Symptoms, assessment and treatment options for …...2019/10/13  · Symptoms, assessment and...

Symptoms, assessment and treatment options for Ovarian

Cancer Dr. Naven Chetty

Gynaecological Oncologist

Queensland Centre for Gynaecological Oncology

Bridges Health Service

Mater Public and Private Hospitals

Introduction

• Median age of diagnosis- 53

• Age-adjusted incidence- 12.8 per 100,000 per year

• 1 in 72 women will be diagnosed with cancer of the ovary during their lifetime

• Second most common gynaecological malignancy

• The most common cause of death among women who develop gynaecological malignancies

• Fifth leading cause of cancer death in females in the United States

Introduction

• The mean age of diagnosis of epithelial ovarian cancer is in the mid-fifties

• Risk of malignancy of adnexal mass in per-menopause is 6-11%, in post-menopause is 29-35%

Risk factors

• Nulligravity

• Early menache and late menopause

• Postmenopausal oestrogen replacement therapy

• Genetic

• Endometriosis

• Talc- small increase risk(RR 1.4)

• Cigarette smoking- mucinous cancer(RR 2.1) dose related

• Obesity-small but significant increase risk with BMI >/= 30, obesity also increases relative risk of death from ovarian cancer

Genetic factors

• Mutations and/or over expression of the oncogenes- HER2 c-myc and K-ras, Akt, and of the tumour suppressor gene p53 have frequently been observed in sporadic ovarian cancer

• Inactivation of the tumour suppressor genes PTEN and p16 may occur

• BRAC 1 and 2 are implicated in small proportion of cases

Protective factors

• OCP- relative risk of 0.64, occurs after 3-6 months of use and lasts for 15yrs after cessation

• Multiparity

• Tubal ligation- reduces risk by 1/3( if BRAC1 carrier by 60%)

• Breastfeeding

• Progesterone

Symptoms

• Ill-defined- therefore advanced at time of presentation

• Rupture or torsion are unusual

• Abdo distension

• Nausea

• Anorexia

• Early satiety due to ascites, omental or bowel metastases

• Dyspnoea due to pleural effusions

Symptoms

• lower abdominal pain/discomfort/pressure/bloating

• Increased abdominal size

• Constipation

• Lack of appetite/nausea/indigestion

• Irregular menstrual cycles/abnormal vaginal bleeding

• Low back pain

• Fatigue

• Urinary frequency

• Dyspareunia

Symptoms

• Paraneoplastic syndrome-• Uncommon

• Hypercalcemia- clear cell EOC

• Sub-acute cerebellar degeneration

• Leser-trelat sign- sudden appearance of multiple seborrheic keratoses

• Trousseau’s sign- migratory thrombophlebitis

Assessment

• Examination

• Ultrasound most useful non-invasive test

• CA 125- elevated(>65U/ml) in 80% of women with EOC

• CT or MRI to plan management

• Exclude extra-ovarian primary- esp. from gastric, colorectal, appendiceal, breast, endometrial

Assessment

• Ca125

• HE4

• Ca19.9

• ROMA-Sensitivity- 86%, specificity-84%

• RMI- Sensitivity- 78%, Specificity- 87%

Assessment

• Nutritional assessment

• Other medical Issues

• Full blood count

• Liver and renal function tests

• Coagulation tests

• Chest radiograph

• Electrocardiogram

• Computed tomography (CT) of the abdomen

• Plural effusions may require drainage to aid respiratory function

Assessment

• Primary cytoreduction vs Neoadjuvant chemo

• Tissue diagnosis prior to Neoadjuvant chemo

• Stage at presentation –• I (23 to 33 percent),

• II (9 to 13 percent),

• III (46 to 47 percent),

• IV (12 to 16 percent)

Treatment

• Stage if no evidence of macroscopic or radiological metastatic disease

• Debulking surgery

• Limitations to optimal cyoreduction-• Comorbidities

• Small bowel mesenteric disease

• Porta hepatis disease

Cytoreduction

• Cytoreductive surgery is the cornerstone of therapy

• Benefits of aggressive cytoreduction• Reduce tumour burden for optimal chemo response

• Reduce disease related symptoms

• Improves immune competence by reducing cytokines produced by tumour

• Debulking procedures only improve survival when optimal cytoreduction can be achieved

• Women with optimally resected tumour have, on average, a 20-month improvement in median survival compared to those with suboptimal resection

Cytoreduction

• Survival Effect of Maximal Cytoreductive Surgery for Advanced Ovarian Carcinoma During the Platinum Era : A Meta-AnalysisRobert E. Bristow, Rafael S. Tomacruz, Deborah K. Armstrong, Edward L. Trimble, and F.J. Montz

• 53 studies• 6885 patients• Each 10% increase in cytoreduction results in a 5.5% increase in median

survival • Therefore require an “expert center” is an optimal resection rate of at least

75%• The specialty of the operating surgeon is an independent determinant of

survival for women with ovarian carcinoma

Cytoreduction

• The effect of maximal surgical cytoreduction on sensitivity to platinum-taxane chemotherapy and subsequent survival in patients with advanced ovarian cancerE. Eisenhauer

• Retrospective• 296 patients• Cytoreduction to no visible disease associated with-

• Improved response to chemo• Less platinum resistance

• Improved disease free and overall survival

Neoadjuvant chemotherapy

• Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer

• EORTC 55971 trial

• No difference in outcome

• Reduced morbidity

Adjuvant treatment

• Chemotherapy- Carbo/Taxol

• IP Chemo

• Dose dense

• Targeted therapies

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Prophylaxis

• 13-15% due to BRCA

• BRCA 1- 40% risk

• BRAC 2- 15% risk

• Consider risk reduction surgery at 35-40 for BRCA 1, and 40-45 for BRCA 2

Screening

• UK Collaborative Trial of Ovarian Cancer Screening study

• 202,638 postmenopausal women

• Ca125, followed by U/S vs no screening

• 12/25 invasive tumours stage I or II

• No mortality reduction

• 10 women had surgery for benign lesions for every 1 cancer found

• 641 women would need to be screened annually for 14 years to prevent 1 death from ovarian cancer