Gynaecology Oncology

Ram AthavaleConsultant Gynaecological Oncology

University Hospitals Coventry & Warwickshire NHS Trust

Aims

A framework for main gynaecological cancers

To provide a foundation for further study

National Cancer Regfistrations UK 2004

Gynaecological malignancies

Cases Incidence/100,000

Lifetime risk

Ovary 5409 21.2 1:48

Uterus 5029 19.7 1:73

Cervix 2221 8.7 1:116

Vulva 824 3.3 1:350

Gynaecological malignancies 5-yr survival better in the USA compared to

the UK

Differences in registriesadvanced stage?Post code lottery - practice variations

- under investment

Lack of specialised servicessome managed by general gynaecologists

No specific referral pattern

Calman Hine report

A policy framework for commissioning cancer services : A report by the Expert Advisory Group on Cancer to the Chief Medical Officers of England and Wales (1995)

Uniform high standard of care Needs of patients and carers purchasers, planners and

professionals

Improving Outcomes for Gynaecological Cancers 1999 (IOG guidelines)

Hub - Cancer Centre Spoke - Cancer Units

Cancer Unit Diagnostic role

Rapid assessment units2 week wait referral clinicsColposcopy

MDT

Manage certain cancers/ suspected cancerCervix up to FIGO IA Uterus IA/IB, grade 1 or 2Ovary- risk of malignancy index< 200Vulva- diagnostic excision of tumours less than 2 cms

Refer all other cases to the Cancer Centre

Cancer targets

Patient seen within 14 days of referral (2 week wait rule)

Specific criteria for referral of suspected cancer

31 day target- max 31 days from decision to treat to 1st treatment

62 day target max 62 days from urgent GP referral to 1st treatment

Cancer Centre

Manage all referred cases from unitsFunction as units for the drainage population

MDT Chemotherapy, radiotherapy Research Training programmes

Role overlap based on service organisation

Treatment of cancer

Surgery

Chemotherapy Radiotherapy

Palliative care Supportive therapy

Multidisciplinary approach critical

Qs

Cervical cancer

Histology

Low grade disease HPV changes CIN I

High grade disease CIN II CIN III

Invasive cancer CGIN

Cervical Cancer

Incidence 8.7/100,000 in England & Wales

Associated with Young age at first intercourse Number of sexual partners HPV 16,18,33 Smoking Immunosuppresion

Pathology

Peaks 35-44 and 75-85

Squamous (70%) Adenocarcinoma (12%) Adenosquamous (12%)

Direct spread - anatomical

Clinical features at presentation

Abnormal bleeding PCB,IMB,PMB

Abnormal smears

Advanced disease relatedoffensive PV dischargeneuropathic painrenal failureDVT

FIGO Staging

I – Confined to cervixIA Micro – invasive (<5mm from basement epithelium from which it originates)IA1 up to 3 mm deep and 7 mm wideIA2 3-5 mm deep and 7 mm wide

IB – macroinvasive tumourIB1 < 4 cms, IB2 > 4 cms

II – Beyond cervixIIA Upper 2/3 of vagina IIB Parametrium not reaching side wall

FIGO stage cervical cancer

III – involves lower third vagina or side wall IIIA lower 1/3 vaginaIIIB Pelvic side wall

IV – Beyond true pelvisIVA Mucosa of bladder or rectumIVB Distant spread

Clinical Staging +/- investigations

Visible tumour PV/PR to check spread to

parametrial/rectovaginal space EUA, cystoscopy +/- Sigmoidoscopy,proctoscopy MRI CXR FBC,U&E,LFT PET?

Treatment

Micro invasive up to IA1cone biopsy to preserve fertility option simple hysterectomy

IA2radical hysterectomy, lymph nodes limited parametrectomy

IB1 and IIA radical hysterectomy

IB2 , IIB and above- chemoradiotherapy

Surgical treatment

Radical hysterectomy and pelvic node dissection BSO in older women or adenocarcinoma Complications

Haemorrhage Infection Damage to bladder/bowel Atonic bladder Fistulae

Laparoscopic RH Coelio- Schauta

Radical vaginal hysterectomy, laparoscopic nodes

Chemoradiotherapy Current gold standard for IB2, IIB or above

(apart from some cases with stage 4 disease)

External beam (teletherapy) Pelvic spread especially nodes Para-aortic

Intracavity (brachytherapy)cervical tumour

Concurrent chemotherapy platinum agent

Fertility preservation- Radical trachylectomy

IA2, small volume IB1excise cervix, limited parametriumlaparoscopic node dissection Fertility preservationLong term survival data unavailableExpertise not always available

Pregnancy outcomes promising

Palliative procedures

ExenterationAnterior or posterior or both

Radiotherapy

Tumour embolisation

Symptom control only

Prognosis

Average 5 year survival

Stage I – 80%, higher for IA disease(95%), role for prevention

Stage II – 61% Stage III – 32% Stage IV – 15%

Follow up

Clinical examination Reassurance Symptom relief – side effects of treatment HRT Psychosexual Early detection of recurrence

Vault smears limited role after radical surgeryNot recommended after radiotherapy

Qs

Ovarian cancer

Ovarian cancer

Killer disease 60-75% stage 3 or 4 Incidence increases with age,

plateaus by 60

Early imaging - More lesions identified

About 6% of all ovarian cysts are malignant

Aetiology

Majority sporadic (90%) Genetic origin (up to 10%)

BRCA1 gene – 40-60 % riskBRCA2 – 10-30%Two or more 1st degree relatives affectedHNPCC

Increased risk in nullips, early menarche, late menopause, ovarian stimulation, abnormal ovarian development

Pathology

85% of all ovarian cancers are epithelial in origin

Sex cord stromal -6% Germ cell 2-3% Secondary tumours – 6%

Epithelial - Borderline or malignant

Presentation

Asymptomatic Pelvic mass (diff. diagnosis) Pressure symptoms/abdominal

distension/GI symptoms Pain Abnormal bleeding Hormonal effects

Screening & Diagnosis

Clinical examination CA-125 & Transvaginal scan/Abd. Scan

Other tumour markers - CEA, CA 19-9 CT/MRI abdomen & pelvis FBC,U&E, LFT, CXR

Overlap between benign and malignant

Benign or malignant?

Risk of malignancy index (RMI)RMI = U X M X CA-125(direct value)

U= ultrasound score 1 or 3bilateral, solid area, septationascites, other depositseach criterion 1 point0-1 criterion = score 12-5 criteria = score 3

M = menopausal statuspremenopausal= score 1postmenopausal=score 3

RMI score

RMI < 200more likely benignmanaged at Cancer Units

RMI > 200more likely malignantmanaged at Cancer Centre

FIGO Staging

Surgical/ pathological I – Confined to ovaries

with or without malignant ascites II – Confined to pelvis

includes spread to uterus/ tubespelvic tissues

III – Confined to peritoneal cavitysize of omental mets decides IIIA/B/C

IV – Distant metastasese.g. liver / lung mets, malignant pleural effusion

Management

Cancer centre Surgery – Laparotomy,peritoneal washings, TAH

BSO, omentectomy lymph nodes, peritoneal and diaphragmatic biopsies

Aim for Complete /Optimal cytoreduction

Adjuvant chemotherapy Platinum based – carboplatin Taxane – paclitaxel Second line agents - caelyx, topotecan

Neoadjuvant chemotherapy followed by surgeryCHORUS trial

Follow up

5 years History, Pelvic exam CA-125 in most cases

Prognosis for recurrent disease poor Overall 5 year survival, all stages together

30-35% Early stage disease 60- 85% depending

upon histological type, role for screening

UKCTOCS trial

UK Collaborative trial for ovarian cancer screening

UKCTOCS trial

No screening v/s USS or CA-125 or combined modalities

Examine role for early diagnosisMorbidity of surgerySurvival benefit in cancer cases

Results by 2012

Qs

Endometrial / Uterine cancer

Endometrial cancer

Predominantly a disease of postmenopausal women

<5% risk under age 40

Numbers increasing, probably obesity related?Diet influence

Risk factors

Excessive endogenous oestrogensPCOperipheral conversion (adipose)

Unopposed oestrogensHRTTamoxifen

Breast cancer HNPCC

Presentation

Postmenopausal bleeding (PMB)10% of women with PMB have endometrial cancer

Postmenopausal PV discharge/pyometra Peri/premenopausal women with IMB

especially if do not respond to hormonal treatment.

Glandular abnormalities on smear

Pathology

Endometrioid adenocarcinoma 80%Grade 1,2,3

10% papillary serous, 4% clear cellremaining other types such as MMT, squamous

Two typesstandard type- obese, low stage low grade, good prognosisnon-standard type – not obese, high grade, high risk histotype

Spread : local / distant70-80% stage 1 confined to uterusperceived as ‘not such a bad cancer’

Investigations

Examination Transvaginal scan

endometrial thickness > 4 mms (5 mms) considered significantendometrial biopsy required all cases

endometrial thickness < 4 mms

Endometrial biopsy Pipelle - outpatient Hysteroscopy OP/IP and curettage

CXR, (MRI)

FIGO stage and prognosis

Stage I Confined to body of uterus IA – Confined to endometrium IB – Invasion less than 50%myometrium IC – Invasion more than 50% myometrium

II – Cervix involvedA glands onlyB stromal invasion

III – Serosa of uterus, peritoneal washings+ve lymph nodes (IIIC)IV – Local/distant mets

Grade Histological type Lymphovascular space invasion

Treatment

SurgicalTAH +BSO, peritoneal washings / LAVH BSO

ASTEC trial – lymph nodes or not Surgery alone sufficient endometrioid type,

invasion<50% thickness of myometrium, grade 1 or 2i.e. up to FIGO stage IA/ IB, grade 1 or 2

Radiotherapy, IC or grade 3, or higher stages Hormone therapy, palliative or recurrence Chemotherapy – higher stages

research ongoing for benefit in lower and higher stages

Prognosis

5 year survival I - 75% II – 58% III – 30% IV – 10%

Qs

Vulvar intraepithelial neoplasia (VIN)

Vulvar Intraepithelial Neoplasia

Most in postmenopausal 41% cases in premenopausal Vulval skin is part of anogenital

epithelium

HPV thought to be involved

Pathology VIN 2 or 3 grouped together- VIN

VIN 1 not recognised (ISSVD)

Undifferentiated (usual) VINHPV associatedBowenoidgenerally good prognosismultifocality – main problem

Differentiated VINassociated with lichen sclerosus/ squamous hyperplasiarelatively older women

Presentation

Pruritus Asymptomatic During investigations for CIN/ VaIN

Lesions may be

raised/flat/sing/multiple/diffuse/discrete Investigation by vulvoscopy +/- acetic acid Adequate biopsies

8 mm punch

Treatment

Multifocal Discomfort/mutilation VIN 3 may progress to cancer

life time risk up to 9% Single lesions excised Multiple lesions – excision or

individualised depending upon location Photodynamic therapy- research HPV vaccine / Topical Imiquimod

Follow up

Vulvoscopy every 6 months until 2 years then individualised

Colposcopy and smears as routine (unless CIN identified)

Vulvar cancer

Vulval cancer

Uncommon Elderly >65 years 90% squamous Other types - more aggressive Associated with smoking, cervical

neoplasia, immunosupression

Presentation

Longstanding vulval pruritus Pain, discharge, bleeding Most common on labia majora Exophytic, ulcerated or flat Younger patients - multicentric disease Diagnosis - Vulvoscopy and punch biopsy

or excision biopsy (single lesion< 2 cms)

Spread & staging

Lymphatic (groin nodes) and local

CXR cervical cytology where appropriate

If multicentric – local inspection of cervix, vagina

FIGO (clinical +surgical) Staging

FIGO stage

I - tumours less than 2 cmsIA up to 1 mm depth of invasionIB more than 1 mm

II Tumour > 2 cms irrespective of depth

III Spread to lower third vagina, unilateral groin nodes

Bilateral groin nodes, bladder/ rectum, distant spread

Treatment

Surgery Wide excision with good margins Vulvectomy and groin incisions for

nodes Sentinel nodes – research

Radiotherapy Node positive Insufficient margins

Chemotherapy/chemoradiotherapy

Morbidity

50% wound breakdown Lymphoedema Lymphocyst formation Rectocele & cystocele Sexual dysfunction

Follow up

Detect early recurrencemore visible

Poor outcome for recurrenceand node positive cases

Five year survivalStage I – 90- 97%Stage II – 85%Stage III – 74%Stage IV – 30%

Qs