Symptoms, assessment and treatment options for …...2019/10/13  · Symptoms, assessment and treatment options for Ovarian Cancer Dr. Naven Chetty Gynaecological Oncologist Queensland

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