1. MANAGEMENT OF EARLY STAGE
OVARIAN MALIGNANCY
AKISEKU A.K

2. OUTLINE
• Introduction
• Epidemiology
• Pathophysiology
• Aetiology/ Risk factor
• Mode of spread
• Clinical presentation
• Staging
• Treatment Of Early Stage Disease
• Fertility sparing surgery
• Onco-fertility
• Conclusion

3. INTRODUCTION
Ovarian cancer remains an important cause of
cancer deaths in women
Although many histologic types of ovarian
tumors have been described, more than 90%
of ovarian malignancies are epithelial tumors.
Geographic variation of ovarian cancer shows
is commoner in northern Europe and the USA
and less common in developing countries and
Japan.(Gynecol Oncol 1991;43:9-23)

4. Epidemiology
 The American Cancer Society estimates for ovarian
cancer in the United States for 2015 are:
 About 21,290 women will receive a new diagnosis of
ovarian cancer.
 About 14,180 women will die from ovarian cancer.
 The occurrence of cancer in Africa varies remarkably
from that in economically developed
 This is largely due to differences in exposures to major
risk factors, availability of diagnostic and screening
services, and availability of treatment.

5. It is the fifth most common cause of cancer in
women overall.
Epithelial ovarian cancer is the second leading
cause of death from gynaecological cancer.
The current lifetime risk is 1 per 70 women,
the incidence being approximately 22 per
100,000 population

6. Enugu: C A Iyoke et al 2013
Epithelial ovarian cancer constituted 68% of
cases of ovarian cancer.
Sex cord and germ cell tumors constituted
16% each.
Approximately 60% of women who had
epithelial ovarian cancer were aged 50 years
or below.
Over 84% of ovarian cancer presented in
stages 3 and 4 of the disease.

7. Kano: I A Yakasai et al 2013
ovarian cancer was the second commonest
gynaecological cancer (30.5%).
The mean age for ovarian (57 ± 4.5years)
The mean age at menarche for ovarian cancer
(15.5 ± 2.1 years)

8. Sagamu: P O Adefuye et al 2014
Ovarian cancer was the second commonest
gynaecological cancer (35.4%).
 The mean age in ovarian cancers was
54.42±10.51 years.
 Similarly the mean parity in ovarian
malignancy was 3.72±1.68 .

9. Pathophysiology
Cause unknown, like many other carcinoma
Increased incidence found in certain postulations;
–incessant ovulation hypothesis
– According to this, "repeated cycles of ovulation-induced
trauma and repair of the ovarian surface epithelium
OSE at the site of ovulation, without pregnancy is a
promoting factor for carcinogensis

10. Aetiology
The risk of developing ovarian cancer appears to
be affected by several factors
• Reproductive factors
1. Nulliparity
2. Early menarche
3. Late menopause

11. Risk factors: Genetic / Hereditary factors
 Family history plays an important role
1. Lifetime risk is 1.6% in the general population compared
to 4-5 % risk when a 1st degree relative , rising to 7%
when 2 relatives are affected
2. From 5-10% of cases of ovarian cancer occur in an
individual with a family history of the disease. Only a
small percentage of these patients have an inherited
genetic abnormality, and the risk of this occurrence
increases with the strength of the family history.

12. At least 2 syndromes of hereditary ovarian cancer
are clearly identified, involving either (1)
disorders of the genes associated with breast
cancer, BRCA1 andBRCA2, or (2) more rarely,
genes within the Lynch II syndrome complex.
BRCA1 is a tumor suppressor gene that inhibits
cell growth when functioning properly.
The inheritance of mutant alleles of BRCA1 leads
to a considerable increase in risk for developing
ovarian cancer.

13. Individuals with a BRCA1 gene mutation have
a 50-85% lifetime risk of developing breast
cancer and a 15-45% risk of developing
epithelial ovarian cancer. Those with
a BRCA2 gene mutation have a 50-85%
lifetime risk of developing breast cancer and a
10-20% risk of developing epithelial ovarian
cancer

14. Families with Lynch II syndrome or hereditary
nonpolyposis colorectal cancer are
characterized by a high risk for developing
colorectal, endometrial, stomach, small
bowel, breast, pancreas, and ovarian cancers.
This syndrome is caused by mutations in the
mismatch repair genes. Mutations have been
demonstrated in mismatch repair
genes MSH2, MLH1, PMS1, and PMS2.

15. Risk factors
• Age: Incidence of OC increases with age.
– In the USA, aver. age @ diagnosis was 57 years
– In Ibadan, > 60% of patient were 50 years or older
– In Benin, peak age incidence was 51-60, mean age
58 years
– In Taiwan, peak age incidence was 50-59

16. Other factors
Race
Women with history of breast cancer
Environmental factors
– Diet
– Smoking
– Residence in industrialised countries
– Exposure to granuloma-inducers such a talc, asbestos
– PID

17. Protective factors
• Notably, some events / conditions have a protective
effect:
• Long term use of COC pills is a protective factor.
Studies have suggested a 40% reduction in risk .
• Multiparity lowers the risk of ovarian cancer
• Early age at 1st pregnancy, older age of final
pregnancy
• The risk is also lower in women who had tubal ligation

18. Modes of spread
• Ovarian cancer typically spreads to the peritoneal
surfaces and omentum.
• Ovarian carcinoma can spread by
– local extension
– lymphatic invasion
– intraperitoneal implantation
– hematogenous dissemination
– transdiaphragmatic passage.
• Intraperitoneal dissemination is the most common
and recognized characteristic of ovarian cancer.

19. Clinical presentation
• Early disease causes minimal and nonspecific, or
no symptoms.
• Therefore, most cases are diagnosed in an
advanced stage.
• The prognosis of ovarian cancer is closely related
to the stage at diagnosis; thus, overall, prognosis
for these patients remains poor

20. Clinical presentation
• Ovarian cancer presents with a wide variety of
vague and nonspecific symptoms,
– bloating
– abdominal distension or discomfort
– pressure effects on the bladder and rectum
– constipation, vaginal bleeding
– indigestion and acid reflux
– shortness of breath, tiredness
– weight loss, and early satiety
– patient may feel an abdominal mass.

21. Table 1-Clinical Presentation at the UBTH
Clinical Features Frequency Percentage (%)
Gastrointestinal symptoms 40 86.90
Abdominal discomfort 32 69.60
Abdominal mass 28 60.90
Urinary symptoms 22 47.80
Abdominal distension 20 43.50
Dysmenorrhoea 16 34.70
Weight loss 14 30.40
Lower limb oedema 14 30.40
Dyspareunia 8 17.40
Abdominal pain 8 17.40
Abnormal vaginal bleeding 4 8.70
Dyspnoea 4 8.70
Asymptomatic 2 4.30
21

22. HISTIOGENESIS OF OVARIAN TUMOUR
EPITHELIAL
ORIGIN
SEX CORD
STROMA
CERM CELL
ELEMENT
CONNECTIVE
TISSUE
MISCELLANEO
US
SECONDARY
TUMOURS
SEROUS Tmr
MUCINOUS Tm
ENDOMETROID
CLEAR CELL Tmr
BRENNER Tmr
MIXED EPITH T.
UNDIFFERENTD
UNCLASSIFIED
BORDERLINE T.
GRANULOSA
THECA CELL
GRAN-THEC
SERTOLI C. T
LEYDIG C. T
SER-LEYD T
DYSGERMIN
ENDODERM
EMBRYONAL
POLYEMBRYO
CHORIOCAR
TERATOMAS
STRUMA OVA
CARCINOID
MXD GERM C
FIBROMA
ADENOFIBRO
MEIG’S SYNDR
LYMPHOMA
SARCOMA
KRUKENBERG
From primary
Dx of;
THYROID
GIT
LIVER
BREAST
OVARY
UTERUS

23. Staging is surgical-pathological:
component of staging laparotomy
• Exploratory laparotomy
• Cytology of ascitic fluid or peritoneal washings
• Measurement of metastases to determine if a
metastasis is ≤2cm or >2cm in widest diameter
• Removal of tissues and lymph nodes for histology
i.e TAH, BSO and Omentectomy
• Biopsies to determine spread: peritoneum;
omentum; diaphragm
• Evaluation of liver parenchyma
• Location of extra-abdominal, extra-pelvic disease

24. Early stage ovarian cancer.
Approximately 30% of women presenting with
epithelial ovarian cancer will be early
stage(stage 1) disease
Multidisciplinary team is central to deciding the
optimal management for these women
Comprehensive staging is important in
determining the need for chemotherapy
The combined ACTION and ICON 1 studies of
chemotherapy showed an improved overall
survival.

25. TREATMENT OF EARLY STAGE DISEASE
• Standard treatment at the staging laparotomy
consists of TAH, BSO, and infracolic omentectomy.
• Only a small percentage of women with epithelial
ovarian cancer can be treated with surgery alone.
This small percentage includes patients with stage
IA (grade 1) and stage IB (grade 1) serous,
mucinous, endometrioid, and Brenner tumors.

26. Approximately 25% of women with apparent
early ovarian cancer will have more advanced
disease if fully staged and this may explain the
higher than expected recurrence rates.

27. Clinical prognostic factors
• Tumour grade and type
• Presence of ascites
• Others considered for high recurrence include
I. Women with clear cell tumour
II. Positive pelvic washing
III. Tumour rupture during surgery

28. • Two large RCT concerning the benefit of
chemotherapy in early stage ovarian cancer
published in 2003 confirms, the benefit in
terms of disease free interval and 5 year
survival of chemotherapy over observation in
the population studied
• Previous evidence suggested that women with
stage 1A and stage 1B grade 1 disease have an
excellent prognosis without further treatment
but stage 1C disease may benefit from
chemotherapy

29. • This study was not able to answer if stage 1A
and 1B grade 2 should benefit from
chemotherapy.

30. Conservative management of early
stage disease
• With the shifting of childbearing towards higher age, EOC
increasingly affects women with active childbearing desire,
resulting in major impacts on treatment management.
• Nowadays, fertility-sparing surgery (FSS) represents an
effective alternative to conventional radical cytoreduction in
younger women with early stage of the disease.
• In these special circumstances , unilateral salpingo-
oophorectomy may be performed with conservation of the
contralateral ovary and the uterus in order to retain fertility

31. Criteria for FSS
1. Desire of reproductive capacity
2. Patient is <35 years of age
3. Comprehensive staging laparotomy showed disease
to be stage 1A
4. Grossly normal contralateral ovary
5. Patient willing and able to have close follow up
6. Histological grade is 1-2
7. Patient agrees to oophorectomy at 35 years of age
or when childbearing is complete or at slightest sign

32. Fertility sparing surgery in early ovarian cancer:
A viable option? C. Fotopoulou (2012)
• According to the 2007 guidelines of ACOG, fertility-
sparing surgery is recommended for highly or
moderately differentiated stage IA disease
• Also, the European Society for Medical Oncology
(ESMO) in 2008 recommended FSS for patients
with stage IA tumor without dense adhesions
showing favourable histology

33. Oncologic Outcomes after FSS in EOC
• FSS is a safe treatment option for early-stage patients with
acceptable oncologic safety profile
• A relapse rate of 8.5% was reported after 10yrs post FSS with
27% of the relapsed patients presenting recurrence
exclusively in the remaining ovary without any distant or
peritoneal metastases.
• Most of the relapsed patient belonged to stage 1C & G3
tumours
• There was no evidence of local or distant recurrence over 5
years

34. Reproductive outcomes after FSS
• Successful conception rate of approx. 30% of all
patients after FSS.
• However, considering only the women with
childbearing wish who actively tried to conceive,
rates of successful conception were substantially
higher 66-100%; indicating that no relevant
reproductive impairment exists after FSS.
• Only the minority of patients required ART for a
successful conception and pregnancy

35. Reproductive outcome after FSS
• Incidence of spontaneous abortion ranged
between 11 and 33%.
• However, 5% of the 121 patients who received
platinum-based chemotherapy presented a
persistent secondary amenorrhea up to 24 months
after completion of 4–6 cycles of systemic
chemotherapy.

36. Reproductive outcome after FSS
• 9.1% of the 55 patients who successfully conceived
received infertility treatment before pregnancy.
• Interestingly, the authors reported four (9.4%) of the
53 patients who gave birth to children had undergone
completion surgery after childbearing, consisting of
hysterectomy and contralateral salpingo-
oophorectomy.
• No higher rates of congenital malformations or
abnormal fetal outcomes was reported.

37. Risk-benefit counselling
• Management of young women diagnosed with
ovarian cancer should be individualized
• The risk of conservative therapy is balanced against the
disadvantages of more radical treatment
• The patient and the family should be extensively
counselled.
• They need to know that these conservative therapeutic
approaches are yet not considered "standard."

38. Risk-benefit counselling
• The patients should be aware that by accepting fertility-
sparing treatment they are assuming a small but
undefined risk for recurrence of the disease.
• Some of them will require assisted reproductive
technology (ARTs) to help achieve a pregnancy,
especially IVF
• They may also consider ovarian tissue, oocyte, or
embryo cryopreservation before definitive cancer
therapies.

39. onco-fertility
• Oncofertility refers to the medical field that bridges
the specialties of oncology and reproductive
endocrinology with the purpose of maximizing the
reproductive potential of cancer patients and
survivors.
• Concern of this onco-fertility group is centred on
– the safety of conservative treatment
– the uncertain efficacy of fertility options
– the detrimental effects of chemotherapy to remaining
reproductive organs
– the timing and execution of fertility workup relative to
disease requiring treatment

40. Fertility preservation options include:
• Shielding of the genital and pelvic
region with a lead apron during
radiation therapy to minimize the
damaging effects of ionizing
radiation on the ovaries and
testes.
• Ovarian Transposition to
physically move the ovaries out of
the pelvis through surgical
techniques in cases where pelvic
radiation is required in order to
minimize the damaging effects of
ionizing radiation on the ovaries.
• Gonadotropin Agonist injections
will chemically down regulate the
ovaries or testes and minimize
their activity prior to receiving
chemotherapy. The belief is that
ovaries and testes with minimal
metabolic activity will experience
less damaging effects from the
chemotherapy.
• Egg Banking to cryopreserve
(freeze) a woman’s eggs for
future fertilization with sperm
when she meets her future life
partner

41. • Embryo Banking to freeze
embryos for future implantation
• In Vitro Maturation (IVM) of
oocytes, where multiple
immature eggs are harvested by
ultrasound guided aspiration
without prior hormone
stimulation. These eggs will then
be matured in the laboratory
either before or after freezing.
• Sperm Banking to freeze sperm
for future use.
• Testicular Sperm Aspiration or
Extraction is a minor surgical
procedure where sperm is
retrieved directly from the
epididymis or testes, which can
frozen for future use. This is only
required when no sperm can be
produced through ejaculation.
• Others are donor egg and sperm,
surrogacy and adoption

42. Conclusion
• The care of the young patient with gynaecologic
malignancy is extremely complex and challenging.
• It necessarily requires a multidisciplinary approach
with the close collaboration of
– gynaecologist-oncologist
– reproductive endocrinologist,
– Pathologist
– Specialist Nurse.

43. Conclusion
• Correct staging in keeping with FIGO
recommendation is critical in identifying women
who will benefit from chemotherapy.
• Preservation of fertility balanced with treatment
of disease is the goal of young patients diagnosed
with ovarian neoplasms.

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Teaching Hospital Kano: a 3 year review. Nigerian journal of clinical
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Sagamu, southwest, Nigeria. East African Medical Journal. 2014; 91(11):
398-406.
• Christina Fotopoulou, et al Fertility-Sparing Surgery in Early Epithelial
Ovarian Cancer: A Viable Option? Obstetrics and Gynecology Intl Vol12
(2012), Article ID 238061 doi:10.1155/2012/238061
• Campos SM et al Young women diagnosed with early-stage ovarian cancer
or borderline malignancy of the ovary: a focus on fertility and sexual
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46. •THANK YOU