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Gynaecology Oncology Ram Athavale Consultant Gynaecological Oncology University Hospitals Coventry & Warwickshire NHS Trust Aims A framework for main gynaecological cancers To provide a foundation for further study Gynaecological malignancies Cases Ovary 5409 Incidence Lifetime /100,000 risk 21.2 1:48 Uterus 5029 19.7 1:73 Cervix 2221 8.7 1:116 Vulva 824 3.3 1:350 National Cancer Regfistrations UK 2004 Gynaecological malignancies 5-yr survival better in the USA compared to the UK Differences in registries advanced stage? Post code lottery - practice variations - under investment Lack of specialised services some 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 Spoke - Cancer Centre - Cancer Units Cancer Unit Diagnostic role Rapid assessment units 2 week wait referral clinics Colposcopy MDT Manage certain cancers/ suspected cancer Cervix up to FIGO IA Uterus IA/IB, grade 1 or 2 Ovary- risk of malignancy index< 200 Vulva- 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 units Function 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 High grade disease HPV changes CIN I 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 related offensive PV discharge neuropathic pain renal failure DVT FIGO Staging I – Confined to cervix IA Micro – invasive (<5mm from basement epithelium from which it originates) IA1 up to 3 mm deep and 7 mm wide IA2 3-5 mm deep and 7 mm wide IB – macroinvasive tumour IB1 < 4 cms, IB2 > 4 cms II – Beyond cervix IIA 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 vagina IIIB Pelvic side wall IV – Beyond true pelvis IVA Mucosa of bladder or rectum IVB 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 IA1 cone biopsy to preserve fertility option simple hysterectomy IA2 radical 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 IB1 excise cervix, limited parametrium laparoscopic node dissection Fertility preservation Long term survival data unavailable Expertise not always available Pregnancy outcomes promising Palliative procedures Exenteration Anterior 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 surgery Not 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 % risk BRCA2 – 10-30% Two or more 1st degree relatives affected HNPCC 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 3 bilateral, solid area, septation ascites, other deposits each criterion 1 point 0-1 criterion = score 1 2-5 criteria = score 3 M = menopausal status premenopausal= score 1 postmenopausal=score 3 RMI score RMI < 200 more likely benign managed at Cancer Units RMI > 200 more likely malignant managed at Cancer Centre FIGO Staging Surgical/ pathological I – Confined to ovaries with or without malignant ascites II – Confined to pelvis includes spread to uterus/ tubes pelvic tissues III – Confined to peritoneal cavity size of omental mets decides IIIA/B/C IV – Distant metastases e.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 surgery CHORUS 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 diagnosis Morbidity of surgery Survival 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 oestrogens PCO peripheral conversion (adipose) Unopposed oestrogens HRT Tamoxifen 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 cell remaining other types such as MMT, squamous Two types standard type- obese, low stage low grade, good prognosis non-standard type – not obese, high grade, high risk histotype Spread : local / distant 70-80% stage 1 confined to uterus perceived as ‘not such a bad cancer’ Investigations Examination Transvaginal scan endometrial thickness > 4 mms (5 mms) considered significant endometrial 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 involved A glands only B stromal invasion III – Serosa of uterus, peritoneal washings+ve lymph nodes (IIIC) IV – Local/distant mets Grade Histological type Lymphovascular space invasion Treatment Surgical TAH +BSO, peritoneal washings / LAVH BSO ASTEC trial – lymph nodes or not Surgery alone sufficient endometrioid type, invasion<50% thickness of myometrium, grade 1 or 2 i.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) VIN HPV associated Bowenoid generally good prognosis multifocality – main problem Differentiated VIN associated with lichen sclerosus/ squamous hyperplasia relatively 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 cms IA up to 1 mm depth of invasion IB 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 Radiotherapy Wide excision with good margins Vulvectomy and groin incisions for nodes Sentinel nodes – research Node positive Insufficient margins Chemotherapy/chemoradiotherapy Morbidity 50% wound breakdown Lymphoedema Lymphocyst formation Rectocele & cystocele Sexual dysfunction Follow up Detect early recurrence more visible Poor outcome for recurrence and node positive cases Five year survival Stage Stage Stage Stage I – 90- 97% II – 85% III – 74% IV – 30% Qs