancer screening programme, signs and symptoms
were important for indicating referral of women to investigate for possible cervical cancer. The
Scottish Cervical Screening Programme was established in 1987 and data predating systematic
screening may no longer reflect the current situation.8
The symptoms associated with cervical cancer are common and non-specific (see Table 1), but
may indicate significant pathology and should be investigated appropriately. Symptoms are
associated with later stage cervical cancers,15 although studies have shown that 15.7-32% of
women with early stage disease had symptoms at presentation.16,17

Women should be encouraged to participate in a screening programme.

Table 1: Signs and symptoms that may suggest cervical cancer15

Sign or symptom

inter-menstrual bleeding (IMB)


post-coital bleeding (PCB)
post-menopausal bleeding (PMB)
abnormal appearance of the cervix (suspicion of malignancy)
vaginal discharge (blood stained)
pelvic pain

Many of the signs and symptoms suggestive of cervical cancer are common to genital Chlamydia
trachomatis infection. Women presenting with these symptoms or with an inflamed or friable 4
cervix which may bleed on contact should be tested for Chlamydia trachomatis and treated if
appropriate.18
Post-menopausal bleeding may also be the presenting symptom of endometrial cancer. Women
presenting with PMB require a pelvic examination during their assessment. Examination by
a general practitioner (GP) or practice nurse can alter the course of clinical management 4
if it expedites referral on grounds of raised suspicion of malignancy (including cervical
carcinoma).19
Abnormal vaginal bleeding, such as IMB and PCB, is common. The point prevalence of PCB in
women in the community is 0.7-9%,20 but only a small proportion of these women are seen in
secondary care. The probability that a woman under the age of 25 who experiences PCB has
cervical cancer is very low (see Annex 1). The probability is higher in women over 35, but is still 2++
low.20 Two per cent of women attending secondary care with PCB have cervical cancer.20 The 2+
duration and extent of symptoms, such as PCB, are not related to the risk of having a cervical
cancer.21 Women referred with PCB where cervical cancer is excluded have no increased risk
of cervical cancer in the future.22
A systematic review identified no evidence to support performing a smear when a woman
2++
presents with PCB if the smear is not due.20
Annex 2 shows an algorithm for the investigation of PCB.
A woman presenting with symptoms who has negative cytology has a greatly reduced risk
of cervical cancer compared to a woman with positive cytology, but the risk is not entirely 2++
2+
eliminated.20,23


3 PRESENTATION AND REFERRAL

D Pre-menopausal women presenting with abnormal vaginal bleeding should be tested


for Chlamydia trachomatis.

D Post-menopausal women presenting with abnormal vaginal bleeding should be referred


for gynaecological investigation.
Chlamydia trachomatis testing should be done if appropriate.

An unscheduled smear is not recommended outwith the screening programme.

3.2 risk factors


Recognised risk factors for cervical cancer are HPV infection, cigarette smoking and
socioeconomic status.24,25 No evidence was identified to stratify patients for investigation based
on these risk factors.

3.3 referral
There is no good evidence to suggest to which clinical setting women with PCB should be
referred for further investigation.

If cervical cancer is suspected on examination when a woman attends for cervical screening
she should be referred to gynaecology.

Women with symptoms suggestive of cervical cancer should be referred to gynaecology


if cervical cancer is suspected on examination.


management of cervical cancer

4 Diagnosis and staging


4.1 diagnosis and prognosis

4.1.1 histopathological reporting


A diagnosis of cervical cancer is made by the histopathological examination of cervical biopsies.
The World Health Organisation (WHO) histological classification of tumours of the uterine
cervix is shown in Annex 3.26 As part of this process it is important for the tissue samples
to be prepared appropriately. Guidance is available from the Royal College of Pathologists
(www.rcpath.org).
The stage of a cervical cancer and the presence of lymph node metastases are important
indicators of prognosis and for determining treatment. Early stage disease is defined by varied
histopathological criteria with conflicting evidence as to their significance.27-36 By definition, the 2+
3
diagnosis of early stage cervical cancer (International Federation of Gynecology and Obstetrics,
4
FIGO stage IA1 and IA2) requires that the entire tumour is excised completely and is available
for histopathological examination.37
There are histological features that can be used to stratify women to higher risk or lower risk of
3
metastatic disease.32,36 These histological features should be included in a pathology report.
Histological reports should follow the minimum dataset of the Royal College of Pathologists
(see Annex 4 for a minimum dataset proforma).38

D Pathology reports of cervical tumours should include the following histological


features:
tumour type
tumour size
extent of tumour (eg involvement of the vaginal wall or parametrium)
depth of invasion
pattern of invasion (infiltrative or cohesive invasive front)
lymphovascular space invasion (LVSI)
status of resection margins (presence of tumour and distance from margin)
status of lymph nodes (including site and number of nodes involved)
presence of pre-invasive disease.

When assessing stromal involvement:


all biopsy material should be taken into account
it is important to be aware that a small tumour may be entirely removed by biopsy.

Pathological assessment should be quality assured and standardised, with readily accessible
specialist review available if required, following discussion by the multidisciplinary
team.

4.1.2 tumour markers


Squamous cell carcinoma antigen (SCCA) belongs to a family of serine and cysteine protease
inhibitors. The antigen is present in normal squamous cervical epithelium and its expression
is increased in cervical squamous cancers.39,40
Pre-treatment levels of SCCA are related to tumour volume but are insufficiently reliable
for identifying patients at risk of having pelvic lymph node metastases or parametrial
involvement.41


4 DIAGNOSIS AND STAGING

4.2 clinical staging


Cervical cancer is clinically staged using the FIGO criteria (see Annex 5).37 FIGO staging does
not take into account results of computerised tomography (CT), magnetic resonance imaging
(MRI) or positron emission tomography (PET).

4.2.1 SENTINEL node surgery


There is evidence from a number of small case studies that it is feasible to identify sentinel lymph
nodes during cervical cancer surgery. The evidence that the status of these nodes accurately
predicts the status of the remaining pelvic lymph nodes is conflicting.31,42-47 Comparison of the 3
results of these studies is hampered by variable methodology, and there have been no long
term studies of follow up.
At present there is no evidence to support the use of sentinel node surgery in preference to
pelvic lymphadenectomy in cervical cancer. Larger standardised studies are required.

4.2.2 pelvic lymphadenectomy


No evidence was identified to address the adequacy of pelvic lymphadenectomy specifically in
cervical cancer. Evidence from many studies indicates that there is considerable variation in the
number of lymph nodes obtained from this procedure.31,48-51 There is no evidence relating the
number of lymph nodes retrieved to long term outcome. Many of the studies lack information
about how the tissue is handled by the pathologist.
This lack of good quality evidence illustrates the need for standardisation of pathological
assessment. Further guidance is available from the Royal College of Pathologists (www.rcpath.
org).

4.3 Radiological staging


Radiological assessment of patients with visible cervical carcinoma is an essential part of
the strategy in determining the most appropriate management of patients, both at primary
presentation and with relapsed disease or complications of treatment.
Radiological studies often have inherent design weaknesses, which are difficult to eliminate.
Some of the disparity of results between individual studies may be dependent on:
heterogeneity of equipment
image interpretation and training
clinical setting (specialist centre compared to district general/community hospital)13,52
MRI, CT methodology and sequences
advances in MRI, CT and PET technology.13,53-56
The staging accuracy (sensitivity and specificity) of MRI, CT, and PET is shown in Table 2.

4.3.1 primary tumour assessment


There is consistent evidence that MRI is more accurate than CT for radiological staging of
cervical carcinoma (accuracies 4097%)13,56-58 and both modalities are more accurate than
clinical staging.56,57
2++
For women with contraindications to MRI scanning CT is appropriate. For women with clinically
apparent stage IVA or IVB disease, post contrast spiral or multislice CT scans of chest, abdomen
and pelvis are more appropriate than MRI.13,58,59


management of cervical cancer

MRI technique is important in correct staging. Thin section axial and sagittal T2 sequences
including axial oblique sections perpendicular to the long axis of the cervix, are of most value in
2++
primary tumour assessment.53,55,60 Intravenous non-dynamic contrast in MRI is non-contributory
2-
in primary tumour staging.55,61-63 4
Ultrasound is not generally reliable in either assessment of primary tumour size or nodal status.58
Transrectal ultrasound may be of value if undertaken by experienced operators.63
PET-CT can assess both the primary tumour and detect metastatic spread.64 PET-CT has potential
2+
for more accurately selecting patients for surgery than PET imaging alone, in addition to
2+
contributing to more accurate treatment planning.64,65

4.3.2 Primary Tumour volume


Primary tumour volume is best assessed by MRI rather than CT.13,58,62,66,67 Tumour diameter less
than 5-10 mm cannot be reliably imaged by either modality.53,67,68 Post-biopsy changes may 2++
also adversely affect tumour measurement, particularly in small tumours.62
Appearances following a loop excision biopsy or cone biopsy cause difficulty in assessing
the size and extent of the primary tumour, which may have important staging and prognostic
consequences.
There is some evidence that PET scans may also measure tumour volume,69 but false negative
2++
uptake also occurs following excision biopsy.65

4.3.3 Vaginal invasion


Vaginal invasion is best assessed by MRI, with accuracies ranging from 78-94%.56,70 Overstaging
errors are reported in association with bulky primary tumours distending the fornices.61,70 CT 2++
staging accuracies are not available.

4.3.4 parametrial staging


Involvement of parametrium indicates inoperable FIGO IIB disease.
Studies report variable accuracy for parametrial staging by MRI and CT,13,56,57 but MRI is generally
superior to CT, with staging accuracy of 75-90%.9,56,57,71
The greatest value of MRI in influencing treatment options lies in the high negative predictive 2++
value for parametrial invasion (85%).13,56,70 Full thickness disruption of the ring of cervical stroma
by tumour on MRI corresponds to FIGO stage IIB disease.70 Confirmation of an intact ring of
cervical stroma, on adequate MRI assessment, confers potentially operable status.
PET imaging alone cannot accurately determine early parametrial involvement.72 Data are not
available comparing the accuracy of PET-CT to MRI.

4.3.5 bladder and rectal invasion


Assessment of bladder and rectal invasion is consistently more accurate with CT and MRI than
clinical staging, with the specificity of MRI considerably greater than CT.57 There is heterogeneity
of results from studies assessing detection of tumour involvement, which may be related to 2++
both procedure methodology and interpretation criteria in specialist hospitals compared to 2+
community/district general hospitals.13 Several studies show 100% negative predictive values
for CT and MRI in bladder, rectal and ureteric invasion.54,73,74
A normal appearance of bladder and rectum on MRI examination obviates the need for
cystoscopy or sigmoidoscopy.
Intravenous urography (IVU) has been superseded as a stand alone investigation, as CT, MRI or
ultrasound are as accurate in determining ureteric obstruction secondary to parametrial invasion 2++
and give additional information.59,73,75 2+
2-
Barium enemas are not routinely indicated.59


4 DIAGNOSIS AND STAGING

4.3.6 pelvic or para-aortic lymph nodes


Although not a part of the FIGO staging criteria, the involvement of pelvic or para-aortic lymph
2++
nodes in most histological types of cervical cancer, is the greatest single predictor of long term
3
survival72,76 and cannot be assessed by clinical examination alone.
Lymphangiography is not routinely available in many radiology departments in Scotland.
Comparable studies with contemporary CT and MRI are not available.
Lymphangiography is probably less sensitive than other contemporary modalities for preoperative
assessment with positive predictive values that are variable in cervical carcinoma (14% to 80%).58
Lymphangiography may interfere with the specificity and interpretation of PET scans.77
There is consistent evidence that both CT and MRI have poor sensitivity for detection of
nodal metastases, based on size criteria (generally 1 cm short axis diameter cut off for positive 2++
involvement) and node morphology, in both the pelvic and para-aortic nodes. Poor sensitivity
is due to the presence of metastases within normal sized lymph nodes. MRI is better than
CT.57,78
PET-CT scans may be the most accurate imaging method of detecting involved lymph nodes
(see section 4.3.7).65,72
Table 2: Staging accuracy (sensitivity and specificity) of MRI, CT and PET

MRI % CT % PET %
Primary tumour detection Sensitivity 93,53 10079 n/a 10079
(macroscopic disease) Specificity 93,53 10079 n/a 10079
Parametrial involvement Sensitivity 74,57 8556 5557 n/a
Specificity 85 56,57
75 57
n/a
Lymph node involvement Sensitivity 6057 4357 8440
Specificity 9157 9157 9540
Bladder involvement Sensitivity 7557 n/a n/a
Specificity 91 57
73 57
n/a
Rectal involvement Sensitivity 7157 n/a n/a
Specificity n/a n/a n/a

B All patients with visible, biopsy proven cervical carcinoma (except those with
FIGO IV disease) should have an MRI scan.

C The MRI scan should include:


thin section T2 weighted images perpendicular to the cervix, and
sequences to include urinary tract and para-aortic nodal areas.

B Post contrast spiral CT should be considered as an alternative to MRI in patients who


cannot have MRI.
Women who have clinically apparent FIGO stage IV disease should have post
contrast spiral or multislice CT scans of chest abdomen and pelvis.

MRI scans should ideally occur prior to excision biopsy, to avoid inflammatory changes
and to allow more accurate measurement of tumour size.


management of cervical cancer

Ultra-small iron oxide particles for MRI lymphangiography will be available for use in the UK
from Spring 2008, which may potentially increase the sensitivity of MRI for detection of nodal
metastases.

4.3.7 PET
PET is more accurate than CT80 or MRI81 in detecting metastatic lymphadenopathy,81 having the 2++
potential to significantly change patient management79 and survival. 2+

Patient numbers in PET studies tend to be small, but there is some evidence that PET is superior
to MRI and CT in the detection of metastatic para-aortic nodes, with higher sensitivities and
specificities.72,82 Sensitivities remain suboptimal, and possibly technique dependent, in nodes
less than 10 mm in size.82 2++
2+
There is wide variation in fdg-PET imaging techniques with respect to the administered isotope
dose, patient preparation and timing of scans post injection, with consequent heterogeneity in
results. PET sensitivity varies from 79%83 in the pelvic nodes to 35%84 to 84%83 in the para-aortic
nodes, with overall sensitivity for detection of pelvic and para-aortic nodes of 80%.80
False positive nodal fdg-PET uptake may be secondary to inflammatory change from a variety
of causes including infection and chronic granulomatous disease.65,83,85,86 It is important that
metastatic involvement is confirmed by sampling or biopsy before there is a change to the
planned treatment regimen.
PET-CT combined is emerging as the most accurate method for detection of nodal metastases 2++
in the pelvis and para-aortic nodes, with sensitivities of 75% and 100% respectively.65 There 2+
is insufficient evidence to support the routine use of PET-CT to confirm operable status in
patients staged as IB1 or less, given the limitations of negative predictive values for PET-CT in
the detection of pelvic nodal metastases.64,65,72
PET or PET-CT scans do not detect all nodes with micrometastases.65 If nodal enlargement is
evident on staging MRI scans in patients with clinically operable disease, then PET scanning
will determine the extent of potential metastatic involvement.
The greatest benefit from PET-CT is in women with inoperable disease, considered potentially
curable with chemoradiotherapy. This group of women is statistically more likely to have nodal
or metastatic disease than those women suitable for surgery.

C Patients not suitable for surgery should be considered for a PET scan.

4.3.8 chest x-ray


Limited data are available on the use of chest X-rays in staging. Chest X-ray has identified
metastases in 4% of women with clinical stage IIB or greater disease.75 In patients with FIGO 2-
stage IB disease there is a very low likelihood of pulmonary metastases.75
CT scans are more accurate in comparison to chest X-ray in identifying pleural effusions, thoracic
2+
nodal status and parenchymal metastases.59

Routine chest X-rays are not indicated in women with operable disease (FIGO IA1, IA2
and IB1).

4.3.9 the Relative benefit of imaging over other options in pre-treatment


staging
Use of MRI or CT in pre-treatment assessment is less invasive, more accurate,87 and confers cost/
time benefits in determining the preoperative stage of patients,13,54,58 compared to conventional 2++
FIGO investigations of IVU, cystoscopy, sigmoidoscopy and barium enema. MRI is more accurate 2+
than CT in correctly staging patients.13,56-58,67
Cystoscopy and sigmoidoscopy should be reserved for women in whom a normal bladder or 2++
rectum cannot be confirmed on clinical or radiological assessment (CT or MRI).58,74,87 2+

10
4 DIAGNOSIS AND STAGING

Nodal staging, which will determine prognosis, operability and radiotherapy fields, is most
2++
effectively determined by PET-CT.65
Lymphangiography is invasive,88 probably less sensitive than other contemporary modalities 2++
for preoperative assessment and may interfere with the specificity and interpretation of PET 2+
scans.77
Assessment of pelvic and para-aortic nodal disease is most accurately determined by laparotomy
2+
or laparoscopic surgery.89
These are invasive, morbid procedures requiring a general anaesthetic. The alternative is to
use pre-treatment imaging to determine nodal status, despite the limitations in sensitivity and
specificities of current techniques (MRI, CT, PET and PET-CT).

C Cystoscopy and sigmoidoscopy should not be routinely performed for staging


purposes.

C If imaging cannot exclude bladder or bowel involvement, cystoscopy and sigmoidoscopy


should be used for staging.

C Ultrasound, IVU and lymphangiography are not recommended for staging.

4.3.10 conveying the diagnosis


The information needs of women diagnosed with cancer and methods of conveying information
are covered in sections 13.3-13.5.

Diagnosis should be conveyed sensitively and in easily understood language.

11
management of cervical cancer

5 Surgery
For early stage disease surgery conserves ovarian function and avoids the effects of early
menopause. Less shortening and fibrosis of the vagina occurs compared to radical radiotherapy
which gives better results in terms of residual sexual function.76 Surgery also allows the status
of the pelvic lymph nodes to be assessed accurately.76 Surgery is the preferred treatment option
in young women provided that there are no contraindications. The outcome following surgery
is associated with a variety of prognostic factors including size of primary tumour, depth of
stromal invasion, presence or absence of LVSI proximity of tumour to vaginal and parametrial
margins (see section 4.1).

The relative risks and benefits of different surgical management approaches should be
thoroughly discussed with the patient on an individual basis.

5.1 radical hysterectomy


Radical hysterectomy (RH) involves the en-bloc removal of uterus, cervix, parametrial tissues and
upper vagina. It is usually combined with pelvic lymphadenectomy. The extent of parametrial
tissue removed determines whether a class II or class III RH has been done. RH is a more
complex procedure than a simple hysterectomy and is undertaken by appropriately trained
gynaecologists.
The combined treatment of radical surgery and postoperative radiotherapy increases overall 1+
morbidity compared to either alone.76,90 3

To minimise post-surgical morbidity, before doing an RH the size of primary tumour should be
accurately assessed radiologically and efforts should be made to ensure that there is no pelvic
lymphadenopathy (see sections 4.3.1 and 4.3.6).
The evidence suggests that there is no difference in disease-free survival or overall survival of
patients with FIGO IB and IIA disease treated by either class III radical hysterectomy or radical
1+
radiotherapy.76 Class II and class III radical hysterectomies are equally effective for the surgical
treatment of FIGO IB and IIA cervical cancer.91
The involvement of pelvic lymph nodes in FIGO IB disease is approximately 16%.58,63 Where the
tumour size is less than 2 cm the incidence of nodal metastases is 6%.58 For tumours measuring 3
more than 4 cm the incidence of lymph node metastases increases to 36%,92 which increases the 4
likelihood of using adjuvant chemoradiotherapy to treat positive nodes (see section 6.2.1).

B Radical surgery is recommended for FIGO IB1 disease if there are no contraindications
to surgery.

RH is not recommended if the tumour measures more than 4 cm to reduce the likelihood
of using chemoradiotherapy post-surgery.

No study was identified comparing radical hysterectomy with chemoradiotherapy for treatment
of cervical cancer. There is good evidence from more recent studies that chemoradiotherapy
is more effective than radiotherapy alone (see section 6.1).
Where positive pelvic nodes are identified at the time of radical hysterectomy, the practice of
aborting the hysterectomy has not been tested in a randomised trial. Descriptive studies suggest
that there is a beneficial effect on prognosis if the pelvic nodes are removed and the radical
hysterectomy completed.90,93 Recurrence after completed hysterectomy and removal of lymph
nodes was significantly lower than after incomplete lymph node removal (25% compared to 3
56%). After adjusting for other prognostic factors, completed lymph node removal showed an
independent effect on disease-free survival.93 Survival in patients whose radical hysterectomy
was abandoned because grossly positive nodes were found and removed, was significantly
worse than that of patients whose node metastases were identified after the operation (58.5%
compared to 93.5%).76,90

12
5 SURGERY

5.2 treatment of cervical cancer after subtotal hysterectomy


In subtotal hysterectomy the cervical stump is not removed. This procedure may be done
when difficulties are encountered whilst doing a hysterectomy for benign disease such as
endometriosis.
The incidence of cervical cancer in women who have had a subtotal hysterectomy is no different
to that in women with an intact uterine cervix. Cancer of the cervical stump behaves like cancer 2+
in an intact uterine cervix.94

C Cancer of the cervical stump should be managed in the same way as cervical cancer
arising in an intact uterus.

5.3 treatment of early stage disease (figo Ia1 and Ia2)

5.3.1 pelvic node metastases


The risk of pelvic lymph node metastases is no more than 1% for stage FIGO IA1 and 3-6% for
FIGO IA2 cervical squamous cell cancer.95 The FIGO classification for early stage squamous 2+
cervical cancer (FIGO IA) is also applicable to early stage adenocarcinomas.95
The presence of LVSI is an indicator of prognosis and should be considered when determining
whether to perform pelvic lymphadenectomy in early stage cervical cancer.33,36 In IA1 disease 2+
with LVSI, no good quality evidence was found to support or preclude pelvic lymph node 4
dissection.
Evaluation of tumour depth and horizontal spread is more difficult in early stage adenocarcinomas
than in squamous cell cancers.95 Measurement of depth and horizontal spread (2-dimensional) 2+
is as effective as determining tumour volume. In FIGO IA1 and IA2 disease tumour volume 3
exceeding 500 mm3 is a significant adverse prognostic indicator.96
Early stage adenocarcinoma with a depth of invasion of 3 mm and horizontal spread of 7
mm or less (FIGO IA1 disease) has little potential for pelvic nodal metastases (less than 1%). 2+
The evidence suggests that there is no need to remove pelvic lymph nodes when treating IA1 3
disease.48,95-98

D Removal of pelvic lymph nodes is not recommended during treatment for FIGO IA1
disease.

D Pelvic lymph nodes should be removed if FIGO IA2 disease is present.

In women with FIGO IA1 disease with LVSI the decision to carry out pelvic
lymphadenectomy must be individualised taking account of the pattern and extent of
invasion.

Diagnosis and measurement of early adenocarcinoma and squamous cell cancer should
be done by specialist gynaecological pathologists.

5.3.2 fertility conservation surgery


No randomised controlled trials (RCTs) were identified comparing different methods of fertility
sparing/conservation surgery.
Standard treatment for IA1 disease is simple hysterectomy if fertility is not an issue. For IA2
disease it is simple hysterectomy and pelvic lymph node dissection (PLND). For FIGO IB1
disease it is RH with PLND (see section 5.1).
In women for whom preservation of fertility is desirable, an alternative to simple hysterectomy
or RH is a radical trachelectomy. This involves vaginal resection of the cervix, the upper 1 to
2 cm of the vaginal cuff and the medial portions of the cardinal and uterosacral ligaments. The
cervix is transected at the lower uterine segment and a prophylactic cerclage is placed at the
time of surgery.

13
management of cervical cancer

Radical trachelectomy does not appear to increase the rate of recurrence, provided the tumour
2+
diameter is no greater than 2 cm and there is no evidence of LVSI.99-105 Radical trachelectomy
3
must be combined with pelvic lymph node dissection for IA2 and IB1 disease.99-105
The safety of radical trachelectomy in women with lesions that are greater than 2 cm in diameter
is unclear as the majority of reported cases of radical trachelectomy have been in women with
tumours less than 2 cm in diameter.
A recent prospective multicentre study of radical trachelectomy combined with laparoscopic
pelvic lymphadenectomy reported three recurrences in 100 treated patients (FIGO IA1, IA2, 2+
and IB1).The median follow-up time was 29 months.106 A meta-analysis of 346 patients with 3
early cervical cancer treated with radical trachelectomy with a median follow up of 44 months
reported a recurrence rate of 4.1%.107
Following radical trachelectomy the majority of women can anticipate conceiving spontaneously
and delivering near term.99,100,105 The rate of first and second trimester miscarriage is comparable
to that in the general population.105 In one study of obstetrical results following RT, 72%
2+
of women progressed into the third trimester of pregnancy.105 Of these, the majority (78%)
3
reached term (>37 weeks of gestation) The pre-term delivery rate was slightly higher than
in the general population at 16% compared to 12%.105 In another study following RT, of 63
women attempting pregnancy there were 28 live births in 19 women.108 In all studies delivery
was usually by caesarean section.99-105,108

C Women requesting fertility conservation should be offered radical trachelectomy


and pelvic lymph node dissection, providing the tumour diameter is less than 2 cm and
no lymphatic-vascular space invasion is present.

Cold knife conisation or large loop excision of the transformation zone (LLETZ) is adequate
treatment for women with IA1 disease where fertility conservation is requested. If LVSI is present 4
PLND needs to be considered (see section 5.3.1).109
A study reported that women with cervical cancers of maximum diameter 2 cm and depth of
infiltration less than 10 mm had a low risk of parametrial involvement. In this study, of 103
patients who had been treated with radical hysterectomy and PLND only two (1.94%) had
parametrial involvement. Both of these patients had LVSI. The study also reviewed literature 3
on 696 patients treated by RH and PLND where the tumour size was less than 2 cm and depth 4
of invasion less than 10 mm and no LVSI was present. Only three (0.43%) had parametrial
involvement. The study concluded that for tumours less than 2 cm in diameter and depth of
invasion less than 10 mm where pelvic lymph nodes are negative and no LVSI is present the
overall risk of parametrial involvement is 0.63%.110
Extrapolated evidence suggests that cold knife conisation and PLND or LLETZ and PLND, rather
3
than radical trachelectomy and PLND, is also adequate treatment for women with FIGO IA2 4
and microscopic FIGO IB1 disease where no LVSI is present.99,110,111
Diagnosis and measurement of early adenocarcinoma and squamous cell cancer should be
done by specialist gynaecological pathologists.
Women who have had LLETZ are more likely than women who have not to have pre-term
delivery (11% compared to 7%), low birth weight babies (8% compared to 4%) and premature 2+
rupture of the membranes (5% compared to 2%) in a subsequent pregnancy.112

D Women with early stage disease and no LVSI (FIGO IA2 and microscopic IB1) requesting
fertility conservation may be offered cold knife conisation or LLETZ combined with
pelvic lymph node dissection.

14
5 SURGERY

There is insufficient evidence to recommend cold knife conisation or LLETZ combined with
pelvic lymph node dissection when LVSI is present.

Women with early stage disease (FIGO IA2 and microscopic IB1) and LVSI requesting
fertility conservation may be at risk of local recurrence and treatment must be
individualised.

As women with early stage IA1/IA2 cancers are diagnosed following LLETZ, the value of MRI for
determining tumour volume is debatable (see section 4.3.2). MRI may have a role in assessing
the nodes in IA2 and microscopic IB1 disease (see section 4.3.6).

5.4 Laparoscopic-vaginal radical hysterectomy


Laparoscopic-vaginal radical hysterectomy (LVRH) for the treatment of FIGO IB1 disease
appears to be a safe and effective alternative to conventional abdominal RH.93,113-117 Lymph
node yield after laparoscopic lymph node dissection is comparable to open surgery.93,113-117
Evidence from a case series reported a non-significant difference in recurrence rate following
LVRH compared to RH (8.5% and 2.1% respectively).115 Patients with a large tumour volume 3
(4.2 cm3) undergoing LVRH had a significantly higher recurrence rate (42.9%) than those with
small volume disease (2.5%).115 There were, however, only seven patients with large volume
disease compared to 40 with small volume disease.115 Descriptive studies show that the mean
duration of surgery was longer for LVRH compared to abdominal RH and more intraoperative
complications occurred when surgery was carried out by surgeons in training.113-115 Patients
hospital stay was shorter after LVRH than after RH.115,116

D Laparoscopic-vaginal radical hysterectomy should not be offered to patients with


tumour diameter greater than 2 cm.

D Surgeons wishing to offer laparoscopic-vaginal radical hysterectomy should have


appropriate training.

MRI should be used to measure tumour volume and diameter.

5.5 total pelvic exenteration


Total pelvic exenteration (TPE) is covered in section 11.1.1.

15
management of cervical cancer

6 Non-surgical treatment
Generally chemoradiotherapy is used to treat women with FIGO IB2, IIA, IIB, IIIA, IIIB and IVA
disease. Surgery is not offered to this group of women because of the significant risk of positive
margins and positive nodes.

6.1 Concurrent chemoradiotherapy


Concurrent chemoradiation is better than radiation alone for the treatment of patients with
cervical cancer who are considered suitable for radical radiotherapy.118 There is a significant
1++
overall survival benefit for treatment with chemoradiation compared to radiation alone. Survival
is increased from 40% to 52% (risk reduction, RR, of death=29%).
Platinum based chemotherapy is better than non-platinum based chemotherapy.118,119 There is
more evidence of a beneficial effect in trials using platinum based chemotherapy. A systematic
review reported a hazard ratio (HR) for platinum based chemotherapy of 0.70 (95% confidence
1++
interval, CI 0.61 to 0.80; p<0.0001) compared to 0.81 (95% CI 0.56 to 1.16; p=0.20) for
non-platinum based chemotherapy.118 Chemoradiation with cisplatin alone results in an RR of
death of 0.74 (95% CI 0.59 to 0.93) compared to 0.70 (95% CI 0.56 to 0.86) for chemoradiation
with cisplatin/5-fluorouracil (5FU).119
Chemoradiation for treatment of cervical cancer is associated with increased acute haematological
and gastrointestinal toxicity.118 Genitourinary toxicity is lower after chemoradiotherapy (odds
ratio, OR, 0.43; 95% CI 0.2 to 0.92; p=0.03).118 There is no difference in neurological and skin 1++
toxicity after chemoradiation compared to radiotherapy alone.118 There is no strong evidence
regarding late toxicities but there is no apparent increase.118,119

A Any patient with cervical cancer considered suitable for radical radiotherapy treatment
should have concurrent chemoradiotherapy with a platinum based chemotherapy, if
fit enough.

The balance of risks and benefits must be addressed before offering chemoradiation for
treatment of cervical cancer.

6.2 Adjuvant chemoradiotherapy/radiotherapy

6.2.1 positive Lymph nodes


There are no randomised controlled trials directly comparing chemoradiotherapy after surgery
to no further treatment in patients with cervical carcinoma and positive nodes.
Following surgery adjuvant chemoradiotherapy is better than radiotherapy alone for patients
with cervical carcinoma and positive nodes.120 Treatment with adjuvant chemoradiotherapy
results in improved overall survival (HR of 1.96; p=0.007), progression free survival (HR of
2.01; p=0.003) and a reduction in local and distant recurrence.120 Four-year survival was
81% for chemoradiotherapy and 71% for radiotherapy alone.120 Twenty two per cent of
patients receiving chemoradiotherapy suffered grade 4 toxicity compared with 3% receiving 1+
radiotherapy alone. The majority of the increased toxicity was haematological. Late toxicity was 2+
not recorded.120 A retrospective analysis of this data found the benefit to be greater in patients
with tumours larger than 2 cm.121 The absolute improvement in 5-year survival with the addition
of chemotherapy to radiotherapy in patients with tumours 2 cm was 5% (77% compared to
82%; p=0.17) and 19% (58% compared to 77%; p=0.009) for those with tumours >2 cm.121
The absolute 5-year survival benefit was less evident among patients with one nodal metastasis
(79% compared to 83%; p=0.438) than when at least two nodes were positive (55% compared
to 75%; p=0.006).121
Adjuvant radiotherapy reduces local recurrence in patients with cervical carcinoma and positive
2+
nodes following surgery.122,123

16
6 NON-SURGICAL TREATMENT

B Patients who have undergone surgery for cervical carcinoma and have positive nodes
should be considered for adjuvant treatment with concurrent chemoradiotherapy with
platinum based chemotherapy.

Consideration should be given to the relative risks and benefits of treatment for each
individual patient.

6.2.2 negative Lymph nodes


Compared to no further treatment, adjuvant radiotherapy reduces the risk of recurrence in
patients with cervical carcinoma with negative lymph nodes following surgery and with at least
two of the following risk factors:124
invasion of more than a third of the total cervical stromal volume 1+
LVSI, or
tumour diameter of >4 cm.
The addition of adjuvant radiotherapy reduces overall risk of recurrence from 30.7% to 17.5%
(HR 0.54; p=0.007), local recurrence from 20.7% to 13.95% and distant recurrence from
8.6% to 2.9%.124
Given the body of evidence supporting the superiority of concurrent chemoradiation over 1++
radiation alone in other settings (see sections 6.1 and 6.2.1),118,120,121 strong consideration should 1+
be given to using concurrent chemoradiation in preference to radiation alone. 2+

B Patients who have undergone surgery for cervical carcinoma, have negative nodes
and any two of the following risk factors should be considered for adjuvant treatment
with radiotherapy, if fit enough:
greater than a third stromal invasion
lymphovascular space invasion
tumour diameter of >4 cm.

Consideration should be given to the relative risks and benefits of treatment for each
individual patient.

D Concurrent chemoradiation should be considered in preference to radiation alone.

6.3 brachytherapy
Brachytherapy is short wave radiotherapy delivered by the insertion of applicators into the
uterus via the vagina.
Guidelines from the American Brachytherapy Society indicate that brachytherapy should be
4
considered an essential component of definitive radiotherapy treatment.125,126

D Brachytherapy should be considered an essential component of radical radiotherapy


or chemoradiotherapy.
Precise applicator placement is essential for improved local control and reduced
morbidity.
Brachytherapy should be carried out by practitioners experienced in the procedures
and dosimetry of brachytherapy.
If a brachytherapy insertion is not possible then a further boost should be given using
external beam radiotherapy.

17
management of cervical cancer

6.4 NeoAdjuvant chemotherapy


No data from RCTs were identified describing the value of using neoadjuvant chemotherapy to
make large inoperable tumours surgically resectable. An ongoing randomised phase III study
of neoadjuvant chemotherapy followed by surgery compared to concomitant radiotherapy
and chemotherapy in patients with FIGO IB2, IIA >4 cm or IIB cervical cancer is addressing
this issue.127

6.5 treatment of stage ivB disease


There have been no randomised trials comparing chemotherapy to best supportive care in stage
IVB cervical carcinoma. Single-agent cisplatin was the treatment of choice until a recent report
demonstrated a modest survival advantage for the combination of toptecan plus cisplatin over
cisplatin alone. There are also data indicating that cisplatin plus paclitaxel is an acceptable
alternative (see section 11.2).

6.6 treatment of anaemia


Anaemia during treatment is a stronger indicator of poor prognosis in patients being treated for
carcinoma of the cervix than the presence of pre-treatment anaemia.128-133 Correction of anaemia 2++
by blood transfusion appears to reverse some of the detrimental effect on prognosis.130,131
A meta-analysis of the use of erythropoietin or darbepoetin in patients with cancer was not
specifically restricted to patients with cervical cancer and included patients with solid and
haematological malignancies.134 Treatment with erythropoietin or darbepoetin decreased the
relative risk of requiring a blood transfusion (RR 0.64; 95% CI 0.60 to 0.68) and decreased
the volume of blood transfusion (on average one unit of blood less than control group).134 For 1++
patients with a baseline haemoglobin below 12 g/dl, haematological response was observed
more often in patients receiving erythropoietin or darbepoetin compared to those not (RR
3.43; 95% CI 3.07 to 3.84).134 Treatment also increased the relative risk for thromboembolic
complications compared to patients receiving placebo/no treatment (RR 1.67; 95% CI 1.35
to 2.06).134 There was no evidence of improved overall survival of patients treated with
erythropoietin or darbepoetin.134

C Patients with cervical carcinoma undergoing radiotherapy or chemoradiotherapy


should have their haemoglobin level monitored and corrected if it falls below
12 g/dl.

B Anaemia should be corrected with either blood transfusion or erythropoietin and iron
products after consideration of the attendant costs, risks and benefits.

6.7 Treatment of radiation induced complications


During radiation treatment of cervical cancer, other pelvic organs receive a significant radiation
dose, resulting in both acute and late toxicity. Late radiation changes occur at least three months
after the completion of radiotherapy. Late radiation complications are due to small vessel injury
with endothelial damage, inflammation, fibrosis, ischaemia and necrosis. The management
of late radiation complications is complex with little high quality evidence to guide practice.
Surgical treatment may be required if medical intervention fails.

Patients should have access to specialist multiprofessional teams for treatment and
management of severe radiation induced complications.

18
6 NON-SURGICAL TREATMENT

6.7.1 bladder
Symptoms of late radiation effects to the bladder can include urinary frequency, urgency,
dysuria, detrusor instability,135,136 haematuria, ulceration and the potential for perforation and
fistula formation. Radiation ischaemia and necrosis may be a cause of ureteric obstruction in
addition to bladder problems.
A Cochrane meta-analysis concluded that the absence of any randomised controlled trials made
it impossible to draw any definitive conclusions regarding the treatment of radiation cystitis.137
Management options included hydration, bladder irrigation, antibiotics to treat infection as
1+
required and blood transfusion. Early cystoscopy with diathermy of bleeding points before
the cycle of repeated bladder washouts, clot retention and mucosal trauma has started may
be beneficial.137 Nineteen case reports and case series suggested that hyperbaric oxygen was
beneficial.137
One phase III RCT was identified showing that intravenous treatment with tetrachlorodecaoxygen
(TCDO, or drug WF10) showed no significant difference in objective or subjective symptoms 1++
on an intention to treat analysis.138

Patients should be managed by a urologist with experience of late radiation effects


to the bladder, who is able to offer complex reconstructive surgery in the event of severe
complications.

6.7.2 rectum
Acute radiation proctitis is frequently experienced during pelvic radiotherapy with symptoms
including tenesmus, urgency, diarrhoea and occasionally bleeding.
An RCT of 87 patients with prostate cancer showed that sucralfate enemas made no difference
compared to placebo for the treatment of acute radiation induced proctitis.139 Another RCT
of 134 patients with prostate cancer randomly assigned to sucralfate (63 patients), mesalazine 1+
(8 patients) or hydrocortisone (63 patients) found that mesalazine was detrimental and there
was no difference between the sucralfate and hydrocortisone. There was no no treatment
control arm.140
Oral sucralfate showed no benefit over placebo for acute radiation induced proctitis in patients
with localised pelvic tumours. Patients receiving sucralfate showed significantly increased 1+
diarrhoea at two and six weeks after pelvic radiotherapy (p=0.49 and p=0.33 respectively),
causing the trial to be stopped.141

B Rectal or oral sucralfate is not recommended to reduce acute radiation induced


proctitis.

Late radiation proctitis can lead to tenesmus, urgency, either diarrhoea or constipation, anal
sphincter dysfunction, mucus discharge, bleeding, stricture, ulceration and fistula formation.
Sucralfate enema reduced the duration and severity of late radiation induced proctitis, compared
to steroid enema in 11 out of 14 patients (13 of whom had cervical cancer) in a small case
series.142 Another study suggested that combining steroid, sulphasalazine and sucralfate enemas 3
is worse than sucralfate alone.143 Patients with late appearance of symptoms had a shorter time
to healing than patients with an early appearance of symptoms.143

D Rectal sucralfate may be considered to reduce late radiation induced proctitis.

19
management of cervical cancer

6.8 hormone replacement therapy


In women with absent ovarian function following surgery and/or radiotherapy for cervical cancer,
hormone replacement therapy (HRT) reduces post-menopausal symptoms. HRT significantly
reduced long term post-radiation rectal, bladder and vaginal complications (p=0.01).144 After 2+
five years symptoms persisted in 17% of women taking HRT and in 45% of patients receiving
no hormonal therapy.144
There is no evidence that HRT increases risk of squamous cell cancer but a small study reported
a possible increase in the risk of recurrence in women with adenocarcinoma.145

C HRT is recommended for women who have lost ovarian function as a result of treatment
for cervical cancer.

20
7 TREATMENT DURING PREGNANCY

7 Treatment during pregnancy


No evidence was identified to suggest that pregnancy accelerates the natural history of cervical
cancer.94 The prognosis for a pregnant patient with cervical cancer is similar to that of a non- 2+
pregnant patient when matched for stage, tumour type and tumour volume.94 Disease-specific
survival is independent of the trimester of pregnancy in which the diagnosis is made.94
The evidence indicates that the choice of therapeutic modality for cervical cancer diagnosed
2+
during pregnancy should be decided in the same manner as for non-pregnant patients.94

C For pregnant women with cervical cancer, the choice of therapeutic modality should
be decided in the same manner as for non-pregnant patients.

The evidence supports immediate treatment for patients diagnosed with cervical cancer at or
before 16 weeks of gestation, irrespective of stage. 46,47,94 After 16 weeks of gestation, in patients 2+
with early stage disease (FIGO 1A1, 1A2, 1B), delivery may be delayed until fetal maturity 3
occurs.46,47,94

C For pregnant women diagnosed with cervical cancer before 16 weeks of gestation,
immediate treatment is recommended.

C For pregnant women with early stage disease (FIGO IA1, IA2, IB) diagnosed after 16
weeks of gestation, treatment may be delayed to allow fetal maturity to occur.

An individualised treatment plan should be determined, in consultation with the patient,



by the multidisciplinary team, which should include an obstetrician.

For women with late stage disease, there is no good evidence to support delaying treatment to
allow fetal maturity as very few cases are described in the literature. No evidence was identified
that compared maternal survival after diagnosis at different periods of gestation.
If gestational age is less than 20 weeks at diagnosis of advanced cervical cancer (FIGO 1B2
or greater) a systematic review supports immediate delivery and treatment of the disease. If
2+
gestational age is more than 20 weeks, delivery and treatment should be initiated within four
weeks of diagnosis.94

C For pregnant women with advanced disease (FIGO 1B2 or greater) diagnosed after
16 weeks of gestation, consideration for delay must be based on gestational age at time
of diagnosis.

No RCTs were identified describing outcomes after delivery by caesarean section compared to
vaginal delivery.
Several retrospective studies concluded that there is no statistically different survival benefit 2+
given either delivery method.46,47,94 3

Decisions on the mode and timing of delivery should be made in consultation with the
patient and her obstetrician.

21
management of cervical cancer

8 Sexual morbidity
Sexual problems suffered by women with cervical cancer may include loss of libido, change in
sexual activity and decreased orgasm. Up to 65% of women experience one or more of these
problems due to vaginal dryness, vaginal bleeding, stenosis, dyspareunia, atrophic vaginitis
and pain.148
Given the incidence of physical and psychosexual dysfunction following cervical cancer
womens sexual function and concerns need to be assessed prior to treatment. There is no good
evidence to suggest when the appropriate time to carry out an assessment is.

The sexual function and concerns of women diagnosed with cervical cancer should be
assessed prior to treatment.

8.1 Physical interventions


A systematic review identified evidence from retrospective studies that vaginal stents/dilators
can prevent development of vaginal stenosis and treat vaginal occlusion in patients receiving
radiotherapy for cervical or uterine cancer.149 Vaginal stenosis was prevented and patency
maintained at one-year follow up in 20/35 patients compared to 4/35 patients who had not 2+
used a stent.149 Vaginal oestrogens appear to be effective for reducing dyspareunia, alterations
in the vaginal epithelium and vaginal narrowing. Benzydamine douches appear to be effective
for treating acute radiation vaginal mucositis. The included studies were old, small and
underpowered and large placebo controlled trials are required.149

C Women should be offered a vaginal stent or dilator to prevent post-radiotherapy vaginal


complications.

Topical oestrogens or benzydamine douches may be considered to alleviate post-


radiotherapy vaginal complications.

A small pilot study suggested that symptoms of sexual dysfunction were reduced with a clitoral
therapy device. The results need to be validated in larger controlled trials before the device
can be recommended.150

8.2 Psychoeducational interventions


Compliance with vaginal dilation following pelvic radiotherapy is variable and generally poor.
Assistance in overcoming womens fears and teaching behavioural skills is likely to reduce
concerns and improve both knowledge of sexual activity and sexual rehabilitation following
pelvic radiotherapy. Consensus guidelines on the use of vaginal dilators in women receiving
pelvic radiotherapy are available.151

Women should be offered training and support to maximise the benefit of using a stent
or dilator.

Psychoeducational group sessions, guided by the information-motivation-behavioural skills


model, provide the necessary information, motivate individuals to engage in the target
behaviours and teach behavioural skills for performing specific tasks, such as objective skills and
a sense of self efficacy for performing them.152 Two one and a half hour sessions significantly 1+
reduced womens fears about their sexuality (p=0.01) and increased their knowledge,
particularly in the older age group (over 41.5 years of age, p<0.001) compared with written
information alone. The intervention also increased vaginal dilation compliance rates and the
ability to have sexual intercourse in younger women.152

22
8 SEXUAL MORBIDITY

In this study group, therapy was delivered at the cancer centre post-radiotherapy. In Scotland
it may prove difficult to gather together women who are at the same stage of treatment. The
intervention-motivation-behavioural skills model could be used to address issues of concern
to women after surgery if tailored to meet the need.
Relaxation and counselling sessions delivered within 24 hours of discharge by a member of
the patients care team significantly reduce anxiety and moderate depression in the first six 1+
weeks after surgery.153

B Information about female sexual function should be offered to patients by a relevantly


trained healthcare professional using a model of care that involves addressing
motivational issues and teaching behavioural skills.

C Patients should be offered support sessions by a designated member of their care team,
as soon as possible after treatment, which may include one or more of the following:
relaxation
personalised information about their disease and treatment
emotional support and care.

Women should be offered one to one sessions if appropriate.

23
management of cervical cancer

9 Lymphoedema
Lymphoedema, presenting as swelling of one or both lower limbs, is a possible complication
of cervical cancer and may be treatment or disease related. Reported incidence rates vary from 3
3.6-49%.154-160 Studies are not generally comparable due to different patient groups, treatment
techniques and lack of standardised reporting of lymphoedema.
Quality of life is affected in patients with lower limb lymphoedema including changes in 2+
sensation, appearance, pain,161,162 restricted activities,158,163 and distress.163 Treatment may 3
positively influence quality of life.161

All healthcare professionals involved in the care of patients with cervical cancer should
receive education on the identification of lymphoedema.

9.1 risk factors


Hysterectomy with pelvic node dissection for early stage cervical cancer has been associated
with a 7-14% incidence of swelling. 163-165 Lymphoedema has also been reported in those who 3
had radiotherapy alone.163,166
The incidence of lymphoedema following pelvic lymph node dissection and radiotherapy for
FIGO IB/IIA cervical cancer in a cohort of 99 patients was reported as 19% at one year and 3
12% at five years.156 Similar figures were reported in a cohort of 77 patients.167
A study of women undergoing surgery for cancer of the uterine corpus showed that removal
3
of 10 lymph nodes is associated with a greater risk of lymphoedema.168
External radiotherapy doses of >50.4Gy to the low pelvis appear to be associated with an
increased risk of complications such as lymphoedema.157 A retrospective study of 118 patients 3
showed no difference in the incidence of lymphoedema in those who had irradiation to small
pelvic field or whole pelvic field.158
Around one third of patients in one study said they had not received either written or oral
information about lymphoedema.162 Well timed advice and appropriate written and oral 3
information on lymphoedema risk and management is needed.162,167

D Patients with lymphoedema, or at risk of lymphoedema, should have access to


appropriate information.

Information should be delivered by a healthcare professional with relevant training.

Specialist lymphoedema practitioners, usually nurses or physiotherapists, are available in


some healthcare settings to provide specialist treatments (see section 9.4). Other healthcare
professionals are trained in some aspects of lymphoedema management but may not provide
regular, specialist treatments.

Designated lymphoedema practitioners should be available at all centres treating women


with cervical cancer.

9.2 trigger factors


Factors that may trigger the onset of clinical lymphoedema include:160
injury or trauma, for example, insect bite, cut, injection, sunburn
3
extreme temperatures
air travel
cellulitis.

24
9 LYMPHOEDEMA

9.3 DIAGNOSIS
Diagnosis is mainly based on clinical examination and the following criteria have been
identified:160,163,167
increase in circumference of the limb
changed sensations such as feelings of fullness, tightness, heaviness, throbbing, shooting 3
pains
reduced flexibility in the limb
palpable changes to the skin or subcutaneous tissue such as fibrosclerosis that may be pitting
or non-pitting.
The International Society of Lymphology identifies staging criteria for lymphoedema according
to severity (see Annex 6).169 4

Lymphoedema often occurs in the first two years following cancer treatment.155-157,160 Swelling
subsides on elevation at early stages but may become chronic, with skin and tissue changes,
including thickening, skin folds and fat deposits.169 Oedema of the trunk can occur in some 3
patients. One study showed that 16% of patients with lymphoedema developed cellulitis 4
requiring antibiotic treatment.159
Lymphoedema may be exacerbated if patients gain weight or have concurrent problems such as
cardiac failure or medication-related fluid retention.168 Intrapelvic or intra-abdominal tumours 3
that involve or compress lymphatic or venous return may produce a severe and intractable 4
oedema, particularly near the end of life.169
Cancer recurrence should be considered in patients with new onset lymphoedema. The
possibility of deep venous thrombosis should also be explored.
Evaluation of lymphoedema risk by healthcare professionals and communication between
healthcare teams is essential to ensure early diagnosis and appropriate referral for treatment 3
and to minimise complications.159,160,167,168

D Patient review should include identification and recording of lower limb


lymphoedema.

D Patients with symptoms suggestive of lymphoedema should be referred early for


assessment by a designated lymphoedema practitioner.

9.4 TREATMENT
Expert opinion supports the use of conservative physical therapies in lymphoedema
management.169 For some patients this includes decongestive lymphatic therapy (DLT)
4
with compression bandaging and manual lymph drainage (MLD) massage, combined with
lymphoedema hosiery, skin care and exercise.
There is evidence from a systematic review to suggest that multi layer bandaging followed by
hosiery is more effective in reducing limb volume than hosiery alone.170 1++

Early and appropriate antibiotic therapy is important in managing cellulitis and antibiotic 3
prophylaxis may be required for patients with recurrent cellulitis.159,169 4

D Patients with severe or poorly controlled lymphoedema should be offered DLT with a
specialist lymphoedema practitioner.

D Early and appropriate use of antibiotic therapy is recommended for patients with
cellulitis.

Prophylactic antibiotic treatment should be considered for patients with more than two
episodes of cellulitis in a year.

25
management of cervical cancer

A consensus report identified no evidence to support the long term use of diuretics to reduce
4
lower limb lymphoedema.169
Two systematic reviews found insufficient evidence to draw conclusions about the effectiveness
1++
of selenium or benzopyrones in the treatment of cellulitis or lymphoedema.171,172
Evidence from a non-randomised study, that did not include patients with cervical cancer,
suggests that intermittent compression pump therapy may lead to genital oedema.173 2+

9.5 Patient self management


Patient self management that may include use of lymphoedema hosiery, exercise, skin care and 3
self massage is recognised as important in the effective management of lymphoedema.160,169 4

A common sense approach to reducing the risk of lymphoedema or preventing complications


such as cellulitis has been described including:159,169
taking care of skin and nails and avoidance of interdigital fungal infection
3
maintaining an optimal body weight
4
avoiding injury to the affected limb/s including scratches and insect bites
avoiding temperature extremes
protecting the limbs from the sun
wearing comfortable, supportive shoes.

D Patients with lymphoedema should be supported to self manage by a practitioner


qualified in lymphoedema management.

26
10 FOLLOW UP

10 Follow up
10.1 post-treatment surveillance
Evidence for the effectiveness of post-treatment surveillance is inconsistent.
In an observational study of 993 patients with FIGO IB disease reviewed after primary surgery
or primary radiotherapy, 13% developed recurrent disease (see Table 3).174 Nine per cent of
surgical patients and 17% of radiotherapy patients developed recurrences. All asymptomatic
recurrences occurred in the first 16 months of follow up.174 Cervical cytology did not detect
a single asymptomatic recurrence.174 Thirty seven of the 993 patients developed recurrent
disease in the central pelvis, 21 patients had recurrences in either lung or pelvic side wall and
22 patients had recurrences in the nodes.174 All asymptomatic pelvic recurrences occurred in
the first 16 months after completion of treatment. Symptom status at time of recurrence is a 3
significant predictor of survival.174 The median survival from recurrence was 11 months for
symptomatic disease and 42 months for asymptomatic.174 Another study reviewed 1,292 women
of all FIGO stages after radiotherapy (see Table 3).175 Twenty nine per cent had either local or
distant recurrence and around a 10% five-year survival rate.175
In a study of 291 patients followed up for five years after surgery for cervical cancer, 18.2%
developed recurrent disease (see Table 3).176 The median time from surgery to recurrence was
17.6 months.176 Recurrent disease was only detected in seven of the 53 patients at routine
follow up and two were asymptomatic. Detection of recurrence on routine follow up was not
an independent prognostic factor for survival when compared with age, stage and whether the
patient received postoperative adjuvant treatment.176
Routine clinical follow up after radical hysterectomy and pelvic lymph node dissection is not
a sensitive way of detecting recurrent disease, as a high proportion of patients are found to be 3
symptomatic at the time of detection of recurrence. Sixty three per cent of recurrences occurred
before 24 months and 77% before 36 months.174
Table 3: Recurrence detected during follow up

Number of patients Number of recurrences


Study Survival
Total Primary treatment Total Type
Bodurka- 933 surgery 461 40 symptomatic 33 11 months*
Bevers,
2000174 asymptomatic 7 42 months*
radiotherapy 532 93 symptomatic 81 11 months*
asymptomatic 12 42 months*
Hong, 1292 radiotherapy 375 local 162 10% (5-year)
2004175
distant 213 11% (5-year)
Lim, 291 surgery 53 symptomatic 5 37.5 months*
2004176
asymptomatic 2 8.3 months*

* median survival post-recurrence



recurrent disease detected at a planned follow-up clinic

D History taking and clinical examination should be carried out during follow up of
patients with cervical cancer to detect symptomatic and asymptomatic recurrence.

D Cervical cytology or vault smears are not indicated to detect asymptomatic recurrence
of cervical cancer.

27
management of cervical cancer

Although routine follow up after radical hysterectomy or radiotherapy is not a sensitive way of
detecting recurrent disease, it is current practice for patients to be followed up because of other
benefits, such as detection of treatment complications, and psychosexual and psychosocial
morbidity.

Patients should be followed up every four months for at least two years.

Patients with early stage disease who have had fertility conserving surgery should have
a smear at six months, 12 months and annually for four years before being returned to
the cervical screening programme.

10.2 detection of relapsed disease


Annex 7 shows an algorithm for the detection of relapsed disease.
CT or MRI is more easily available, cheaper and in symptomatic patients is better than PET
at differentiating metastatic complications from post-treatment complications,177 for example,
insufficiency fractures of the pelvis.
There is some evidence supporting the use of intravenous contrast in post-therapy MRI scans
in symptomatic and asymptomatic patients to differentiate fibrosis post-radiotherapy from
recurrent tumour.56 There is evidence from a small study (19 patients) that PET-CT scans may 2++
be more accurate than either postcontrast CT or MRI in differentiating post-treatment fibrosis
from recurrent disease.178
A whole body PET or PET-CT scan is a sensitive post-therapy surveillance modality for the 2++
detection of recurrent and persistent cervical carcinoma in both asymptomatic and symptomatic 2+
patients.64,81,179-181 4

There is little evidence to support the optimal timing or frequency of post-therapy scans.179 In
several studies whole body PET scans were generally performed no sooner than three months
post primary treatment to avoid false positives associated with post-surgical or radiotherapy
oedema or inflammatory response in the pelvis. A PET scan at nine months would be expected 2++
to detect the majority of recurrences, whether or not patients are symptomatic.181-183 Recurrence
may still occur before and after nine months, but rarely after 30 months. A study of 152 patients
showed that early persistent post-therapy fdg-PET uptake may be predictive of tumour recurrence
and death from cervical cancer.182
PET is more accurate in the detection of metastatic or nodal disease than CT or MRI.81 At the
time of publication PET-CT imaging combined is the modality of choice rather than PET scans
2++
alone. CT, CT-PET or MRI are more accurate in the detection of recurrent disease than clinical
examination alone.
If fdg-PET uptake is positive only in the pelvis and cross-sectional imaging has not been
performed, CT or MRI is still required to assess resectibility.64,85 2++

If performed prior to pelvic exenteration, a whole body PET or PET-CT scan can improve
2++
selection of operable patients and potentially improve their survival rates,180,184 and can eliminate
2+
unnecessary morbidity associated with salvage procedures in unsuitable patients.180,181,184,185
There is no evidence to demonstrate that prior radiotherapy or chemotherapy alters the sensitivity
of detection of recurrence.

C MRI or CT should be considered initially to assess potential clinical recurrence in


symptomatic patients.

B A whole body PET scan or PET-CT should be performed on all patients in whom
recurrent or persistent disease has been demonstrated on MRI or CT and in whom
salvage therapy (either pelvic exenteration or radiotherapy) is being considered.

A PET-CT scan at nine months of follow up is recommended in women who have had
chemoradiotherapy.

28
10 FOLLOW UP

10.2.1 tumour markers


The clinical value of routine SCCA measurement during follow up of patients with early stage
cervical cancer treated by radical hysterectomy and PLND with or without radiotherapy has
been investigated.186 SCCA analysis resulted in earlier detection of recurrence in only 14% 3
of patients (in 5/35 who had recurrent disease elevated SCCA was the first measured clinical
indicator), but did not contribute to better overall survival.186
Routine post-treatment SCCA monitoring is not cost effective for all stages of squamous cervical
cancer in the absence of curative treatment for recurrent disease (see section 15.7).187

The routine use of SCCA to determine disease recurrence is not recommended.

29
management of cervical cancer

11 Management of recurrent disease


The prognosis for patients with recurrent disease is six months to two years. In addition, women
may experience substantial morbidity from both local recurrence and metastatic disease.
Therapeutic options for those patients with cervical cancer whose first line treatment has failed
include:
surgery (salvage)
chemotherapy
palliative treatment only, including best supportive care (see sections 12 and 13), if further
surgery or chemotherapy is not appropriate either due to the advanced nature of the tumour,
the poor general condition of the patient, or at the patients request.

Decisions regarding the appropriate management of recurrent cervical cancer should be


made on an individual basis taking into account:
the patients wishes
the stage of recurrent tumour and its potential resectability
previous treatment
likely treatment efficacy
likely treatment-related morbidity and functional outcome and consequent effects
on quality of life
the patients general health.

Decisions regarding the management of recurrent cervical cancer should be made by


the multidisciplinary team in consultation with the patient following histological or
cytological confirmation of recurrence and full restaging (clinical and radiological).

Patients and their relatives or carers should be carefully counselled about the likely
outcome of treatment for recurrent disease, with respect to survival, risk of treatment-
related morbidity and mortality and quality of life.

Early referral to palliative care services for symptom control should be considered.

11.1 surgery
Following primary treatment for cervical cancer the incidence of isolated relapse confined to
the pelvis is infrequent. For women who do present with relapsed disease following biopsy
confirmation additional restaging is needed to rule out extrapelvic metastases. The majority
of women who develop recurrent disease will have previously received pelvic radiotherapy.
For these women the only potentially curative option is pelvic exenteration provided relapsed
disease is confined to the central pelvis.

11.1.1 total pelvic exenteration


Total pelvic exenteration (TPE) is a high morbidity procedure.188 Less than 50% of patients
survive five years after TPE.188
A whole body PET or PET-CT can identify distant nodal and metastatic disease which may not
be detected on CT or MRI scans.
If performed prior to pelvic exenteration, a whole body PET or PET-CT scan can improve the
selection of operable patients and potentially improve their survival rates,180,184 and eliminate 2++
unnecessary morbidity associated with salvage procedures in unsuitable patients.180,181,184,185 CT 2+
or MRI is still required to assess resectibility.64,85

30
11 MANAGEMENT OF RECURRENT DISEASE

In one small study, postoperative morbidity following TPE was reported as 35.7%, with
reoperations being carried out in 28.6% of patients.189 Having a dedicated multiprofessional 3
team reduces morbidity and mortality. Recurrence occurred in 50% of cases.189
In a phase II trial, the survival and operative mortality rates attainable with TPE for recurrent 3
cervical cancer are comparable to those achieved with chemoradiotherapy.190
Urinary diversion represents a fundamental part of surgical reconstruction at the time of TPE.
In the UK the most commonly performed procedure is an ileal loop urinary diversion.
A self selected series of patients with prior pelvic irradiation were given an ileocolic continent
pouch rather than loop ileal conduit with no apparent increase in morbidity.191 Good 3
postoperative nutrition, and adequate stenting of the ureteric/intestinal anastomosis site decrease
the incidence of complications and increase quality of life.188
Reconstruction of the vagina and pelvic floor at the time of pelvic exenteration can be safely
done. Surgical time is increased but morbidity is not significantly increased. The rectus abdominal 3
flap is the preferred reconstruction technique. Incidence of flap necrosis was 18.8%.192

D Pelvic exenteration should be reserved as salvage surgery for women with recurrent
cervical cancer in the central pelvis whose chemoradiotherapy has failed.

C MRI or CT should be considered initially to assess potential clinical recurrence in


symptomatic patients.

B A whole body PET scan or PET-CT should be performed on all patients in whom
recurrent or persistent disease has been demonstrated on MRI or CT and in whom
salvage therapy (either pelvic exenteration or radiotherapy) is being considered.

To minimise mortality and morbidity, a dedicated multiprofessional team should carry


out total pelvic exenteration in women with recurrent cervical cancer.

11.2 chemotherapy
There have been no randomised trials comparing chemotherapy to best supportive care in
advanced cervical carcinoma. Cisplatin is the standard chemotherapy despite low response
rates.
A trial published in 1985 randomised patients to three different schedules of cisplatin. There
was no difference in overall survival or time to progression although response rates were higher
with a higher dose of cisplatin.193 As a result cisplatin at 50 mg/m2 three weekly has been the
standard approach.
Two trials looked at the addition of ifosfamide to cisplatin therapy.194,195 One closed early due
to poor accrual,194 but no significant differences were seen in survival in either trial. There was 1+
an improved progression free survival with cisplatin and ifosfamide but significantly increased
toxicity.195
The addition of paclitaxel (135 mg/m2) to cisplatin resulted in an increase in overall response
rate from 19% to 36% and a statistically significant increase in the median progression-free 1+
survival of two months from 2.8 months to 4.8 months but there was no improvement in overall
survival.196 Quality of life was the same in both treatment arms.197

31
management of cervical cancer

A statistically significant 2.9 month improvement in median survival was seen with the
combination of cisplatin and topotecan (50 mg/m2 on day one plus topotecan 0.75 mg/m2 on
days one to three every three weeks) compared with cisplatin alone (50 mg/m2 every three
weeks) from 6.5 months to 9.4 months.198 The unadjusted RR estimate for survival was 0.76 1+
(p=0.017). The 95% confidence interval comes close to unity (0.593 to 0.979), so the actual
overall benefit may be small. When adjusted for covariates of performance status, age, and
disease status at entry, the RR estimate is 0.738 (p=0.0075) favouring cisplatin and topotecan.
The greatest benefit was seen in patients who had not previously received chemotherapy, and
was poorest in those who received platinum therapy in the previous 12 months.198
Increased toxicity, primarily haematological, was associated with the combination regimen.
There was an increase in episodes of febrile neutropenia from 7.5% to 17.7% and the incidence
of grade 3 or 4 thrombocytopenia increased from 3.4% to 31.3%. There was no reduction 1+
in the recorded quality of life of patients treated with the combination regimen despite the
increased toxicity.199
The SMC has assessed topotecan in combination with cisplatin (see section 14.1.1).

B Palliative chemotherapy should be offered to women with FIGO stage IVB or recurrent
cervical carcinoma, after discussion of the relative benefits and risks, with either:
cisplatin 50 mg/m2 on day 1 plus topotecan 0.75 mg/m2 on days 1 to 3 every 3
weeks, or
cisplatin 50 mg/m2 on day 1 plus paclitaxel 135 mg/m2 every 3 weeks.

Cisplatin and topotecan combination should be restricted to cisplatin nave patients.

Patients of performance status 0-2 should be considered for treatment with cisplatin and
topotecan combination.

Discussion of new drugs in the clinical trial setting should be considered with patients
who have relapsed within 12 months.

Chemotherapy should be prescribed, dispensed, administered and supervised in a safe and


effective manner in accordance with the Joint Collegiate Council for Oncology
guidelines,200,201 clinical oncology good practice guidelines and Scottish Government
advice.202,203

32
11 MANAGEMENT OF RECURRENT DISEASE

11.3 fistulae
Fistula formation is a rare but grave feature of cervical cancer. Few women are affected but
the distress created by rectovaginal or vesicovaginal fistula development is considerable. The
evidence for managing fistulae is poor and management is based on expert opinion.204
Fistulae may occur as a late complication of radiotherapy (with a mean latent time of 17 months
to 8.1 years)205 or as a result of progressive disease. Radiation dose and dose distribution are
the main risk factors for the development of post radiation rectovaginal fistulae.206
Symptoms include:
persistent continuous watery discharge
persistent continuous faeculant discharge with pneumaturia.
For a bowel fistula, after appropriate radiological investigations to establish the site and
complexity of the fistula (see section 4.3.5), a treatment option may be stoma formation.
Urological fistulae due to radiotherapy may require temporary diversion by percutaneous
nephrostomies or insertion of internal ureteric stents prior to ureteric occlusion and
diversion.205
Patients with advanced disease who develop fistulae are seldom able to undergo surgery to
attempt repair and are constantly reminded of the incurable nature of their condition. Appropriate
non-surgical treatments should be offered to maximise comfort and include:
octreotide, hyoscine butyl bromide or glycopyrronium to reduce volume of discharge
codeine phosphate or loperamide to firm stool
barrier creams to protect the perineal skin
topical steroids, for example, prednisolone foam enemata administered vaginally for local
effect
vaginal moulds
tampons
low residue diet.

33
management of cervical cancer

12 Management of complications in advanced


disease
Comprehensive palliative care will be required as the patients condition declines and the end
of life nears.207 Symptoms may be challenging and patients may benefit from input from a wide
variety of clinical services.
Consideration of every symptom is outwith the scope of this guideline. Guidance on palliative
care is available208 and specialist palliative care advice is available from all Scottish Hospices and
Hospital Palliative Care Support Teams. Contact details can be found in the annual Directory
of Hospice and Palliative Care Services (www.hospiceinformation.info). Local resources which
consider the spiritual and psychosocial aspects of palliative care as well as physical problems
are also available, for example, the Forth Valley Palliative Care Resource Pack, (http://intranet.
fv.scot.nhs.uk/web/site/Depts/CoreCancer/PalliativeCareResourcePack.asp) and the Lothian
Palliative Care Guidelines (www.scan.scot.nhs.uk).

Patients with incurable cervical cancer should be managed on an individual basis.

This section of the guideline addresses distressing problems specifically associated with advanced
cervical cancer. These may occur singly or in combination and include:
pain
renal failure from bilateral ureteric obstruction
thrombosis and haemorrhage
malodorous discharge
lymphoedema (see section 9)
fistulae.

12.1 Pain control


Pain control in advanced cancer is addressed in SIGN 44: Control of pain in patients with
cancer.209 In advanced cervical cancer the following may also be appropriate:
early recourse to nerve-blocking procedures in addition to analgesic drugs
spinal therapy, using combinations of opiates, local anaesthetics and clonidine, to provide
regional blockade for pelvic pain, incident neuropathic pain or pain from metastatic disease
in the spine or pelvis
percutaneous cementoplasty for painful lytic bony metastases of the pubic ramus or
acetabulum, if pain is refractory to conservative treatment.210,211

12.2 Renal failure


Renal failure in advanced cervical cancer generally has a post-renal aetiology from
lymphadenopathy or direct tumour invasion but concomitant pre-renal and renal causes should
be excluded. Ureteric obstruction may initially produce no biochemical evidence of impaired
renal function but if left unmanaged will inevitably lead to renal loss.

Investigations should be performed to exclude additional treatable causes of renal


failure.

There should be a careful assessment of results of the investigations and discussion with
the patient.

34
12 MANAGEMENT OF COMPLICATIONS IN ADVANCED DISEASE

The management of extrinsic malignant ureteric obstruction is a balance of the patients quality
of life, renal preservation and the risk of complications in a setting of poor prognosis.212 There
is a lack of consensus on optimal management,213 and treatment may differ between patients
with advanced disease at presentation and those with progressive disease following treatment.
Initial management options are:
no treatment
percutaneous nephrostomy (PCN), or
retrograde stenting.

Urology and gynaecology specialists should be involved in any discussion on the best
treatment for individual patients.

Advanced decisions taken by the patient should be recorded and respected.

In an emergency situation, and in the absence of an advanced directive, initial treatment


should be in favour of life.

An algorithm for the management of renal failure is shown in Annex 8.


PCN can substitute a peaceful uraemic death for a painful, poor quality life with minimal
improved survival.214 Internal stents fail in at least a third of patients within six months.212 3
Stent failure is represented by an increase in creatinine by 50% from nadir, pain, infection or
hydronephrosis.212
A retrospective study of cancer patients receiving primary retrograde stents for malignant ureteric
obstruction indicated that gross tumour invasion at cystoscopy is a significant risk factor for 3
stent failure and progression to PCN. There is insufficient evidence to compare different types
of stent.212
Long term stents are designed to remain in place for either six or 12 months but some urologists
perform more frequent changes to keep the stents patent.212 The frequency of change depends
on the level of ureteric obstruction. If the obstruction is due to pelvic cancer it may be more 3
appropriate to consider PCN.212 If retroperitoneal lymphadenopathy is the cause of the
obstruction, stents will remain patent for considerably longer and will require less frequent
change.212
If retrograde stent is unsuccessful PCN and/or antegrade stent may be a successful alternative.212 3
Consequently open discussion with the patient and relatives is essential.212

D Retrograde ureteric stents should be changed according to the level of ureteric


obstruction (ranging from 3-12 months).

D If a retrograde stent is unsuccessful:


the stent should be changed more frequently
an alternative stent should be tried
patients should be offered PCN and/or antegrade stent.
If stent placement permits further treatment, such as radiotherapy or chemotherapy, in patients
with advanced disease at presentation, urinary diversion may subsequently become feasible.
Patients require careful follow up,215,216 with regular monitoring of renal status.217 Patient selection
3
and counselling are important.216

D Urinary diversion may be considered in suitable patients.

D Patients should have careful follow up and access to counselling.

35
management of cervical cancer

12.3 THROMBOTIC and bleeding problems


Patients with advanced cervical cancer are at risk of both thrombosis and haemorrhage as a
consequence of their cancer or metastatic disease.218

Treatment should take account of the patients personal views and circumstances. In
particular, physical state, prognosis and options for future therapy should be
considered.

12.3.1 DEEP VENOUS thrombosis


Risk factors for thrombosis include:
presence of pelvic masses which compress large veins
impaired mobility
effect of treatment
- radiotherapy
- surgery
- chemotherapy.
The frequency of thrombosis is underestimated as concomitant lymphoedema and oedema
from hypoalbuminaemia make diagnosis difficult and a high index of suspicion is required
(see section 9.3).
The diagnosis of deep venous thrombosis (DVT) is usually made clinically but in mobile
patients further investigation, such as whole blood D-dimer testing or ultrasound scanning 2+
may be appropriate, but need not delay the initiation of therapy for clinically diagnosed
thromboses.219
Treatment with low molecular weight heparin (LMWH) was shown to be more effective than
an oral anticoagulant in reducing the risk of recurrent thromboembolism, without increasing 2++
the risk of bleeding.220
Patients were shown to find treatment with LMWH acceptable compared to warfarin.221,222 The 4
duration of treatment should be considered on an individual basis.223

C Low molecular weight heparin should be considered for treatment of DVT and
prevention of recurrent thromboembolism.

Traditionally bed rest was advocated for mobile patients with acute DVT to reduce the risk of
pulmonary thromboembolism (PTE), leg pain and leg swelling. However bed rest can promote
stasis and may cause propagation of clot.
Some studies have shown a better clinical outcome when compression garments are used in
conjunction with LMWH and early ambulation.224,225 The American College of Chest Physicians 4
(ACCP) consensus document recommends ambulation as tolerated for DVT and the use of
elastic compression stockings to prevent post-thrombotic syndrome.226

D Compression garments, in conjunction with LMWH and early walking exercises should
be considered in patients with DVT.

All patients with suspected thrombosis should receive symptomatic relief with leg
elevation at rest and analgesia.

Compression garments should be well fitting.

36
12 MANAGEMENT OF COMPLICATIONS IN ADVANCED DISEASE

12.3.2 Haemorrhage
Relapsed cervical cancer can present with vaginal bleeding and massive haemorrhage may
occur. Bladder or bowel invasion may cause haematuria or rectal bleeding but haemorrhage
from thrombocytopenia related to marrow infiltration is unusual in cervical cancer.218
Drugs with antiplatelet activity, for example, non-steroidal anti-inflammatory drugs (NSAIDs)
or antithrombotic activity, for example, LMWH may exacerbate bleeding.227
Minor bleeds and/or infection may herald a major haemorrhage.

12.3.3 treatment of minor HAEMORRHAGE



If a minor haemorrhage occurs:
systemic causes of bleeding should be excluded
drugs that may exacerbate bleeding should be discontinued
antibiotics should be considered if sepsis is present.
Fibrinolytic inhibitors, such as oral tranexamic acid or aminocaproic acid, have been shown
to reduce bleeding.228 Topical application of tranexamic acid to superficial fungating wounds 3
or by rectal or bladder instillation may also reduce bleeding228 as may a single fraction of 4
radiotherapy.229

D Treatment for minor haemorrhage may include:


oral tranexamic acid or aminocaproic acid
tranexamic acid applied topically to superficial fungating wound
tranexamic acid by rectal or bladder instillation
a single fraction of radiotherapy.

12.3.4 management of Major haemorrhage


A major haemorrhage is defined as arterial blood loss of 1.5 litres in 30 seconds in a patient for
whom active treatment is neither appropriate nor possible and which will inevitably be fatal
within minutes in the palliative situation.
The aim is to relieve patient distress as quickly as possible. Drugs which are beneficial in this
situation are:230
midazolam for its anxiolytic effect (10 mg subcutaneously or by the buccal route), and
diamorphine for its hypotensive effect (10 mg subcutaneously if opiate-nave, two to four
times normal breakthrough dose if on regular opiates).
If the patient is peripherally constricted intravenous or intramuscular routes can be used.

If the patient wishes to be at home to die the risks of anticipated haemorrhage should
be explained to the relatives and appropriate support should be offered.
If haemorrhage is predictable when at home, dark coloured towels or blankets should
be made available to relatives to mask the extent of the haemorrhage.
Appropriate drugs should be immediately available by the bedside.
If bleeding is due to erosion of a major artery, local pressure with adequate packing
should be applied.

It is important to ensure that the patient is not left alone and, if possible, that a doctor or
nurse remains with the patient until death or resolution of the acute event.

37
management of cervical cancer

12.4 Malodour
Malodour and discharge frequently reflect advancing cancer. It is an uncommon but distressing
symptom for patients. Malodour has complex significance for a patient with advanced cervical
cancer. It impacts on body image, sense of worth and self as a social being and specifically
reinforces the fact of ill health.231
Malodourous discharges are usually due to the breakdown of tissue causing loss of fluid from
a necrotic tumour or from erosion of the bowel or urinary tract causing leakage of faeces or
urine. In addition infection may contribute to malodour.231

A careful history, psychological assessment, physical examination, imaging, microbiological


examination and biopsy may all be required to fully assess malodourous discharge.

Management should be tailored to treat infection and reduce or confine fluid loss, while
minimising local irritation or discomfort and maximising quality of life.

It may be helpful to use the patients estimated prognosis as a guide to discussing appropriate
treatment.
Most patients will require non-surgical measures to reduce malodour. If the tumour burden is
small, surgery or radiotherapy may be beneficial. A single fraction of radiotherapy may reduce
malodour. Surgery may involve:
removal or debridement of necrotic tissue
defunctioning colostomy for fistula-related faecal incontinence
bilateral percutaneous nephrostomies for fistula-related urinary incontinence.
Little published evidence is available on the treatment of malodour, although limited data exist
for the treatment of malodourous cutaneous lesions. In a prospective cohort, 41/43 patients 3
with benign or malignant disease treated with topical metronidazole gel assessed at 14 days of
treatment reported decreased smell.232
Given the paucity of evidence on malodour, the guideline development group devised a
questionnaire, which was sent to all hospices, specialist palliative care units and Gynaecology
Specialist Nurses in Scotland, to obtain a view of current practice for non-surgical treatment
of malodour and associated symptoms in patients with cervical cancer (see supplementary
material, www.sign.ac.uk).
Nine responses out of 17 were received. The results are summarised below:
all units personalised treatment to the individual patient
all units used systemic or topical metronidazole for malodour
seven units used aromatherapy, including eucalyptus and tea tree oils vaporised on a burner
for malodour
six units used charcoal outer dressings for malodour
other suggestions were the use of trays of cat litter under the bed to absorb malodour, silver
dressings and fragranced tumble dryer sheets as an odour-absorbing outer layer
all units used tranexamic acid for tumour-related vaginal bleeding either orally or topically.
Vaginal tampons were used in five units and one unit described the use of vaginal
steroids
tumour-related vaginal discharge was treated by vaginal douche, metronidazole or other
antibiotic, antifungal (oral or topical) and topical steroid. Pads and tampons were used
as dictated by patient comfort. Barrier creams to prevent skin irritation and excoriation were
used

38
12 MANAGEMENT OF COMPLICATIONS IN ADVANCED DISEASE

suprapubic catheterisation was suggested for fistula-related urinary incontinence


for fistula-related faecal incontinence subcutaneous octreotide via a syringe driver was used
to reduce faecal loss and reduce malodour. Hyoscine butyl bromide to reduce bowel activity,
and constipating agents were also used
no unit was able to supply references but all the suggestions above have been recommended
on the Association of Palliative Medicine palliative drugs bulletin board (www.palliative-
medicine.org, www.bulletinboard@palliativedrugs.com).

39
management of cervical cancer

13 Psychosocial care and support for patients and


carers
Cervical cancer has a significant psychological and psychosocial impact on the individual and
it is important to develop strategies to deal with this.233

13.1 Psychological and psychosocial distress


Psychological distress is common in patients with all forms of cancer and usually remains
undetected.234 Regardless of sociodemographic characteristics or clinical characteristics, the
well-being of patients with cervical cancer changes during the course of their disease.235 A
study of 119 patients newly diagnosed with gynaecological cancer evaluated psychological
3
well-being and functions of daily living before surgery, three months after surgery and one year
after surgery.235 There was a decline in psychological well-being and functions of daily living
scores at three months after surgery.235 After one year there was a significant improvement in
psychological well-being (p<0.05) and no significant difference in functions of daily living
compared to before surgery.235 In patients treated with surgery, the level of psychological distress
may be related to the extent of surgery.235

Patients should be advised that their physical and psychological function is likely to
deteriorate in the initial post-treatment period, but that they should anticipate
improvement.

13.1.1 identifying psychological distress


A diagnosis of cancer can be difficult to cope with and may lead to psychological distress due
to the interplay of a number of factors, including previous history of psychological disorder,
coping or adjustment style, and status and characteristics of the disease and its treatment.
Routine screening for psychological distress among people with cancer has been recommended
by the US National Comprehensive Cancer Network.236 The National Health and Medical
Research Council of Australia recommends an approach to screening for significant psychological 4
problems that includes advice to document risk factors for the presence of psychological distress
(see Table 4).148
Not all patients who present with risk factors will experience psychological distress and some
patients who present with no risk factors will present with very high levels of distress.
An example of a screening tool developed by the US National Comprehensive Cancer Network
is shown in Annex 9.236

The multidisciplinary team (MDT) should routinely screen for the presence of
psychological distress and be aware of risk factors for very high levels of psychological
distress from the point of diagnosis onwards (including during follow-up review
phases).
Multidisciplinary teams across healthcare settings should have agreed protocols
for psychological distress assessment and management. These should include
recommendations for referral and care pathways.
Liaison psychiatry and clinical psychology services should be contacted if the results
from distress screening raise concerns about the psychological well-being of a
patient.

40
13 PSYCHOSOCIAL CARE AND SUPPORT FOR PATIENTS AND CARERS

Table 4: Factors associated with increased risk of psychosocial problems in patients with
cancer148

Characteristics of the individual

Younger
Single, separated, divorced or widowed
Living alone
Children younger than 21 years
Economic adversity
Lack of social support, perceived poor social support
Poor marital or family functioning
History of psychiatric problems
Cumulative stressful life events
History of alcohol or other substance abuse
Characteristics of disease and treatment

At the time of diagnosis and recurrence


During advanced stage of the disease
Poorer prognosis
More treatment side effects
Greater functional impairment and disease burden
Experiencing lymphoedema
Experiencing chronic pain
Fatigue

13.1.2 issues that lead to psychological distress


Many of the psychological, physical and practical challenges facing women with cervical cancer
are common to all cancer patients. These include:
coping with the shock of diagnosis
pain, nausea, fatigue and disfigurement as a result of treatment
worries over practical issues such as travel costs and loss of income.
Other issues are specific to patients with cervical cancer. The level of psychological distress
experienced will vary between individuals. Table 5 lists issues that are likely to be important 4
for patients with cervical cancer.148

13.2 support needs


There is evidence that providing psychological and practical support may have a positive effect
on patients well-being.237 Evidence identified in relation to the support needs of cancer patients
was from small heterogeneous studies and the types of help offered are very varied.238-240 None 1+
of the studies was specific to patients with cervical cancer but were generalisable to the cervical 2+
cancer population. The interventions included structured psychological support, relaxation 3
techniques, orientation programmes and general psychological support. The interventions
reduced anxiety levels and improved quality of life.

41
management of cervical cancer

Table 5: Summary of issues that may be important for patients with cervical cancer148

Psychological issues

body image
new relationships post-diagnosis
sexuality.
Physical issues

bowel dysfunction
fertility
incontinence
lymphoedema
malnutrition due to lack of appetite
odour.
Practical issues

child care needs


difficulties with business dealings
loss of income
reconstructive surgery.
Survival issues

embryo storage
guilt.

There are many national and local support services, for example, voluntary agencies, clinical
nurse specialists, liaison psychiatry, clinical psychologists, local support groups, drop-in centres
and day centres (see section 13.5). These support services may offer complementary therapy
services, such as yoga, aromatherapy and reiki. It is important that only those services which
are mutually agreed to be relevant to the individual are offered.

D Patients with cervical cancer should be offered psychological support at the time of
diagnosis and at intervals throughout their management.

D Information about local support services should be made available to patients.

Voluntary sector agencies should be considered to expand the level of support available
to patients.

Women should be assessed for support needs in relation to dependants in their care
(children, older adults) and referred to the appropriate support agencies.

Partners and children of patients with cancer are also vulnerable to psychological distress. Studies
measuring stress levels of patients with colon and prostate cancer and their partners, show that
partners experience significantly more distress than patients and receive less support.148 Children 4
of parents with cancer are susceptible to levels of stress, dependent on the age and the sex of
the child, a key issue being that the childs usual support sources are often disrupted.148

D Carers, families and dependants should be made aware of support available including
local and national organisations.

Multidisciplinary teams across healthcare settings should have agreed protocols for
offering support for carers, families and dependants of patients with cervical cancer.

42
13 PSYCHOSOCIAL CARE AND SUPPORT FOR PATIENTS AND CARERS

13.3 information needs


Patients diagnosed with cancer for the first time often want information addressing their
immediate concerns regarding their disease, treatment options, what they might expect during
return appointments and who to go to for information.
Among women with gynaecological cancer, the level of knowledge about their disease has
1+
been found to be poor.241
Four studies indicate that cancer patients want information on their treatment and prognosis.242-
245
A cohort study carried out in the West of Scotland highlighted that cancer patients want 1+
to know the medical name of their illness, their treatment choices, how treatments work, the 2+
likely side effects and the chances of cure.243
The preference for, and ability to cope with, information varies between patients.246 Some patients
do not want extensive information, and the reasons for this may be complex.247 Discrepancies 3
between the need for, and actual communication of, information can contribute to difficulties
in coping with psychosocial problems.246
A systematic review of studies involving women with gynaecological cancer show that
providing patients with information is beneficial, can improve ability to cope and facilitate their 1+
participation in treatment decisions.241

C Patients should be offered information throughout their journey of care.

Health professionals should appreciate that information helps patients to understand


how their disease may affect them and to anticipate problems and plan their lives.

Patients should be offered the amount of information that is appropriate to their wishes
in a way which is sensitive, understandable and accurate.

Multidisciplinary teams across healthcare settings should have agreed protocols for
offering information to patients with cervical cancer.

13.4 communication methods


Effective communication with patients is a cornerstone of good practice. Poor communication
can increase patients psychological distress. Complaints from cancer patients about poor 4
communication with healthcare professionals and lack of continuity of care are common.248
Communication skills training delivered by expert facilitators results in demonstrable
improvements in communication behaviours of participating senior clinicians.249 1++

There is evidence that training programmes for nurses can improve listening and communication
3
skills.250
Although the included trials were small and heterogeneous, one systematic review suggested
that providing a record of the consultation with a specialist can increase both the amount of
information recalled and satisfaction with the information given.245 One randomised trial showed 1+
that patients preferred information based on their own medical records rather than general
information about their type of cancer.251
Patients prefer to receive written information to assist in making an informed choice.244 2+

B Healthcare professionals in cancer care should be trained in listening and communication


skills.

B Healthcare professionals in cancer care should consider giving either written summaries
or audiotapes of consultations to people who have expressed a preference for them.

43
management of cervical cancer

13.5 sources of further information


Many cancer care centres and public libraries have access to the internet. While the internet can
provide a vast range of information, patients should be advised to act cautiously as they may
not have the means of determining the accuracy or reliability of a site. Healthcare professionals
should guide patients to appropriate sites and advise patients that any information found on the
internet should be discussed with members of their multidisciplinary team.

13.5.1 organisations specific to cervical cancer


Jos Trust
Weedon Villa, Everdon, Northamptonshire NN11 3BQ
Tel: 01327 341965 Fax: 01327 349397
www.jotrust.co.uk Email: pamela@jotrust.co.uk
Provides online cervical cancer information and free confidential expert medical advice and
support within 12-72 hours.

13.5.2 national organisations related to Cancer


Cancer in Scotland
Scottish Government Health Department, St Andrews House, Regent Road,
Edinburgh, EH1 3DG
Tel: 0131 244 2364 Fax: 0131 244 2989
www.show.scot.nhs.uk/sehd/cancerinscotland/ Email: Cancer@scotland.gsi.gov.uk
Cancer in Scotland identifies the wide range of actions necessary to prevent, detect and improve
treatment and care for people with cancer in Scotland.
Cancer Research UK Scotland
Federation House, 222 Queensferry Road, Edinburgh EH4 2BN
Tel: 0131 343 1344
www.cancerresearchuk.org Email: christine.jason@cancer.org.uk
A free information service for patients with cancer and their families.
Cancer Research UK
PO Box 123, Lincolns Inn Fields, London WC2A 3PX
Tel: (Supporter Services) 020 7121 6699 Tel: (Switchboard) 020 7242 0200
Fax: 020 7121 6700
www.cancerresearchuk.org
A UK based charity dedicated to cancer research, which offers information about all aspects
of cancer.
Cancerbackup Scotland
Suite 2, Third Floor, Cranston House, Morrison Court, 104/114 Argyle Street,
Glasgow G2 8BH
Tel: 0141 223 7676 Fax: 0141 248 8422 Freephone: 0808 800 1234
www.cancerbackup.org.uk
A free one to one service which provides counselling and emotional support for people with
cancer and their families and friends. Produces over 60 booklets free of charge.
Macmillan Cancer Support
89 Albert Embankment, London, SE1 7UQ
Cancerline: 0808 808 2020 Fax: 020 7840 7841
www.macmillan.org.uk Email: cancerline@macmillan.org.uk
A UK charity which supports people with cancer and their families with specialist information,
treatment and care.

44
13 PSYCHOSOCIAL CARE AND SUPPORT FOR PATIENTS AND CARERS

Maggies Centres Scotland


www.maggiescentres.org
Maggies provides practical, emotional and social support to people with cancer, their family
and friends. Built alongside NHS cancer hospitals and staffed with professional experts, Maggies
Centres are warm and welcoming, full
of light and open space, with a big kitchen table at their heart.
Maggie's Dundee, Ninewells Hospital, Tom McDonald Avenue, Dundee DD2 1ZV
Tel: 01382 632 999 Fax: 01382 632998
Email: dundee@maggiescentres.org
Maggies Edinburgh, The Stables, Western General Hospital, Crewe Road South,
Edinburgh EH6 6AX.
Tel: 0131 537 3131 Fax: 0131 537 3130
Email: edinburgh@maggiescentres.org
Maggie's Fife, Victoria Hospital, Kirkcaldy, Fife, KY2 5AH
Tel: 0159 264 3355, ext. 8868 Fax: 0159 264 8062
Email: ruth@maggiescentres.org
Maggies Glasgow, The Gatehouse, Western Infirmary, 10 Dumbarton Road,
Glasgow G11 6PA
Tel: 0141 330 3311 Fax: 0141 330 3363
Email: glasgow@maggiescentres.org
Maggie's Highlands, Raigmore Hospital, Old Perth Road, Inverness IV2 3UJ
Tel: 01463 706306
Email: highlands@maggiescentres.org
Maggie's Lanarkshire, c/o Ward 9, Wishaw General, 50 Netherton Street, Wishaw ML2 0DP
Tel: 01698 366 107
Email: mhairi@maggiescentres.org
Marie Curie Cancer Care (Scotland)
29 Albany Street, Edinburgh, EH1 3QN
Tel: 0131 456 3700 Fax: 0131 456 3701
www.mariecurie.org.uk
Marie Curie Cancer Care, a comprehensive cancer care charity, provides practical nursing care
at home and specialist multidisciplinary care through its ten Marie Curie Centres.
Pain Association Scotland
Cramond House, Cramond Glebe Road, Edinburgh EH4 6NS
Tel: 0131 312 7955 Freephone: 0800 783 6059 Fax: 0131 312 6007
www.painassociation.com
For all cancer patients suffering from pain. Offers the opportunity for patients and their carers
to join support groups.
Tak Tent Cancer Support Scotland
Flat 5, 30 Shelley Court, Gartnavel Complex, Glasgow G12 0YN
Tel: 0141 211 0122 Fax: 0141 211 0010
www.taktent.org Email: tak.tent@care4free.net
Promotes the care of cancer patients, their families, friends and the staff involved professionally
in cancer care by providing practical and emotional support, information, counselling and
therapies as required. Network of local support groups throughout Scotland, including a youth
project for 16-25 year olds.

45
management of cervical cancer

13.5.3 local organisations related to Cancer


Cancer Link Aberdeen and North (CLAN)
Cancer Support Centre, Clan House, Caroline Place, Aberdeen AB25 2TH
Tel: 01224 647 000 Freephone: 0800 783 7922 Fax: 01224 640 802
www.clanhouse.org Email: enquiries@clanhouse.org
Provides emotional support and information through a team of volunteers trained in listening
skills; CLAN counsellors, with their personal experience of cancer, provide the opportunity to
talk with someone who cares and understands.
Macmillan Citizens Advice Bureau Partnership
Raigmore Hospital, Old Perth Road, Inverness, IV2 3UJ
Tel: 01463 706178
Email: macmillan.macmillancab@virgin.net
A service for those living with cancer, their carers and families. It provides advice on many
issues including benefits, employment, housing, debt, holiday insurance and community care
issues.
NoSCAN (North of Scotland cancer network)
Westburn House, Foresterhill, Westburn Road, Aberdeen, AB25 2XG
Tel: 01224 552 745 Fax: 01224 553 941
www.noscan.scot.nhs.uk Email: ruth.nisbet@.nhs.net
A network of the people in the north of Scotland striving to improve cancer care and improve
information to patients, the public and health professionals.
SCAN (South East Scotland cancer network)
Deaconess House, 148 The Pleasance, Edinburgh, EH8 9RS
Tel: 0131 536 9304 Fax: 0131 536 9071
www.scan.scot.nhs.uk Email: scan@lhb.scot.nhs.uk
Aims to bring together up-to-date, relevant and accurate information about local services for
people affected by cancer and healthcare professionals in south east Scotland.
WoSCAN (West of Scotland cancer network)
www.woscan.scot.nhs.uk Email: susan.paton@ggc.scot.nhs.uk
Strives to produce a regional service, which provides equitable access to good quality clinical
care for all cancer patients regardless of any geographical or socioeconomic factors.

13.5.4 National organisations


Dipex (Database of individual experiences)
www.dipex.org
Dipex is a website that reports on a wide variety of personal experiences of health and illness.
People can watch, listen to or read interviews, find reliable information on treatment choices
and where to find support. The site covers heart disease, epilepsy, screening programmes and
cancers.
Family Planning and Reproductive Health Care
The Sandyford Initiative, 6 Sandyford Place, Sauchiehall Street, Glasgow G3 7NB
Tel: 0141 211 8130 Fax: 0141 211 8139
www.sandyford.org/sandyford/pubpages/reproductivehealth/reproductivehealth.html
Family Planning Association Scotland
Unit 10, Firhill Business Centre, 76 Firhill Road, Glasgow, G20 7BA
Tel: 0141 576 5088 Helpline: 0141 576 5088 (Monday to Thursday 9am - 5pm, Friday
9am - 4.30pm)

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13 PSYCHOSOCIAL CARE AND SUPPORT FOR PATIENTS AND CARERS

Family Planning and Well Woman Services


Dean Terrace Clinic, 18 Dean Terrace, Edinburgh, EH4 1NL
Tel: 0131 332 7941 / 0131 343 6243
Open: Monday-Thursday: 9 30 am to 7.30 pm; Friday: 9.00 am to 3.30 pm; Saturday: 9.30 am
to 12 noon (drop-in clinic for under-25s)
British Lymphology Society
Tracy Hirst-Marsden, Administration Office, British Lymphology Society, PO Box 196,
Shoreham, Sevenoaks, Kent TN13 9BF
Tel: 01959 525524 Fax: 01959 525524
www.lymphoedema.org/bls/ Email: admin@blsac.demon.co.uk
Aims to promote awareness about lymphoedema to the public and healthcare professionals.
Produces guidelines and evidence based standards to underpin treatment for the long term
management of lymphoedema.
Lymphoedema Support Network
St Lukes Crypt, Sydney Street, London, SW3 6NH
Tel: 020 7351 0990 Fax: 020 7349 9809 Helpline: 020 7351 4480
www.lymphoedema.org/lsn Email: adminlsn@lymphoedema.freeserve.co.uk
A national patient-led organisation educating and supporting patients with lymphoedema by
providing a high standard of information and promoting self help.
Samaritans
The Upper Mill, Kingston Road, Ewell, Surrey, KT17 2AF
Tel: 020 8394 8300 Fax: 020 8394 8301 Helpline: 08457 90 90 90
www.samaritans.org.uk Email: jo@samaritans.org
Write to: Chris, PO Box 90 90, Stirling, FK8 2SA
Samaritans is available 24 hours a day to provide confidential emotional support for people who
are experiencing feelings of distress or despair, including those which may lead to suicide.
Well-being of Women
27 Sussex Place, Regents Park, London, NW1 4SP
Tel: 020 7772 6400 Fax: 020 7724 7725
www.wellbeingofwomen.org.uk Email: wellbeingofwomen@rcog.org.uk
Funds research that will translate into patient treatments, increases knowledge amongst experts
and publishes widely the outcomes of work funded and improves awareness of obstetric and
gynaecological conditions amongst women.
Womens Health Concern
Womens Health Concern Ltd, Whitehall House, 41 Whitehall, London, SW1A 2BY
Helpline: 0845 123 2319 Fax: 01628 474 042
www.womens-health-concern.org Email: info@womens-health-concern.org
Provides advice through a telephone helpline managed by experienced nurse counsellors, a
confidential question-answering service via email and information leaflets and fact sheets on
the most common gynaecological conditions.

47
management of cervical cancer

14 Implementation and recommendations for


research
14.1 local implementation
Implementation of national clinical guidelines is the responsibility of each NHS Board and is
an essential part of clinical governance. It is acknowledged that every Board cannot implement
every guideline immediately on publication, but mechanisms should be in place to ensure
that the care provided is reviewed against the guideline recommendations and the reasons for
any differences assessed and, where appropriate, addressed. These discussions should involve
both clinical staff and management. Local arrangements may then be made to implement the
national guideline in individual hospitals, units and practices, and to monitor compliance. This
may be done by a variety of means including patient-specific reminders, continuing education
and training, and clinical audit.

14.1.1 advice to nhsscotland from the scottish medicines consortium


The SMC advises that topotecan is accepted for restricted use within NHSScotland in combination
with cisplatin for patients with carcinoma of the cervix recurrent after radiotherapy, and for
patients with stage IVB disease. It is restricted to patients who are cisplatin-nave (www.
scottishmedicines.org.uk).
Overall survival and progression-free survival are significantly longer for cisplatin plus topotecan
compared with cisplatin alone. Topotecan plus cisplatin is cost effective compared to cisplatin
alone in cisplatin-nave patients. The treatments cost in relation to its health benefit is not
sufficient to be accepted by SMC for use in patients with previous exposure to cisplatin.

14.2 recommendations for research

Only 30% of cervical cancers are screen detected and the majority of cases occur in women
who have never had a smear or have not been regular participants in the screening
programme. Research is required to explore how to encourage patients who do not attend
for screening to take advantage of early detection.
During radiation treatment of cervical cancer other pelvic organs receive a significant
radiation dose resulting in both acute and late toxicity. The management of late radiation
complications is complex and requires high quality evidence to guide practice.
What are the specific support needs of women, who are diagnosed with cervical cancer or
who are undergoing treatment, at different stages of their patient journey?
Research is required on the sexual rehabilitation needs of women following treatment for
cervical cancer.
Compliance with vaginal dilation following pelvic radiotherapy is variable and generally
poor. Assistance in overcoming womens fears and teaching behavioural skills is likely
to reduce concerns and improve both knowledge of sexual activity and sexual rehabilitation
following pelvic radiotherapy. Research into psychoeducational interventions to aid this is
required.
Less radical forms of surgery for early invasive disease (eg cold knife conisation and large
loop excision of the transformation zone) need to be evaluated.
A comparison of ileal loop conduit with other methods of urinary diversion.
More research is required on the incidence and prevalence of cervical cancer related
lymphoedema. Evidence is lacking and studies are not generally comparable due to different
patient groups, treatment techniques and lack of standardised reporting of lymphoedema.

48
14 IMPLEMENTATION AND RECOMMENDATIONS FOR RESEARCH

Alternative methods of performing post-treatment surveillance. Designing programmes that


are more individualised to suit patients needs and expectations (including nurse-led follow
up compared to hospital-led) are required.
Evaluating the measurement of SCCA after treatment and using elevated levels post-
treatment to trigger PET-CT scanning to identify persistent or recurrent disease before it
becomes symptomatic.
Evidence is lacking on how to manage malodour. Good quality studies are required to
guide practice.

49
management of cervical cancer

15 Resource implications
This section is based on discussions with the guideline development group regarding current
resource use in Scotland and the likely impact of implementing the recommendations made in
the guideline. Where current practice will not change as a result of the recommendations it is
unlikely there will be resource implications.

15.1 HPV vaccination


The introduction of an HPV vaccination programme has a resource implication, but may cause
the incidence of cervical cancer to fall in the future, reducing the overall cost of cervical cancer
management.

15.2 cross-sectional imaging


The use of accurate cross-sectional imaging in staging cervical cancer is more cost effective
and less invasive than routine use of FIGO recognised investigations of IVU, barium enemas,
cystoscopy and examination under anaesthesia, with cost savings estimated at 1,100 per patient
(2.76 million across the UK, based on UK wide incidence of 2,990 cervical cancer patients
annually).13,54,58 It is also a more effective use of the pre-treatment investigative period, without
use of day or inpatient beds for anaesthetic/investigative purposes. This strategy should also
allow more compliance with government targets of urgent referral by GP to time of treatment
of 62 days.252

15.3 MRI
The use of MRI in staging is more costly (144 per patient)253 and has more limited availability
than CT (101 per patient).253 The number of patients with invasive carcinoma cervix in 2003
in Scotland was 258 (General Register Office for Scotland; data extracted 2005).254 This is likely
to represent fewer than four patients per week in Scotland requiring initial MRI staging scans,
given that stage IA1 disease does not generally require imaging. The diminishing incidence
of invasive disease as a result of screening supports the concept of image interpretation by a
limited number of experienced radiologists. The Government cancer targets are that patients
with initial cancer diagnosis should be imaged within two weeks of referral.

15.4 CT
Patients with clinically advanced FIGO IV disease may be effectively assessed with CT, as this
provides more accurate assessment of metastatic spread to lungs, thoracic lymph nodes and
other organs not included in routine MRI assessment of pelvis and abdomen. Some patients
may require a CT scan following MRI, if unexpected stage IV disease is revealed. This is likely
to reflect fewer than six patients per year. The West of Scotland incidence figures for 2005
reported three patients with stage IV disease (available from WoSCAN, see section 13.5.3).

15.5 pet
At the time of publication PET scanning has very limited availability in Scotland. It is likely that
the greatest impact of PET in initial staging will be in patients with inoperable FIGO II and III
disease. PET scans cannot replace the accuracy of surgical staging as micrometastases in lymph
nodes may not be detectable.65 The detection of possible para-aortic nodal metastases and
unexpected distant metastases in patients with inoperable disease may result in changes to the
planned radiotherapy fields. While reported sensitivities are variable for detection of metastatic
para-aortic nodes with fdg-PET, the alternative gold standard of laparoscopic staging carries
significant risk of morbidity and has estimated costs of 1,628-4,646 per patient compared to
approximate NHS costs for PET reported by ISD Scotland and the Scottish Government Health
Department of 750.253 The general reported sensitivity and specificity of fdg-PET still make

50
15 RESOURCE IMPLICATIONS

PET imaging a cost-effective alternative to inadequate radiotherapy fields, or inappropriate


treatment options.83
False positive results in PET scanning, usually secondary to inflammatory change are recognised,
and histological confirmation of metastatic disease is required before implementing a change
of treatment.65
The use of fdg-PET in assessing the extent of initial disease extent in patients with FIGO II and
III disease would amount to approximately 77 patients annually in Scotland, based on stage at
presentation from the West of Scotland incidence figures from 2005, (available from WoSCAN,
see section13.5.3) of 32 patients with FIGO II and III disease extrapolated to the total incidence
figures for Scotland (258 patients in 2003). Fewer than 150 patients per year in Scotland will
require a nine month PET-CT scan based on these incidence figures.

15.6 chest x-raY


Approximately 30% of women with cervical cancer are screen detected. The majority of these
will have operable disease. Not subjecting them to a chest X-ray stops unnecessary exposure
to radiation. There will also be a cost saving.

15.7 Squamous cell carcinoma antigen


Detection of SCCA is costly and routine post-treatment surveillance costs approx $4,750 per
recurrence detected (2001 prices, equivalent to 3,325) with a median of seven samples per
patient in a non-selected patient population comprising almost 50% early stage disease.187
Routine screening surveillance is not cost effective,187 but it may be a cost-effective test in higher
risk patients with squamous cell carcinoma to trigger an indication for a PET scan in patients
found to have elevated SCCA at pre-treatment assessment. At present this test is not routinely
available in the UK.

15.8 surgery
As a consequence of the screening programme, in time the incidence of cervical cancer will
fall, causing the throughput of patients with operable disease to become too small to maintain
the appropriate expertise in some centres.

15.9 chemotherapy
The combination of cisplatin and topotecan chemotherapy for palliation of recurrent disease
would result in the additional cost of topotecan, of treating a potential increase in the frequency
of febrile neutropenia, increased pharmacy preparation time and increased nursing and clinic
time administering drugs.

15.10 Brachytherapy
Brachytherapy must be carried out by experienced and skilled practitioners, which will have
resource implications for facilities and medical, dosimetry and physics staff.

15.11 screening for distress


Screening for distress, appropriate training to do this, and training in communication skills will
all require additional clinician time and funding.

51
management of cervical cancer

16 Development of the guideline


16.1 introduction
SIGN is a collaborative network of clinicians, other healthcare professionals and patient
organisations and is part of NHS Quality Improvement Scotland. SIGN guidelines are developed
by multidisciplinary groups of practising clinicians using a standard methodology based on a
systematic review of the evidence. Further details about SIGN and the guideline development
methodology are contained in SIGN 50: A Guideline Developers Handbook, available at
www.sign.ac.uk

16.2 the guideline development group

Dr Nadeem Siddiqui Consultant Gynaecological Oncologist,


(Chair) Glasgow Royal Infirmary
Dr Mohamed Allam Consultant Obstetrician and Gynaecologist,
Monklands Hospital, Airdrie
Dr Gerry Beattie Consultant Obstetrician and Gynaecologist,
St Johns Hospital, Livingston
Dr Rachel Connor Consultant Radiologist, Victoria Infirmary, Glasgow
Dr Maggie Cruickshank Senior Lecturer in Obstetrics and Gynaecology,
Aberdeen Maternity Hospital
Dr Fiona Downs Consultant in Palliative Medicine, Strathcarron
Hospice, Stirlingshire
Ms Diane Florence Patient Representative and Health Psychology Practitioner,
Markinch
Ms Sarah Howlett Oncology Pharmacist, Aberdeen Royal Infirmary
Sister Yvonne Hydes Ward Sister in Gynaecological Oncology,
Glasgow Royal Infirmary
Dr Jocelyn Imrie Consultant Cytopathologist, Monklands Hospital, Airdrie
Dr Roberta James Programme Manager, SIGN
Dr Carol MacGregor Macmillan Consultant in Clinical Oncology,
Raigmore Hospital, Inverness
Dr Rona McCarthy Clinical Assistant in Genitourinary Medicine, Fife
Dr David Millan Consultant Pathologist, Glasgow Royal Infirmary
Dr Kathryn Morton Consultant Pathologist, Stirling Royal Infirmary
Dr Gordon Narayansingh Consultant Gynaecological Oncologist,
Aberdeen Royal Infirmary
Dr Nicholas Reed Consultant Oncologist, Beatson Oncology Centre, Glasgow
Dr Azmat Sadozye Consultant Oncologist, Beatson Oncology Centre, Glasgow
Mr Duncan Service Senior Information Officer, SIGN
Mrs Rhona Scott Clinical Nurse Specialist in Gynaecological Oncology,
Crosshouse Hospital, Kilmarnock
Dr Emily Stenhouse Consultant Paediatric Radiologist,
Yorkhill Hospital for Sick Children, Glasgow
Mrs Allison Tait Practice Nurse, Marchmont Surgery, Edinburgh
Ms Anne Williams Cancer Nursing Research Fellow,
Napier University, Edinburgh
The membership of the guideline development group was confirmed following consultation
with the member organisations of SIGN. All members of the guideline development group
made declarations of interest and further details of these are available on request from the SIGN
Executive. Guideline development and literature review expertise, support and facilitation were
provided by the SIGN Executive.

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16 DEVELOPMENT OF THE GUIDELINE

16.3 acknowledgements
SIGN is grateful to the following former members of the guideline development group.

Ms Moira Boyle Lymphoedema Nurse Specialist, Strathcarron


Hospice, Stirlingshire
Ms Jenni Brockie Information Officer, SIGN
Ms Grace MacLeod Nurse, Cancer BACKUP, Glasgow
Ms Jacqui McGhee Liaison Radiographer, Glasgow
Mr Satchi Swami Consultant Urologist, Aberdeen Royal Infirmary
Ms Cynthia Tsang Medical Student (Year 4), Edinburgh University

16.4 systematic literature review


The evidence base for this guideline was synthesised in accordance with SIGN methodology.
A systematic review of the literature was carried out using an explicit search strategy devised
by a SIGN Information Officer. Databases searched include Medline, Embase, Cinahl, and
the Cochrane Library. The year range covered was 1999-2005, although searches for certain
questions went back to 1990. Internet searches were carried out on various websites including
the New Zealand Guidelines Programme, the Canadian Medical Association, NELH Guidelines
Finder, and the US National Guidelines Clearinghouse. The main searches were supplemented
by material identified by individual members of the development group. Each of the selected
papers was evaluated by two members of the group using standard SIGN methodological
checklists before conclusions were considered as evidence.

16.5 consultation

16.5.1 national open meeting


A national open meeting is the main consultative phase of SIGN guideline development, at
which the guideline development group presents its draft recommendations for the first time.
The national open meeting for this guideline was held on 31st August 2006 and was attended
by 130 representatives of all the key specialties relevant to the guideline. The draft guideline
was also available on the SIGN website for a limited period at this stage to allow those unable
to attend the meeting to contribute to the development of the guideline.

16.5.2 specialist review


This guideline was also reviewed in draft form by the following independent expert referees,
who were asked to comment primarily on the comprehensiveness and accuracy of interpretation
of the evidence base supporting the recommendations in the guideline. SIGN is very grateful
to all of these experts for their contribution to the guideline.

Dr Mhairi Bender General Practitioner, South Beach Surgery, Ardrossan


Dr Esther Black Clinical Psychologist in Psychosocial Oncology,
Ayrshire Central Hospital, Irvine
Dr Peter Blake Consultant Clinical Oncologist,
Royal Marsden Hospital, London
Dr Tony Branson Consultant Clinical Oncologist, Northern Centre for Cancer
Treatment, Newcastle
Dr Laurence Brown Consultant Histopathologist and Honorary Senior Lecturer,
Leicester Royal Infirmary
Dr Mairi Chong General Practitioner, Townhead Practice,
Links Health Centre, Montrose
Dr Jo Davis Consultant Gynaecological Oncologist,
Glasgow Royal Infirmary

53
management of cervical cancer

Dr Heather Deans Consultant Radiologist, Aberdeen Royal Infirmary


Dr Sonia Devereux Macmillan Lead Cancer GP, Newburgh Surgery, Tayside
Mr Michael Fraser Consultant Urologist, Stobhill Hospital, Glasgow
Mr Graham Hollins Consultant Urologist, Ayr Hospital
Professor Hedvig Hricak Chair of Radiology Department, Memorial Sloan-Kettering
Cancer Center, New York
Ms Hilary Jeffries Macmillan CNS/Lead Cancer Nurse,
Birmingham Womens Hospital
Professor Henry Kitchener Professor of Gynaecological Oncology,
St Marys Hospital, Manchester
Professor Glen McCluggage Consultant Gynaecological Pathologist,
Royal Victoria Hospital, Belfast
Ms Laura McKay Lay Reviewer, Aberdeen
Dr Graham McKillop Consultant Radiologist, Royal Infirmary of Edinburgh
Dr Kathleen W McMullen Consultant in Obstetrics and Gynaecology,
Stirling Royal Infirmary
Ms Elizabeth McNeil Gynaecological Oncology Nurse Specialist,
Raigmore Hospital, Inverness
Dr David Parkin Consultant Gynaecological Oncologist,
Aberdeen Royal Infirmary
Mr David Paul Lay Reviewer, Glasgow
Mrs Elizabeth Porterfield Head of Cancer Strategies, Scottish Government
Health Department
Mr Ian Rudd Macmillan Principal Pharmacist,
Raigmore Hospital, Inverness
Dr Anju Sahdev Radiology Consultant, St Bartholomews Hospital, London
Dr Allison Scott Consultant Gynaecologist, Family Planning and Well
Woman Services, Edinburgh
Dr Paul Symonds Reader Consultant in Clinical Oncology,
Leicester Royal Infirmary

16.5.3 sign editorial group


As a final quality control check, the guideline was reviewed by an editorial group comprising
the relevant specialty representatives on SIGN Council to ensure that the specialist reviewers
comments were addressed adequately and that any risk of bias in the guideline development
process as a whole has been minimised. The editorial group for this guideline was as
follows:

Dr Keith Brown Royal College of Psychiatrists


Professor Hillary Capell Royal College of Physicians and Surgeons of Glasgow
Professor Gordon Lowe Chair of SIGN; Co-Editor
Dr Safia Qureshi SIGN Programme Director; Co-Editor
Dr Sara Twaddle Director of SIGN; Co-Editor

54
ABBREVIATIONS

Abbreviations
5FU 5-fluorouracil
ACCP American College of Chest Physicians
CI confidence interval
CIN cervical intraepithelial neoplasia
CNS clinical nurse specialist
CT computerised tomography
DLT decongestive lymphatic therapy
DVT deep venous thrombosis
fdg-PET fluorodeoxy glucose positron emission tomography
FIGO International Federation of Gynecology and Obstetrics
GP general practitioner
Gy Gray
HPV human papillomavirus
HR hazard ratio
HRT hormone replacement therapy
IMB inter-menstrual bleeding
ISD Information Services Division, NHS National Services Scotland
IVU intravenous urography
JCVI Joint Committee on Vaccination and Immunisation
LLETZ large loop excision of the transformation zone
LMWH low molecular weight heparin
LVRH laparoscopic-vaginal radical hysterectomy
LVSI lymphovascular space invasion
MCN managed clinical network
MDT multidisciplinary team
MLD manual lymph drainage
MRI magnetic resonance imaging
MTA multiple technology appraisal
NCCN National Comprehensive Cancer Network
NHS QIS NHS Quality Improvement Scotland
NICE National Institute for Health and Clinical Excellence
NSAID non-steroidal anti-inflammatory drug
OR odds ratio
PCB post-coital bleeding
PCN percutaneous nephrostomy
PET positron emission tomography

55
management of cervical cancer

PET-CT positron emission tomography-computerised tomography


PLND pelvic lymph node dissection
PMB post-menopausal bleeding
PTE pulmonary thromboembolism
RH radical hysterectomy
RCT randomised controlled trial
RR risk reduction
SCCA squamous cell carcinoma antigen
SIGN Scottish Intercollegiate Guidelines Network
SMC Scottish Medicines Consortium
TCDO tetrachlorodecaoxygen
TPE total pelvic exenteration
WHO World Health Organisation

56
ANNEXES

Annex 1
The probability that a woman developing post-coital bleeding in the
community has cervical cancer20

There is no evidence describing how many women in the community with PCB go on to
present to primary care or how many of these women are referred on to secondary care.20
These probabilities are derived from studies carried out, in part, in secondary care so they may
result in a higher positive predictive value for cervical cancer than in women who do not get
referred for further investigation.20

Age (years) Annual Women with Annual Probability that a


cumulative cervical cancer incidence of woman developing
incidence of who present cervical cancer PCB in the
PCB per 100 with PCB (%) in England per community has
women (%) 100,000 women cervical cancer
20-24 12.6 2.6 1 in 44,000

}
25-34 7.2 11.7 1 in 56,000
11
35-44 4.8 15.8 1 in 2,800
45-54 3.4 12.7 1 in 2,400

57
management of cervical cancer

Annex 2
Algorithm for the investigation of post-coital bleeding

Women with symptoms Asymptomatic women


suggestive of cervical cancer attending for cervical
eg abnormal vaginal bleeding screening

Clinical suspicion of cancer

Local cause No clinically Clinical cancer of


(eg polyp) obvious cancer the cervix

Refer
Treat or refer to to gynaecology
gynaecology

Pre-menopausal Post-menopausal

D Test for Chlamydia trachomatis D Refer for a gynaecological


investigation
Chlamydia trachomatis testing
should be done if appropriate

Chlamydia -ve
Chlamydia +ve
no local cause

Refer to gynaecology
Refer to SIGN 42: Refer to SIGN 62:
Management of Investigation of post-
genital Chlamydia menopausal bleeding
trachomatis Include visual
Treat as appropriate inspection of cervix

58
Mesenchymal tumours and tumour-like Mixed epithelial and
Epithelial tumours Epithelial tumours (continued)
conditions mesenchymal tumours
Squamous tumours and Adenocarcinoma Carcinosarcoma (malignant
Leiomyosarcoma
precursors Endometrioid adenocarcinoma mllerian mixed tumour)
Squamous cell carcinoma, not
Annex 3
Clear cell adenocarcinoma Endometrioid stromal sarcoma, low grade Adenosarcoma
otherwise specified
Keratinizing Serous adenocarcinoma Undifferentiated endocervical sarcoma Wilms tumour
Non-keratinizing Mesonephric adenocarcinoma Sarcoma botryoides Adenofibroma
Basaloid
Verrucous Early invasive adenocarcinoma Alveolar soft part sarcoma Adenomyoma
Warty Other epithelial tumours Angiosarcoma
Papillary
Lymphoepithelioma-like Adenosquamous carcinoma Malignant peripheral nerve sheath tumour
Squamotransitional Glassy cell carcinoma variant Leiomyoma
Adenoid cystic carcinoma Genital rhabdomyoma
Early invasive (microinvasive)
Adenoid basal carcinoma Postoperative spindle cell nodule
squamous cell carcinoma
Glandular tumours and
Neuroendocrine tumours
precursors
Adenocarcinoma Carcinoid
Mucinous adenocarcinoma Atypical carcinoid
- Endocervical Small cell carcinoma
- Intestinal Large cell neuroendocrine
- Signet-ring cell carcinoma
- Minimal deviation Undifferentiated carcinoma
- Villoglandular
WHO histological classification of tumours of the uterine cervix26

Melanocytic tumours Miscellaneous tumours Lymphoid and haematopoetic Secondary tumours

Malignant melanoma Tumours of germ cell type Malignant lymphoma (specify type)
Blue naevus Yolk sac tumour Leukaemia (specify type)
Dermoid cyst
Mature cystic teratoma

59
ANNEXES
management of cervical cancer

Annex 4
National minimum dataset proforma for the histopathological reporting of
cervical neoplasia (see footnote)38

National Minimum Dataset Cervical Biopsy Histopathology Report

Surname ........................... Forenames .............................. Date of birth .......... Sex.....

Hospital ......................... Hospital No ........... NHS No ..............

Date of request .................. Date of reporting............. Report No.....

Pathologist .................. Surgeon .................

MACROSCOPY

Wedge Cone Loop biopsy of cervix measuring ....mm x .. mm and mm deep

The cervix was divided into .. blocks labelled A ..

(A) separate fragment(s) labelled , was (were) also received.

MICROSCOPY

Wart virus (HPV) infection Absent Koilocytosis HPV-associated features

CIN (cervical intra-epithelial neoplasia) Absent Epithelial changes of uncertain significance


CIN 1 CIN 2 CIN 3

Endocervical edge Clear Involved

Ectocervical edge Clear Involved

Deep lateral edge Clear Involved

Endocervical epithelium Normal Low grade CGIN High Grade CGIN

Endocervical epithelium at end of canal Yes No

Invasive malignancy Absent Microinvasive Squamous cell carcinoma


Adenocarcinoma Adenosquamous carcinoma

Microinvasive carcinoma, early stromal invasion

Microinvasive carcinoma, small confluent tumour


Maximum horizontal dimension .. mm
Maximum depth of invasion mm

N.B. If invasive foci are seen in three or more blocks of tissue, the third dimension of the lesion
(which is not routinely measured) may exceed 7 mm (i.e. more than Stage IA2).

Is there lymphovascular space involvement? Yes No

Comments

SNOMED codes
T83000 (Cervix) E3345 (HPV) / M74001 (Koilocytosis) / M74005 (Epithelial changes, uncertain
significance)
*M74008 (CIN 3) / *M74007 (CIN 2) / *M74006 (CIN 1)
M80715 (Microinvasive squamous cell carcinoma)
M80703 (Squamous cell carcinoma) M74009 (CGIN, low or high grade)
M81402 (Adenocarcinoma in situ) / M81403 (Adenocarcinoma)

Signature ....................... Date .../..../....


Signature ..................................................... Date................/....................../......................

Footnote 2007, The Royal College of Pathologists www.rcpath.org Registered charity in England and Wales, no. 261035

60
ANNEXES

Annex 4 (continued)
National minimum dataset proforma for the histopathological reporting of
cervical neoplasia (see footnote)38
National Minimum Dataset Cervical Cancer Histopathology Report

Surname ........................... Forenames .............................. Date of birth .......... Sex.....

Hospital ......................... Hospital No ........... NHS No ..............

Date of request .................. Date of reporting............. Report No.....

Pathologist .................. Surgeon .................

Gross description
Dimensions of uterus: Length ..........mm Transverse .......mm Antero-posterior........mm

Vaginal cuff: Present Absent Length .......mm

Maximum dimensions of tumour: .......mm

Histology
Type: squamous carcinoma adenocarcinoma adenosquamos
other (please specify) .

Histological differentiation: Well Moderate Poor

Tumour size: maximum horizontal dimension .......mm depth of invasion .......mm


distance from closest resection margin (minimum tumour-free rim) .......mm position of
this .

Paracervical involvement: Yes No


Parametrical involvement: Yes No
Vaginal involvement: Yes Distance from vaginal margin .......mm No
Lymphovascular invasion: Present Absent
CIN: Present Grade (please circle) 1 2 3 Absent
CGIN: Present Grade (please circle) High Low Absent

Pelvic nodes right left Common iliac nodes right left


(including obturator,
internal and external iliac)
total number of nodes total number of nodes
retrieved .. .. retrieved .. ..
lymph nodes with lymph nodes with
tumour deposits .. .. tumour deposits .. ..
Extranodal spread Yes No Yes No

Para-aortic nodes: not sampled positive negative

Extranodal spread: Yes No


Endometrium: Normal Abnormal (please state) .
Myometrium: Normal Abnormal (please state) .
Right ovary/tube: Normal Abnormal (please state) .
Left ovary/tube: Normal Abnormal (please state) .

Comments

SNOMED codes
T83000 (Cervix) M80703 (Squamous cell carcinoma) M81403 (Adenocarcinoma)
T08000 (Lymph node) M85603 (Adenosquamos carcinoma)
M80706 (Metastatic squamous carcinoma) M81406 (Metastatic Adenocarcinoma)

Signature ..................................................... Date................/....................../......................


Footnote 2007, The Royal College of Pathologists www.rcpath.org Registered charity in England and Wales, no. 261035

61
management of cervical cancer

Annex 5
FIGO staging classification for cancer of the cervix uteri37

FIGO
Description
stage
0 Carcinoma in situ (pre-invasive carcinoma)
Cervical carcinoma confined to uterus (extension to corpus should be
I disregarded)
Invasive carcinoma diagnosed only by microscopy. All macroscopically
IA
visible lesions even with superficial invasion are stage IB
Stromal invasion no greater than 3.0 mm in depth and 7.0 mm or less in
IA1
horizontal spread
Stromal invasion more than 3.0 mm and not more than 5.0 mm with a
IA2
horizontal spread 7.0 mm or lessa
Clinically visible lesion confined to the cervix or microscopic lesion
IB
greater than IA2
IB1 Clinically visible lesion 4.0 cm or less in greatest dimension

IB2 Clinically visible lesion more than 4.0 cm in greatest dimension


Tumour invades beyond the uterus but not to pelvic wall or to lower third
II of the vagina
IIA Without parametrial invasion

IIB With parametrial invasion


Tumour extends to pelvic wall and/or involves lower third of vagina and/or
III causes hydronephrosis or non-functioning kidney
IIIA Tumour involves lower third of vagina no extension to pelvic wall
Tumour extends to pelvic wall and/or causes hydronephrosis or non-
IIIB
functioning kidney
Tumour invades mucosa of bladder or rectum and/or extends beyond true
IVA
pelvisb
IVB Distant metastasis

a: The depth of invasion should not be more than 5 mm taken from the base of the epithelium, either
surface or glandular, from which it originates. The depth of invasion is defined as the measurement
of the tumour from the epithelial-stromal junction of the adjacent most superficial epithelial papilla
to the deepest point of invasion. Vascular space involvement, venous or lymphatic, does not affect
classification.

b: The presence of bullous oedema is not sufficient to classify a tumour as stage IV.

62
ANNEXES

Annex 6
Staging criteria for lymphoedema155

Stage Criteria

Subclinical stage, where swelling is not evident but lymphatic damage has
0
occurred.

1 Early onset of oedema that subsides with elevation.

2 Pitting oedema that does not subside on elevation.

3 Oedema with fibrotic changes.

Skin and tissue changes including thickening, skin folds, fat deposits and warty
4
overgrowths.

63
management of cervical cancer

Annex 7
Algorithm of imaging to detect relapsed disease

Cervical cancer treated with chemoradiotherapy

asymptomatic symptomatic

c MRI or CT should be
PET-CT scan at
considered to assess potential
nine months.
clinical recurrence.

Consider for salvage therapy

c
Pelvic MRI should Whole body PET scan or
be considered for PET-CT for all patients
surgical planning if with recurrent or persistent
pelvic exenteration disease demonstrated on
appropriate. MRI or CT.

64
ANNEXES

Annex 8
Algorithm for management of renal failure in patients with cervical cancer
(adapted from Ganatra et al)212

Identify obstructive uropathy

Investigations should be performed to exclude


additional treatable causes of renal failure
There should be a careful assessment of results
of the investigations and discussion with the
patient

bladder outlet ureteric


obstruction obstruction

urethral catheter no retrograde


PCN
suprapubic catheter treatment stent
debulking therapy

unsuccessful successful

D PCN and D More frequent D Change


attempt changes or stent
antegrade alternative every 3-4
stent stents months

D Urinary
diversion may
be considered in
suitable patients

65
management of cervical cancer

Annex 9
Screening tool for measuring distress (see footnote)236

Memory/concentration

Tingling in hands/feet
Changes in urination
YES NO Physical Problems

Other Problems: __________________________________________


________________________________________________________
Nose dry/congested
problem for you in the past week including today. Be sure to

Bathing/dressing

Feeling Swollen

Getting around
Second, please indicate if any of the following has been a

Skin dry/itchy
Constipation

Mouth sores
Appearance

Indigestion
Breathing

Diarrhea

Nausea
Fatigue

Fevers

Sexual
Eating

Sleep
Pain





















Emotional Problems
Dealing with children
YES NO Practical Problems

Dealing with partner

Spiritual/religious
Insurance/financial
check YES or NO for each.

Family Problems

Loss of interest in
usual activities
Transportation

Nervousness
Work/school

Depression
Child care

concerns
Sadness
Housing

Worry
Fears





describes how much distress you have been experiencing in
Instructions: First please circle the number (0-10) that best
SCREENING TOOLS FOR MEASURING DISTRESS

10

0
9
8
7
6
5
4
3
2
1
0
10
the past week including today.

Extreme distress

No distress

Reproduced with permission from The NCCN 1.2007 Distress Management Clinical Practice Guidelines in Oncology. National Comprehensive
Cancer Network, 2007. Available at: http://www.nccn.org. Accessed [August 1, 2007]. To view the most recent and complete version of the guideline,
go online to www.nccn.org.
These Guidelines are a work in progress that will be refined as often as new significant data becomes available. The NCCN Guidelines are a statement
of consensus of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN
guideline is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patients care or
treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application
and disclaims any responsibility for their application or use in any way. These Guidelines are copyrighted by the National Comprehensive Cancer
Network. All rights reserved. These Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express
written permission of the NCCN.

66
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72
99

ALGORITHM FOR THE INVESTIGATION OF POST-COITAL BLEEDING

Women with symptoms Asymptomatic women


suggestive of cervical cancer attending for cervical
eg abnormal vaginal bleeding screening

Clinical suspicion of cancer

Local cause No clinically Clinical cancer of


(eg polyp) obvious cancer the cervix

Refer
Treat or refer to to gynaecology
gynaecology

MANAGEMENT OF CERVICAL CANCER


Pre-menopausal Post-menopausal

D Test for Chlamydia trachomatis D Refer for a gynaecological


investigation
Chlamydia trachomatis testing
should be done if appropriate

Chlamydia -ve
Chlamydia +ve
no local cause

Refer to gynaecology
Refer to SIGN 42: Refer to SIGN 62:
Management of Investigation of post-
genital Chlamydia menopausal bleeding
trachomatis Include visual
Treat as appropriate inspection of cervix