Management of ovarian cancer

1. Ovarian Carcinoma
Arvinthran
Mentor : Dr Soo

2. Malaysian National Cancer Registry Report 2007-2011
Epidemiology

7. Aetiology
Believed to be due to irritation of ovarian surface epithelium by
damage during ovulation
Thus, risk increased if multiple ovulations and decreased if ovulation
suppressed:
- Nulliparity
- Early Menarche and late menopause
- COCP
- Pregnancy

9. Cells of origin

10. Ovarian Ca: Types
• Epithelial 65%
• Serous Cystadenocarcinoma
• Mucinous Cystadenocarcinoma
• Clear Cell Carcinoma
• Endometrioid Carcinoma
• Transitional cell tumours
- Malignant Brenner tumour
- Transitional cell carcinoma
• Epithelial-stromal
- Adenosarcoma
- Carcinosarcoma
• Sex Cord/Stromal (10%)
• Granulosa Cell Tumour
• Sertoli-Leydig Cell Tumour

11. Ovarian Ca: Types
• Germ Cell (15%)
• Dysgerminoma
• Immature Malignant Teratoma
• Endodermal Sinus Tumour
• Choriocarcinoma
• Metastatic Tumour
• Endometrium
• Cervix
• Fallopian tube
• Krukenberg tumours- breast, stomach, colong lymphoma, melanoma carcinoid

12. Serous adenocarcinoma
• Most common type of epithelial ovarian cancer
• May contain psammoma bodies
• Often associated with CA125 elevation

13. Mucinous adenocarcinoma
• Rarely be associated with pseudomyxoma peritonei
• CA 125 levels may not be markedly elevated
• CA19.9 may be elevated
• Relatively chemoresistant
• Differential diagnosis of a mucinous ovarian tumour includes metastatic
disease from an appendiceal primary

14. Endometriod carcinoma
• Associated with endometriosis or and independent uterine cancer of
similar histology
• May occur with early stage disease in younger patients, although
advanced disease is possible

15. Clear cell carcinoma
• Most chemoresistant type
• Often contains “hobnail” cells with cleared out cytoplasm due to
glycogen

16. Granulosa Cell tumour
• Include granulosa cell tumour, themocas and fibroma
• Cells of granulosa cell tumours produce estrogenic or less commonly,
androgenic steroids (eg Oestradiol)
• May secrete other factors such as inhibin and Mullerian inhibitory
substance, useful as a tumour markers during follow up
• Peak incidence in young girls and post menopausal women
• Present will PMB, menstrual problems or precocious puberty
• May be associated with concurrent endometrial cancer

17. Sertoli-Leydig cell tumour
• Mostly produce androgens
• Present with hirsuitism, amenorrheoea and virilization ( male pattern
baldness, clitoromegaly, deepening of voice, hairiness, oily skin)
• Normally benign tumours- treated surgically

18. Dysgerminoma
• Median age 18
• Raised AFP
Endodermal Sinus Tumour ( Yolk Sac)
• Secrete LDH
• Spread earlier through lymphatic
• Female equivalent of a seminoma
• Common in XY karyotypically abnormal gonads ( Turner’s’ syndrome)

19. Chroriocarcinoma
• Rare
• Usually younger than 20 years old
• Raused hCG levels ( choriocarcinoma) or hCG and AFP (embryonal
carcinoma)

20. Symptoms:
• Abdominal discomfort
• Urinary frequency/ pressure effects upon bladder & rectum
• Abdominal fullness
• GIT symptoms – abdominal discomfort/pain, change in
bowel habit
• Abnormal bleeding (rarely)
• Menstrual irregularities (associated with sex cord-stromal
tumours)
• Postmenopausal bleeding

21. Physical signs:
•Abdominal mass
•Ascites
•Cachexia
•Pleural effusion
•Bowel obstruction

22. Investigations
Haematological
Full blood count, biochemical profile and serum tumour markers
Imaging
• Pelvic and abdominal ultrasound
• Chest x-ray
• Other imaging modalities may be appropriate such as intravenous
urogram, CT/MRI of the abdomen & pelvis

23. Serum Tumour Markers
• CA125
- 80 percent epithelial ovarian tumour
- Also increased in endometrial , pancreatic and breast cancer and benign
conditions such as endometriosis , inflammatory bowel disease and
hepatitis
- Valuable as an early marker for disease recurrence, treatment response
and early treatment failure
• CA19.9
• CEA : May be elevated in stage III disease
• AFP and Beta HCG
- Measure if less than 40 years old to help rule out germ cell tumour

24. TVS
• Important in evaluation of patients with a pelvic mass
• Classic sonographic finding of malignancy is a complex cyst, defined as
containing both solid and cystic components, sometimes with septations
and internal echogenecity

26. CT/MRI abdomen/pelvis
• Helpful preoperatively if advanced disease
• Useful in assessment of retroperitoneal lymph node involvement

27. Staging

28. Staging

29. Staging

30. Staging

31. Staging

32. Staging

33. Staging

34. Treatment
•The aim of Primary surgery is to :
• confirm diagnosis
• stage the disease
• remove all cancer or optimally cytoreduce or debulk the cancer
•Full staging laparotomy
- Laparotomy
- Hysterectomy
- Bilateral salpingo-oophorectomy
- Omentectomy
- Lymph node sampling ( pelvic and para aortic)
- Omentectomy
- Pelvic washing /asciting sampling

35. Debulking Surgery
•The current recommendation is to aim
for minimum residual disease, leaving
deposits with a maximum individual
diameter of 1 cm

36. Choice of surgeon
• Ovarian cancer or cases with high level of suspicion should be
managed by a trained gynaecological oncologist (i.e. RMI >200)

37. Classification of Chemotherapy
Agents
Department of Obstetrics & Gynaecology, RCSI
•Alkylating Agents:
• impair cell function by forming covalent bonds with amino, carboxyl,
sulfhydral and phosphate groups.
• This alkylation occurs in DNA, RNA, and proteins.
• Alkylating agents are classified according to their chemical
structures and mechanisms of covalent bonds.
1. Nitrogen Mustards: cyclophosphamide,chlorambucil
2. Nitrosureas: highly lipid soluble, mainly used in brain
tumours
3. Platinum complexes: carboplatin, cisplatin

38. Classification of Chemotherapy
Agents
Department of Obstetrics & Gynaecology, RCSI
• Antimetabolites: are structural analogues of naturally occurring
compounds.
•They exert toxicity either by competing with normal
metabolites or substituting for a metabolite that is
normally incorporated into DNA or RNA.
•They are divided as follows:
1. Folate Analogues: methotrexate
2. Purine/Pyrimidine/ Adenosine analogues:
Mercaptopurine

39. Classification of Chemotherapy
Agents
•Natural Products: a variety of compounds with anti-
tumour activity have been isolated from natural
substances such as plants, fungi, bacteria.
1. Taxanes: Paclitaxel/Docetaxel are semi-synthetic
derivatives from yew plants. They cause
microtubular assembly and stability which blocks
the cell in mitosis.
2. Anti-tumour antibiotics: doxorubicin
3. Epipodophyllotoxins: etoposide

40. Side Effects
•Taxanes (Paclitaxel): bone marrow suppression,
cardiotoxicity, peripheral neuropathy, rash, hair loss,
mucositis, myalgia
•Carboplatin: bone marrow suppression, nausea and
vomiting, peripheral neuropathy, ototoxicity
•Cisplatin: renal damage, nausea, vomiting,
peripheral neuropathy, bone marrow depression,
ototoxicity

41. Side Effects
• Chemotherapy can have life-threatening complications.
• A number of baseline investigations are performed before deciding on the
most appropriate treatment regime.
• Baseline investigations include:
• Renal Function - 24 hour creatinine clearance
• Liver Function Tests
• Audiometry
• Cardiac Function – echo
• The treatment regime involves anti-emetics and steroids to
reduce the side effects of vomiting and hypersensitivity
reactions

42. Stage IA, IB or grade 1/2
• Do not require adjuvant chemotherapy
• However they must have undergone appropriate surgical staging

43. Stage IC or stage IA/IB grade 3
• Adjuvant chemotherapy warranted
• Paclitaxel and carboplatin is the combination regimen of choice
• Those allergic to paclitaxel, combination of carboplatin and docetaxel
is a suitable alternative
• Recurrence rate of ovarian cancer in patient completing 6 cycles was
24% lower than those receiving 3 cycles. However the difference was
not statistically significant
• Six cycles associated with more toxicity (neurotoxicity , anaemia and
granulocytopenia)

44. Stage II,III and IV ( completely or
optimally debulked
• Intraoperative histology to confirm ovarian ca
• Surgery followed by chemo preferred
• Those who are not surgical candidates, neoadjuvant Chemo should
be considered
• If advanced disease discovered, maximal surgical effort to debulk all
tumour deposits Necessary
• Those who undergo complete or optimal debulking surgery(no
nodule >1cm) IP chemo with cisplatin and paclitaxel recommended.

45. Stage II,III and IV ( sub-optimally
debulked)
• Surgery followed by chemo preferred
• Those who are not surgical candidates, neoadjuvant Chemo should
be considered
• Paclitaxel and carboplatin for 6 to 8 cycles

46. Platinum-sensitive recurrent
disease
Those who are treatment free for more than 6 months after achieving
complete response post first line tx
• Combination therapy with carboplatin+liposomal doxorubicin,
carboplatin+paclitaxel , carboplatin +gemtricitabine

47. Platinum-resistant recurrent
disease
Those who are treatment free for less than 6 months
• Palliative chemotherapy – doxorubicin liposomal, topotecan,
gemcitabine, paclitaxel, bevacizumab, pemetrexed and etoposide
• Palliative surgery
- Colostomy
- Lysis of adhesions
- Management of small bowel obstruction
• No universal standard
• Selection based on patient factors (performance status, bone marrow
reserve, quality of life)

48. Tumours with BRCA1/BRCA2
mutations
Poly adenosine diphosphonate (ADP) ribose polymerase (PARP) act by
interfering repair in cancer cells with aberrant BRCA genes
Olaparib – has been approved by European Medicines Agency for
women with relapsed ovarian cancer with mutations in one of the two
BRCA genes who have responded to platinum based chemotherapy

49. Role of radiotherapy
• Radiotherapy is used infrequently in the treatment of ovarian
carcinoma
• There is no evidence to support the use of adjuvant radiotherapy in
epithelial ovarian cancer
Adjuvant Whole Abdominal Radiation Therapy (WART)
- Used in stage III ovarian cancer
- >2cm residual
- Complication of WART
• Acute – diarrhea, nausea/vomiting, leukopenia, thrombocytopenia
• Chronic- transient lft elevation, chronic diarrhea, basal pneumonitis,
serious bowel obstruction
• Can also be used for bone and brain mets

50. Follow-up
• The ideal and most effective follow-up of asymptomatic women who
have completed primary debulking surgery and chemotherapy and
have no clinical evidence of disease is unclear
• Current practice
•Follow-up every three months in the first
two years and to reduce that to six monthly
interval until five years have elapsed

51. Palliative Care
• Is a comprehensive approach towards the optimization of
quality of life in patients with a life-limiting illness.
Pain Management:
In gynaecological malignancies patients can develop severe
neuropathic pain secondary to lumbosacral plexus invasion or
visceral or perineal pain.
1. Treatment of nausea, vomiting, constipation.
2. Correction of anemia
3.. Psychological issues

52. References
1.Malaysian National Cancer Registry Report 2007-2011
2.Björkholm Elisabet, Pettersson Folke, Einhorn Nina, Krebs I, Nilsson Bjorn, Tjernberg B. Long-term follow-
up and prognostic factors in ovarian carcinoma; the radiumhemmet series 1958 to 1973. Acta Radiologica
Oncol. 1982;21:413–9. [PubMed]
3.Högberg Thomas, Carstensen John, Simonsen Ernst. Treatment results and prognostic factors in a
population-based study of epithelial ovarian cancer. Gynecol Onco. 1993;48:38–49. [PubMed] Society of
Gynecologic Oncology
4.Sorbe Bengt, Frankendal Bo, Veress Bela. Importance of histologic grading in the prognosis of epithelial
ovarian carcinoma. Obstet Gynecol. 1982;59:576–82. [PubMed] ACOG practice bulletin
5.Nice CG122 Ovarian cancer: recognition and initial management
6.BMJ best practice- ovarian cancer
7.Oxford handbook of obstetrics and gynaecology 3rd edition
8.NCCN Guidelines for Patients Ovarian Cancer version 1 2017
9. WHO classification of ovarian neoplasms. PathologyOutlines.com website.
http://www.pathologyoutlines.com/topic/ovarytumorwhoclassif.html. Accessed January 26th, 2019.