Ovarian cancer and treatment

Question 1

What are the risk factors for ovarian cancer?

Answer 1

• > 50yrs
• Nulliparity (orlow)
• delayed pregnancy
• FH breast cancer/ovarian cancer
• BRCA1 (40%)
• BRCA2 (18%)

the more times ovulated, the higher the risk

Question 2

Is screening done for ovarian cancer?

Answer 2

Not for general population

in high risk women – FH that appears to place them at high risk:
• should be offered referral to a clinical genetics service for assessment, confirmation of FH and consideration of genetic testing of an affected family member

Screening in high risk groups only through research

Question 3

What is a ‘high risk’ group for ovarian cancer?

Answer 3

• all women with non-mucinous ovarian or fallopian tube cancer should be offered BRCA 1 and BRCA2 mutation testing
• women with ovarian cancer and FH of breast/ovarian/colon cancer should have genetic risk assessment
• BRCA1 and BRCA2 mutation testing considered in family with a 10% or more risk of mutation

Primary care and specialist cancer genetic services should be encouraged to work in close collaboration to ensure efficient genetic cancer risk assessment in medium/high risk individuals.

Question 4

Prophylactic salpingo-oophorectomy:

• who is offered this?
• what can be used after oophorectomy until natural time of menopause?
• what does any patient recieving a prophylactic oophorectomy recieve?

Answer 4

• BRCA1 or BRCA2 mutation positive women offered prophylactic oophorectomy and removal fallopian tubes at a relevant time of their life
• High risk women with no identified mutations can discuss pros and cons of prophylactic salpingo-oophorectomy.
• HRT can be used after oophorectomy till natural time of menopause without losing benefits of breast cancer risk reduction.
• Any prophylactic salpingo-oophorectomy pt should be offered counselling, support and info before and after surgery.

Question 5

How can ovarian cancer present?

Answer 5

¥ often presents late (60% late stage at diagnosis)

¥	non-specific presentation
Ð	ascites/ bloating
Ð	pelvic mass/ bladder dysfunction
Ð	pleural effusion/shortness of breath
Ð	incidental finding

Question 6

What is BEAT?

Answer 6

BEAT – ovarian cancer awareness
B is for bloating that is persistent (doesn’t come and go)
E is for eating less and feeling fuller (difficulty eating)
A is for abdominal pain
T is for telling your GP

Question 7

What is included in the general diagnosis of ovarian cancer?

Answer 7

¥ Blood test- CA125
¥ ultrasound- transvaginal/abdominal
¥ cytology- pleural fluid/ ascites
¥ pathology

Question 8

What are the SIGN guidelines for considering a diagnosis of ovarian cancer?

Answer 8

Diagnosis of ovarian cancer should be considered in women with:
• 1+ symptoms of:
o abdominal distension
o bloating (with or without abdominal pain)
o feeling full quickly
o difficulty eating
o urinary symptom
of a duration of LESS than 12mths and occurring more than 12 times per month

Question 9

what are the SIGN guidelines for CA125 and urgent pelvic ultrasound?

Answer 9

• persistent abdominal distension
• feeling full and/or loss of appetite
• pelvic or abdominal pain
• increased urinary urgency and/or frequeny
particularly if occurring more than 12 times per month/if she is over 50yrs

Question 10

If symptoms persist or worsen despite normal CA 125 and a negative ultrasound scan - what is done?

Answer 10

refer to secondary care.

Question 11

What is calculated in secondary care using information from USS and Ca125?

Answer 11

RMI (risk malignancy index)

USS features:
-multilocular cyst
-solid areas
-bilateral lesions
-ascites
-intra-abdo mets
Give a score of:
0= none
1 = 1 abnormality
3 = 2+ abnormalities

Premenopausal = 1
Post menopausal = 3

Ca125 in U/ml

RMI score = USS score X menopausal score X CA125 level

Patients with an RMI >200 should be referred to a gynaecology- oncology multidisciplinary team.

Question 12

Describe the staging for ovarian cancer

Answer 12

FIGO stage:-
I. confined to 1 or both ovaries
II. spread to other pelvic organs eg uterus, fallopian tubes
III. spread beyond the pelvis within the abdomen
IV. spread into other organs eg liver, lungs

Question 13

What is the prognosis of ovarian cancer?

Answer 13

Stage 1 = 80/90% 5yr survival

Stage 2 = 65% 5yr survival

Stage 3 = 15-35%

up to 15%

Question 14

Describe the patterns of spread of ovarian cancer

Answer 14

1. transcoelomic spread/ peritoneal seeding within pelvis → abdominal cavity
2. haematogenous spread → liver, lungs,
   brain- late and rare
3. incidence of brain metastases in ovarian cancer <2%

Question 15

Describe the treatment options in general for ovarian cancer

Answer 15

¥ Surgery (TAH, BSO, omentectomy, optimal debulking)
¥ surgery and chemotherapy
¥ chemotherapy and surgery
¥ timing and sequence

Question 16

Describe the surgical management of early ovarian cancer

Answer 16

Management of early disease:
• don’t do routine systematic lymphadenectomy in early stage epithelial ovarian cancer
• retroperitoneal lymph node sampling should be considered as part of staging apparent early stage disease
• in stages 1a, grade 1 or grade 2 disease do fertility conserving surgery (if contralateral ovary appears normal and no evidence omental/peritoneal disease)
• optimal surgical staging should be done, including biopsy of suspicious peritoneal nodules, infracolic omentectomy and iliac and peri-aortic lymph node sampling.

Question 17

Describe surgical therapy of advanced disease

Answer 17

• aim = complete cytoreduction
• use of neoadjuvant chemo in stage 3c or 4 may be considered as alternative to primary debulking surgery
• With regard to selecting who will benefit from neoadjuvant chemotherapy, treatment should be individualised to the patient taking into account resectability, age, histology, performance status and after ruling out the possibility of other primary tumours, and after full discussion at multidisciplinary team meetings.”

Debulking:
• Complete” if there is no visible tumour left after surgery,
• ”optimal” if the residual tumour is <1cm
• “suboptimal” if >1cm.

Question 18

What is the surgical treatment for relapsed disease?

Answer 18

• if platinum-sensitive relapsed epithelial ovarian cancer, secondary cytoreductive surgery may be appropriate and improve overall survival
• The aim should be complete resection of all macroscopic disease. Where possible, this should be done in the context of a clinical trial.”

Question 19

Chemotherapy for ovarian cancer:

• which agents are used?
• does ovarian cancer tend to recur

Answer 19

¥ response rates of 60-70%- carboplatin/ paclitaxel
¥ relapse rates high
¥ palliative chemotherapy- carboplatin, paclitaxel, etoposide, caelyx, topotecan, gemcitabine, chlorambucil etc etc
¥ most with advanced disease recur (70%)
¥ relapsing, chronic illness
¥ some receive many classes of chemotherapeutic agents before their disease becomes truly drug resistant

carboplatin does not cause alopecia, taxol is more toxic and causes alopecia and peripheral neuropathy

Question 20

What chemotherapy is used for early disease?

Answer 20

• all women with high grade, early stage 1a-1b, consider adjuvant chemo
• for early stage, maintenance cytotoxic chemo not given

Question 21

What chemotherapy is used for advanced disease?

Answer 21

• first line chemo of epithelial ovarian cancer includes platinum agent, in combo or as single agent (unless specifically contraindicated)
• Carboplatin is the platinum drug of choice in both single and combination therapy.
• Paclitaxel is recommended in combination therapy with platinum in the first line post-surgery treatment of epithelial ovarian cancer (where the potential benefits justify the toxicity of the therapy.)
• In those unable to tolerate paclitaxel, peglated liposomal doxorubicin or gemcitabine in combination with carboplatin can be used as an alternative.
• Patients who are unfit for combination therapy should be offered single agent carboplatin.
• A third cytotoxic agent should not be added to carboplatin and paclitaxel.
• Carboplatin AUC 6 (day 1 q21) and paclitaxel 80 mg/m2 (day 1, 8, 15 q21) may be considered for the treatment of first line ovarian cancer.
• The increased toxicity and frequency of visits need to be discussed with the patient.

Question 22

When is intraretroperitoneal chemo used?

Answer 22

Chemo which includes an intraperitoneal element can be considered for:
• New diagnosis of epithelial ovarian cancer
• AND
• Residual disease of ≤1cm after primary surgery
Provided that a regimen of proven benefit in a clinical trial compared to IV therapy is used, it is delivered in a centre with appropriate expertise and potential toxicities are fully explained.

Where possible, women receiving intraperitoneal chemo should be enrolled in ongoing clinical trials.

Question 23

What is the treatment for relapsed ovarian cancer?

Answer 23

• Women with platinum-sensitive relapsed ovarian cancer should be treated with
a platinum based combination with paclitaxel, PLDH or gemcitabine.

Hormonal therapy with tamoxifen or an aromatase inhibitor (letrozole) can be used:
• women with recurrent, platinum-resistant, ovarian cancer
or
• in those wishing to avoid or delay further chemotherapy
o particularly where their original tumour is expressing the oestrogen receptor.

Question 24

what is included in follow up of ovarian cancer?

Answer 24

Treatment of first relapse of ovarian cancer should be guided by the development of symptoms.
• In the absence of symptoms, routine measurement of CA 125 during follow up is not mandatory

Question 25

What is different about BRCA mutations in ovarian cancer?

Answer 25

¥	different presentation
¥	different sites of relapse
¥	different prognosis
¥	different response to treatment
¥	different treatments

different treatments
¥	Less paclitaxel, more carboplatin
¥	PARP inhibitors
¥	oral, well tolerated, effective treatments for BRCA related  Ovarian Cancer
improved prognosis