EPITHELIAL OVARIAN TUMORS

UniT One
Presented by: Dr Akintoye O. (Registrar)
Dr Abubakar M. (Senior Registrar)
Supervised by Dr Adenekan
Outline
• Introduction
• Incidence
• Aetiology
• Risk factors
• Pathology
• Classifications
• Clinical features
• Investigations
• Screening
• Management
• Summary
Introduction
• Epithelial ovarian tumors are tumors derived from the coelomic
epithelial covering of the ovary
• May be benign, borderline or malignant
• Occurs primarily in adults
• In the early stages are mostly asymptomatic and painless
• May grow to a large size and tend to undergo mechanical
complications
• Only 25% are diagnosed in stage 1
Incidence
• Relatively uncommon
• 2% of total cancer cases in UK
• Ovarian cancer is the second commonest gynecological malignancy
among Nigerian women after cervical cancer
• There is no available statistics on ovarian Cancer in LIMH
• EOC is the commonest type of ovarian cancer (70-80%)
• The most lethal of all gynaecological cancers.
• More common in developed countries than developing countries
• Median age at diagnosis is 61yrs
AETIOLOGY
• NOT WELL KNOWN
• incessant ovulation is a contributing factor.
• Repeated epithelial trauma
• Hereditary or familial ovarian cancer
PATHOLOGY
• ORIGIN: mesoepithelial cells on ovarian surface
• Of several subtypes:
- Serous (50%) composed of ciliated columnar(tubal type) epithelium
- Mucinous (12-15%) composed of mucus secreting(cervical canal type)
- Endometroid (10%) composed of glandular (endometrium like)
- Clear cells (mesonephroid) 5%
- Brenner composed of transitional (urothelium like) epithelium
Serous tumors
• Form 40% of all ovarian Cancer
• 33% are bilateral
• Most are large, spherical to ovoid cystic structures
• 5-10cm and might be 30-40cm
• The surface of benign tumors are smooth and glistening
• In contrast to the malignant forms, the surface is nodular and
irregular
• Ca 125 is positive in >80%
2004 SHIH & KURMAN
CLASSIFICATION
Clinical presentation
• Often been described as a ‘silent killer’, with approximately 75% of
patients being diagnosed at a late stage (stage III/IV).
• The current 5‐year survival for EOC is 30–40%, but that of early‐stage
disease (e.g. stage I) is 84–94%
• This is mainly because the symptoms and signs of early‐stage EOC are
subtle or absent
Clinical features
• those of advanced EOC include
-abdominal distension due to bowel gas or ascites,
-a pelvic mass,
-abnormal bowel sounds,
- difficulty in passing urine,
- palpable abdominal masses,
- lymphadenopathy,
- pleural effusion,
- an umbilical mass (sister Mary Joseph nodule)
- rarely, intra‐abdominal organomegaly
Evaluation
• abdominopelvic examination,
• transvaginal ultrasound scan (TV‐USS),
• serum Tumor markers e.g. CA125 , CEA
• CT/MRI
CA125 Ovarian tumor marker
• serum glycoprotein
• the current gold‐standard biomarker for EOC.
• it is an approved test both for the differential diagnosis of a pelvic
mass and as a serial response marker in patients undergoing
treatment for EOC,
• it has poor specificity for the disease.
• It is elevated in other benign and malignant ovarian and non‐ovarian
related conditions
CA125
• CA125 is elevated in only 80% of women with established EOC, and in
only 50% of those with early‐stage disease
• normal range 0–35IU/L
Human Epididymis 4
• Other markers have been evaluated for use in combination with CA125
to diagnose EOC
• the most well‐known being human epididymis 4 (HE4), a marker of
proliferation in ovarian cancer cells.
• When used in combination with CA125 as a diagnostic, HE4 has been
shown to marginally improve on the specificity of CA125 alone
• particularly in discriminating endometriosis from malignancy.
• However, the lack of prospective evidence of superiority compared
with existing methods of diagnosis (ultrasound, etc.) means HE4 is not
approved for use as a diagnostic
Ovarian cancer screening studies
● PLCO study: no survival improvement using annual CA125 or TV‐USS
versus controls in women aged 55–74 years (sample size 28 000).
● UKCTOCS: no survival improvement using annual CA125 algorithm
plus TV‐USS or annual TV‐USS alone versus controls in women aged 50–
74 years (sample size 200 000), although extended survival analysis is
ongoing.
● UKFOCSS: no survival improvement in 3500 high‐risk women aged
over 35 using annual TV‐USS and CA125.
Risk of Malignancy index (RMI)
• In ovarian tumors is a validated clinical tool used for risk stratification
of ovarian lesions to guide further management.
• The score incorporates the patient's menopausal status (M),
ultrasound features of the lesion (U), and the serum CA-125 level.
• RMI = U x M x CA-125 (U/ml)
• U score
0 = no features of malignancy on ultrasound
1 = one feature of malignancy on ultrasound
3 = two or more features of malignancy on ultrasound
Features of malignancy on ultrasound include:
-multi-loculated cystic mass
-solid area
-ascites
-bilaterality
-metastases
• M score
1 = premenopausal
3 = postmenopausal
Interpretation
RMI score less than 25: low risk, repeat clinical assessment advised
RMI score 25-200: intermediate risk
RMI score greater than 200: high risk, referral to specialist
gynecological cancer service
MANAGEMENT
• EOC is optimally managed by centralized, integrated, multidisciplinary
teams.
• This has been shown to improve outcomes.
• In general, the team consists of a surgical oncologist, a
medical/clinical oncologist, a radiologist, a pathologist and specialist
nurses. A Palliative care specialist input may be required in all phases
of the disease.
• The definitive management of ovarian tumor starts with laparotomy
and staging
• Comprehensive staging laparotomy is surgicopathological.
• It involves careful inspection, palpation and biopsy of peritoneal
surfaces, pelvic washing, removal of affected ovary (TAH/BSO),
infracolic omentectomy and systemic pelvic and paraaortic lymph
node dissection.
• Correct staging is important for choice of treatment and prognosis
• Aim of surgery is to total macroscopic debulking of tumor.
Mgt cont’d
- FIGO stage IA and IB lower‐grade tumours, surgery is probably
sufficient and chemotherapy is generally omitted, although the option
of giving postoperative chemotherapy is the subject of ongoing
debate.
- - FIGO stage 1C–IV high grade EOC is to perform primary debulking
surgery with the explicit aim of total macroscopic clearance and to
enable complete surgical staging. This is followed by adjuvant
carboplatin‐containing chemotherapy for all patients.
Mgt cont’d
• In those with advanced disease with poor performance status or
where primary debulking surgery is predicted to be too hazardous,
chemotherapy is given alone (without surgery) or as neoadjuvant
treatment, the latter with the intention of allowing delayed debulking
surgery once disease bulk and overall health has been optimized
CHEMOTHERAPY
• The current standard of care following surgery is a combination of
platinum-based (cisplatin and carboplatin) and a Taxane (paclitaxel
and doxitaxel)
• Treatment consists of six cycles given 3‐4weeks apart.
• The combination can be:
----- Paclitaxel + Cisplatin
------Paclitaxel + Carboplatin
------Docetaxel + Carboplatin
Chemotherapy cont’d
• However the Gold Standard is combination of Paclitaxel + Carboplatin
as they have the most favorable outcome as measured by response
rate, time to disease progression and overall survival rate
• In
Recurrent ovarian cancer
• Recurrent EOC is currently an incurable clinical situation, although
survival improvement can still be achieved using appropriate
chemotherapy and a multidisciplinary approach.
• The goal of 2nd line therapy is Palliation and optimization of quality of
life.
• Depending on the time interval between primary platinum‐based
treatment and relapse, recurrent EOC is arbitrarily divided into
platinum refractory (within 4weeks), resistant (<6months) or
potentially sensitive disease(>12months).
Recurrent EOC
• In Platinum refractory and Platinum resistance, a single agent
chemotherapy –doxorubicin is the drug of choice
• Radiotherapy is generally reserved for Palliation of symptomatic
disease particularly pelvic recurrence, cutaneous and intracerebral
disease
Prognosis
• Unfortunately, the majority of patients with ovarian cancer will
relapse and ultimately die from their disease.
• While the prognosis from earlier stage, low‐grade EOC is good, with a
cure rate of greater than 90%
• Across all stages (I–IV) the prognosis is poor, with:
---- 1‐year survival of 71%
----- 5‐year survival of 40%
-----10‐year survival of 33%
New advances
• Emerging therapeutic intervention include:
1. Farletuzumab- a monoclonal antibody against Alpha folate receptor
which is over expressed in majority of patient with advanced ovarian
has demonstrated impressive activity in Phase 2 clinical trial and Phase
3 trial are underway.

2. Dasatanib- a sarcoma protein inhibitor has also shown impressive

preclinical activity in ovarian cancer and clinical trial are currently
ongoing
Summary
• The management of ovarian cancer is complex by virtue of its
insidious presentation, heterogeneous histology and often rapid
development of chemotherapy resistance mechanisms.
• Ovarian cancer still remains the most lethal of gynaecological cancers,
warranting exploration into novel therapeutic strategies including
research into screening to detect early stages of the disease.
References

• Dewheurst Textbook of Obs and Gynae, 9th edition

• NiCE guidelines on Ovarian cancer : Sept 2010
• www.cancerresearchuk.org
• Int J Womens Health. 2017; 9: 855–860. Published online 2017 Nov 22. doi:
10.2147/IJWH.S130340
• MENURadiopaedia.org
• https://doi.org/10.2147%2FIJWH.S130340
• https://doi.org/10.4103%2F2141-9248.117947
• Comprehensive Gynaecology in the tropics, 2nd edition
Gracias!!!!!!