medical protocol oncological management of cervical cancer
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MEDICAL PROTOCOL
ONCOLOGICAL MANAGEMENT OF CERVICAL
CANCER
These guidelines have been developed by members of the Gynaecological Oncology
Guidelines Group, for approval by the Merseyside and Cheshire Gynaecological
Cancer Network Group.
1. Introductions .................................................................................................................... 2
2. Prevention – Cervical Screening and Colposcopy ............................................................ 3
3. Referral ............................................................................................................................ 5
4. Histological Types and Incidence ...................................................................................... 5
5. Stage Information ............................................................................................................. 6
6. Pre-Treatment Assessment .............................................................................................. 7
Clinical Staging .................................................................................................................. 7
Pre-operative imaging ........................................................................................................ 7
7. Treatment overview ........................................................................................................... 8
8. Management of Invasive Disease .................................................................................... 8
I. Superficially invasive cervical carcinoma (microinvasive carcinoma). ............................. 9
II. Stage IBI and stage IIA less than 4 cms ......................................................................... 9
III. More advanced stage (1B2, bulky IIA and higher) and patients unsuitable for surgery
irrespective of stage ......................................................................................................... 10
9. Incidental finding of invasive cancer of the cervix found after Simple Hysterectomy ........ 10
10. Fertility-sparing treatment ............................................................................................. 10
11. Relapse ........................................................................................................................ 11
12. Adjuvant Surgery........................................................................................................... 11
13. Primary Non-Surgery for Carcinoma of the Cervix......................................................... 12
I. Concurrent Chemoradiation .......................................................................................... 12
II. Stage IA disease .......................................................................................................... 12
III. Stage IB1 and IIA disease (non bulky) ........................................................................ 12
IV. Bulky stageIB and IIA disease and stages IIB–IVA ..................................................... 13
V. Neoadjuvant chemotherapy ......................................................................................... 13
VI. Small cell cervical carcinomas (neurendocrine tumours, malignant carcinoids) .......... 13
14. Postoperative radiotherapy .......................................................................................... 14
I. Patients with involved pelvic lymph nodes: ................................................................... 14
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II. Patients with minimal resection margin and no lymphovascular space invasion: .......... 14
III. Patients with high-risk node negative disease (high grade, close resection margins and
presence of lymphovascular space invasion): .................................................................. 14
V. Patients with gross residual disease: ........................................................................... 15
Morbidity of combined treatment with radical hysterectomy and radiotherapy. ................. 15
15. Extended field radiotherapy .......................................................................................... 15
I. Prophylactic extended field radiotherapy: ...................................................................... 15
II. Irradiation of patients with known para-aortic nodal metastases: .................................. 15
16. Radiotherapy for patients with isolated local failure in the pelvis after radical
hysterectomy ...................................................................................................................... 16
17. Palliative radiotherapy .................................................................................................. 16
18. Improving Effectiveness of Radiotherapy: Hb Levels .................................................... 16
19. Chemotherapyfor advanced or recurrent cervical cancer .............................................. 17
20. Follow-Up ..................................................................................................................... 17
21. Maintenance of Quality................................................................................................. 17
22. Audit and Clinical Outcome ....................................................................................... 18
23. Clinical Trials ................................................................................................................. 18
24. Palliative Care and Nursing care ................................................................................... 18
Appendix I ........................................................................................................................... 20
Appendix II .......................................................................................................................... 22
Appendix III ......................................................................................................................... 23
References ......................................................................................................................... 24
1. Introductions
Carcinoma of the cervix is the third most common gynaecological malignancy in
women, accounting for 2500 new cases in 2011 and 919 deaths in 2012 in
England1,2. World-wide, cervical cancer is third most common cancer in women, with
an estimated 529,000 new cases diagnosed in 2008, more than 85% of the global
burden occurs in developing countries3. Overall the mortality: incidence ratio is 52%
and cervical cancer was responsible for 275,000 deaths in 2008, 88% of which
occurred in developing countries.
There is a very strong aetiological link identified between human papillomavirus and
cervical cancer. With the advent of HCII/PCR, HPV DNA has been found in 99% of
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all tested cervical cancers4. Smoking, low socioeconomic status, early age of sexual
intercourse, high number of sexual partners, use of oral contraceptive pill and history
of STDs are all thought to be surrogates for HPV exposure or relevant cofactors in
the presence of HPV DNA. All these factors are prevalent in the populations of high
deprivation as seen in the North West. Combined with poor uptake of the cervical
screening, this has resulted in high incidence and mortality rates of cervical cancer.
Among the major factors that influence prognosis are stage, tumour volume and
grade of tumour, histological type, lymphatic spread, and vascular invasion, depth of
stromal invasion with the latter being most important and reproducible5,6. A
multivariate analysis of prognostic variables in 626 patients with locally advanced
disease (II, III, and IV) studied by the GOG revealed that para-aortic and pelvic
lymph node status, tumour size, patient age, and performance status were significant
for progression-free interval and survival.
2. Prevention – Cervical Screening and Colposcopy
Compelling evidence exists that large numbers of cervical cancers can be prevented
by a well-organised cervical screening programme7. These programmes combine
cervical cytology and HPV triage as a primary screen with colposcopy, and treatment
where appropriate, for those who are screen positive. In the United Kingdom, “Health
of the Nation” targets for the reduction of cervical carcinoma incidence have been
reached many years ahead of target. A consistent fall in incidence in women aged
35 and over follows improvements in the NHS Cervical Screening Programme
(NHSCSP) and the introduction of computerised “call and recall” systems in the late
1980’s. This success reflects the high percentage of the target population who are
screened currently at 77-80%. The incidence of developing cervical cancer in
younger women is increasing and may reflect an increase in their exposure to risk
factors.
The NHSCSP has produced a number of publications which outline the standards
that are expected from those who participate in all aspects of the screening process7
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The main role of the cervical screening programme is to lower the incidence and
mortality of cervical carcinoma. However, there will be referrals to colposcopy where
it is felt that an invasive lesion may be present, and these patients should receive
urgent management on the grounds of clinical suspicion.
Merseyside and Cheshire presently has one of the highest regional incidence (10.4
per 100,000) and lowest screening cover (64-77%) for cervical cancer in the country.
The regional quality assurance team are co-ordinating initiatives to correct this
through use of social media campaigns and highlighting public health issues to NHS
commissioning boards.
Recent data have shown that Merseyside and Cheshire has the highest mortality
rate of 3.3 per 100,000 nationally1. There is strong evidence of the relationship of
deprivation and mortality rate in cervical cancer. The most deprived areas had the
highest rates of cervical cancer and were associated with poor uptake of cervical
screening. For women who do not attend regular screening, cervical cancer is
usually diagnosed at a more advanced stage which cannot be effectively treated.
Alongside the NHSCSP, to further impact of the incidence of cervical cancer, HPV
vaccination was commenced in 2008 in girls aged 12-13 with a two-year catch up
programme for girls aged up to 18. With 80% coverage of the vaccination
programme, predictions suggest its’ full effect will not be seen until 2025 and will
reduce the incidence of cervical cancer from 22-24 per 100,000 to 3 per 100,000 in
those aged less than 30. The effect on falling CIN 3 incidence is expected to be
seen five years earlier than that of cervical cancer8
Despite the vaccination programme, all women must be encouraged to attend
NHSCSP. Those born before 1990 are not affected by the HPV vaccine and those
who are vaccinated will only be protected against 70% of infections. There will be
future changes to the NHSCSP as we move towards HPV primary screening test
and development of HPV self-screening tests.
Major change occurred in 2012 to current colposcopy practice as BSCCP/NHSCSP
Colposcopy Alert was issued to recommend use of HPV testing to triage low grade
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cytological abnormalities, as well as use as an adjunct in test of cure post LLETZ
and allow appropriate discharge back to 3 year normal recall (ref 1 -HPV triage and
test of cure: implementation guidance. NHSCSP Good Practice Guide No 3 July
20119. More recently HPV testing is used to triage completely excised high grade
CGIN back to normal recall following two negative test of cure at 6 and 18 months.
3. Referral
Any woman with either post-coital or inter-menstrual bleeding, persistent vaginal
discharge or whose cervix looks abnormal should be referred by a suspected
gynaecological cancer referral (“two week wait”) to ideally a Colopscopy clinic or
alternatively a Gynaecology Rapid Access Clinic. If the patient appears to have
microscopic disease (clinically 1a1), a loop or cold knife cone biopsy should be
performed by the lead clinician locally. If a stage 1b or more (visible to the naked
eye) tumour is suspected, a biopsy only should be performed. The specimens should
be reported by a pathologist with special interest in gynaecological malignancies and
reviewed by the MDT. When the disease is higher than stage IA1, and for all non-
squamous invasive lesions, referral of the patient to the specialist gynaecological
team is indicated. All patients with biopsy proven invasive disease should be
considered for pathological review.
4.Histological Types and Incidence
Squamous cell carcinoma remains the most common histological type of cervical
cancer accounting for two-thirds of cases whereas one fifth of cases are
adenocarcinomas. Variation of morphology types are seen with deprivation, with
squamous cell carcinoma found more in highly deprived areas and adenocarcinoma
found in more affluent areas. The majority of risk factors are common for both types
of cancer, but smoking appears to be a risk factor for squamous cell carcinomas.
Screening has been most effective at detecting squamous cell carcinoma, the
incidence halved from 1988 to 2000, but in recent years it has risen again with an
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11% increase from 2008-2009. The number of adenocarcinomas had remained
stable since cervical screening in 1988 but there has been a 20% increase in 2008-
2009. Microinvasive adenocarcinomas are more difficult to diagnose than their
squamous counterparts, but when diagnosed with confidence may be amenable to
local treatment. High grade glandular intraepithelial neoplasia (adenocarcinoma in-
situ), is diagnosed and treated by cone biopsy but radical treatment tends to be
recommended for most invasive lesions. Prognosis for adenocarcinoma versus
squamous cell carcinoma is thought to be poorer due to the presence of bulkier
disease, lymph node metastasis and an increased resistance to radiotherapy. This
less favourable outcome appears to hold true in stage II cervical adenocarcinoma12.
Observed survival rates for adenocarcinoma versus squamous cell carcinoma were
poorer for regional but not localised or distant disease13.
Adenosquamous carcinomas account for 4% of cases and the percentage of cases
is lowest in women aged 75 and over. It is associated with a much poorer prognosis
in advanced stage disease than adenocarcinoma and this may be related to the high
grade seen in adenosquamous carcinoma14. Small cell carcinomas, primary
sarcomas of the cervix, malignant lymphomas of the cervix, both primary and
secondary account for a small proportion of cervical cancers. The numbers of
neuroendocrine cervical cancer have increased and are highest in women aged 20-
241. See section 13.VI.
Villoglandular adenocarcinoma is a recognised variant of cervical adenocarcinoma
associated with a good prognosis and hence require less radical surgery.
Ascertaining an accurate diagnosis of villoglandular adenocarcinoma is difficult and
poor outcomes of patients with this diagnosis have been reported due to the
presence of an underlying adenocarcinoma15.
5. Stage Information
The precursor lesion is cervical intraepithelial neoplasia [CIN], which can
subsequently become invasive cancer. This process can be quite slow. Longitudinal
studies have shown that in untreated patients with CIN 3, 18% will develop invasive
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carcinoma over a period of 10 years. Extension of the tumour in the cervix may
ultimately manifest as an exophytic growth (70%), ulceration (20%) endocervical
barrel shaped cervix or with extensive infiltration of underlying tissue including
bladder or rectum. In addition to local invasion, carcinoma of the cervix can spread
via the regional lymphatics or blood stream. Tumour dissemination is generally a
function of the extent and invasiveness of the local lesion. For this reason, patients
must be carefully evaluated for metastatic disease. Treatment is very dependent on
stage and can therefore affect management and outcome16.
FIGO Staging System (See Appendix I)
6. Pre-Treatment Assessment
Examination under anaesthetic, cystoscopy and biopsy of the cervix for histology
Sigmoidoscopy may be performed if clinically indicated
Other investigations should include:
FBC, Biochemical Profile
Chest X-Ray
MRI abdomen and pelvis
Clinical Staging
The staging should be performed by an experienced examiner under GA, including a
cystoscopy. There are occasions where outpatient clinical assessment and imaging
may be sufficient. The clinical staging should not be changed on the basis of
subsequent findings, thus allowing more accurate comparison to other treatment
regimes. There are however limitations to clinical staging.
Pre-operative imaging
Magnetic Resonance Imaging (MRI) is accurate in evaluating cervical disease, early
parametrial extension and lymph node status which translates into prognosis and
survival predictions. MRI, in terms of determining extent of tumour, is generally
superior to CT 17and ultrasound18,19, but in many cases clinical examination will be
the overriding factor. PET CT scanning should be considered in those found to have
pelvic nodal disease as they are at higher risk of disseminated disease.
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7. Treatment overview
Radiotherapy and surgery are equally effective in terms of survival for the majority of
women with early cervical cancer20. Surgical treatment should be offered to women
with early stage cancer for whom a cone biopsy is inadequate. This should be
carried out by a specialist gynaecological oncologist working within a Cancer Centre.
Radical radiotherapy should be offered when surgery is unlikely to remove the
tumour completely. The effects of radiotherapy can cause long term damage to
other organs; bowel, bladder and ovary, and this is worst when combined with
surgery. Two meta-analyses have shown convincing evidence of survival benefit for
chemoradiation over radiotherapy alone in locally advanced disease, at a cost of
greater short term toxicity and an uncertain increase in late effects20,21.
Pregnancy
Treatment of invasive cervical cancer during pregnancy depends on the stage of the
cancer, gestational age at diagnosis and patient’s wishes. All treatment options are
available for the patient and hence management is on an individual basis.
Treatment is based upon the stage of disease and patients have the option to pursue
immediate treatment following termination of pregnancy or consider fertility-sparing
surgery during pregnancy. A delay to treatment for continuation of pregnancy and
delivery when fetal maturity is reached is a reasonable strategy when the disease is
diagnosed in the second or third trimester. Depending on the stage of disease,
neoadjuvant chemotherapy can be given to stabilise the disease until delivery when
definitive treatment can occur. There is no evidence that delaying treatment will
adversely affect the outcome of the disease22,23.
8. Management of Invasive Disease
All patients with a diagnosis of invasive cervical cancer are referred for MDT opinion.
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I. Superficially invasive cervical carcinoma (microinvasive carcinoma).
Early stromal invasion consistent with stage IA1 invasive component can be
diagnosed and treated by LLETZ or knife cone biopsy at the cancer unit. The risk of
lymph node metastasis is minimal and does not justify the need for pelvic node
dissection. If fertility is not an issue, simple hysterectomy may be considered as an
alternative to ongoing cervical screening after treatment.
Stage IA2 disease within the current staging definition is treated at the centre as the
risk of pelvic and para-aortic lymph node metastasis is 5-10% and 1-3%,
respectively24. Standard treatment is by modified radical hysterectomy (Meigs 2),
with pelvic node dissection up to the aortic bifurcation. Intermediate cases of
superficially invasive disease are reviewed on an individual basis at the central
diagnostic MDT meeting and the individual management thereby determined. In pre-
menopausal patients, ovarian conservation can be recommended as the risk of
metastasis is negligible in microinvasive disease. In patients who have not
completed their family can be considered for fertility-sparing treatments (see section
10).
II. Stage IBI and stage IIA less than 4 cms
Treatment of choice is Meigs 3 radical hysterectomy with pelvic lymphadenectomy
up to the aortic bifurcation. The standard approach is for surgery to be performed
through a midline incision, though a wide transverse scar may be sufficient in
patients with a low BMI. A laparoscopic approach to a radical hysterectomy is an
accepted approach25 and is to be encouraged in appropriately selected patients. In
these patients however, there appears to be a possible increased risk of ureteric
injury (2% compared to 1%) and this should be discussed with the patient
preoperatively.
Ovarian conservation can be discussed on a case by case basis. The incidence of
ovarian metastasis in early stage cervical cancer is reported at 0.9%, 0.5% in
squamous histology and 2.4% in adenocarcinoma26 The most useful prognostic
marker for ovarian metastasis appears to be the unaffected peripheral stromal
thickness (<3mm), however this cannot be reliably identified preoperatively hence at
present macroscopically normal ovaries in young patients can be conserved.
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For patients not suitable for surgery, see section 13.1.
III. More advanced stage (1B2, bulky IIA and higher) and patients unsuitable for
surgery irrespective of stage
The preferred treatment is chemoradiation. See sections 13.IV.
9. Incidental finding of invasive cancer of the cervix found after
Simple Hysterectomy
Further management is based on the above principles. Treatment options will
therefore, lie between expectant management, node dissection (open or
laparoscopic) with or without radical parametrectomy, or chemoradiation.
10. Fertility-sparing treatment
Radical trachelectomy combined with laparoscopic pelvic lymphadenopathy has
been shown to be an effective option for women who wish to preserve their fertility
whilst treating early stage cervical cancer. Successful outcomes for pregnancy and
cure rates have been demonstrated by various groups27,28,29,30 . The procedure
involves wide excision of the cervical tumour with surrounding para-cervical and
upper vaginal tissue whilst preserving the uterine body and is performed in
conjunction with laparoscopic pelvic lymphadenopathy. In carefully selected
patients, stage IA1 with LVSI, stage IA2 and small (<2cm) stage IB1, recurrence and
mortality rates, 4.7% and 3% respectively, are comparable to radical hysterectomy31.
Trachelectomy has been performed in larger stage IB1 tumours but recurrence rates
approach 20%30.
Preoperative evaluation prior to consideration of a trachelectomy includes a EUA
(and assessment of the cervical length), MRI and careful counselling regarding the
risks associated with the procedure. Published figures have shown a 30% chance of
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pregnancy following trachelectomy with 62% having a successful outcome30. One
study has shown that the chance for pregnancy was actually higher, 66% when the
outcome was measured only in women attempting conception after trachelectomy32.
Patients must be counselled regarding 15-35% risk of a preterm (potentially
extremely preterm) delivery31,33. In the Liverpool Women’s Hospital, all women who
have undergone a radical trachelectomy have a prophylactic cervical cerclage
placed at the time of the original surgery, and are followed up during any subsequent
pregnancy by the recurrent miscarriage/preterm clinic as they are highlighted as a
high risk pregnancy.
Conservative surgical management of small stage IA2 and IB1in the absence of
LVSI has been shown to be as effective as radical treatment34,35. Treatment involves
knife cone biopsy and laparoscopic pelvic lymphadenectomy.
11. Relapse
Local relapse after primary surgery is considered in most cases for radical
chemoradiation. Patients who relapse centrally after radiotherapy are carefully
assessed for salvage surgery. Assessment involves histological confirmation, formal
EUA, MRI and PET scan as pelvic exenteration is associated with significant
morbidity and mortality and is considered only in carefully selected patients.
Metastatic disease is managed with palliative chemotherapy +/- radiotherapy.
12. Adjuvant Surgery
The place of hysterectomy as a routine adjunct to pelvic radiotherapy is
controversial. The increased risk of combined modality treatment is not necessarily
balanced by improved outcome36. Neoadjuvant chemotherapy with surgery has
been proposed. The results from a Cochrane review of neoadjuvant chemotherapy
and surgery versus surgery alone suggested there may be benefit from NAC but the
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only statistically significant result was for progression-free survival37. At present
there is no evidence to offer neoadjuvant chemotherapy and surgery over
chemoradiation.
In this centre, adjuvant surgery may be considered for patients who have persistent
disease following a poor response to chemoradiotherapy for stage IB2 bulky disease
where further treatment with brachytherapy is not appropriate. If surgery is
contemplated, it should ideally be performed within 6 weeks of completing
chemoradiation to minimise the effects of fibrosis.
13. Primary Non-Surgery for Carcinoma of the Cervix
I. Concurrent Chemoradiation
This is now standard practice for patients with bulky or locally advanced disease who
are fit for the combined approach. There have been six North American based
randomised trials published since April 1999, and there have been 2 meta-analyses,
one of 19 studies20, the other comprising 8 English language publications using only
cisplatin based chemotherapy38. All except one of the US trials showed a clear
benefit for this approach in terms of improved disease control in the pelvis and a 10–
15% improvement in overall survival38,39,40,41,42,43. The overview demonstrated both
an improvement in overall survival but also improved local and distant control rates20.
The acute toxicity is greater with concurrent chemotherapy and potentially higher
rate of late complications. This approach is considered in all patients with locally
advanced carcinoma of the cervix who have good performance status and
considered suitable for radical treatment44.
II. Stage IA disease
Radiotherapy is not recommended for early-stage disease.
III. Stage IB1 and IIA disease (non bulky)
There is agreement that for these patients either radical chemoradiation or radical
hysterectomy are equally effective treatments with approximately 85-90% of patients
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being cured with either modality45,46. Radical hysterectomy and radiotherapy are
associated with different types of complications. The choice of treatment depends
on the general health of the patient. Surgery is generally recommended for pre-
menopausal women as preservation of ovarian function is possible and vaginal
stenosis can be avoided. The risk of late bladder and bowel toxicity is also less after
surgery. For less fit patients surgery with prolonged general anaesthesia is best
avoided and these patients are generally treated with radiotherapy or
chemoradiation. As the risk of pelvic lymph node involvement is estimated to be
15%, our policy is to treat these patients with a combination of external beam
radiotherapy and intracavitary treatment. For less fit patients, intracavity treatment
alone can be considered accepting a higher risk for nodal failure.
IV. Bulky stageIB and IIA disease and stages IIB–IVA
These patients are best treated with a radical course of chemoradiation. Less fit
patients may be treated with radiotherapy alone.
V. Neoadjuvant chemotherapy
This is not routinely recommended.
VI. Small cell cervical carcinomas (neurendocrine tumours, malignant
carcinoids)
Combined modality treatment is recommended with chemotherapy and radiotherapy
in patients with good performance status. The standard regimen in Clatterbridge
Centre for Oncology for small cell tumours is : Carboplatin AUC 6 and Etoposide
100mg/m2 daily X 4 cycles, followed by radiotherapy for localised disease.
Radical hysterectomy and pelvic lymphadenectomy should be considered in patients
with stage IA - IBI (<2cm) as survival benefit has been shown compared to those
who did not have radical hysterectomy47.
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14. Postoperative radiotherapy
This is considered for patients at high risk for disease recurrence. These include the
following groups of patients.
I. Patients with involved pelvic lymph nodes:
There are no randomised trials looking at the benefit of postoperative XRT in this
situation. One study showed that for patients with a single positive node with small
primary tumours the prognosis is good without radiotherapy48.
Our current policy is to consider adjuvant chemoradiation to patients with more than
one involved pelvic lymph node, or where there is extracapsular spread.
II. Patients with minimal resection margin and no lymphovascular space
invasion:
Patients with a margin of 1mm and no lymphovascular invasion after radical
hysterectomy do not require adjuvant radiotherapy.
Our policy is to offer close surveillance.
III. Patients with high-risk node negative disease (high grade, close resection
margins and presence of lymphovascular space invasion):
Patients with high grade disease, close resection margins with the presence of
lymphovascular invasion seen in the radical hysterectomy specimen should be
considered on an individual basis for postoperative chemoradiation.
Our policy is to discuss postoperative chemoradiation.
IV. Patients with high-risk node negative patients (involved resection margins):
A GOG randomised study showed that for patients with negative pelvic nodes and
either large primary tumours, lymphovascular invasion or deep stromal invasion,
there was an advantage for postoperative radiotherapy in terms of reducing the risk
of recurrence. No survival advantage was seen and the rate of major complications
was 6% in the combined treatment group vs 2% in the patients treated with radical
hysterectomy45.
Our current policy is for discussion for chemoradiation with these patients.
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V. Patients with gross residual disease:
Patients with gross residual disease after radical hysterectomy have poor outcomes.
These patients should be offered radical course of chemoradiation.
Morbidity of combined treatment with radical hysterectomy and radiotherapy.
There is evidence that the major complication rate is increased with combined
treatment. One randomised study comparing surgery with radiotherapy described a
28% rate of major complications in the surgical arm versus 12% with radiotherapy49.
For this reason it is important to predict patients who are likely to need postoperative
radiotherapy if treated with radical hysterectomy, such as those with tumours >4cm.
These patients are best treated with chemoradiation.
Our aim is to carefully select patients for surgery and to avoid postoperative
radiotherapy as it is associated with much greater morbidity.
15. Extended field radiotherapy
Extended field radiotherapy, which includes para-aortic nodes, is associated with an
increased rate of acute and late toxicity.
I. Prophylactic extended field radiotherapy:
There is evidence from one randomised study that extended field radiotherapy offers
a survival advantage compared with pelvic radiotherapy for stage I and II patients
with a high risk of para-aortic nodal metastases i.e. those with either bulky disease or
involved pelvic lymph nodes8. However one of the recent chemoradiation trials
compared extended field radiotherapy with chemoradiation and found the latter to be
better in terms of overall and disease free survival50.
II. Irradiation of patients with known para-aortic nodal metastases:
The management of patients with multiple grossly involved para-aortic nodes is
generally palliative. A published single arm study using extended field radiotherapy
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and concurrent chemotherapy reported a three year overall survival rate of 39% for
patients with para-aortic nodal metastases51. Both acute and late toxicity was
substantial. In highly selected patients this approach may have a curative potential.
16. Radiotherapy for patients with isolated local failure in the pelvis
after radical hysterectomy
Patients with small volume central recurrences can be salvaged with exenterative
surgery or chemoradiation. Patients with bulky recurrences have a poor prognosis
and may be considered for neoadjuvant or concurrent chemotherapy. Decisions
regarding the use of chemotherapy are made on an individual basis.
17. Palliative radiotherapy
This is considered for patients with either advanced, recurrent, metastatic disease or
for unfit patients with any stage of disease. Palliative local radiotherapy is
particularly effective for bleeding, discharge or pain. Depending on the performance
status of the patient external beam or intracavitary or combinations of both can be
used.
18. Improving Effectiveness of Radiotherapy: Hb Levels
The presence of oxygen has important implications in effectiveness of radiotherapy.
Hypoxia plays an important role in tumour resistance in most solid tumours including
carcinoma of the cervix. There is growing evidence in the literature that local control
by radiotherapy is closely related with haemoglobin levels and this reflects the
overall survival. Our policy at CCC is that all patients with cervical carcinoma
undergoing radical radiotherapy should have weekly blood test for FBC and would
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require blood transfusion if Hb is <12g/dl. Selected patients may benefit from
prophylactic use of growth factors (Erythropoetin) where the Hb level prior to starting
chemoradiation is <12.0g/dl52.
19. Chemotherapyfor advanced or recurrent cervical cancer
The role for chemotherapy in this setting is palliative. The benefits and side effects
need to be discussed and decision made on an individual basis. Cisplatin
chemotherapy remains the drug of choice with a response rate is in the region of
30% and duration of response of 6-9 months. The national UK survey on use of
palliative chemotherapy showed no consensus on chemotherapy regimes in this
setting53.
The current options used at CCC include
Single agent platinum
BMC (bleomycin, mitomycin C, cisplatin)
Carboplatin and taxol
Cisplatin and topotecan has shown a high response rate but with
significant toxicity54
20. Follow-Up
Standard: Four monthly for years 1 and 2, six monthly to 3 years. Discharge with
open access to CNS in the event of new symptoms or concerns. CNS holistic
assessment is carried out 6 weeks after the completion of primary treatment.
21. Maintenance of Quality
These guidelines conform to:
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Improving outcomes in Gynaecological Cancers NHS Executive 1999-10-21
RCOG recommendations on specialists in gynaecological oncology 1996
NIH Consensus Statement on Chemoradiation 1999
22. Audit and Clinical Outcome
Gynaecological database is now in place which will facilitate clinical audit and
research.
23. Clinical Trials
The Cancer Network is committed to an active involvement in research, both at a
local /national/international level. Please refer to CCC live clinical trials database for
current trials in Gynaecological Oncology.
MCCRN trials website
24. Palliative Care and Nursing care
Palliative care input is appropriate to consider at all stages of the patient’s cancer
journey. Please refer to the separate palliative care guideline for detailed advice. All
women with a diagnosis of a Gynaecological Cancer should be offered the support
of, and have access to a Clinical Nurse Specialist (CNS), in order to facilitate the
woman’s needs throughout the Cancer Journey, including those of her partner or
carer.
The skills of the C.N.S. as a consultant, practitioner and educator can be drawn upon
at all stages throughout their illness, from the pre-diagnosis to the terminal stage –
incorporating the Specialist Palliative Care Services provided in the hospital and the
community setting. Bereavement Support will also be available, if appropriate.
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Important aspects of the role are to provide advice, support, and information and to
effectively incorporate appropriate resources. The C.N.S. will be receptive to the
social, physical, psychological, cultural, sexual and spiritual needs of the patient.
The aim of the patient support is to assist with the improvement in the quality of their
lives, allowing them to become more empowered; to help take control and enhance
their self-esteem.
The C.N.S. works closely with Surgeons, Oncologists, Radiotherapists, Consultants
in Palliative Medicine and others (Nurses & P.A.M.s).
They will undertake a number of key responsibilities including:
Linking with other professionals who can help the patients throughout the
system
A resource for information and support to the patient carer and other H.C.P.s
Liaison point for other health care professionals in primary and secondary
care
Teacher and Educator
Researcher
Standards and Audit Co-ordinator
Co-ordinate Care Services
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Appendix I
FIGO Staging System
Stage I Clinical lesions strictly confined to cervix
IA Preclinical carcinomas of cervix diagnosed only by microscopy. All
gross lesions even with superficial invasion are stage IB cancers. Invasion is
limited to measured stromal invasion with maximum depth of 5.0 mm and no
wider than 7.0 mm (1)
IAI Stromal invasion no greater than 3.0 mm and no wider than 7.00
mm
IA2 Maximum depth of invasion of stroma greater than 3 mm and no
greater than 5 mm taken from base of epithelium, either surface or glandular,
from which it originates; horizontal invasion not more than 7 mm
IB Clinical lesions confined to the cervix or preclinical lesions greater than stage
IA
IBI Clinical lesion no greater than 4.0 cm in size
IB2 Clinical lesion greater than 4.0 cm in size
Stage II Extension beyond cervix but not to pelvic wall. Involves vagina, but not
the lower third
IIA Involves vagina, but not lower third. No obvious extension to
parametria
IIB Obvious parametrial involvement but not extending to pelvic sidewall
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Stage III Extension to pelvic wall.On rectal examination, no cancer-free space
between tumour and pelvic wall. Involves lower third of vagina
IIIA Involves lower third of vagina
IIIB Extension to pelvic side wall and/or hydronephrosis or non-functioning
kidney
Stage IV Extension beyond true pelvis or involvement of bladder or rectal
mucosa. Bullous oedema does not permit a case to be assigned to
Stage IV (IVa = local spread; IVb = distant mets)
Notes: Diagnosis of both Stages IA1 and IA2 is based on microscopic examination of
biopsy specimens, preferably a cone, which must include the entire lesion.
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Appendix II
Radiotherapy Details
External Beam radiotherapy:
All patients are planned using CT imaging to outline the gross tumour and clinical
target volume.
Dose Fractionation:
Stage IB1and non-bulky IIA:
XRT: 45 Gy in 25 fractions over 35 days
Brachytherapy: HDR: 7Gy x 3 to point “A”: over 10 days using
MRI compatible ring applicator
Stage IB2, IIB, III and IVA:
XRT: 50.4 Gy in 28 Fractions over 38 days
Brachytherapy: HDR: 7Gy x 3 to point “A”: over 10 days using
MRI compatible ring applicator
Palliative XRT:
30 Gy in 10 fractions over 14 days or
20 Gy in 5 Fractions over 7 days
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Appendix III
Chemotherapy Regimes
Adjuvant treatment for Cervical Cancer Not currently recommended as standard therapy Pre-XRT BMC Bleomycin 30,000 iu IV day 1 Mitomycin-C 10mg/m2 IV cycles 1,3 Cisplatin 50mg/m2 IV day 1 Repeat every 14 days for 2-4 cycles Advanced Squamous Carcinoma Cervical Cancer Cisplatin / Topotecan Criteria 1.>6m from completion of chemo-radiation to relapse
2. no prior radiosensitisingcisplatin 3. PS 0-1
Cisplatin 50mg/m2 IV day 1 Topotecan 0.75mg/m2 IV days 1-3 Repeat at 21 day intervals for 4-6 cycles
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