cancer template draft #1 - nhs wales carcinoma... · web viewthe known increased incidence of...

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CERVICAL CARCINOMA

Index

1. Screening

2. Ref erral pathway 2.1 For GP2.2 For non-oncological consultants/ firms2.3 For referral from unit to centre

3. Diagnosis 3.1 Early invasion3.2 Clinical invasive disease

4. Investigations 4.1 Examination under anaesthesia4.2 MR and CT imaging 4.3 Other investigations4.4 Relative benefit over other management options and resource implications

5. Gynaecological cancer multidisciplinary team 5.1 Information

6. Pathology 6.1 Modified WHO histological classification

7. Staging

8. Histopathology minimum dataset

9. Treatment 9.1 Surgery9.1.1 Loop/ cone9.1.2 Radical trachelectomy 9.1.3 Wertheim hysterectomy 9.1.4 Shauta hysterectomy9.1.5 Laparoscopic node dissection9.1.6 Cancer complicating pregnancy9.1.7 Cervical stump carcinoma/ management of unsuspected carcinoma after simple hysterectomy9.1.8 Management of stage Ib2 carcinoma9.2 Radiotherapy and chemoradiation 9.2.1 Radical treatment9.2.2 Adjuvant treatment9.3 Chemotherapy9.4 Management of advanced disease

North Wales Cancer Guidelines, Cervical Cancer (June, 2008) 1

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10. Dealing with recurrent disease 10.1 Imaging10.2 Chemotherapy10.3 Pelvic exenteration10.4 Palliative care10.5 Obstructive uropathy

11. Survival 11.1 Cancer dataset/ inventory of active trials

12. Follow up 12.1 Identification and management of late effects of treatment

13. Contact names/ numbers

14. Algorithm

15. Summary

16. References

Appendix 1: Relative benefit over other management options and resource implications for imaging


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IntroductionCervical carcinoma is the second commonest cause of female cancer worldwide but accounts for about 2% of all cancers in women in the UK. 3400 new cases are diagnosed each year in England and Wales of which about 1200 women die of their disease (NHS Executive, 1999). The incidence and death rate for cervical carcinoma has been declining since records began in the early part of this century. However, the incidence of adenocarcinoma in 2001 had increased by 45% from 1971 (1.6/100,000 in 2001). The incidence of squamous carcinoma declined by 54% since 1971 (8.6/100,000 in 2001). Indeed the incidence has fallen by 42% between 1988 and 1997 in England and Wales. Incidence is declining in all age groups but over 25% of women are diagnosed over 65 years of age. Mortality for all cases has declined by 67% from 1971-2001 (2.7/100,000 in 2001; Quinn et al, 2001). This appears to be despite the increasing incidence of CIN and may reflect the apparent success of the national cervical screening programme which has been estimated to save 4500 lives/ year in England. Carcinoma of the cervix is most prevalent in Wales and the North of England and in the unskilled.

The patient may be asymptomatic and detected up by cervical cytology. Fifty percent of women present at an early stage appropriate for a surgical cure.

1. Screening Following the introduction of computerised recall in 1988 the incidence of cervical cancer has declined by 7% per annum and has been the major contribution to the decline in mortality from this disease. Presently 3 yearly screening is from 20–65 years of age in Wales. There are slight variations throughout the rest of the UK. HPV testing and HPV vaccination are currently undergoing evaluation.

2. Referral pathway (see 13. Contact names/ numbers)

2.1 For GPIf cervical cancer is suspected then referral should be to a general gynaecologist, the lead in the cancer unit or gynaecological oncologist in the cancer centre.

2.2 For non-oncological consultants/ firmsIf the diagnosis is suspected or confirmed referral to the local unit lead or gynaecological cancer centre should be made.

2.3 For referral from unit to centreThis is appropriate for all cancer cases FIGO substage Ia2 or greater.


StandardsRapid access to the specialist should be available with the patient seen within 2 weeks of date of receipt of the referral letter/ fax.

Definitive treatment should be commenced no later than 62 days after receipt of the referral letter/ fax.

Definitive treatment should be commenced no later than 31 days after diagnosis for non urgent suspect cancer referrals.

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3. Diagnosis This usually depends upon colposcopic examination where features of high grade CIN (large lesion, mosaic, punctation) or invasion (abnormal vasculature, ulceration) may be present. Diagnosis depends on a suitable sized biopsy (loop or cone). Punch biopsy may not be satisfactory as a means of colposcopic diagnosis (ie for lesions that are not macroscopically visible).

3.1 Early invasion (see 9.1. Surgery)The diagnosis of Ia disease requires a loop or cone biopsy. The term microinvasive is used in different senses by different authors and is probably best dropped from common usage. Stage Ia1 and Ia2 squamous carcinoma is defined by the FIGO staging system ( see 7 ) . Debate surrounds the prognostic value of lymphovascular space involvement in stage Ia tumours. In the United States prevailing opinion is that if a tumour shows lymphovascular space invasion it cannot be included in the stage Ia category but others feel that evidence of the value of lymphovascular space invasion prognostically is still unclear or that it is probably only of value in the 3-5mm deep early invasive group. A diagnosis of stage Ia disease cannot be made in a biopsy where excision of tumour is incomplete.Whilst the FIGO classification does not specifically exclude the application of stage Ia1 and 2 categories to invasive adenocarcinoma it has in the past been felt that there is insufficient data to define stage Ia1 and Ia2 adenocarcinoma in prognostic terms. What data is accumulating suggests that for tumours less than 2-3mm deep outcome in invasive adenocarcinomas is probably very good and similar to that for stage Ia squamous carcinoma. Management of multifocal < 3mm depth of penetration disease must be discussed with the cancer centre MDT team.

3.2 Clinical invasive diseaseMore advanced lesions may present with a mass detectable at digital examination and diagnosed with a wedge, loop biopsy or punch biopsy.

4. Investigations The patient with a bulky stage Ib or more advanced tumour may require an examination under anaesthesia to determine suitability for operative treatment.

4.1 Examination under anaesthesiaExamination under anaesthesia requires a vaginal examination to determine the degree of encroachment of tumour into the vagina, to the pelvic side wall and the mobility of any mass. A biopsy is then taken. Cystoscopy and sigmoidoscopy may be helpful but cystoscopy and sigmoidoscopy should not be routinely performed for staging purposes for all cancers (grade B recommendation).Rectal examination allows assessment of parametrial involvement and spread of tumour toward the pelvic sidewall. Simultaneous rectal and vaginal examination may provide improved assessment of the uterosacral ligaments and pelvic sidewall compared to rectal examination. Clinical staging may underestimate the extent of tumour due to difficulties in assessing parametrial, pelvic sidewall, rectal and bladder invasion as well the presence or absence of metastatic disease.

4.2 MR and CT imaging Primary tumour size (>1cm diameter; Fujiwara et al, 2000), vaginal invasion, presence of lymphadenopathy (>1cm diameter) and ureteric involvement are ideally assessed with an MR scan of the pelvis and abdomen (NHS Executive, 1999; grade B recommendation). MR imaging is therefore appropriate for all patients with biopsy proven invasive cervical cancer that is colposcopically visibleie. > 7mm diameter or > stage Ia2. Exceptions are those patients with clinically advanced stage IV disease or contraindications to MR scanning when post contrast CT scanning will suffice.MR technique is identified as being important in correct staging. Thin section T2 sequences including those perpendicular to the long axis of the cervix, are of most value in primary tumour assessment (Sironi et al, 2002; Shiraiwa et al, 1999) Intravenous contrast in MR is non contributory in primary tumour staging (Sheu et al, 2001; Choi et al, 2004; Sironi et al, 2002).


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There are variable results of accuracy of parametrial staging of MR and CT (Bipat et al 2003; MSAC 2001, Hricak et al. 2005a), but MR is generally superior, with specificity of approximately 85% and sensitivity of approximately 55-70%. The greatest value of MR in influencing correct management options lies in the high negative predictive value (85%) for parametrial invasion (Hricak et al, 2005b), thus conferring operable versus inoperable status. Absence of bladder and rectal invasion can be assessed reliably by MR (Rockall et al, 2006; evidence level IIb, grade B recommendation) and if combined by vaginal examination in clinic can accurately stage cervical cancer in the majority of cases. Sensitivities to bladder (75%) and rectal involvement (71%) are better with MR than CT (60% and 42% respectively), but MR has a considerably higher specificity than CT in determining bladder invasion (91% versus 71%). Specificities are similar (80%) for determining rectal involvement (Bipat et al, 2003). MR therefore provides a high negative predictive value for bladder or rectal invasion.Post contrast spiral CT is a good alternative in patients who may not be MR compatible (good practice point). CT imaging of the abdomen and pelvis is a useful alternative for advanced (stage IV) disease, assessing lymph nodes, mapping for radiotherapy and guidance for directed biopsies.

4.3 Other investigationsLimited recent data is available on the use of chest X rays in staging, but as the yield of metastases in patients with clinical stage IIb or greater is reported as 4%, this is likely to be an accepted, widely available, non controversial and inexpensive imaging addition to determining FIGO stage in these patients.CT scans are more accurate in identifying pleural effusions, thoracic nodal status and parenchymal metastases (ACR Appropriateness Criteria, 2005).Intravenous urography has been superceded as a stand alone investigation, as CT or MR (or ultrasound) are as accurate in determining ureteric obstruction secondary to parametrial invasion and give additional information.Barium enemas are not routinely indicated (ACR appropriateness criteria, 2005). Ultrasound is not reliable in either assessment of primary tumour size or nodal status (Hricak and Yu, 1996).Despite lack of inclusion in FIGO staging criteria, it is generally agreed that the involvement of pelvic or para-aortic lymph nodes in most histological types of cervical cancer, is the greatest single predictor of long term survival. Lymphangiography is an invasive test, not now routinely available in many radiology departments and positive predictive values in cervical carcinoma values are variable, but probably comparable to MR and CT for the detection of involved pelvic and para-aortic nodes. There is consistent evidence that both CT and MR have poor sensitivity for detection of nodal metastases, based on size criteria. PET/CT is likely to become a standard investigation tool over the next 5 years. In particular PET may provide precise restaging information for patients with recurrent or locally advanced cervical cancer being evaluated for salvage therapy (Nakamoto et al, 2005). Patient numbers in PET studies tend to be small, (due to the more recent introduction of this imaging technique) but results appear consistent that PET is superior to MR and CT in the detection of metastatic pelvic and para-aortic nodes, with higher sensitivities and specificities (Rose et al, 1999a). However, sensitivities remain suboptimal, and perhaps technique dependent, in <10mm sized nodes. PET shows improved accuracies over CT or MR in the detection of metastatic lymphadenopathy and therefore the potential to significantly change patient management.Patients with inoperable tumour (stage IIb+; or bulky Ib2 tumours, if node negative on MR or CT cross sectional imaging), should be considered for PET/CT imaging to determine optimal radiotherapy fields as more than 30% of these patients will have nodal metastases.

4.4 Relative benefit over other management options and resource implications (see appendix 1)


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5. Gynaecological cancer multidisciplinary team

Core team Named team member Additional member or Cover (core team only)

Gynae oncologist Mr Leeson / Mr ToonGynae lead cancer surgeon Mr Bickerton/ tbaMedical oncologist Prof Stuart Dr WilliamsClinical Oncologist Dr Al-Sammarie tbaPathologist/ Cytopathologist Dr Lord tbaPalliative care team Dr Williams tbaRadiologist Dr Barwick Dr WenhamMDT co-ordinator Ms Jones tbaCNS Ms HallExtended team

Ultrasonographer tbaJunior doctorsPsychologistGeneticist Ms GrierSocial worker tbaWard Sister Sr WilliamsResearch nurseColorectal/ urological/ plastics as required

5.1 Information


StandardsAll patients must have access to a gynaecological oncology clinical nurse specialist within 24 hours of the patient being informed of her diagnosis (this should include a daytime contact telephone number for the clinical nurse specialist). Preferably the nurse specialist should be at the consultation when the patient is given her diagnosis.

All referring practitioners and/ or patients GP’s should be informed by letter or secure fax within 24 hours of the patient being informed of her diagnosis.

All patients must be given appropriate literature about the management, treatment and outcome for cervical cancer such as a Cancerbackup leaflet or equivalent.

All these activities must be documented in the patient’s case record.

Core/ extended teams to include members from YGC/ NEWT

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6. Pathology Squamous carcinoma of the cervix makes up 60-90% of all carcinomas at this site, followed by adenocarcinoma making up 10-34% of cases. There are significant problems with classification of carcinomas of the cervix and dependent on the definition used adenosquamous carcinomas in some series may make up to 30-40% of all cases. The known increased incidence of adeno- or adenosquamous carcinoma may be real or apparent due to increased awareness and reporting of these histological types. Other variants such as adenoid cystic and adenoid basal carcinoma are much less frequent as well as the so-called as are adenoma malignum (minimum deviation carcinoma), the small and large cell neuroendocrine type carcinomas and other tumours such as malignant melanoma. A histological classification of invasive carcinomas of the uterine cervix (as modified by Wright et al, 2002) is given below.

6.1 Modified WHO histological classificationSquamous cell carcinoma

Invasive squamous cell carcinomaKeratinizing

Large cellSmall cell

Non keratinizingLarge cellSmall cell

Verrucous carcinomaWarty (condylomatous) carcinomaPapillary squamo-transitional carcinomaLymphoepithelioma-like carcinoma

AdenocarcinomaMucinous adenocarcinoma

Endocervical typeIntestinal typeSignet-ring type

Endometrioid adenocarcinomaEndometrioid adenocarcinoma with squamous metaplasia

Clear cell carcinomaMinimal deviation carcinoma

Endocervical type (adenoma malignum)Endometrioid type

Well-differentiated villoglandular adenocarcinomaSerous adenocarcinomaMesonephric adenocarcinoma

Other epithelial tumoursAdenosquamous carcinomaGlassy cell carcinomaClear cell adenosquamous carcinomaMucoepidermoid carcinomaAdenoid cystic carcinomaAdenoid basal carcinomaTypical carcinoid tumourAtypical carcinoid tumourSmall and large cell neuroendocrine carcinomaUndifferentiated carcinoma.


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Within an individual stage the known significant pathological prognostic factors for surgically treated stage Ib and 2a squamous carcinoma are tumour size, depth of invasion, parametrial involvement and nodal status. Presence or absence of lymphovascular space involvement also appears important. All histological reports should include all of the information laid out in the minimum dataset of the Royal College of Pathologists, or the tumours should be reported using minimum data set proformas.

Variants of squamous carcinoma of the cervix include true verrucous carcinomas, which produce extensive, large, local tumours without nodal metastases, so-called warty or condylomatous carcinomas and papillary squamo-transitional carcinomas that resemble transitional cell carcinomas of the bladder. Lympho-epithelioma-like carcinomas, with a dramatic stromal inflammatory infiltrate, are rare but appear to be more frequent in Asia than in the West and appear to have a better prognosis than usual squamous carcinoma. Most adenocarcinomas of the cervix are of endocervical type though there has been great variability in the literature as to what proportion is better considered endometrioid in type. Intestinal type mucinous carcinomas and signet ring carcinomas are well described and clear cell carcinomas make up around 4% of adenocarcinomas of the cervix. Those in women exposed to DES tend to occur at a much younger age than those without DES exposure. So-called minimal deviation or adenoma malignum type adenocarcinoma is rare but probably has the same prognosis as other adenocarcinomas. Well differentiated villoglandular adenocarcinoma is an important tumour to separate from other types. This is a tumour with a papillary pattern and only mild cytological atypia. It tends to occur in women between the age of approximately 25 and 55 and in the majority of cases is only superficially invasive. Clinical outcome for such carcinomas, in cases published to date, has been excellent and those treated by a simple excisional biopsy or cone biopsy were alive and well with no evidence of recurrent disease on follow up. There is however some recent evidence that if there is lymphovascular space involvement, invasion >3mm or admixture with any other tumour type, then prognosis worsens considerably and so local excision is not always appropriate. There has been considerable debate as to whether adenosquamous carcinomas have a poorer prognosis than other types but at the moment there is no clear evidence of this. Some evidence exists that its incidence is higher in younger women and that metastases to pelvic lymph nodes may be more frequent than in squamous carcinoma or adenocarcinoma but there is no clear evidence that prognosis differs. So-called glassy carcinomas are best considered a variant of adenosquamous carcinoma and these have been reported to have an aggressive clinical course. Adenoid cystic carcinomas account for less than 1% of adenocarcinomas. It is debatable whether they exist as a true entity in the cervix comparable to those seen, for example, in salivary glands. These tumours commonly show lymphatic involvement, have an aggressive local course but may also metastasise. They should be differentiated from adenoid basal carcinomas which are commonly a coincidental finding in the elderly or found in older women being investigated for CIN. These tumours are much less aggressive than adenoid cystic carcinomas and because they have a very indolent course it has recently been suggested they are reclassified as adenoid basal epitheliomas. Neuroendocrine tumours of the cervix include classical carcinoid tumours which are very rare, small cell and large cell neuroendocrine carcinoma. Some also recognise an atypical carcinoid tumour in the cervix. It is important to identify small and large cell neuroendocrine carcinomas as these appear to be aggressive tumours and in the literature some series have shown a median survival of only twelve months. Only around 40% of small cell carcinomas of neuroendocrine type are actually positive with neuroendocrine markers and differentiation of small cell squamous and small cell neuroendocrine carcinoma can be difficult.

Spread of cervical carcinoma is by direct extension of the primary tumour into adjacent structures, permeating lymphatics and at a late stage to blood vessels. Direct is spread to the vaginal, cardinal ligaments and to the pelvic sidewall, involving the ureters, bladder or rectum at a late stage. Lymph nodes are initially involved close to the parametrium, then to pelvic nodes around the obturator, internal iliac, external iliac and common iliac vessels. Para-aortic lymphadenopathy and blood borne distant metastases are generally believed to be late developments.


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7. Staging

Stage I Carcinoma confined to the cervix.Ia Invasive carcinoma diagnosed only by microscopy; all macroscopically

visible lesions, even with superficial invasion, are stage Ib.Ia1 Invasion < 3mm depth of invasion from parent epithelial base, horizontal

spread < 7mmIa2 Invasion > 3mm depth of invasion not greater than 5mm from parent epithelial

base, the horizontal spread < 7mmIb1 Carcinoma confined to cervix > 7mm wide or 5mm deep but < 4cm in sizeIb2 Carcinoma > 4cm diameter

Stage II Carcinoma extending beyond the cervix but not extending to the pelvic sidewall or involving the lower third of vagina.

a No parametrial involvementb Parametrial involvement

Stage III Tumour extends to the pelvic sidewall, or involves the lower third of vagina.On rectal examination there is no tumour free space between the tumourand pelvic sidewall. All cases of hydronephrosis with non functioning kidney should be included unless it is known to be from another cause.

a No extension to pelvic sidewallb Extension to sidewall or non functioning kidney

Stage IV Extension beyond the true pelvis or to mucosa of the bladder or rectum.a Adjacent organ involvement*

b Distant organ involvement

* the presence of bullous oedema is not sufficient to classify tumour as stage IV.

FIGO, 1995


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8. Histopathology minimum dataset

National Minimum Dataset – Cervical Cancer Histopathology Report

Gross descriptionDimensions of uterus: Length ..........mm Transverse .......mm Antero-posterior........mm

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

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

HistologyType: squamous carcinoma ¨ adenocarcinoma ¨ adenosquamous ¨

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 (including obturator, internal and external iliac)

Right left Common iliac nodes right left

Total number of nodes retrieved …….. ……..

total number of nodes retrieved …….. ……..

lymph nodes with tumour deposits …….. ……..

lymph nodes with 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 codesT83000 (Cervix) M80703 (Squamous cell carcinoma) M81403 (Adenocarcinoma) T08000 (Lymph node) M85603 (Adenosquamous carcinoma)M80706 (Metastatic squamous carcinoma) M81406 (Metastatic Adenocarcinoma)


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9. Treatment

9.1 Surgery (see 14. Algorithm and 15. Summary)Generally less than 1% of patients with Ia1 disease has pelvic lymph node involvement and do not need nodal assessment. 6% of patients have pelvic lymph node metastases in lesions extending deeper than 3mm (Duncan, 1986) and for these tumours radical surgery/ radiotherapy or chemoradiation is usually required (Robertson and Grant, 1998; grade C recommendation). With a Ia2 lesion, a 2cm deep loop or cone may be suitable if the invasive component or any CIN is completely excised. However, it will be necessary to examine the lymph nodes and this can be performed laparoscopically. Retrospective case series suggest that a simple hysterectomy and pelvic lymphadenectomy is adequate for Ia2 disease (Selman et al, 2005; Steed et al, 2006). An alternative would be to offer a radical hysterectomy and pelvic lymphadenectomy. Lymphovascular space involvement may be a marker for more aggressive disease (Van Nagell et al, 1983). Incompletely excised early invasive disease at loop excision or cone biopsy requires radical treatment.Stage for stage survival for adenocarcinoma of the cervix appears similar to squamous cell carcinoma and it is treated in a similar manner.

9.1.1 Loop/ cone (suitable for FIGO stage Ia1- Ia2)For stage Ia1 disease, the pathology should be reviewed by the local cancer MDT and involve review by a pathologist with an interest in gynaecological oncology (good practice point). However assessment of the depth of infiltration is dependant on the quality of local preparation of the histological sections. Lymphovascular space involvement and multifocal disease may require lymph node dissection. Completely excised stage Ia1 disease can be treated in a cancer unit.

9.1.2 Radical trachelectomy (suitable for FIGO stage Ib1 - IIa)Radical trachelectomy combined with pelvic lymphadenectomy appears a suitable alternative to Wertheim hysterectomy for women wishing to preserve their fertility with tumours under 2cm in size. Recurrence rates appear acceptable (Shepherd et al, 1998; grade B recommendation). Experience of this in the UK is limited and should still be considered as experimental with radical hysterectomy being the gold standard treatment. Completion treatment may be necessary in 10% of patients because of either positive pelvic lymph nodes or close/ incomplete excision margins.

9.1.3 Wertheim hysterectomy (suitable for FIGO stage Ib1 - IIa)This procedure involves a radical hysterectomy, removing parametrium, the upper third of vagina and a formal bilateral lymphadenectomy, removing the common iliac, internal and external iliac and obturator lymph nodes. The para-aortic nodes may be selectively sampled at the start of the procedure and suspicious nodes sent for frozen section. If they are involved then surgery should be abandoned as disease will be widely disseminated. Para-aortic nodal involvement is seen in up to 6% of stage I disease and 11-29% of stage II disease. Para-aortic sampling appears difficult to justify in stage Ia2 disease in the absence of histologically involved pelvic nodes (Monaghan and Burghardt, 1993; grade C recommendation). The fallopian tubes should be removed and if the ovaries are conserved then they are lifted out of the pelvis away from any intended radiotherapy. The ovaries are only removed if there is coincident ovarian pathology or if the patient is approaching or beyond her menopause.

Patients wishing future fertility by surrogacy may wish cryopreservation of eggs and should contact the Hewitt Fertility Centre at Liverpool Womens Hospital.

9.1.4 Shauta hysterectomyThis is not part of the management algorithm for North Wales patients.

9.1.5 Laparoscopic node dissectionPatients are to be referred to the Liverpool Womens Hospital as part of management of FIGO stage Ia2 disease treated by cone biopsy and wishing preservation of fertility.

9.1.6 Cancer complicating pregnancyPregnancy itself does not appear to alter the biological behaviour of cervical carcinoma but a difficult decision is almost always encountered as to whether preterm delivery or termination of pregnancy is to be considered in a trade off between the survival of the fetus versus the mother. Vaginal delivery is North Wales Cancer Guidelines, Cervical Cancer (June, 2008) 11

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contraindicated as disease can disseminate through the large cervical venous sinuses and be implanted into the vagina or perineum during the course of delivery. These tumours should be managed as in the non-pregnant patient stage for stage.

9.1.7 Cervical stump carcinoma/ management of unsuspected carcinoma after simple hysterectomyStump carcinoma is a rare problem where cervical carcinoma occurs after a subtotal hysterectomy. A radical trachelectomy would be ideal and could be combined with post operative radiotherapy. Radical radiotherapy is an alternative but there can be difficulty with the intrauterine applicators. Following simple hysterectomy after excision of an unsuspected stage Ib+ carcinoma a radical parametrectomy with excision of a cuff of vagina is possible but can be difficult. Again radical pelvic radiotherapy is an option.

Patients are to be referred to Liverpool Womens Hospital or to the Royal Marsden if radical Parametrectomy to be considered. Generally radiotherapy preferred but all cases must be discussed at the gynae cancer MDT to decide further treatment.

9.1.8 Management of stage Ib2 carcinoma ( also see 9.2.1 Radical treatment ) To refer for radical radiotherapy or chemoradiotherapy at YGC.

9.2 Radiotherapy and chemoradiation

9.2.1 Radical treatmentRadiotherapy is preferred for more advanced disease (stage IIb and beyond) and for surgically unfit women with early stage disease. This can provide radical or palliative treatment. It is administered by external beam radiation to deal with the central tumour, pelvic sidewall extension and the pelvic lymph nodes. This is then supplemented by a remote after loading brachytherapy technique whereby intra-uterine and vaginal radioactive sources are inserted. After treatment, rectovaginal or vesicovaginal fistulae can rarely occur; more frequent are troublesome proctitis and cystitis. Current practice in UK would be to give external beam radiotherapy (EBRT) to a dose of between 45-50 Gy with daily fractions of 1.8-2 Gy with minimal interruptions or gaps in treatment. Some centres use a parametrial/ sidewall boost with EBRT. This would be followed by a brachytherapy boost with MDR intracavity doses of 24-28 Gy to the “A” point whereas for HDR the dose would be 28-30 Gy in 4 or 5 insertions. An interstitial boost sometimes may be delivered for bulky residual disease. Planning of the radiation therapy should optimally be performed using CT simulator (or MRI) to determine the fields and organs at risk.Recent studies have shown statistically highly significant improved survival after chemoradiotherapy (relative risks between 0.61-0.52; Keys et al, 1999; Morris et al, 1999; Rose et al, 1999b) with low dose weekly cisplatin or combination cisplatin regimens given during radiotherapy. Newer schedules including cisplatin and gemcitabine, vinorelbine, paclitaxel are under investigation and induction therapy with carboplatin and paclitaxel is in trial. The Italian SNAP 01 study showed paclitaxel, ifosfamide and cisplatin to be significantly better than ifosfamide and cisplatin (Buda et al, 2005; evidence level Ib). Chemoradiation is now recommended as standard treatment for patients having primary non-surgical treatment (grade A recommendation; evidence level Ia) and are fit enough to tolerate the additional morbidity (particularly neutropaenia and emesis).

9.2.2 Adjuvant treatmentRadiotherapy is also offered to patients with histologically involved nodes after hysterectomy/ lymphadenectomy or for undifferentiated tumours as their chance of recurrent disease is increased (grade A North Wales Cancer Guidelines, Cervical Cancer (June, 2008) 12

StandardsRadiotherapy should start 14 days after referral for radical treatment (good practice) although 28 days is acceptable (minimum standard).

Radiotherapy should start 28 days after referral for adjuvant treatment (minimum standard).

JCCO/RCR guidance

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recommendation; evidence level Ib). A close vaginal surgical margin is an indication for radiotherapy but there is no agreed measurement (<3 and <5mm are examples). The effect of adjuvant radiotherapy upon patient survival is not clinically proven (Baltzer et al, 1984) but this may have been due to small trial size (Thomas and Dembo, 1991). However a recent GOG randomised controlled study of 277 women found a 47% reduction in the risk of recurrence (from 28% to 15%) in women given adjuvant radiotherapy. Patients were all node negative but had other high risk features (Sedlis et al, 1999). A single study suggests a survival advantage for chemoradiation in the adjuvant setting for 268 women following treatment for stage Ia2, Ib or IIa disease (Peters et al, 2000).Patients with bulky nodal disease (larger than 2cm diameter) may gain a 1-4% survival benefit (from stage Ib-III respectively) with surgical cytoreduction prior to chemoradiotherapy (Kinney et al, 1995; Kupets et al, 2002) and therapeutic adenectomy may be considered in selected cases (grade B recommendation). Furthermore previously unsuspected nodal involvement detected at frozen section during surgery could have a bilateral pelvic lymphadenectomy and para-aortic nodal dissection but the uterus and cervix conserved in order to assist brachytherapy dosing. This must be discussed with local clinical oncologists before implementing as a local policy.

All cases must be discussed at the gynae cancer MDT to decide further treatment. Patients wishing future fertility by surrogacy may wish cryopreservation of eggs and should contact the Hewitt Fertility Centre at Liverpool Womens Hospital.

9.3 ChemotherapyChemotherapy followed by radical radiotherapy may be considered for small cell neuroendocrine tumours. Four cycles of etoposide and cisplatin (with or without additional paclitaxel) in combination with radiotherapy may significantly reduce local failure in comparison to radical hysterectomy with an acceptable overall and progression free survival (Randall et al, 2005).

All cases must be discussed at the gynae cancer MDT to decide further treatment.

9.4 Management of advanced disease ( see 10.3-5 Pelvic exenteration, Palliative care, Obstructive uropathy ) All cases must be discussed at the gynae cancer MDT to decide further treatment.

10. Dealing with recurrent disease Recurrent disease is seen in 20-25% of women after primary therapy and may be amenable to radiotherapy if this has not been given before. EUA, biopsy, colposcopy, MR/CT scanning, contrast studies and PET/CT (if available) all need to be considered.

10.1 ImagingMR, CT and isotope bone scans have an important role in the assessment of potential recurrence with pelvic pain and the diagnosis of insufficiency fractures post radiotherapy.MR and/or CT scans should be performed prior to exenterative surgery to allow consideration of resection margins.If performed prior to pelvic exenteration a whole body PET or PET/CT scan may improve selection of patients and therefore improve survival and reduce morbidity. If performed prior to radiotherapy a whole body PET or PET/CT scan may change planned radiotherapy fields.False positives for detection of recurrence with PET/CT include inflammatory change, post radiotherapy change initially and uptake related to the urinary tract. There is limited sensitivity of PET in the detection of positive lymph nodes less than 10mm size. MR or CT may be more appropriate to assess potential clinical recurrence initially.

10.2 ChemotherapyChemotherapy can be considered for patients with advanced disease who are otherwise fit and capable of withstanding treatment. Single agent cisplatin at modest doses (50mg/m2) gives the best balance of response and toxicity and is standard treatment. Responses are said to be less frequent when the disease is within the irradiated fields. Prior cisplatin therapy also lowers the response rate and since most relapsing patients have received this as first line and so may create problems for treatment of relapse. New drugs and combinations are needed urgently. Combination chemotherapy gives a higher response rate but also a substantial increase in toxicity. The GOG 179 study of 294 women has shown a statistically significant overall survival benefit with cisplatin and topotecan vs cisplatin alone with median overall survivals of 9.4 vs 2.9 months and response rates of 27% and 13% (Long et al, 2005; grade A recommendation; evidence North Wales Cancer Guidelines, Cervical Cancer (June, 2008) 13

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level Ib). There was a higher incidence of febrile neutropaenia in the combination arm. Newer studies are looking at molecular targeted agents.

All cases must be discussed at the gynae cancer MDT to decide further treatment.

10.3 Pelvic exenterationPelvic exenteration is an option where there is no evidence of extra-pelvic disease and the pelvic recurrence is central. This usually involves concomitant removal of the bladder or rectum or both. Careful pre-operative counselling with a multi-specialist team is essential. Five year survival may approach 50% but survival at 5 years is rare in node positive patients.

Patients are to be referred to Liverpool Womens Hospital if exenteration to be considered and all cases must be discussed at the gynae cancer MDT to decide further treatment.

10.4 Palliative care (see palliative care file)The provision of palliative and supportive care for patients with gynaecological malignancies should be an integral part of service provision. The NICE guidance Improving Supportive and Palliative Care for Adults with Cancer was published in March 2004 and provides detailed recommendations which complement and inform this guidance (NICE, 2004).There is little robust evidence from the palliative care literature that is specific to patients with advanced gynaecological malignancies, therefore this guidance is based on evidence from studies looking at patients with a broad range of advanced malignancies.

10.5 Obstructive uropathyAnuria due to bilateral ureteric compression is usually a feature of locally advanced disease and placement of bilateral ureteric stents is not usually in the best interests of the patient. This must be sensitively discussed with the patient and her family and the informed wishes of the patient respected where possible. Any discussion must involve the Palliative Care team.

11. Survival 5 year survival:

76-87% for stage Ib disease85-90% for node negative patients60-70% if 1-2 nodes are involved30-40% if 3 or more nodes are involved

If common iliac nodes are involved then survival only 25%.Well differentiated tumour 84% versus poorly differentiated tumour 45%.

11.1 Cancer dataset/ inventory of active trialsCaNISC data items to be developed.Active trials – nil.

12. Follow up Careful inspection and palpation of the vaginal vault and palpation for any pelvic masses should be performed 3 monthly for 2 years, 6 monthly for 1 year and then annually. Hospital follow up should be for 5 years. Vault cytology is not helpful if the patient has had radiotherapy. Cervical cytology is necessary if the cervix has been conserved for early disease or after trachelectomy.All patients must be encouraged to report any symptoms suggestive of recurrent disease immediately by contacting their CNS rather than wait until their next outpatient appointment.

12.1 Identification and management of late effects of treatmentPyschosexual, emotional, bowel, genitourinary, neuropraxia other problems may need detailed discussion with the clinical nurse specialist and psychological, lymphoedema, pain, spiritual and other support services.

13. Contact names/ numbers Simon Leeson Obstetrician and Gynaecologist YG (t 01248 384954); CNS Sr Liz Hall (t 01248 385003)Philip Toon Obstetrician and Gynaecologist NEWT (t 01978 725834)Nigel Bickerton Obstetrician and Gynaecologist YGC (t 01745 534655)


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14. Algorithm

Algorithm for management of patients with cervical cancer

Stage Ia1

Excisional local treatment (loop/ cone)

@complete incomplete (CIN/cGIN or carcinoma)

Stage Ia2

Fertility requested Family complete

Stage Ib1/IIa

Stage Ib2*/IIb/III/IV

Post Radiotherapy Recurrence

ERT = external beam radiotherapy@if no lymphovascular space involvement, not multifocal disease, clear margins*management of Ib2 tumours to be according to local policyNorth Wales Cancer Guidelines, Cervical Cancer (June, 2008) 15

Radical trachelectomy or @loop/ cone and pelvic

lymphadenectomy

Radical hysterectomy (or simple hysterectomy) andpelvic lymphadenectomy

ERT if node positive or ERT + Brachytherapy Close margins, poor differentiation for surgically unfit (consider adjuvant chemoradiation)

Chemoradiotherapy/ ERT + Brachytherapy depending upon patients fitness

Cytological/ colposcopic follow up

Further excision

Exenteration for solitary central pelvic disease/ or chemotherapy/ palliative care Chemotherapy/ palliative care for multiple metastases

Radical trachelectomy (for Ib1 only) / radical hysterectomy and pelvic lymphadenectomy

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15. Summary

Pre-op assessment cervical biopsy/ loop excision/ cone biopsyCone biopsy/ loop excision is suitable treatment for Ia1 disease <3mm depth of invasion, no lymphovascular space involvement and excision carcinoma/ CIN is complete. Ia2 may also be treated with a cone/ loop with pelvic lymphadenectomy if satisfies above criteria. For palpable disease – EUA/ cystoscopy/ biopsy/ sigmoidoscopy or

VE/PR in clinic. MR scan abdomen/ pelvis (> Ia2). Consider CT abdomen/ pelvis (IV). chest X-ray (> Ia2). consider PET/CT (>IIb / Ib2 and node negative on imaging).

Surgery Cone biopsy/ loop excision (as above). Simple hysterectomy - this is suitable for remaining Ia2 disease. Wertheim hysterectomy - this is suitable for remaining Ia2 disease; 3-

5mm depth of penetration, lymphovascular space involvement or incomplete excision of carcinoma; Ib and IIa disease. If following cone/ loop then should ideally be performed <2 weeks later or at 6 weeks. Oophorectomy if peri-/ post menopausal.

Radical Trachelectomy – tumours under 2cm if fertility desired. Post radiation isolated central pelvic recurrence - anterior/ posterior

exenteration.

Radiotherapy/ chemotherapy ERT – as adjuvant treatment for poorly differentiated and node positive

surgical patients or those with narrow/ incomplete margins of excision or extensive lymphovascular space invasion; surgically unfit; recurrent disease if initially received surgery alone. Consider chemoradiation.

Chemoradiation + HDR Brachytherapy – consider for fit patients with Ib2, bulky IIa, IIb-IVa disease; recurrent disease if initially received surgery alone.

ERT + HDR Brachytherapy – if unfit for surgery/ chemoradiation. Chemotherapy - consider platinum based chemotherapy if unsuitable for

exenteration or for multiple metastases.


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16. References

ACR Appropriateness Criteria. (2005) http://www.acr.org/s_acr/bin.asp?CID=1201&DID=11860&DOC=file.PDF. Accessed 09 September 2006.

Baltzer J, Kopcke W, Lohe KJ et al. (1984) Die operative behandlungder zervixkarzinoms. Gerburtshilte Frauenheilkd, 44, 279-85.

Bipat S, Glas AS, van der Velden J et al. (2003) Computed tomography and magnetic resonance imaging in staging of uterine cervical carcinoma: a systematic review. Gynecol Oncol; 91, 59-66.

Buda A, Fossati R, Colombo N et al. (2005) Randomised trial of neoadjuvant chemotherapy comparing Paclitaxel, Ifosfamide, and Cisplatin with Ifosfamide and Cisplatin followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the SNAP01 (Studio Neo-Adjuvante Portio) Italian Collaboration Study. J Clin Oncol, 23, 4137-45.

Choi SH, Kim SH, Choi HJ, et al. (2004) Preoperative magnetic resonance imaging staging of uterine cervical carcinoma: Results of prospective study. J Computer Ass Tomography; 28, 620-7.

Davis JR, Moon LB. (1975) Increased incidence of adenocarcinoma of the uterine cervix. Obster Gynecol, 45, 79-83.

Duncan ID. (1986) Carcinoma of the cervix: microinvasion. In: Clinical Gynaecological Oncology. Eds. Shepherd JH, Monaghan JM. Blackwell, Oxford.

FIGO. (1995) Modifications in the staging for stage I vulvar and stage I cervical cancer. Int J Gynecol Obstet, 50, 215.

Fujiwara K, Yoden E, Asakawa T et al. (2000) Negative MRI findings with invasive cervical biopsy may indicate stage IA cervical carcinoma. Gynecol Oncol; 79, 451-6.

Hricak H, Yu KK. (1996) Radiology in invasive cervical cancer. Am J Roentgenol; 167, 1101-8.

Hricak H, Akin O, Sala E et al. (2005) Role of imaging in cancer of the cervix. [online publication]. Available from [Accessed. 17.08.06].

Hricak H, Gatsonis C, Chi DS et al. (2005) Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the intergroup study American College of RadiologyImaging Network 6651-Gynecologic Oncology Group 183. J Clin Oncol: 23, 9329-37.

Keys HM, Bundy BN, Stehman FB et al. (1999) Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Eng J Med, 340, 1154-61.

Kinney WK, Hodge DO, Egorshin EV et al. (1995) Surgical treatment of patients with stages Ib and IIa carcinoma of the cervix and palpably positive pelvic lymph nodes. Gynecol Oncol, 57, 145-149.

Kupets R, Thomas GM, Covens A. (2002) Is there a role for pelvic lymph node debulking in advanced cervical cancer? Gynecol Oncol, 87, 163-170.

Long HJ, Bundy BN, Grendys Jr. EC et al. (2005) Randomised phase III trial of Cisplatin with or without Topotecan in carcinoma of the uterine cervix: a Gynaecologic Oncology Group Study. J Clin Oncol, 23, 4626-4633.


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Medical Services Advisory Committee. (2001) Magnetic resonance imaging for staging cervical and endometrial cancer. Canberra: Medical Services Advisory Committee.

Monaghan JM, Burghardt E. (1993) Cervical intraepithelial neoplasia (preinvasive cancer). In: Surgical gynaecologic oncology. Ed Burghardt E. Thieme, New York.

Morris M, Eifel PJ, Lu J et al. (1999) Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Eng J Med, 340, 1137-43.

Nakamoto Y, Saga T, Fujii S. (2005) Positron emission tomography application for gynaecologic tumors. Int J Gynecol Cancer, 15, 701-9.

NHS Executive. (1999) Guidance on commissioning cancer services. Improving outcomes in gynaecological cancer. The manual. Department of Health.

NHS Executive. (1999) Guidance on commissioning cancer services. Improving outcomes in gynaecological cancer. The research evidence. Department of Health.

NICE. (2004) Improving Supportive and Palliative Care for Adults with Cancer.

Peters WA, Liu PY, Barrett RJ et al. (2000) Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol, 18, 1606-13.

Quinn M, Babb P, Brock A. (2001) Cancer trends in England and Wales 1950-1999. SMPS no. 66. Office for National Statistics, London.

Robertson G, Grant P. (1998) Cancer of the cervix. In: Essentials of gynaecological cancer. Eds Lawton F, Friedlander M, Thomas G. Chapman and Hall Medical. London.

Randall ME, Michael H, Ver Morken J et al. (2005) Uterine cervix. In: Principles and practice of gynecologic oncology. Eds Hoskins WJ, Perez CA, Young RC, Barakat R, Markman M, Randall M. Lippincott Williams and Wilkins. Philadelphia.

Rockall AG, Ghosh S, Alexander-Sefre F et al. (2006) Can MRI rule out bladder and rectal invasion in cervical cancer to help select patients for limited EUA? Gynecol Oncol, 101, 244-9.

Rose PG, Adler LP, Rodriguez M et al. (1999) Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: asurgicopathologic study. J Clin Oncol; 17, 41-5.

Rose PG, Bundy BN, Watkins EB et al. (1999) Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Eng J Med, 340, 1144-53.

Sedlis A, Bundy BA, Rotman MZ et al. (1999) A randomised trial of pelvic radiation therapy versus no further therapy in selected patients with stage Ib carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy. A gynaecologic oncology group study. Gynecol Oncol, 73, 177-83.

Selman TJ, Luesley DM, Murphy DJ et al. (2005) Is radical hysterectomy for early stage cervical cancer an outdated operation? Br J Obstet Gynaecol, 112, 363-5.

Shepherd JH. (1990) Cervical cancer: the surgical management of early stage disease. In. Clinical Gynaecological Oncology. Eds. Shepherd JH, Monaghan JM. Blackwell, Oxford.


Draft 1Shepherd JH, Crawford RAF, Oram DH. (1998) Radical trachelectomy: a way to preserve fertility in the treatment of early cervical cancer. Br J Obstet Gynaecol, 105, 912-6.

Sheu MH, Chang CY, Wang JH et al. (2001) Preoperative staging of cervical carcinoma with MR imaging: a reappraisal of diagnostic accuracy and pitfalls. Eur Radiol; 11, 1828-33.

Shiraiwa M, Joja I, Asakawa T et al. (1999) Cervical carcinoma: efficacy of thin-section oblique axial T2-weighted images for evaluating parametrial invasion. Abdominal Imaging; 24, 514-9.

Sironi S, Bellomi M, Villa G et al. (2002) Clinical stage I carcinoma of the uterine cervix value of preoperative magnetic resonance imaging in assessing parametrial invasion. Tumori; 88, 291-5.

Steed H, Capstick V, Schepansky A et al. (2006) Early cervical cancer and parametrial involvement: Is it significant? Gynecol Oncol; 103, 53-7.

Thomas GM, Dembo AJ. (1991) Is there a role for adjuvant pelvic radiotherapy after radical hysterectomy in early-stage cervical cancer? Int J Gynecol Cancer, 1, 1-8.

Van Nagell JR Jr., Greenwell N, Powell DF et al. (1983) Microinvasive carcinoma of the cervix. Am J Obstet Gynecol, 145, 981-9.

Wright TC, Ferenczy A, Kurman RJ. (2002) Blausteins Pathology of the Female Genital Tract, 326. Springer-Verlag, New York.


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Classification of evidence levels

Ia Evidence obtained from meta-analysis of randomised controlled trials

Ib Evidence obtained from at least one randomised controlled trial

IIa Evidence obtained from at least one well designed controlled study without randomisation

IIb Evidence obtained from at least one other type of well designed quasi-experimental study

III Evidence obtained from well designed non-experimental descriptive studies, such as comparative studies, correlation studies and case studies

IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities

Lower limit of acceptable evidence base is level IIa.

Grades of recommendation

A Requires at least 1 randomised controlled trial as part of a body ofliterature of overall good quality and consistency addressing the specific recommendation

B Requires the availability of well controlled clinical studies but no randomised clinical trials on the topic of recommendation

C Requires evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities. Indicates an absence of directly applicable clinical studies of good quality

Lower limit of acceptable grade of recommendation is B.


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Appendix 1: Relative benefit over other management options and resource implications for imaging

Use of MR or CT in pre treatment assessment is less invasive and more accurate, as well as conferring cost/time benefits in the staging schedule of patients (Hricak et al, 1996; Hricak et al, 2005; Rockall et al, 2005) compared to conventional ‘approved’ FIGO investigations of IVU, cystoscopy, sigmoidoscopy and barium enema. Cystoscopy and sigmoidoscopy should be reserved for those patients with > stage Ib1 tumour on clinical exam or imaging (Liang et al, 2000; Chung et al, 2001; Hricak and Yu, 1996).Lymphangiography is unreliable for preoperative assessment and may interfere with the specificity and interpretation of PET scans (Reinhardt et al, 2001).Assessment of pelvic and para-aortic nodal disease is most accurately determined by laparotomy or laparoscopic surgery. This is an invasive procedure not routinely practised as part of pre treatment staging and thus the contribution of pre operative or pre radiotherapy imaging determination of nodal status is still worthwhile, despite the limitations in sensitivity of current techniques of MR, CT and PET.

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 enema, cystoscopy and examination under anaesthesia, with cost savings estimated at approximately £1100/ patient (£2.76 million across the UK, based on UK wide incidence of 2990 cervical cancer patients annually and that some early stage cancers do not require staging investigations – Rockall et al, 2005; Hricak et al, 2005, Hricak et al, 1996).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 waiting time referral targets.

PET/CT scanning has very limited availability at present. It is likely that the greatest impact of PET in initial staging will be for inoperable patients with stage IIb and III disease, in the detection of possible para-aortic nodal metastases, and unexpected distant metastases, with subsequent change in planned radiotherapy fields.Whilst reported sensitivities are variable for detection of metastatic para-aortic nodes with PET, the alternative gold standard of laparoscopic staging carries significant risk of morbidity and has estimated costs of £1,628 -£4,646 compared to NHS costs for PET of approximately £750. (ISD data 2004/5 and Scottish Executive Health Dept). The general reported sensitivity and specificity of PET/CT still make PET imaging a cost effective alternative to inadequate radiotherapy fields, or inappropriate treatment options.

References:

Chung H, Ahn HS, Kim YS et al.(2001) The value of cystoscopy and intravenous urography after magnetic resonance imaging or computed tomography in the staging of cervical carcinoma. Yonsei MedicalJournal; 42: 527-31.

Hricak H, Yu KK. (1996) Radiology in invasive cervical cancer. Am J Roentgenol; 167: 1101-8.

Hricak H, Powell CB, Yu KK et al. (1996) Invasive cervical carcinoma: role of MR imaging in pretreatment work up – cost minimization and diagnostic efficiency analysis. Radiology; 198: 403-9.

Hricak H, Gatsonis C, Chi DS et al. (2005) Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the intergroup study American College of RadiologyImaging Network 6651-Gynecologic Oncology Group 183. J Clin Oncol: 23: 9329-37.

Liang CC, Tseng CJ, Soong YK. (2000) The usefulness of cystoscopy in the staging of cervical cancer. Gynecol Oncol; 76:200-3.


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Reinhardt MJ, Ehritt-Braun C, Vogelgesang D et al. (2001) Metastatic lymph nodes in patients with cervical cancer: detection with MR imaging and FDG PET. Radiology; 218: 776-82.

Rockall AG, Sohaib SA, Harisinghani MG, et al. (2005) Diagnostic performance of nanoparticle-enhanced magnetic resonance imaging in the diagnosis of lymph node metastases in patients with endometrial and cervical cancer. J Clin Oncol; 23: 2813-21.


This guideline has been developed from the Guideline Group of the British Gynaecological Cancer Society

Simon Leeson Obstetrician and Gynaecologist (chair)Rachel Connor Consultant RadiologistRichard Edmondson Gynaecological OncologistMark Heatley Gynaecological PathologistNick Johnson Gynaecological Oncologist Sean Kehoe Gynaecological OncologistTracy Miles Nurse Specialist Gynaecological OncologyAlison Mitchell Palliative Care SpecialistNick Reed Clinical OncologistKarina Reynolds Gynaecological OncologistTerry Rollason Gynaecological Pathologist

North Wales Cancer Centre Guideline Group

Simon Leeson Obstetrician and Gynaecologist (chair)Philip Toon Obstetrician and GynaecologistNigel Bickerton Obstetrician and Gynaecologist

cancer template draft #1 - nhs wales carcinoma... · web viewthe known increased incidence of...

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