Explaining ovarian cancer

1. OVARIAN CANCER
UQU-ONCOLOGY CLUB. PREPARED BY RAKAN ALOTAIBI

2. BRIEF ANATOMY REVIEW
The ovaries are considered the female
gonads. Each ovary is whitish in color and
located alongside the lateral wall of the
uterus in a region called the ovarian fossa.
The ovarian fossa is the region that
is bounded by the external iliac
artery and in front of the ureter and
the internal iliac artery.
The ovaries lie within the peritoneal
cavity, and is attached on both
sides by a fibrous ligament called
the ovarian ligament.

3. OVARIAN FUNCTION & PHYSIOLOGY
• At puberty, the ovaries begin to secrete a higher level of hormones allowing the
development of secondary sexual characteristics.
• Hormones secretions of the ovaries are also involved in fertility (ovulation) and
menstruation.
• The ovaries release oocytes which are mature fluid-filled follicles. Multiple occytes
are formed each month, but only one occyte develop. This release of multiple
occyte is stimulated by the leutinizing hormone secreted by the pituitary gland
which stimulates the follicles to rupture onto multiple occytes, this process is
termed ovulation.

4. CONTINUE
• The remaining unmaturating follicles re-organize to form the corpus luteum
which secretes progesterone preparing the uterus for pregnancy if fertilization
occurs.
• At puberty, the ovaries secrete estrogen, inhibin, and progesterone hormone,
estrogen stimulates the secondary sexual characteristics (causing breast
enlargement, widening of the hips, elongation of the upper arms, more growth of
the labia minora). While progesterone causes thickening of the endometrium to
prepare the uterus for possible pregnancy.

5. DEFINITION OF OVARIAN CANCER
• Ovarian cancer is the leading cause of death in gynecological cancer. Why?
Because it is rapidly invasive, has no screening test, and it has vague symptoms.
• It is the fifth leading cause of cancer deaths in women (known as the silent killer)
and the second most commonly disgnosed gynecological malignancy.
• There are classes of ovarian cancer which are epithelial (the most common) and
non-epithelial.

6. EPIDEMIOLOGY
• Ovarian cancer accounts for approximately 239,000 cases and 152,000 deaths
annually.
• The highest rate of prevalence is seen in Eastern and Central Asia with 11.4 cases
per 100,000 capita and 6 deaths per 100,000 capita.
• The commonest class of ovarian cancer is epithelial ovarian cancer.
• The highest incidence is seen in white women followed by Hispanics.
• The median age of onset is 50.

7. PATHOLOGICAL TYPES OF OVARIAN CANCER
• It includes epithelial and non epithelial cancer types
• Epithelial ovarian cancer includes :1- serous carcinoma: the most common
(represents 70% of all epithelial cancers),
inherited due to BRCA1/2 mutation and
hereditary breast and ovarian cancer (HBOC)
2-clear cell carcinoma: inherited from Lynch
syndrome
3-Endometrioid carcinoma
4- Low-grade serous carcinoma
5-mucinius carcinoma

8. CONTINUE
• Non-epithelial ovarian cancer includes:
1-Germ cell origin: -Dysgerminomas (the commonest type,
representing 40% of all germ cell tumors) –Mature teratoma -Dermoid
cyst –Immature teratoma -Embyonal carcinoma -Non-gestional
choriocarcinoma –Gonadoblastoma (combined germ cell and specialized
gonadal-stromal elements)
2-Specialized gonadal-stromal origin: -Granulosa-theca cell
tumor –Granulosa cell tumor -thecoma -Sertoli-leying cell tumor -Lipid
cell tumor -Arrheniblastoma
3-Mesenchymal origin: -Fibroma –hemoangioma -
Leiomyoma -Lymphoma -sarcoma

9. RISK FACTORS
• White race
• Late age of menopause (unknown mechanism but it is suggested that recurrent
ovulation will cause surface damage to the ovaries increasing the malignancy
potential)
• Family history of ovarian, breast or bowel cancer
• Prolonged interval of ovulation
• Nulliparity
• Infertility

10. CONTINUE- NOTABLE RISK FACTORS
• In general, most cases are sporadic, but genetic cases represents 10-15% of all ovarian cancers.
The commonest genetic risk factor is BRCA1 and BRCA2. Other genetic risk factors include HBOC
and Lynch syndrome (also known as non-polyposis colorectal cancer) and positive family history
for ovarian and/or breast cancer.
• Mutations in BRCA1 and BRCA2 are mostly seen in Ashkenazi Jewish. It is inherited by an
autosomal dominant pattern.
• All patients who have BRCA1 and/or BRCA2, or Lynch syndrome or a strong family history
should receive a genetic counseling. Those patients (especially who has BRAC1 and BRCA2 gene
mutations) should be offered a prophylactic bilateral salpingo-oophrectomy (PBSO), if the
patient has completed her family or reached menopause.
• PBSO reduces the risk of both ovarian (96%) and breast (53%) cancers.

11. FACTORS PROTECTING FROM OVARIAN CANCER
(PROTECTIVE FACTORS)
• Using oral contraceptives: it provides the strongest protection reducing the risk
by 50%
• Multiparity: combining oral contraceptives with multiparity reduces the risk by
75%
• Tubal ligation
• Hysterectomy
• Lactation
• Bilateral oopherectomy

12. CLINICAL FEATURES
• Unfortunately, the clinical features of ovarian cancer in most patients are non-specific
as most patients present late (usually stage III or VI).
• In early stage, the patient has vague, abdominal pain, abdominal bloating, urinary
frequency or constipation (due to tumor compression of the bladder and rectum
respectively), dyspareunia [dyspareunia is persistent or recurrent genital pain during
intercourse, commonly known as “painful intercourse”], and irregular menses in
premenopausal women.
• In advanced stages, the patient has a more severe abdominal swelling (resembling
ascites), nausea, vomiting, dyspepsia ( it is an impaired digestion leading to bleching,
heartburn and abdominal bloating), anorexia, lethargy, and menorrhagia or
menometrorrhagia in premenopause.

13. HISTORICAL FINDINGS RAISING THE SUSPICION
• Because the symptomatology of ovarian cancer are non-specific, and patients very
commonly present in late stages. Therefore, any women presenting with a non-specific
clinical features especially in the presence of constitutional symptoms (weight loss, fatigue,
loss of appetite, night sweating, and fever) and/or has the aforementioned risk factors, ask
for a pelvic ultrasound. In this case, if a mass is detected, then the physician may be able to
intervene in early stages.

14. PHYSICAL SIGNS
• Ovarian malignancy signs include:
• These physical findings may not be detectable in all patients, but the presence of
a cluster of these signs (especially the first two) should make the suspicion high.
1- A vaginal or rectal examination will show a solid, irregular
and fixed pelvic mass
2- An abdominal examination will show an upper abdominal
mass and/or ascites
3- A respiratory examination will show pleural effusion
findings (dullnes to percussion, decreased tactile fermitus, and
assymetricsl chest expansion)
4- A pelvic exam will reveal inguinal lymphadenopathy

15. STAGING
• Staging of ovarian cancer is based on a classification system called International
Federation of Gynecology and Obstetrics (FIGO).
• The higher the stage, the worse prognosis.
• Stage III and especially IV carry the worst prognosis.

16. DIAGNOSIS
• Take a full history, including risk factors, family history of ovarian cancer, and
previous malignancies.
• Perform a full chest, breast, abdominal, and most importantly pelvic examination.
• If there is a suspicion for ovarian cancer, perform a pelvic exam AND request
Cancer antigen-125 (CA125) with a pelvic ultrasound (US).
• If the CA-125 and/or pelvic US is positive with a historical or physical findings
suspicious of ovarian cancer, then a more diagnostic testing is needed.

17. CONTINUE
• Request a CT scan of the chest, abdomen and most importantly the pelvis (chest and abdomen to
evaluate for metastasis).
• Abdominal and pelvic MRI might be indicated if clinically required, as MRI can increase the specificity
of the imaging evaluation (MRI has an excellent soft tissue evaluation).
• Positron emission tomography (PET) scan is an excellent tool in detecting metastatic lesions, but it is
not indicated for diagnosing a primary ovarian cancer.
• MRI or PET scan may be indicated if the CT scan detection of metastatic lesion is intermediate.

18. TUMOR MARKER (VERY IMPORTANT)
• Certain tumor types in ovarian cancer release serum markers in the circulation, which serve a as diagnostic tool.
• The most common well-known tumor marker is CA125 which is secreted by epithelial ovarian carcinoma. Rarely, it may also secrete
carcinoembryonic antigen (CEA), but CEA is more specific for colon cancer.
• Serous carcinomas (which is the commonest type of epithelial cancer) secrete CA125.
• Mucinous carcinomas secrete CEA.
• Dysgerminomas produce lactate dehydrogenase (LDH) and alkaline phosphatase.
• Edodermal (also called yolk sac) tumors produce alpha-fetoprotein (AFP).
• Embryonal carcinomas secrete AFP and human chorionic gonadotropin (hCG).
• Granulosa cell tumors (thecomas) mainly secrete inhibin, but also secrete estrogen and progesterone. The secretion of estrogen may cause
endometrial cancer.
• Sertoli-leydig cell tumors secrete testosterone. Characteristically, these tumors present with virilizing features which includes progressive
masculinization, amenorrhea, acne, hirsutism, voice deepening, clitoromegaly, and temporal hair recession.
• Lipid cell tumors ( a specialized gonadal-stromal tumor) secrete adrenal corticosteroid. It causes Cushing’ syndrome (causing central obesity, buffalo
hump, moon face, skin thinning, red abdominal striae, hirsutism, and baldness).

19. SPECIFIC PATHOLOGIC FEATURES
• Granulosa-theca cell tumors (which is the commonest type of specialized gonadal-stromal
carcinoma) has a characteristic pathologic finding called Call-Exner bodies which are a small
group of cells.
• Immature teratomas contain different tissues including neural (the most common), epithelial and
cartilaginous tissue.
• Mucinous tumors tissues resemble the endocervical epithelium.
• Endometroid tumors resemble an endometrial carcinoma and may arise in association with
endometrial cancer in some patients.
• Krukenberg tumor is a metastatic ovarian carcinoma mostly originating from the stomach.
Characteristically, they show signet ring cells on a pathology specimen.

20. PREOPERATIVE EVALUATION
• Laparoscopy is not recommended if the suspicion of cancer is high because this may cause spillage and exfoliation of cells leading to metastasis and
increasing the stage.
• Preoperative evaluation includes : CBC, electrolytes, LFT, RFT, coagulation profile, ECG, crossmatching, blood grouping, VTE risk assessment, HbA1c as
well as random blood glucose, serum total bilirubin, serum beta-hCG, serum tumor markers, urine analysis, occult blood stool, CRP, and ESR.
• Endometrial biopsy should be done in any women with abnormal vaginal bleeding because a concomitant endometrial cancer might be present.
• If the patient has ascites, an abdominal paracentesis should be done for cytology.
• Patient with positive occult blood or significant bowel symptoms should undergo barium enema or lower GI endoscopy to rule out colon metastasis.
• Patient with gastric symptoms should have an upper GI endoscopy.
• Bilateral mammogram should be done to evaluate for breast cancer.
• Chest, abdominal and pelvic CT is done to evaluate for metastasis.
• Transvaginal US is indicated for evaluating tumor characteristics.

21. WHAT ABOUT SCREENING?
• Ovarian cancer does not lend itself to screening because it has a relatively low prevalence within the
general population and no proven precursor lesion exists that can be detected and treated to prevent
the cancer from occurring.
• The U.S. Preventive Services Task Force (USPSTF) recommends against screening for ovarian cancer in
the general population.
• The USPSTF found evidence that screening with serum CA-125 level or transvaginal ultrasonography in
only high risk populations (mainly BRCA1 and BRCA2 mutations) is beneficial, these high risk patients
are followed up by a periodic transvaginal US and serum CA125 allowing to detect early stages and
therefore improving the survival.

22. CONTINUE

23. TREATMENT
• The management should be always only be conducted by a gynecologic oncologist.
• Surgery is the initial treatment of choice for ovarian cancer, provided patients are medically fit.
Patients who are not candidates for optimal debulking should be considered for neoadjuvant
chemotherapy followed by an interval debulking surgery and further chemotherapy. Patients
who are not fit for surgery may be given chemotherapy and considered for surgery later, or
treated primarily with chemotherapy.
• Definitive diagnosis requires an intraoperative frozen section. So ovarian cancer is a surgical
staging.
• The standard care for ovarian cancer includes surgical exploration for primary staging and for
cytoreduction or debulking. If the disease appears to be confined to the pelvis, comprehensive
surgical staging is indicated.
• The staging procedure should include the following: -peritoneal fluid cytology -peritoneal
biopsies –omentecomy -Pelvic and para-aortic lymph nodes sampling

24. DEBULKING SURGERY
• cytoreductive (debulking) surgery should be done for all patients with ovarian cancer
wether epithelial or non-epithelial.
• The debulking surgery is a major surgery which involves laparatomy.
• The standard of care for all types of ovarian cancers is to perform a combined
procedures of total abdominal hysterectomy + bilateral salpingo-oopherectomy
(BSO) + pelvic lymphadenectomy + infracolic omentectomy with surgical
staging, followed by 6 cycles of chemotherapy. The BSO causes permanent loss
of fertility.
• Fertility sparing is ONLY applicable in a young women before menopause with
non-epithelial cancer (NOT epithelial cancer) in which all the above procedure
are done except that the salpingio-oopherctomy is unilateral with sparing of the
uterus.

25. CONTINUE -DEBULKING SURGERY
• Fertility sparing requires confirming the absence of endometrial adenocarcinoma by dilation
and curettage of the uterus to be sent for pathology test.
• If the women has completed her family or is postmenopausal. Fertility sparing is not an option in non-
epithelial cancer.
• In patient with early stage disease (grade I, and II tumors) confined to one or both ovaries, no
treatment is required after the debulking surgery.
• In advanced stages (grade III, and IV), debulking surgery and resection of the peritoneal metastasis is
done. Attempt to remove all macroscopic diseases.
• If all the macroscopic diseases are removed to 1 cm or less, these patients are said to have an optimal
cytoreduction.
• After removing all the macroscopic diseases, systemic chemotherapy is indicated.

26. TREATMENT OF ADVANCED DISEASE
• As described before, debulking surgery in addition to resection of all the visible
metastatic lesions (especially in the peritoneum) is done.
• Patients who are unfit for surgery, which is usually due a large pleural effusion or
massive ascites are given neoadjuvant chemotherapy before surgery or until
spontaneous or therapeutic resolution of the preventive factor.
• Usually the effusions or ascites resolves with chemotherapy. If the disease doesn’t
respond to chemotherapy, then only palliative care is given.

27. CHEMOTHERAPY
• Chemotherapy is indicated in most types of ovarian cancer. Only very few patient
don’t need chemotherapy. These include patients with stage IA grade 1 and stage IB
grade 1 serous, mucinous, and endometrioid tumors.
• Chemotherapy is initiated as 6 cycles of a combined IV or intraperitoneal injection of
cisplatin (or caboplatin) with paclitaxel.
• During chemotherapy, the patient is followed up with serum CA-125 or other tumors
markers as well as imaging.
• Interval debulking: is indicated in patient whose cancer was not adequately debulked
at the time of initial surgery, as it is done after the patient has received three cycles of
chemotherapy. After this, additional three cycles are given.

28. PALLIATIVE CARE
• When curative treatment options are unavailable or are ineffective, the goal changes from cure
to palliation.
• Bowel obstruction is a common terminal effect of ovarian cancer. Rectosigmoid obstruction in
the face of progressive disease is best palliated with a transverse loop colostomy. A
somatostatin analog to decrease gastrointestinal secretions can be combined with erythromycin
to improve motility in the management of small bowel obstruction.
• For anorexia, treatment with megestrol acetate or steroids can stimulate appetite.
• Fatigue or dyspnea secondary to anemia can be treated with blood transfusions or
erythropoietin.
• Ascites can result from widespread tumor infiltration over the peritoneum, preventing
absorption of peritoneal fluid.Diuretics are of limited efficacy, and relief is best obtained by
repetitive paracentesis.

29. PROGNOSIS
• Patients with stage I disease have 5-year survival rates of 75-95%.
• Almost all patients with in stage IA, grade 1 ovarian cancer are cured surgically.
• The 5-year survival rate for patients with stage II disease is about 65%.
• Sadly. despite aggressive surgery and combination chemotherapy, the 5-year
survival rate for patients with advanced-stage disease is only about 20%.

30. • Thank you, any questions?